Jennifer Wilson MD, MS

All Publications

• Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity-IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Ma, K. C., Surie, D., Lauring, A. S., Martin, E. T., Leis, A. M., Papalambros, L., Gaglani, M., Columbus, C., Gottlieb, R. L., Ghamande, S., Peltan, I. D., Brown, S. M., Ginde, A. A., Mohr, N. M., Gibbs, K. W., Hager, D. N., Saeed, S., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Khan, A., Hough, C. L., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Parikh, B., Exline, M. C., Vaughn, I. A., Ramesh, M., Safdar, B., Mosier, J., Harris, E. S., Shapiro, N. I., Felzer, J., Zhu, Y., Grijalva, C. G., Halasa, N., Chappell, J. D., Womack, K. N., Rhoads, J. P., Baughman, A., Swan, S. A., Johnson, C. A., Rice, T. W., Casey, J. D., Blair, P. W., Han, J. H., Ellington, S., Lewis, N. M., Thornburg, N., Paden, C. R., Atherton, L. J., Self, W. H., Dawood, F. S., DeCuir, J. 2024

  Abstract

  Assessing variant-specific COVID-19 vaccine effectiveness (VE) and severity can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial divergence from co-circulating XBB lineages.We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression.585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations.Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB.

  View details for DOI 10.1093/cid/ciae405

  View details for PubMedID 39107255

• Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccination Against SARS-CoV-2 Omicron XBB and BA.2.86/JN.1 Lineage Hospitalization and a Comparison of Clinical Severity - IVY Network, 26 Hospitals, October 18, 2023-March 9, 2024. medRxiv : the preprint server for health sciences Ma, K. C., Surie, D., Lauring, A. S., Martin, E. T., Leis, A. M., Papalambros, L., Gaglani, M., Columbus, C., Gottlieb, R. L., Ghamande, S., Peltan, I. D., Brown, S. M., Ginde, A. A., Mohr, N. M., Gibbs, K. W., Hager, D. N., Saeed, S., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Khan, A., Hough, C. L., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Parikh, B., Exline, M. C., Vaughn, I. A., Ramesh, M., Safdar, B., Mosier, J., Harris, E. S., Shapiro, N. I., Felzer, J., Zhu, Y., Grijalva, C. G., Halasa, N., Chappell, J. D., Womack, K. N., Rhoads, J. P., Baughman, A., Swan, S. A., Johnson, C. A., Rice, T. W., Casey, J. D., Blair, P. W., Han, J. H., Ellington, S., Lewis, N. M., Thornburg, N., Paden, C. R., Atherton, L. J., Self, W. H., Dawood, F. S., DeCuir, J. 2024

  Abstract

  Assessing COVID-19 vaccine effectiveness (VE) and severity of SARS-CoV-2 variants can inform public health risk assessments and decisions about vaccine composition. BA.2.86 and its descendants, including JN.1 (referred to collectively as "JN lineages"), emerged in late 2023 and exhibited substantial genomic divergence from co-circulating XBB lineages.We analyzed patients hospitalized with COVID-19-like illness at 26 hospitals in 20 U.S. states admitted October 18, 2023-March 9, 2024. Using a test-negative, case-control design, we estimated the effectiveness of an updated 2023-2024 (Monovalent XBB.1.5) COVID-19 vaccine dose against sequence-confirmed XBB and JN lineage hospitalization using logistic regression. Odds of severe outcomes, including intensive care unit (ICU) admission and invasive mechanical ventilation (IMV) or death, were compared for JN versus XBB lineage hospitalizations using logistic regression.585 case-patients with XBB lineages, 397 case-patients with JN lineages, and 4,580 control-patients were included. VE in the first 7-89 days after receipt of an updated dose was 54.2% (95% CI = 36.1%-67.1%) against XBB lineage hospitalization and 32.7% (95% CI = 1.9%-53.8%) against JN lineage hospitalization. Odds of ICU admission (adjusted odds ratio [aOR] 0.80; 95% CI = 0.46-1.38) and IMV or death (aOR 0.69; 95% CI = 0.34-1.40) were not significantly different among JN compared to XBB lineage hospitalizations.Updated 2023-2024 COVID-19 vaccination provided protection against both XBB and JN lineage hospitalization, but protection against the latter may be attenuated by immune escape. Clinical severity of JN lineage hospitalizations was not higher relative to XBB lineage hospitalizations.

  View details for DOI 10.1101/2024.06.04.24308470

  View details for PubMedID 38883802

  View details for PubMedCentralID PMC11177903

• Association between emergency department disposition and mortality in patients with COVID-19 acute respiratory distress syndrome. Journal of the American College of Emergency Physicians open Lebold, K. M., Moore, A. R., Sanchez, P. A., Pacheco-Navarro, A. E., O'Donnell, C., Roque, J., Parmer, C., Pienkos, S., Levitt, J., Collins, W. J., Rogers, A. J., Wilson, J. G. 2024; 5 (3): e13192

  Abstract

  Patients hospitalized for COVID-19 frequently develop hypoxemia and acute respiratory distress syndrome (ARDS) after admission. In non-COVID-19 ARDS studies, admission to hospital wards with subsequent transfer to intensive care unit (ICU) is associated with worse outcomes. We hypothesized that initial admission to the ward may affect outcomes in patient with COVID-19 ARDS.This was a retrospective study of consecutive adults admitted for COVID-19 ARDS between March 2020 and March 2021 at Stanford Health Care. Mortality scores at hospital admission (Coronavirus Clinical Characterization Consortium Mortality Score [4C score]) and ICU admission (Simplified Acute Physiology Score III [SAPS-III]) were calculated, as well as ROX index for patients on high flow nasal oxygen. Patients were classified by emergency department (ED) disposition (ward-first vs. ICU-direct), and 28- and 60-day mortality and highest level of respiratory support within 1 day of ICU admission were compared. A second cohort (April 2021‒July 2022, n = 129) was phenotyped to validate mortality outcome.A total of 157 patients were included, 48% of whom were first admitted to the ward (n = 75). Ward-first patients had more comorbidities, including lung disease. Ward-first patients had lower 4C and similar SAPS-III score, yet increased mortality at 28 days (32% vs. 17%, hazard ratio [HR] 2.0, 95% confidence interval [95% CI] 1.0‒3.7, p = 0.039) and 60 days (39% vs. 23%, HR 1.83, 95% CI 1.04‒3.22, p = 0.037) compared to ICU-direct patients. More ward-first patients escalated to mechanical ventilation on day 1 of ICU admission (36% vs. 14%, p = 0.002) despite similar ROX index. Ward-first patients who upgraded to ICU within 48 h of ED presentation had the highest mortality. Mortality findings were replicated in a sensitivity analysis.Despite similar baseline risk scores, ward-first patients with COVID-19 ARDS had increased mortality and escalation to mechanical ventilation compared to ICU-direct patients. Ward-first patients requiring ICU upgrade within 48 h were at highest risk, highlighting a need for improved identification of this group at ED admission.

  View details for DOI 10.1002/emp2.13192

  View details for PubMedID 38887225

  View details for PubMedCentralID PMC11180691

• Early trajectories of virological and immunological biomarkers and clinical outcomes in patients admitted to hospital for COVID-19: an international, prospective cohort study. The Lancet. Microbe Jensen, T. O., Murray, T. A., Grandits, G. A., Jain, M. K., Grund, B., Shaw-Saliba, K., Matthay, M. A., Abassi, M., Ardelt, M., Baker, J. V., Chen, P., Dewar, R. L., Goodman, A. L., Hatlen, T. J., Highbarger, H. C., Holodniy, M., Lallemand, P., Laverdure, S., Leshnower, B. G., Looney, D., Moschopoulos, C. D., Mugerwa, H., Murray, D. D., Mylonakis, E., Nagy-Agren, S., Rehman, M. T., Rupert, A., Stevens, R., Turville, S., Weintrob, A., Wick, K., Lundgren, J., Ko, E. R. 2024

  Abstract

  Serial measurement of virological and immunological biomarkers in patients admitted to hospital with COVID-19 can give valuable insight into the pathogenic roles of viral replication and immune dysregulation. We aimed to characterise biomarker trajectories and their associations with clinical outcomes.In this international, prospective cohort study, patients admitted to hospital with COVID-19 and enrolled in the Therapeutics for Inpatients with COVID-19 platform trial within the Accelerating COVID-19 Therapeutic Interventions and Vaccines programme between Aug 5, 2020 and Sept 30, 2021 were included. Participants were included from 108 sites in Denmark, Greece, Poland, Singapore, Spain, Switzerland, Uganda, the UK, and the USA, and randomised to placebo or one of four neutralising monoclonal antibodies: bamlanivimab (Aug 5 to Oct 13, 2020), sotrovimab (Dec 16, 2020, to March 1, 2021), amubarvimab-romlusevimab (Dec 16, 2020, to March 1, 2021), and tixagevimab-cilgavimab (Feb 10 to Sept 30, 2021). This trial included an analysis of 2149 participants with plasma nucleocapsid antigen, anti-nucleocapsid antibody, C-reactive protein (CRP), IL-6, and D-dimer measured at baseline and day 1, day 3, and day 5 of enrolment. Day-90 follow-up status was available for 1790 participants. Biomarker trajectories were evaluated for associations with baseline characteristics, a 7-day pulmonary ordinal outcome, 90-day mortality, and 90-day rate of sustained recovery.The study included 2149 participants. Participant median age was 57 years (IQR 46-68), 1246 (58·0%) of 2149 participants were male and 903 (42·0%) were female; 1792 (83·4%) had at least one comorbidity, and 1764 (82·1%) were unvaccinated. Mortality to day 90 was 172 (8·0%) of 2149 and 189 (8·8%) participants had sustained recovery. A pattern of less favourable trajectories of low anti-nucleocapsid antibody, high plasma nucleocapsid antigen, and high inflammatory markers over the first 5 days was observed for high-risk baseline clinical characteristics or factors related to SARS-CoV-2 infection. For example, participants with chronic kidney disease demonstrated plasma nucleocapsid antigen 424% higher (95% CI 319-559), CRP 174% higher (150-202), IL-6 173% higher (144-208), D-dimer 149% higher (134-165), and anti-nucleocapsid antibody 39% lower (60-18) to day 5 than those without chronic kidney disease. Participants in the highest quartile for plasma nucleocapsid antigen, CRP, and IL-6 at baseline and day 5 had worse clinical outcomes, including 90-day all-cause mortality (plasma nucleocapsid antigen hazard ratio (HR) 4·50 (95% CI 3·29-6·15), CRP HR 3·37 (2·30-4·94), and IL-6 HR 5·67 (4·12-7·80). This risk persisted for plasma nucleocapsid antigen and CRP after adjustment for baseline biomarker values and other baseline factors.Patients admitted to hospital with less favourable 5-day biomarker trajectories had worse prognosis, suggesting that persistent viral burden might drive inflammation in the pathogenesis of COVID-19, identifying patients that might benefit from escalation of antiviral or anti-inflammatory treatment.US National Institutes of Health.

  View details for DOI 10.1016/S2666-5247(24)00015-6

  View details for PubMedID 38815595

• Severity of Respiratory Syncytial Virus vs COVID-19 and Influenza Among Hospitalized US Adults. JAMA network open Surie, D., Yuengling, K. A., DeCuir, J., Zhu, Y., Lauring, A. S., Gaglani, M., Ghamande, S., Peltan, I. D., Brown, S. M., Ginde, A. A., Martinez, A., Mohr, N. M., Gibbs, K. W., Hager, D. N., Ali, H., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Leis, A. M., Khan, A., Hough, C. L., Bender, W. S., Duggal, A., Bendall, E. E., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Shapiro, N. I., Columbus, C., Vaughn, I. A., Ramesh, M., Mosier, J. M., Safdar, B., Casey, J. D., Talbot, H. K., Rice, T. W., Halasa, N., Chappell, J. D., Grijalva, C. G., Baughman, A., Womack, K. N., Swan, S. A., Johnson, C. A., Lwin, C. T., Lewis, N. M., Ellington, S., McMorrow, M. L., Martin, E. T., Self, W. H. 2024; 7 (4): e244954

  Abstract

  On June 21, 2023, the Centers for Disease Control and Prevention recommended the first respiratory syncytial virus (RSV) vaccines for adults aged 60 years and older using shared clinical decision-making. Understanding the severity of RSV disease in adults can help guide this clinical decision-making.To describe disease severity among adults hospitalized with RSV and compare it with the severity of COVID-19 and influenza disease by vaccination status.In this cohort study, adults aged 18 years and older admitted to the hospital with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 US states from February 1, 2022, to May 31, 2023. Clinical data during each patient's hospitalization were collected using standardized forms. Data were analyzed from August to October 2023.RSV, SARS-CoV-2, or influenza infection.Using multivariable logistic regression, severity of RSV disease was compared with COVID-19 and influenza severity, by COVID-19 and influenza vaccination status, for a range of clinical outcomes, including the composite of invasive mechanical ventilation (IMV) and in-hospital death.Of 7998 adults (median [IQR] age, 67 [54-78] years; 4047 [50.6%] female) included, 484 (6.1%) were hospitalized with RSV, 6422 (80.3%) were hospitalized with COVID-19, and 1092 (13.7%) were hospitalized with influenza. Among patients with RSV, 58 (12.0%) experienced IMV or death, compared with 201 of 1422 unvaccinated patients with COVID-19 (14.1%) and 458 of 5000 vaccinated patients with COVID-19 (9.2%), as well as 72 of 699 unvaccinated patients with influenza (10.3%) and 20 of 393 vaccinated patients with influenza (5.1%). In adjusted analyses, the odds of IMV or in-hospital death were not significantly different among patients hospitalized with RSV and unvaccinated patients hospitalized with COVID-19 (adjusted odds ratio [aOR], 0.82; 95% CI, 0.59-1.13; P = .22) or influenza (aOR, 1.20; 95% CI, 0.82-1.76; P = .35); however, the odds of IMV or death were significantly higher among patients hospitalized with RSV compared with vaccinated patients hospitalized with COVID-19 (aOR, 1.38; 95% CI, 1.02-1.86; P = .03) or influenza disease (aOR, 2.81; 95% CI, 1.62-4.86; P < .001).Among adults hospitalized in this US cohort during the 16 months before the first RSV vaccine recommendations, RSV disease was less common but similar in severity compared with COVID-19 or influenza disease among unvaccinated patients and more severe than COVID-19 or influenza disease among vaccinated patients for the most serious outcomes of IMV or death.

  View details for DOI 10.1001/jamanetworkopen.2024.4954

  View details for PubMedID 38573635

• Interim Effectiveness of Updated 2023-2024 (Monovalent XBB.1.5) COVID-19 Vaccines Against COVID-19-Associated Emergency Department and Urgent Care Encounters and Hospitalization Among Immunocompetent Adults Aged ≥18 Years - VISION and IVY Networks, September 2023-January 2024. MMWR. Morbidity and mortality weekly report DeCuir, J., Payne, A. B., Self, W. H., Rowley, E. A., Dascomb, K., DeSilva, M. B., Irving, S. A., Grannis, S. J., Ong, T. C., Klein, N. P., Weber, Z. A., Reese, S. E., Ball, S. W., Barron, M. A., Naleway, A. L., Dixon, B. E., Essien, I., Bride, D., Natarajan, K., Fireman, B., Shah, A. B., Okwuazi, E., Wiegand, R., Zhu, Y., Lauring, A. S., Martin, E. T., Gaglani, M., Peltan, I. D., Brown, S. M., Ginde, A. A., Mohr, N. M., Gibbs, K. W., Hager, D. N., Prekker, M., Mohamed, A., Srinivasan, V., Steingrub, J. S., Khan, A., Busse, L. W., Duggal, A., Wilson, J. G., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Columbus, C., Vaughn, I. A., Safdar, B., Mosier, J. M., Harris, E. S., Casey, J. D., Chappell, J. D., Grijalva, C. G., Swan, S. A., Johnson, C., Lewis, N. M., Ellington, S., Adams, K., Tenforde, M. W., Paden, C. R., Dawood, F. S., Fleming-Dutra, K. E., Surie, D., Link-Gelles, R., CDC COVID-19 Vaccine Effectiveness Collaborators, Ghamande, S., Gottlieb, R., McNeal, T., Raver, C., Bender, W., Fletcher, L., Heaton, P., Kane, S., McEvoy, C., Thapa, S., Vazquez-Benitez, G., Frosch, A., Lamerato, L. E., Ramesh, M., Arnofer, J., Ali, H., Hopkins, J., Crane, B., Dandamudi, P., Goddard, K., Hansen, J., Timbol, J., Zerbo, O., Allen, K., Duszynski, T., Fadel, W., Rogerson, C., Qadir, N., Chavez, C., Doyle, B., Mayer, D., Rao, S., Rivas, C., Johnson, N. J., Baughman, A., Lwin, C. T., Rhoads, J. P., Womack, K. N., Dunne, M., Ciesla, A., Mak, J., Najdowski, M., Ray, C. 2024; 73 (8): 180-188

  Abstract

  In September 2023, CDC's Advisory Committee on Immunization Practices recommended updated 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination for all persons aged ≥6 months to prevent COVID-19, including severe disease. However, few estimates of updated vaccine effectiveness (VE) against medically attended illness are available. This analysis evaluated VE of an updated COVID-19 vaccine dose against COVID-19-associated emergency department (ED) or urgent care (UC) encounters and hospitalization among immunocompetent adults aged ≥18 years during September 2023-January 2024 using a test-negative, case-control design with data from two CDC VE networks. VE against COVID-19-associated ED/UC encounters was 51% (95% CI = 47%-54%) during the first 7-59 days after an updated dose and 39% (95% CI = 33%-45%) during the 60-119 days after an updated dose. VE estimates against COVID-19-associated hospitalization from two CDC VE networks were 52% (95% CI = 47%-57%) and 43% (95% CI = 27%-56%), with a median interval from updated dose of 42 and 47 days, respectively. Updated COVID-19 vaccine provided increased protection against COVID-19-associated ED/UC encounters and hospitalization among immunocompetent adults. These results support CDC recommendations for updated 2023-2024 COVID-19 vaccination. All persons aged ≥6 months should receive updated 2023-2024 COVID-19 vaccine.

  View details for DOI 10.15585/mmwr.mm7308a5

  View details for PubMedID 38421945

• Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Aggarwal, N. R., Nordwall, J., Braun, D. L., Chung, L., Coslet, J., Der, T., Eriobu, N., Ginde, A. A., Hayanga, A. J., Highbarger, H., Holodniy, M., Horcajada, J. P., Jain, M. K., Kim, K., Laverdure, S., Lundgren, J., Natarajan, V., Nguyen, H. H., Pett, S. L., Phillips, A., Poulakou, G., Price, D. A., Robinson, P., Rogers, A. J., Sandkovsky, U., Shaw-Saliba, K., Sturek, J. M., Trautner, B. W., Waters, M., Reilly, C. 2024

  Abstract

  Persistent mortality in adults hospitalized due to acute COVID-19 justifies pursuit of disease mechanisms and potential therapies. The aim was to evaluate which virus and host response factors were associated with mortality risk among participants in Therapeutics for Inpatients with COVID-19 (TICO/ACTIV-3) trials.A secondary analysis of 2625 adults hospitalized for acute SARS-CoV-2 infection randomized to 1 of 5 antiviral products or matched placebo in 114 centers on 4 continents. Uniform, site-level collection of participant baseline clinical variables was performed. Research laboratories assayed baseline upper respiratory swabs for SARS-CoV-2 viral RNA and plasma for anti-SARS-CoV-2 antibodies, SARS-CoV-2 nucleocapsid antigen (viral Ag), and interleukin-6 (IL-6). Associations between factors and time to mortality by 90 days were assessed using univariate and multivariable Cox proportional hazards models.Viral Ag ≥4500 ng/L (vs <200 ng/L; adjusted hazard ratio [aHR], 2.07; 1.29-3.34), viral RNA (<35 000 copies/mL [aHR, 2.42; 1.09-5.34], ≥35 000 copies/mL [aHR, 2.84; 1.29-6.28], vs below detection), respiratory support (<4 L O2 [aHR, 1.84; 1.06-3.22]; ≥4 L O2 [aHR, 4.41; 2.63-7.39], or noninvasive ventilation/high-flow nasal cannula [aHR, 11.30; 6.46-19.75] vs no oxygen), renal impairment (aHR, 1.77; 1.29-2.42), and IL-6 >5.8 ng/L (aHR, 2.54 [1.74-3.70] vs ≤5.8 ng/L) were significantly associated with mortality risk in final adjusted analyses. Viral Ag, viral RNA, and IL-6 were not measured in real-time.Baseline virus-specific, clinical, and biological variables are strongly associated with mortality risk within 90 days, revealing potential pathogen and host-response therapeutic targets for acute COVID-19 disease.

  View details for DOI 10.1093/cid/ciad780

  View details for PubMedID 38376212

• COMMON ICU DIAGNOSES ASSOCIATED WITH EARLY ED DOWNGRADE BY A NOVEL EMERGENCY CRITICAL CARE PROGRAM Gupta, P., Levin, N., Gordon, A., Wilson, J., Mitarai, T. LIPPINCOTT WILLIAMS & WILKINS. 2024

  View details for Web of Science ID 001131541100310

• Vaccine Effectiveness Against Influenza A-Associated Hospitalization, Organ Failure, and Death: United States, 2022-2023. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Lewis, N. M., Zhu, Y., Peltan, I. D., Gaglani, M., McNeal, T., Ghamande, S., Steingrub, J. S., Shapiro, N. I., Duggal, A., Bender, W. S., Taghizadeh, L., Brown, S. M., Hager, D. N., Gong, M. N., Mohamed, A., Exline, M. C., Khan, A., Wilson, J. G., Qadir, N., Chang, S. Y., Ginde, A. A., Mohr, N. M., Mallow, C., Lauring, A. S., Johnson, N. J., Gibbs, K. W., Kwon, J. H., Columbus, C., Gottlieb, R. L., Raver, C., Vaughn, I. A., Ramesh, M., Johnson, C., Lamerato, L., Safdar, B., Casey, J. D., Rice, T. W., Halasa, N., Chappell, J. D., Grijalva, C. G., Talbot, H. K., Baughman, A., Womack, K. N., Swan, S. A., Harker, E., Price, A., DeCuir, J., Surie, D., Ellington, S., Self, W. H. 2023

  Abstract

  Influenza circulation during the 2022-2023 season in the United States largely returned to pre-coronavirus disease 2019 (COVID-19)-pandemic patterns and levels. Influenza A(H3N2) viruses were detected most frequently this season, predominately clade 3C.2a1b.2a, a close antigenic match to the vaccine strain.To understand effectiveness of the 2022-2023 influenza vaccine against influenza-associated hospitalization, organ failure, and death, a multicenter sentinel surveillance network in the United States prospectively enrolled adults hospitalized with acute respiratory illness between 1 October 2022, and 28 February 2023. Using the test-negative design, vaccine effectiveness (VE) estimates against influenza-associated hospitalization, organ failures, and death were measured by comparing the odds of current-season influenza vaccination in influenza-positive case-patients and influenza-negative, SARS-CoV-2-negative control-patients.A total of 3707 patients, including 714 influenza cases (33% vaccinated) and 2993 influenza- and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-negative controls (49% vaccinated) were analyzed. VE against influenza-associated hospitalization was 37% (95% confidence interval [CI]: 27%-46%) and varied by age (18-64 years: 47% [30%-60%]; ≥65 years: 28% [10%-43%]), and virus (A[H3N2]: 29% [6%-46%], A[H1N1]: 47% [23%-64%]). VE against more severe influenza-associated outcomes included: 41% (29%-50%) against influenza with hypoxemia treated with supplemental oxygen; 65% (56%-72%) against influenza with respiratory, cardiovascular, or renal failure treated with organ support; and 66% (40%-81%) against influenza with respiratory failure treated with invasive mechanical ventilation.During an early 2022-2023 influenza season with a well-matched influenza vaccine, vaccination was associated with reduced risk of influenza-associated hospitalization and organ failure.

  View details for DOI 10.1093/cid/ciad677

  View details for PubMedID 38051664

• Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19. The Journal of infectious diseases Jensen, T. O., Grandits, G. A., Jain, M. K., Murray, T. A., Grund, B., Shaw-Saliba, K., Matthay, M. A., Abassi, M., Ardelt, M., Baker, J. V., Chen, P., Dewar, R. L., Goodman, A. L., Hatlen, T. J., Highbarger, H. C., Holodniy, M., Lallemand, P., Laverdure, S., Leshnower, B. G., Looney, D., Moschopoulos, C. D., Mugerwa, H., Murray, D. D., Mylonakis, E., Nagy-Agren, S., Rehman, M. T., Rupert, A., Stevens, R. A., Turville, S., Weintrob, A., Wick, K., Lundgren, J., Ko, E. R. 2023

  Abstract

  Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood.Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and d-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models.Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P < .001), and a steeper rate of decline through the first 5 days (P < .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale.Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed.NCT04501978.

  View details for DOI 10.1093/infdis/jiad446

  View details for PubMedID 37948759

• Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years - IVY Network, 20 US States, February 2022-May 2023 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Surie, D., Yuengling, K. A., DeCuir, J., Zhu, Y., Gaglani, M., Ginde, A. A., Talbot, H., Casey, J. D., Mohr, N. M., Ghamande, S., Gibbs, K. W., Files, C., Hager, D. N., Ali, H., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Leis, A. M., Khan, A., Hough, C. L., Bender, W. S., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Lauring, A. S., Shapiro, N. I., Columbus, C., Vaughn, I. A., Ramesh, M., Safdar, B., Halasa, N., Chappell, J. D., Grijalva, C. G., Baughman, A., Rice, T. W., Womack, K. N., Han, J. H., Swan, S. A., Mukherjee, I., Lewis, N. M., Ellington, S., McMorrow, M. L., Martin, E. T., Self, W. H., IVY Network 2023; 72 (40): 1083-1088

  Abstract

  On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making. Informed use of these vaccines requires an understanding of RSV disease severity. To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023. Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death. Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza. Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza. Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26). Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza. High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.

  View details for Web of Science ID 001084585300001

  View details for PubMedID 37796753

  View details for PubMedCentralID PMC10564326

• Further advancing emergency department triage prediction. Resuscitation Levin, N. M., Gordon, A. J., Htet, N., Wilson, J. G. 2023; 191: 109930

  View details for DOI 10.1016/j.resuscitation.2023.109930

  View details for PubMedID 37748821

• Elevated Plasma Interleukin-18 Identifies High-Risk Acute Respiratory Distress Syndrome Patients not Distinguished by Prior Latent Class Analyses Using Traditional Inflammatory Cytokines: A Retrospective Analysis of Two Randomized Clinical Trials. Critical care medicine Moore, A. R., Pienkos, S. M., Sinha, P., Guan, J., O'Kane, C. M., Levitt, J. E., Wilson, J. G., Shankar-Hari, M., Matthay, M. A., Calfee, C. S., Baron, R. M., McAuley, D. F., Rogers, A. J. 2023

  Abstract

  Interleukin-18 (IL-18) plasma level and latent class analysis (LCA) have separately been shown to predict prognosis and treatment response in acute respiratory distress syndrome (ARDS). IL-18 is a measure of inflammasome activation, a pathway potentially distinct from inflammation captured by biomarkers defining previously published LCA classes. We hypothesized that elevated IL-18 would identify distinct "high-risk" patients not captured by prior LCA classifications.Statins for acutely injured lungs from sepsis (SAILS) and hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction trial (HARP-2) are two large randomized, controlled trials in ARDS in which both LCA assignments and IL-18 levels were shown to predict mortality. We first evaluated the overlap between high IL-18 levels (≥ 800 pg/mL) with prior LCA class assignments using McNemar's test and then tested the correlation between IL-18 and LCA biomarkers using Pearson's exact test on log-2 transformed values. Our primary analysis was the association of IL-18 level with 60-day mortality in the hypoinflammatory LCA class, which was assessed using the Fisher exact test and Cox proportional hazards modeling adjusting for age, Acute Physiology and Chronic Health Evaluation score, and gender. Secondary analyses included the association of IL-18 and LCA with mortality within each IL-18/LCA subgroup.Secondary analysis of two multicenter, randomized controlled clinical trials of ARDS patients.Six hundred eighty-three patients in SAILS and 511 patients in HARP-2.None.We found that 33% of patients in SAILS and HARP-2 were discordant by IL-18 level and LCA class. We further found that IL-18 level was only modestly correlated (0.17-0.47) with cytokines used in the LCA assignment. A substantial subset of individuals classified as hypoinflammatory by LCA (14% of SAILS and 43% of HARP-2) were classified as high risk by elevated IL-18. These individuals were at high risk for mortality in both SAILS (42% 60-d mortality, odds ratio [OR] 3.3; 95% CI, 1.8-6.1; p < 0.001) and HARP-2 (27% 60-d mortality, OR 2.1; 95% CI, 1.2-3.8; p = 0.009).Plasma IL-18 level provides important additional prognostic information to LCA subphenotypes defined largely by traditional inflammatory biomarkers in two large ARDS cohorts.

  View details for DOI 10.1097/CCM.0000000000006028

  View details for PubMedID 37695136

• Right Ventricular Dysfunction Patterns Among Patients with COVID-19 in the Intensive Care Unit - a Retrospective Cohort Analysis. Annals of the American Thoracic Society Sanchez, P. A., O'Donnell, C. T., Francisco, N., Santana, E. J., Moore, A. R., Pacheco-Navarro, A., Roque, J., Lebold, K. M., Parmer, C. M., Pienkos, S. M., Celestin, B. E., Levitt, J. E., Collins, W. J., Lanspa, M. J., Ashley, E. A., Wilson, J. G., Haddad, F., Rogers, A. J. 2023

  Abstract

  Right ventricular (RV) dysfunction is common among patients hospitalized with COVID-19; however, its epidemiology may depend on the echocardiographic parameters used to define it.To evaluate the prevalence of abnormalities in three common echocardiographic parameters of RV function among COVID-19 patients admitted to the intensive care unit, as well as the effect of RV dilatation on differential parameter abnormality and the association of RV dysfunction with 60-day mortality.Retrospective cohort study of COVID-19 ICU patients between March 4th,2020 to March 4th, 2021, who received a transthoracic echocardiogram within 48 hours before to at most 7 days after ICU admission. RV dysfunction and dilatation respectively defined by guideline thresholds for tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), RV free wall longitudinal strain (RVFWS), and RV basal dimension or RV end-diastolic area. Association of RV dysfunction with 60-day mortality assessed through logistic regression adjusting for age, prior history of congestive heart failure, invasive ventilation at time of TTE and APACHE II score.116 patients were included, of which 69% had RV dysfunction by > 1 parameter and 36.3% of these had RV dilatation. The three most common patterns of RV dysfunction included: Presence of 3 abnormalities, the combination of abnormal RVFWS and TAPSE, and isolated TAPSE abnormality. Patients with RV dilatation had worse RVFAC (24% vs 36%, p = 0.001), worse RVFWS (16.3% vs 19.1%, p = 0.005), higher RVSP (45mmHg vs 31mmHg, p = 0.001) but similar TAPSE (13mm vs 13mm, p = 0.30) compared to those with normal RV size. After multivariable adjustment, 60-day mortality was significantly associated with RV dysfunction (OR 2.91, 95% CI 1.01 - 9.44), as was the presence of at least 2 parameter abnormalities.ICU patients with COVID-19 had significant heterogeneity in RV function abnormalities present with different patterns associated with RV dilatation. RV dysfunction by any parameter was associated with increased mortality. Therefore, a multiparameter evaluation may be critical in recognizing RV dysfunction in COVID-19.

  View details for DOI 10.1513/AnnalsATS.202303-235OC

  View details for PubMedID 37478340

• Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. The Lancet. Respiratory medicine Brown, S. M., Barkauskas, C. E., Grund, B., Sharma, S., Phillips, A. N., Leither, L., Peltan, I. D., Lanspa, M., Gilstrap, D. L., Mourad, A., Lane, K., Beitler, J. R., Serra, A. L., Garcia, I., Almasri, E., Fayed, M., Hubel, K., Harris, E. S., Middleton, E. A., Barrios, M. A., Mathews, K. S., Goel, N. N., Acquah, S., Mosier, J., Hypes, C., Salvagio Campbell, E., Khan, A., Hough, C. L., Wilson, J. G., Levitt, J. E., Duggal, A., Dugar, S., Goodwin, A. J., Terry, C., Chen, P., Torbati, S., Iyer, N., Sandkovsky, U. S., Johnson, N. J., Robinson, B. R., Matthay, M. A., Aggarwal, N. R., Douglas, I. S., Casey, J. D., Hache-Marliere, M., Georges Youssef, J., Nkemdirim, W., Leshnower, B., Awan, O., Pannu, S., O'Mahony, D. S., Manian, P., Awori Hayanga, J. W., Wortmann, G. W., Tomazini, B. M., Miller, R. F., Jensen, J. U., Murray, D. D., Bickell, N. A., Zatakia, J., Burris, S., Higgs, E. S., Natarajan, V., Dewar, R. L., Schechner, A., Kang, N., Arenas-Pinto, A., Hudson, F., Ginde, A. A., Self, W. H., Rogers, A. J., Oldmixon, C. F., Morin, H., Sanchez, A., Weintrob, A. C., Cavalcanti, A. B., Davis-Karim, A., Engen, N., Denning, E., Taylor Thompson, B., Gelijns, A. C., Kan, V., Davey, V. J., Lundgren, J. D., Babiker, A. G., Neaton, J. D., Lane, H. C. 2023

  Abstract

  There is a clinical need for therapeutics for COVID-19 patients with acute hypoxemic respiratory failure whose 60-day mortality remains at 30-50%. Aviptadil, a lung-protective neuropeptide, and remdesivir, a nucleotide prodrug of an adenosine analog, were compared with placebo among patients with COVID-19 acute hypoxaemic respiratory failure.TESICO was a randomised trial of aviptadil and remdesivir versus placebo at 28 sites in the USA. Hospitalised adult patients were eligible for the study if they had acute hypoxaemic respiratory failure due to confirmed SARS-CoV-2 infection and were within 4 days of the onset of respiratory failure. Participants could be randomly assigned to both study treatments in a 2 × 2 factorial design or to just one of the agents. Participants were randomly assigned with a web-based application. For each site, randomisation was stratified by disease severity (high-flow nasal oxygen or non-invasive ventilation vs invasive mechanical ventilation or extracorporeal membrane oxygenation [ECMO]), and four strata were defined by remdesivir and aviptadil eligibility, as follows: (1) eligible for randomisation to aviptadil and remdesivir in the 2 × 2 factorial design; participants were equally randomly assigned (1:1:1:1) to intravenous aviptadil plus remdesivir, aviptadil plus remdesivir matched placebo, aviptadil matched placebo plus remdesvir, or aviptadil placebo plus remdesivir placebo; (2) eligible for randomisation to aviptadil only because remdesivir was started before randomisation; (3) eligible for randomisation to aviptadil only because remdesivir was contraindicated; and (4) eligible for randomisation to remdesivir only because aviptadil was contraindicated. For participants in strata 2-4, randomisation was 1:1 to the active agent or matched placebo. Aviptadil was administered as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3. Remdesivir was administered as a 200 mg loading dose, followed by 100 mg daily maintenance doses for up to a 10-day total course. For participants assigned to placebo for either agent, matched saline placebo was administered in identical volumes. For both treatment comparisons, the primary outcome, assessed at day 90, was a six-category ordinal outcome: (1) at home (defined as the type of residence before hospitalisation) and off oxygen (recovered) for at least 77 days, (2) at home and off oxygen for 49-76 days, (3) at home and off oxygen for 1-48 days, (4) not hospitalised but either on supplemental oxygen or not at home, (5) hospitalised or in hospice care, or (6) dead. Mortality up to day 90 was a key secondary outcome. The independent data and safety monitoring board recommended stopping the aviptadil trial on May 25, 2022, for futility. On June 9, 2022, the sponsor stopped the trial of remdesivir due to slow enrolment. The trial is registered with ClinicalTrials.gov, NCT04843761.Between April 21, 2021, and May 24, 2022, we enrolled 473 participants in the study. For the aviptadil comparison, 471 participants were randomly assigned to aviptadil or matched placebo. The modified intention-to-treat population comprised 461 participants who received at least a partial infusion of aviptadil (231 participants) or aviptadil matched placebo (230 participants). For the remdesivir comparison, 87 participants were randomly assigned to remdesivir or matched placebo and all received some infusion of remdesivir (44 participants) or remdesivir matched placebo (43 participants). 85 participants were included in the modified intention-to-treat analyses for both agents (ie, those enrolled in the 2 x 2 factorial). For the aviptadil versus placebo comparison, the median age was 57 years (IQR 46-66), 178 (39%) of 461 participants were female, and 246 (53%) were Black, Hispanic, Asian or other (vs 215 [47%] White participants). 431 (94%) of 461 participants were in an intensive care unit at baseline, with 271 (59%) receiving high-flow nasal oxygen or non-invasive ventiliation, 185 (40%) receiving invasive mechanical ventilation, and five (1%) receiving ECMO. The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54). Up to day 90, 86 participants in the aviptadil group and 83 in the placebo group died. The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78). The primary safety outcome of death, serious adverse events, organ failure, serious infection, or grade 3 or 4 adverse events up to day 5 occurred in 146 (63%) of 231 patients in the aviptadil group compared with 129 (56%) of 230 participants in the placebo group (OR 1·40, 95% CI 0·94-2·08; p=0·10).Among patients with COVID-19-associated acute hypoxaemic respiratory failure, aviptadil did not significantly improve clinical outcomes up to day 90 when compared with placebo. The smaller than planned sample size for the remdesivir trial did not permit definitive conclusions regarding safety or efficacy.National Institutes of Health.

  View details for DOI 10.1016/S2213-2600(23)00147-9

  View details for PubMedID 37348524

• Changing Severity and Epidemiology of Adults Hospitalized With Coronavirus Disease 2019 (COVID-19) in the United States After Introduction of COVID-19 Vaccines, March 2021-August 2022. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Kojima, N., Adams, K., Self, W. H., Gaglani, M., McNeal, T., Ghamande, S., Steingrub, J. S., Shapiro, N. I., Duggal, A., Busse, L. W., Prekker, M. E., Peltan, I. D., Brown, S. M., Hager, D. N., Ali, H., Gong, M. N., Mohamed, A., Exline, M. C., Khan, A., Wilson, J. G., Qadir, N., Chang, S. Y., Ginde, A. A., Withers, C. A., Mohr, N. M., Mallow, C., Martin, E. T., Lauring, A. S., Johnson, N. J., Casey, J. D., Stubblefield, W. B., Gibbs, K. W., Kwon, J. H., Baughman, A., Chappell, J. D., Hart, K. W., Jones, I. D., Rhoads, J. P., Swan, S. A., Womack, K. N., Zhu, Y., Surie, D., McMorrow, M. L., Patel, M. M., Tenforde, M. W. 2023

  Abstract

  Understanding the changing epidemiology of adults hospitalized with coronavirus disease 2019 (COVID-19) informs research priorities and public health policies.Among adults (≥18 years) hospitalized with laboratory-confirmed, acute COVID-19 between 11 March 2021, and 31 August 2022 at 21 hospitals in 18 states, those hospitalized during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron-predominant period (BA.1, BA.2, BA.4/BA.5) were compared to those from earlier Alpha- and Delta-predominant periods. Demographic characteristics, biomarkers within 24 hours of admission, and outcomes, including oxygen support and death, were assessed.Among 9825 patients, median (interquartile range [IQR]) age was 60 years (47-72), 47% were women, and 21% non-Hispanic Black. From the Alpha-predominant period (Mar-Jul 2021; N = 1312) to the Omicron BA.4/BA.5 sublineage-predominant period (Jun-Aug 2022; N = 1307): the percentage of patients who had ≥4 categories of underlying medical conditions increased from 11% to 21%; those vaccinated with at least a primary COVID-19 vaccine series increased from 7% to 67%; those ≥75 years old increased from 11% to 33%; those who did not receive any supplemental oxygen increased from 18% to 42%. Median (IQR) highest C-reactive protein and D-dimer concentration decreased from 42.0 mg/L (9.9-122.0) to 11.5 mg/L (2.7-42.8) and 3.1 mcg/mL (0.8-640.0) to 1.0 mcg/mL (0.5-2.2), respectively. In-hospital death peaked at 12% in the Delta-predominant period and declined to 4% during the BA.4/BA.5-predominant period.Compared to adults hospitalized during early COVID-19 variant periods, those hospitalized during Omicron-variant COVID-19 were older, had multiple co-morbidities, were more likely to be vaccinated, and less likely to experience severe respiratory disease, systemic inflammation, coagulopathy, and death.

  View details for DOI 10.1093/cid/ciad276

  View details for PubMedID 37255285

• Comparison of mRNA vaccine effectiveness against COVID-19-associated hospitalization by vaccination source: Immunization information systems, electronic medical records, and self-report-IVY Network, February 1-August 31, 2022. Vaccine Surie, D., Bonnell, L. N., DeCuir, J., Gaglani, M., McNeal, T., Ghamande, S., Steingrub, J. S., Shapiro, N. I., Busse, L. W., Prekker, M. E., Peltan, I. D., Brown, S. M., Hager, D. N., Ali, H., Gong, M. N., Mohamed, A., Khan, A., Wilson, J. G., Qadir, N., Chang, S. Y., Ginde, A. A., Huynh, D., Mohr, N. M., Mallow, C., Martin, E. T., Lauring, A. S., Johnson, N. J., Casey, J. D., Gibbs, K. W., Kwon, J. H., Baughman, A., Chappell, J. D., Hart, K. W., Grijalva, C. G., Rhoads, J. P., Swan, S. A., Keipp Talbot, H., Womack, K. N., Zhu, Y., Tenforde, M. W., Adams, K., Self, W. H., McMorrow, M. L. 2023

  Abstract

  BACKGROUND: Accurate determination of COVID-19 vaccination status is necessary to produce reliable COVID-19 vaccine effectiveness (VE) estimates. Data comparing differences in COVID-19 VE by vaccination sources (i.e., immunization information systems [IIS], electronic medical records [EMR], and self-report) are limited. We compared the number of mRNA COVID-19 vaccine doses identified by each of these sources to assess agreement as well as differences in VE estimates using vaccination data from each individual source and vaccination data adjudicated from all sources combined.METHODS: Adults aged≥18years who were hospitalized with COVID-like illness at 21 hospitals in 18 U.S. states participating in the IVY Network during February 1-August 31, 2022, were enrolled. Numbers of COVID-19 vaccine doses identified by IIS, EMR, and self-report were compared in kappa agreement analyses. Effectiveness of mRNA COVID-19 vaccines against COVID-19-associated hospitalization was estimated using multivariable logistic regression models to compare the odds of COVID-19 vaccination between SARS-CoV-2-positive case-patients and SARS-CoV-2-negative control-patients. VE was estimated using each source of vaccination data separately and all sources combined.RESULTS: A total of 4499 patients were included. Patients with≥1 mRNA COVID-19 vaccine dose were identified most frequently by self-report (n=3570, 79 %), followed by IIS (n=3272, 73 %) and EMR (n=3057, 68 %). Agreement was highest between IIS and self-report for 4 doses with a kappa of 0.77 (95 % CI=0.73-0.81). VE point estimates of 3 doses against COVID-19 hospitalization were substantially lower when using vaccination data from EMR only (VE=31 %, 95 % CI=16 %-43 %) than when using all sources combined (VE=53 %, 95 % CI=41 %-62%).CONCLUSION: Vaccination data from EMR only may substantially underestimate COVID-19 VE.

  View details for DOI 10.1016/j.vaccine.2023.05.028

  View details for PubMedID 37301704

• Effect of P2Y12 Inhibitors on Organ Support-Free Survival in Critically Ill Patients Hospitalized for COVID-19: A Randomized Clinical Trial. JAMA network open Berger, J. S., Neal, M. D., Kornblith, L. Z., Gong, M. N., Reynolds, H. R., Cushman, M., Althouse, A. D., Lawler, P. R., McVerry, B. J., Kim, K. S., Baumann Kreuziger, L., Solomon, S. D., Kosiborod, M. N., Berry, S. M., Bochicchio, G. V., Contoli, M., Farkouh, M. E., Froess, J. D., Gandotra, S., Greenstein, Y., Hade, E. M., Hanna, N., Hudock, K., Hyzy, R. C., Ibáñez Estéllez, F., Iovine, N., Khanna, A. K., Khatri, P., Kirwan, B. A., Kutcher, M. E., Leifer, E., Lim, G., Lopes, R. D., Lopez-Sendon, J. L., Luther, J. F., Nigro Maia, L., Quigley, J. G., Wahid, L., Wilson, J. G., Zarychanski, R., Kindzelski, A., Geraci, M. W., Hochman, J. S. 2023; 6 (5): e2314428

  Abstract

  Platelet activation is a potential therapeutic target in patients with COVID-19.To evaluate the effect of P2Y12 inhibition among critically ill patients hospitalized for COVID-19.This international, open-label, adaptive platform, 1:1 randomized clinical trial included critically ill (requiring intensive care-level support) patients hospitalized with COVID-19. Patients were enrolled between February 26, 2021, through June 22, 2022. Enrollment was discontinued on June 22, 2022, by the trial leadership in coordination with the study sponsor given a marked slowing of the enrollment rate of critically ill patients.Participants were randomly assigned to receive a P2Y12 inhibitor or no P2Y12 inhibitor (usual care) for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death and, for participants who survived to hospital discharge, the number of days free of cardiovascular or respiratory organ support up to day 21 of the index hospitalization. The primary safety outcome was major bleeding, as defined by the International Society on Thrombosis and Hemostasis.At the time of trial termination, 949 participants (median [IQR] age, 56 [46-65] years; 603 male [63.5%]) had been randomly assigned, 479 to the P2Y12 inhibitor group and 470 to usual care. In the P2Y12 inhibitor group, ticagrelor was used in 372 participants (78.8%) and clopidogrel in 100 participants (21.2%). The estimated adjusted odds ratio (AOR) for the effect of P2Y12 inhibitor on organ support-free days was 1.07 (95% credible interval, 0.85-1.33). The posterior probability of superiority (defined as an OR > 1.0) was 72.9%. Overall, 354 participants (74.5%) in the P2Y12 inhibitor group and 339 participants (72.4%) in the usual care group survived to hospital discharge (median AOR, 1.15; 95% credible interval, 0.84-1.55; posterior probability of superiority, 80.8%). Major bleeding occurred in 13 participants (2.7%) in the P2Y12 inhibitor group and 13 (2.8%) in the usual care group. The estimated mortality rate at 90 days for the P2Y12 inhibitor group was 25.5% and for the usual care group was 27.0% (adjusted hazard ratio, 0.96; 95% CI, 0.76-1.23; P = .77).In this randomized clinical trial of critically ill participants hospitalized for COVID-19, treatment with a P2Y12 inhibitor did not improve the number of days alive and free of cardiovascular or respiratory organ support. The use of the P2Y12 inhibitor did not increase major bleeding compared with usual care. These data do not support routine use of a P2Y12 inhibitor in critically ill patients hospitalized for COVID-19.ClinicalTrials.gov Identifier: NCT04505774.

  View details for DOI 10.1001/jamanetworkopen.2023.14428

  View details for PubMedID 37227729

• Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period - IVY Network, 19 US States, February 1, 2022-January 31, 2023 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT DeCuir, J., Surie, D., Zhu, Y., Gaglani, M., Ginde, A. A., Douin, D. J., Talbo, H., Casey, J. D., Mohr, N. M., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Phan, M., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Bender, W. S., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Lauring, A. S., Shapiro, N. I., Columbus, C., Gottlieb, R., Vaughn, I. A., Ramesh, M., Lamerato, L. E., Safdar, B., Halasa, N., Chappell, J. D., Grijalva, C. G., Baughman, A., Womack, K. N., Rhoads, J. P., Hart, K. W., Swan, S. A., Lewis, N., McMorrow, M. L., Self, W. H., Ivy Network 2023; 72 (17): 463-468

  View details for Web of Science ID 001000720700007

• Effectiveness of Monovalent mRNA COVID-19 Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron Variant Period-IVY Network, 19 US States, February 1, 2022-January 31, 2023 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT DeCuir, J., Surie, D., Zhu, Y., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H., Casey, J. D., Mohr, N. M., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Phan, M., Prekker, M. E., Gong, M. N., Mohamed, A., Johnson, N. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Bender, W. S., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Lauring, A. S., Shapiro, N., Columbus, C., Gottlieb, R., Vaughn, I. A., Ramesh, M., Lamerato, L. E., Safdar, B., Halasa, N., Chappell, J. D., Grijalva, C. G., Baughman, A., Womack, K. N., Rhoads, J. P., Hart, K. W., Swan, S. A., Lewis, N., McMorrow, M. L., Self, W. H., IVY Network 2023; 72 (17): 463-468

  Abstract

  As of April 2023, the COVID-19 pandemic has resulted in 1.1 million deaths in the United States, with approximately 75% of deaths occurring among adults aged ≥65 years (1). Data on the durability of protection provided by monovalent mRNA COVID-19 vaccination against critical outcomes of COVID-19 are limited beyond the Omicron BA.1 lineage period (December 26, 2021-March 26, 2022). In this case-control analysis, the effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses was evaluated against COVID-19-associated invasive mechanical ventilation (IMV) and in-hospital death among immunocompetent adults aged ≥18 years during February 1, 2022-January 31, 2023. Vaccine effectiveness (VE) against IMV and in-hospital death was 62% among adults aged ≥18 years and 69% among those aged ≥65 years. When stratified by time since last dose, VE was 76% at 7-179 days, 54% at 180-364 days, and 56% at ≥365 days. Monovalent mRNA COVID-19 vaccination provided substantial, durable protection against IMV and in-hospital death among adults during the Omicron variant period. All adults should remain up to date with recommended COVID-19 vaccination to prevent critical COVID-19-associated outcomes.

  View details for Web of Science ID 000989713500001

  View details for PubMedID 37104244

• Renin-Angiotensin System Modulation With Synthetic Angiotensin (1-7) and Angiotensin II Type 1 Receptor-Biased Ligand in Adults With COVID-19: Two Randomized Clinical Trials. JAMA Self, W. H., Shotwell, M. S., Gibbs, K. W., de Wit, M., Files, D. C., Harkins, M., Hudock, K. M., Merck, L. H., Moskowitz, A., Apodaca, K. D., Barksdale, A., Safdar, B., Javaheri, A., Sturek, J. M., Schrager, H., Iovine, N., Tiffany, B., Douglas, I. S., Levitt, J., Busse, L. W., Ginde, A. A., Brown, S. M., Hager, D. N., Boyle, K., Duggal, A., Khan, A., Lanspa, M., Chen, P., Puskarich, M., Vonderhaar, D., Venkateshaiah, L., Gentile, N., Rosenberg, Y., Troendle, J., Bistran-Hall, A. J., DeClercq, J., Lavieri, R., Joly, M. M., Orr, M., Pulley, J., Rice, T. W., Schildcrout, J. S., Semler, M. W., Wang, L., Bernard, G. R., Collins, S. P., ACTIV-4 Host Tissue Investigators, Becker, R. C., Del Zoppo, G., Henke, P., Holubkov, R., Johnson, M., Kerr, K., Lipman, H. I., Lurie, F., Pitt, B., Vesely, S. K., Fleg, J. L., Aamodt, D., Ayers, J., Clark, D., Collins, J., Cook, M., Dixon, S., Graves, J., Jordan, C., Lindsell, C. J., Lopez, I., McKeel, D., Orozco, D., Prato, N., Qi, A., Qutab, M., Stoughton, C., Vermillion, K., Walsh, K., Winchell, S., Young, T., Franklin, R., Wagner, E., Walther, T., Demitrack, M., Johnson, J., Walsh, R., Bales, B., Miller, K., Torr, D., Barot, H., Landreth, L., LaRose, M., Parks, L., Teixeira, J. P., Cardenas, S., Ceniceros, J. A., Cunningham, A. G., Kunkel, S., Lovato, D. M., Zimmerman, B., Nguyen, T., Zeger, W., Nichols, H., Wiedel, N., Javaheri, A., Stilinovic, S., Brokowski, C., Lu, J., Solberg, M., Lee, D., Roach, K., Tiffany, B., Tanner, C., Taylor, A., Zumbahl, J., Syed, A., Mason, J., Jackson, P. E., Coleman, R. W., Haughey, H. M., Cherabuddi, K., James, N., Wakeman, R., Duncan, C., Montero, C., Rogers, A. J., Wilson, J. G., Vojnik, R., Perez, C., Wyles, D., Hiller, T. D., Oakes, J. L., Garcia, A. Z., Gong, M., Mohamed, A., Andrea, L., Nair, R., Nkemdirim, W., Lopez, B., Boujid, S., Torres, M., Garcia, O., Martinez, F., Baduashvili, A., Bastman, J., Chauhan, L., Douin, D. J., Finck, L., Licursi, A., Ten Lohuis, C., Zhang, S., Bender, W., Tovar, S., Hayes, S., Kurtzman, N., Rosseto, E., Scaffidi, D., Shapiro, N., Pak, J., Allada, G., Briceno, G., Pena, J., Oh, M., Ali, H., Beselman, S., Eby, Y., Klimov, V., Hite, R. D., Tanzeem, H., Droege, C., Winter, J., Jackman, S., Caudill, A., Bayoumi, E., Pascual, E., Chen, P., Mucha, S., Thiruchelvam, N., Siuba, M., Mehkri, O., Driver, B. E., Hendrickson, A. F., Kaus, O. R., Ontiveros, C., Riehm, A., Laudun, S., Hudock, D., Ensley, C., Shaner, V., Gentile, N., Isenberg, D., Reimer, H., Cincola, P., Harris, E. S., Callahan, S. J., Yamane, M. B., Barrios, M. A., Desai, N., Bharara, A., Keller, M., Majumder, P., Dohe, C., D'Armiento, J., Goldklang, M., Wagener, G., Fonseca, L., Valezquez-Sanchez, I., Johnson, N. J., Petersen, E., Fuentes, M., Newton, M., Gundel, S., Srinivasan, V., Steel, T., Robinson, B. 2023; 329 (14): 1170-1182

  Abstract

  Importance: Preclinical models suggest dysregulation of the renin-angiotensin system (RAS) caused by SARS-CoV-2 infection may increase the relative activity of angiotensin II compared with angiotensin (1-7) and may be an important contributor to COVID-19 pathophysiology.Objective: To evaluate the efficacy and safety of RAS modulation using 2 investigational RAS agents, TXA-127 (synthetic angiotensin [1-7]) and TRV-027 (an angiotensin II type 1 receptor-biased ligand), that are hypothesized to potentiate the action of angiotensin (1-7) and mitigate the action of the angiotensin II.Design, Setting, and Participants: Two randomized clinical trials including adults hospitalized with acute COVID-19 and new-onset hypoxemia were conducted at 35 sites in the US between July 22, 2021, and April 20, 2022; last follow-up visit: July 26, 2022.Interventions: A 0.5-mg/kg intravenous infusion of TXA-127 once daily for 5 days or placebo. A 12-mg/h continuous intravenous infusion of TRV-027 for 5 days or placebo.Main Outcomes and Measures: The primary outcome was oxygen-free days, an ordinal outcome that classifies a patient's status at day 28 based on mortality and duration of supplemental oxygen use; an adjusted odds ratio (OR) greater than 1.0 indicated superiority of the RAS agent vs placebo. A key secondary outcome was 28-day all-cause mortality. Safety outcomes included allergic reaction, new kidney replacement therapy, and hypotension.Results: Both trials met prespecified early stopping criteria for a low probability of efficacy. Of 343 patients in the TXA-127 trial (226 [65.9%] aged 31-64 years, 200 [58.3%] men, 225 [65.6%] White, and 274 [79.9%] not Hispanic), 170 received TXA-127 and 173 received placebo. Of 290 patients in the TRV-027 trial (199 [68.6%] aged 31-64 years, 168 [57.9%] men, 195 [67.2%] White, and 225 [77.6%] not Hispanic), 145 received TRV-027 and 145 received placebo. Compared with placebo, both TXA-127 (unadjusted mean difference, -2.3 [95% CrI, -4.8 to 0.2]; adjusted OR, 0.88 [95% CrI, 0.59 to 1.30]) and TRV-027 (unadjusted mean difference, -2.4 [95% CrI, -5.1 to 0.3]; adjusted OR, 0.74 [95% CrI, 0.48 to 1.13]) resulted in no difference in oxygen-free days. In the TXA-127 trial, 28-day all-cause mortality occurred in 22 of 163 patients (13.5%) in the TXA-127 group vs 22 of 166 patients (13.3%) in the placebo group (adjusted OR, 0.83 [95% CrI, 0.41 to 1.66]). In the TRV-027 trial, 28-day all-cause mortality occurred in 29 of 141 patients (20.6%) in the TRV-027 group vs 18 of 140 patients (12.9%) in the placebo group (adjusted OR, 1.52 [95% CrI, 0.75 to 3.08]). The frequency of the safety outcomes was similar with either TXA-127 or TRV-027 vs placebo.Conclusions and Relevance: In adults with severe COVID-19, RAS modulation (TXA-127 or TRV-027) did not improve oxygen-free days vs placebo. These results do not support the hypotheses that pharmacological interventions that selectively block the angiotensin II type 1 receptor or increase angiotensin (1-7) improve outcomes for patients with severe COVID-19.Trial Registration: ClinicalTrials.gov Identifier: NCT04924660.

  View details for DOI 10.1001/jama.2023.3546

  View details for PubMedID 37039791

• Association of an Emergency Critical Care Program With Survival and Early Downgrade Among Critically Ill Medical Patients in the Emergency Department. Critical care medicine Mitarai, T., Gordon, A. J., Nudelman, M. J., Urdaneta, A. E., Nesbitt, J. L., Niknam, K., Graber-Naidich, A., Wilson, J. G., Kohn, M. A. 2023

  Abstract

  OBJECTIVES: To determine whether implementation of an Emergency Critical Care Program (ECCP) is associated with improved survival and early downgrade of critically ill medical patients in the emergency department (ED).DESIGN: Single-center, retrospective cohort study using ED-visit data between 2015 and 2019.SETTING: Tertiary academic medical center.PATIENTS: Adult medical patients presenting to the ED with a critical care admission order within 12 hours of arrival.INTERVENTIONS: Dedicated bedside critical care for medical ICU patients by an ED-based intensivist following initial resuscitation by the ED team.MEASUREMENTS AND MAIN RESULTS: Primary outcomes were inhospital mortality and the proportion of patients downgraded to non-ICU status while in the ED within 6 hours of the critical care admission order (ED downgrade <6hr). A difference-in-differences (DiD) analysis compared the change in outcomes for patients arriving during ECCP hours (2 pm to midnight, weekdays) between the preintervention period (2015-2017) and the intervention period (2017-2019) to the change in outcomes for patients arriving during non-ECCP hours (all other hours). Adjustment for severity of illness was performed using the emergency critical care Sequential Organ Failure Assessment (eccSOFA) score. The primary cohort included 2,250 patients. The DiDs for the eccSOFA-adjusted inhospital mortality decreased by 6.0% (95% CI, -11.9 to -0.1) with largest difference in the intermediate illness severity group (DiD, -12.2%; 95% CI, -23.1 to -1.3). The increase in ED downgrade less than 6 hours was not statistically significant (DiD, 4.8%; 95% CI, -0.7 to 10.3%) except in the intermediate group (DiD, 8.8%; 95% CI, 0.2-17.4).CONCLUSIONS: The implementation of a novel ECCP was associated with a significant decrease in inhospital mortality among critically ill medical ED patients, with the greatest decrease observed in patients with intermediate severity of illness. Early ED downgrades also increased, but the difference was statistically significant only in the intermediate illness severity group.

  View details for DOI 10.1097/CCM.0000000000005835

  View details for PubMedID 37010317

• Total and subgenomic RNA viral load in patients infected with SARS-CoV-2 Alpha, Delta, and Omicron variants. The Journal of infectious diseases Dimcheff, D. E., Blair, C. N., Zhu, Y., Chappell, J. D., Gaglani, M., McNeal, T., Ghamande, S., Steingrub, J. S., Shapiro, N. I., Duggal, A., Busse, L. W., Frosch, A. E., Peltan, I. D., Hager, D. N., Gong, M. N., Exline, M. C., Khan, A., Wilson, J. G., Qadir, N., Ginde, A. A., Douin, D. J., Mohr, N. M., Mallow, C., Martin, E. T., Johnson, N. J., Casey, J. D., Stubblefield, W. B., Gibbs, K. W., Kwon, J. H., Talbot, H. K., Halasa, N., Grijalva, C. G., Baughman, A., Womack, K. N., Hart, K. W., Swan, S. A., Surie, D., Thornburg, N. J., McMorrow, M. L., Self, W. H., Lauring, A. S., Investigating Respiratory Viruses in the Acutely Ill (IVY) Network 2023

  Abstract

  BACKGROUND: SARS-CoV-2 genomic and subgenomic RNA levels are frequently used as a correlate of infectiousness. The impact of host factors and SARS-CoV-2 lineage on RNA viral load is unclear.METHODS: Total nucleocapsid (N) and subgenomic N (sgN) RNA levels were measured by RT-qPCR in specimens from 3,204 individuals hospitalized with COVID-19 at 21 hospitals. RT-qPCR cycle threshold (Ct) values were used to estimate RNA viral load. The impact of time of sampling, SARS-CoV-2 variant, age, comorbidities, vaccination, and immune status on N and sgN Ct values were evaluated using multiple linear regression.RESULTS: Ct values at presentation for N (mean ±standard deviation) were 24.14±4.53 for non-variants of concern, 25.15±4.33 for Alpha, 25.31±4.50 for Delta, and 26.26±4.42 for Omicron. N and sgN RNA levels varied with time since symptom onset and infecting variant but not with age, comorbidity, immune status, or vaccination. When normalized to total N RNA, sgN levels were similar across all variants.CONCLUSIONS: RNA viral loads were similar among hospitalized adults, irrespective of infecting variant and known risk factors for severe COVID-19. Total N and subgenomic RNA N viral loads were highly correlated, suggesting that subgenomic RNA measurements adds little information for the purposes of estimating infectivity.

  View details for DOI 10.1093/infdis/jiad061

  View details for PubMedID 36883903

• Autoantibodies are highly prevalent in non-SARS-CoV-2 respiratory infections and critical illness. JCI insight Feng, A., Yang, E. Y., Moore, A. R., Dhingra, S., Chang, S. E., Yin, X., Pi, R., Mack, E. K., Völkel, S., Geßner, R., Gündisch, M., Neubauer, A., Renz, H., Tsiodras, S., Fragkou, P. C., Asuni, A. A., Levitt, J. E., Wilson, J. G., Leong, M., Lumb, J. H., Mao, R., Pinedo, K., Roque, J., Richards, C. M., Stabile, M., Swaminathan, G., Salagianni, M. L., Triantafyllia, V., Bertrams, W., Blish, C. A., Carette, J. E., Frankovich, J., Meffre, E., Nadeau, K. C., Singh, U., Wang, T. T., Luning Prak, E. T., Herold, S., Andreakos, E., Schmeck, B., Skevaki, C., Rogers, A. J., Utz, P. J. 2023; 8 (3)

  Abstract

  The widespread presence of autoantibodies in acute infection with SARS-CoV-2 is increasingly recognized, but the prevalence of autoantibodies in non-SARS-CoV-2 infections and critical illness has not yet been reported. We profiled IgG autoantibodies in 267 patients from 5 independent cohorts with non-SARS-CoV-2 viral, bacterial, and noninfectious critical illness. Serum samples were screened using Luminex arrays that included 58 cytokines and 55 autoantigens, many of which are associated with connective tissue diseases (CTDs). Samples positive for anti-cytokine antibodies were tested for receptor blocking activity using cell-based functional assays. Anti-cytokine antibodies were identified in > 50% of patients across all 5 acutely ill cohorts. In critically ill patients, anti-cytokine antibodies were far more common in infected versus uninfected patients. In cell-based functional assays, 11 of 39 samples positive for select anti-cytokine antibodies displayed receptor blocking activity against surface receptors for Type I IFN, GM-CSF, and IL-6. Autoantibodies against CTD-associated autoantigens were also commonly observed, including newly detected antibodies that emerged in longitudinal samples. These findings demonstrate that anti-cytokine and autoantibodies are common across different viral and nonviral infections and range in severity of illness.

  View details for DOI 10.1172/jci.insight.163150

  View details for PubMedID 36752204

• ASSOCIATION BETWEEN AN EMERGENCY CRITICAL CARE PROGRAM AND DKA CRITICAL CARE UTILIZATION IN THE ED Gupta, P., Gordon, A., Mitarai, T., Nudelman, M., Kohn, M., Wilson, J. LIPPINCOTT WILLIAMS & WILKINS. 2023: 129

  View details for Web of Science ID 000921450900252

• Absolute and Relative Vaccine Effectiveness of Primary and Booster Series of COVID-19 Vaccines (mRNA and Adenovirus Vector) Against COVID-19 Hospitalizations in the United States, December 2021-April 2022. Open forum infectious diseases Lewis, N. M., Murray, N., Adams, K., Surie, D., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Ali, H., Prekker, M. E., Frosch, A. E., Exline, M. C., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Lauring, A. S., Khan, A., Hough, C. L., Busse, L. W., Bender, W., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Chappell, J. D., Halasa, N., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Lindsell, C. J., Hart, K. W., Rhoads, J. P., McMorrow, M. L., Tenforde, M. W., Self, W. H., Patel, M. M. 2023; 10 (1): ofac698

  Abstract

  Coronavirus disease 2019 (COVID-19) vaccine effectiveness (VE) studies are increasingly reporting relative VE (rVE) comparing a primary series plus booster doses with a primary series only. Interpretation of rVE differs from traditional studies measuring absolute VE (aVE) of a vaccine regimen against an unvaccinated referent group. We estimated aVE and rVE against COVID-19 hospitalization in primary-series plus first-booster recipients of COVID-19 vaccines.Booster-eligible immunocompetent adults hospitalized at 21 medical centers in the United States during December 25, 2021-April 4, 2022 were included. In a test-negative design, logistic regression with case status as the outcome and completion of primary vaccine series or primary series plus 1 booster dose as the predictors, adjusted for potential confounders, were used to estimate aVE and rVE.A total of 2060 patients were analyzed, including 1104 COVID-19 cases and 956 controls. Relative VE against COVID-19 hospitalization in boosted mRNA vaccine recipients versus primary series only was 66% (95% confidence interval [CI], 55%-74%); aVE was 81% (95% CI, 75%-86%) for boosted versus 46% (95% CI, 30%-58%) for primary. For boosted Janssen vaccine recipients versus primary series, rVE was 49% (95% CI, -9% to 76%); aVE was 62% (95% CI, 33%-79%) for boosted versus 36% (95% CI, -4% to 60%) for primary.Vaccine booster doses increased protection against COVID-19 hospitalization compared with a primary series. Comparing rVE measures across studies can lead to flawed interpretations of the added value of a new vaccination regimen, whereas difference in aVE, when available, may be a more useful metric.

  View details for DOI 10.1093/ofid/ofac698

  View details for PubMedID 36695662

  View details for PubMedCentralID PMC9868348

• Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Hospitalization Among Immunocompetent Adults Aged ≥65 Years - IVY Network, 18 States, September 8-November 30, 2022 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Surie, D., DeCuir, J., Zhu, Y., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Ali, H., Taghizadeh, L., Gong, M. N., Mohamed, A., Johnson, N. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Khan, A., Bender, W. S., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Kwon, J. H., Exline, M. C., Lauring, A. S., Shapiro, N. I., Columbus, C., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Hart, K. W., Swan, S. A., Lewis, N. M., McMorrow, M. L., Self, W. H., IVY Network 2022; 71 (51-52): 1625-1630

  Abstract

  Monovalent COVID-19 mRNA vaccines, designed against the ancestral strain of SARS-CoV-2, successfully reduced COVID-19-related morbidity and mortality in the United States and globally (1,2). However, vaccine effectiveness (VE) against COVID-19-associated hospitalization has declined over time, likely related to a combination of factors, including waning immunity and, with the emergence of the Omicron variant and its sublineages, immune evasion (3). To address these factors, on September 1, 2022, the Advisory Committee on Immunization Practices recommended a bivalent COVID-19 mRNA booster (bivalent booster) dose, developed against the spike protein from ancestral SARS-CoV-2 and Omicron BA.4/BA.5 sublineages, for persons who had completed at least a primary COVID-19 vaccination series (with or without monovalent booster doses) ≥2 months earlier (4). Data on the effectiveness of a bivalent booster dose against COVID-19 hospitalization in the United States are lacking, including among older adults, who are at highest risk for severe COVID-19-associated illness. During September 8-November 30, 2022, the Investigating Respiratory Viruses in the Acutely Ill (IVY) Network§ assessed effectiveness of a bivalent booster dose received after ≥2 doses of monovalent mRNA vaccine against COVID-19-associated hospitalization among immunocompetent adults aged ≥65 years. When compared with unvaccinated persons, VE of a bivalent booster dose received ≥7 days before illness onset (median = 29 days) against COVID-19-associated hospitalization was 84%. Compared with persons who received ≥2 monovalent-only mRNA vaccine doses, relative VE of a bivalent booster dose was 73%. These early findings show that a bivalent booster dose provided strong protection against COVID-19-associated hospitalization in older adults and additional protection among persons with previous monovalent-only mRNA vaccination. All eligible persons, especially adults aged ≥65 years, should receive a bivalent booster dose to maximize protection against COVID-19 hospitalization this winter season. Additional strategies to prevent respiratory illness, such as masking in indoor public spaces, should also be considered, especially in areas where COVID-19 community levels are high (4,5).

  View details for Web of Science ID 001139651400001

  View details for PubMedID 36580424

  View details for PubMedCentralID PMC9812444

• Comparison of test-negative and syndrome-negative controls in SARS-CoV-2 vaccine effectiveness evaluations for preventing COVID-19 hospitalizations in the United States. Vaccine Turbyfill, C., Adams, K., Tenforde, M. W., Murray, N. L., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Keipp Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Clark Files, D., Hager, D. N., Shehu, A., Prekker, M. E., Frosch, A. E., Exline, M. C., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Lauring, A. S., Khan, A., Busse, L. W., Ten Lohuis, C. C., Duggal, A., Wilson, J. G., June Gordon, A., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Kwon, J. H., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Rhoads, J. P., Lindsell, C. J., Hart, K. W., McMorrow, M., Surie, D., Self, W. H., Patel, M. M. 2022; 40 (48): 6979-6986

  Abstract

  BACKGROUND: Test-negative design (TND) studies have produced validated estimates of vaccine effectiveness (VE) for influenza vaccine studies. However, syndrome-negative controls have been proposed for differentiating bias and true estimates in VE evaluations for COVID-19. To understand the use of alternative control groups, we compared characteristics and VE estimates of syndrome-negative and test-negative VE controls.METHODS: Adults hospitalized at 21 medical centers in 18 states March 11-August 31, 2021 were eligible for analysis. Case patients had symptomatic acute respiratory infection (ARI) and tested positive for SARS-CoV-2. Control groups were test-negative patients with ARI but negative SARS-CoV-2 testing, and syndrome-negative controls were without ARI and negative SARS-CoV-2 testing. Chi square and Wilcoxon rank sum tests were used to detect differences in baseline characteristics. VE against COVID-19 hospitalization was calculated using logistic regression comparing adjusted odds of prior mRNA vaccination between cases hospitalized with COVID-19 and each control group.RESULTS: 5811 adults (2726 cases, 1696 test-negative controls, and 1389 syndrome-negative controls) were included. Control groups differed across characteristics including age, race/ethnicity, employment, previous hospitalizations, medical conditions, and immunosuppression. However, control-group-specific VE estimates were very similar. Among immunocompetent patients aged 18-64years, VE was 93% (95% CI: 90-94) using syndrome-negative controls and 91% (95% CI: 88-93) using test-negative controls.CONCLUSIONS: Despite demographic and clinical differences between control groups, the use of either control group produced similar VE estimates across age groups and immunosuppression status. These findings support the use of test-negative controls and increase confidence in COVID-19 VE estimates produced by test-negative design studies.

  View details for DOI 10.1016/j.vaccine.2022.10.034

  View details for PubMedID 36374708

• Effectiveness of Monovalent mRNA Vaccines Against COVID-19-Associated Hospitalization Among Immunocompetent Adults During BA.1/BA.2 and BA.4/BA.5 Predominant Periods of SARS-CoV-2 Omicron Variant in the United States - IVY Network, 18 States, December 26, 2021-August 31, 2022. MMWR. Morbidity and mortality weekly report Surie, D., Bonnell, L., Adams, K., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Frosch, A. P., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Khan, A., Bender, W. S., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Kwon, J. H., Exline, M. C., Lauring, A. S., Shapiro, N. I., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Womack, K. N., Hart, K. W., Swan, S. A., Zhu, Y., DeCuir, J., Tenforde, M. W., Patel, M. M., McMorrow, M. L., Self, W. H. 2022; 71 (42): 1327-1334

  Abstract

  The SARS-CoV-2 Omicron variant (B.1.1.529 or BA.1) became predominant in the United States by late December 2021 (1). BA.1 has since been replaced by emerging lineages BA.2 (including BA.2.12.1) in March 2022, followed by BA.4 and BA.5, which have accounted for a majority of SARS-CoV-2 infections since late June 2022 (1). Data on the effectiveness of monovalent mRNA COVID-19 vaccines against BA.4/BA.5-associated hospitalizations are limited, and their interpretation is complicated by waning of vaccine-induced immunity (2-5). Further, infections with earlier Omicron lineages, including BA.1 and BA.2, reduce vaccine effectiveness (VE) estimates because certain persons in the referent unvaccinated group have protection from infection-induced immunity. The IVY Network† assessed effectiveness of 2, 3, and 4 doses of monovalent mRNA vaccines compared with no vaccination against COVID-19-associated hospitalization among immunocompetent adults aged ≥18 years during December 26, 2021-August 31, 2022. During the BA.1/BA.2 period, VE 14-150 days after a second dose was 63% and decreased to 34% after 150 days. Similarly, VE 7-120 days after a third dose was 79% and decreased to 41% after 120 days. VE 7-120 days after a fourth dose was 61%. During the BA.4/BA.5 period, similar trends were observed, although CIs for VE estimates between categories of time since the last dose overlapped. VE 14-150 days and >150 days after a second dose was 83% and 37%, respectively. VE 7-120 days and >120 days after a third dose was 60%and 29%, respectively. VE 7-120 days after the fourth dose was 61%. Protection against COVID-19-associated hospitalization waned even after a third dose. The newly authorized bivalent COVID-19 vaccines include mRNA from the ancestral SARS-CoV-2 strain and from shared mRNA components between BA.4 and BA.5 lineages and are expected to be more immunogenic against BA.4/BA.5 than monovalent mRNA COVID-19 vaccines (6-8). All eligible adults aged ≥18 years§ should receive a booster dose, which currently consists of a bivalent mRNA vaccine, to maximize protection against BA.4/BA.5 and prevent COVID-19-associated hospitalization.

  View details for DOI 10.15585/mmwr.mm7142a3

  View details for PubMedID 36264830

  View details for PubMedCentralID PMC9590291

• Vaccine effectiveness of primary series and booster doses against covid-19 associated hospital admissions in the United States: living test negative design study. BMJ (Clinical research ed.) Adams, K., Rhoads, J. P., Surie, D., Gaglani, M., Ginde, A. A., McNeal, T., Talbot, H. K., Casey, J. D., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Frosch, A. E., Exline, M. C., Mohamed, A., Johnson, N. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Lauring, A. S., Khan, A., Busse, L. W., Duggal, A., Wilson, J. G., Chang, S. Y., Mallow, C., Kwon, J. H., Chappell, J. D., Halasa, N., Grijalva, C. G., Lindsell, C. J., Lester, S. N., Thornburg, N. J., Park, S., McMorrow, M. L., Patel, M. M., Tenforde, M. W., Self, W. H., Influenza and other Viruses in the AcutelY ill (IVY) Network, Ghamande, S., Calhoun, N., Murthy, K., Herrick, J., McKillop, A., Hoffman, E., Zayed, M., Smith, M., Kozikowski, L., De Souza, L., Ouellette, S., Bolstad, M., Coviello, B., Ciottone, R., Devilla, A., Grafals, A., Higgins, C., Ottanelli, C., Redman, K., Scaffidi, D., Weingart, A., Lewis, N., Mehkri, O., Mitchell, M., Griffith, Z., Brennan, C., Ashok, K., Poynter, B., Ten Lohuis, C., Stanley, N., Zhang, S., Prekker, M., Erickson, H., Hendrickson, A., Caspers, S., Tordsen, W., Kaus, O., Scharber, T., Lumpkin, J., Smith, C., Marshall, H., Shehu, A., Ali, H., Rothman, R. E., Mohamed, A., Nair, R., Chen, J. T., Karow, S., Robart, E., Maldonado, P. N., Khan, M., So, P., So, M., Schwartz, E., Botros, M., Hough, C. L., Jung, H., Martinez, J., Luong, A., Huynh, B., Ibrahim, H., Villanueva-Vargas, C., Villanueva-Vargas, J., Quadri, S., Gordon, A. J., Levitt, J., Perez, C., Visweswaran, A., Roque, J., Qadir, N., Frankel, T., Garner, O., Chandrasekaran, S., Douin, D., Jensen, K., Huynh, D., Steinwand, A., Withers, C., Mohr, N., Nassar, P., Landers, S., Nielsen, K., Briggs, N., Fairfield, C., Gershengorn, H., Rivas, C., Monto, A., McSpadden, E. J., Truscon, R., Kaniclides, A., Thomas, L., Bielak, R., Valvano, W. D., Fong, R., Fitzsimmons, W. J., Blair, C., Gilbert, J., Baker, L., Srinivasan, V., Crider, C. D., Steinbock, K. A., Paulsen, T. C., Anderson, L. A., Jones, I., Womack, K., Baughman, A., Kampe, C., Johnson, J., Hart, K., Rice, T., Stubblefield, W. B., Zhu, Y., Short, L. L., Ezzell, L. J., Whitsett, M. E., McHenry, R. E., Hargrave, S. J., Blair, M., Luther, J. L., Pulido, C. G., Peterson, B. P., LaRose, M., Landreth, L., Hicks, M., Parks, L., Babcock, H., Bongu, J., McDonald, D., Cass, C., Seiler, S., Park, D., Hink, T., Wallace, M., Burnham, C., Arter, O. G. 2022; 379: e072065

  Abstract

  OBJECTIVE: To compare the effectiveness of a primary covid-19 vaccine series plus booster doses with a primary series alone for the prevention of hospital admission with omicron related covid-19 in the United States.DESIGN: Multicenter observational case-control study with a test negative design.SETTING: Hospitals in 18 US states.PARTICIPANTS: 4760 adults admitted to one of 21 hospitals with acute respiratory symptoms between 26 December 2021 and 30 June 2022, a period when the omicron variant was dominant. Participants included 2385 (50.1%) patients with laboratory confirmed covid-19 (cases) and 2375 (49.9%) patients who tested negative for SARS-CoV-2 (controls).MAIN OUTCOME MEASURES: The main outcome was vaccine effectiveness against hospital admission with covid-19 for a primary series plus booster doses and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. Vaccine effectiveness analyses were stratified by immunosuppression status (immunocompetent, immunocompromised). The primary analysis evaluated all covid-19 vaccine types combined, and secondary analyses evaluated specific vaccine products.RESULTS: Overall, median age of participants was 64 years (interquartile range 52-75 years), 994 (20.8%) were immunocompromised, 85 (1.8%) were vaccinated with a primary series plus two boosters, 1367 (28.7%) with a primary series plus one booster, and 1875 (39.3%) with a primary series alone, and 1433 (30.1%) were unvaccinated. Among immunocompetent participants, vaccine effectiveness for prevention of hospital admission with omicron related covid-19 for a primary series plus two boosters was 63% (95% confidence interval 37% to 78%), a primary series plus one booster was 65% (58% to 71%), and for a primary series alone was 37% (25% to 47%) (P<0.001 for the pooled boosted regimens compared with a primary series alone). Vaccine effectiveness was higher for a boosted regimen than for a primary series alone for both mRNA vaccines (BNT162b2 (Pfizer-BioNTech): 73% (44% to 87%) for primary series plus two boosters, 64% (55% to 72%) for primary series plus one booster, and 36% (21% to 48%) for primary series alone (P<0.001); mRNA-1273 (Moderna): 68% (17% to 88%) for primary series plus two boosters, 65% (55% to 73%) for primary series plus one booster, and 41% (25% to 54%) for primary series alone (P=0.001)). Among immunocompromised patients, vaccine effectiveness for a primary series plus one booster was 69% (31% to 86%) and for a primary series alone was 49% (30% to 63%) (P=0.04).CONCLUSION: During the first six months of 2022 in the US, booster doses of a covid-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing hospital admissions with omicron related covid-19.READERS' NOTE: This article is a living test negative design study that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

  View details for DOI 10.1136/bmj-2022-072065

  View details for PubMedID 36220174

• The Association of Baseline Plasma SARS-CoV-2 Nucleocapsid Antigen Level and Outcomes in Patients Hospitalized With COVID-19. Annals of internal medicine 2022

  Abstract

  Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19.To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2.Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge.114 centers in 10 countries.Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms.Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively.Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity.Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available.Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

  View details for DOI 10.7326/M22-0924

  View details for PubMedID 36037469

  View details for PubMedCentralID PMC9447373

• Ascertainment of vaccination status by self-report versus source documentation: Impact on measuring COVID-19 vaccine effectiveness. Influenza and other respiratory viruses Stephenson, M., Olson, S. M., Self, W. H., Ginde, A. A., Mohr, N. M., Gaglani, M., Shapiro, N. I., Gibbs, K. W., Hager, D. N., Prekker, M. E., Gong, M. N., Steingrub, J. S., Peltan, I. D., Martin, E. T., Reddy, R., Busse, L. W., Duggal, A., Wilson, J. G., Qadir, N., Mallow, C., Kwon, J. H., Exline, M. C., Chappell, J. D., Lauring, A. S., Baughman, A., Lindsell, C. J., Hart, K. W., Lewis, N. M., Patel, M. M., Tenforde, M. W., IVY Network Investigators 2022

  Abstract

  BACKGROUND: During the COVID-19 pandemic, self-reported COVID-19 vaccination might facilitate rapid evaluations of vaccine effectiveness (VE) when source documentation (e.g., immunization information systems [IIS]) is not readily available. We evaluated the concordance of COVID-19 vaccination status ascertained by self-report versus source documentation and its impact on VE estimates.METHODS: Hospitalized adults (≥18years) admitted to 18 U.S. medical centers March-June 2021 were enrolled, including COVID-19 cases and SARS-CoV-2 negative controls. Patients were interviewed about COVID-19 vaccination. Abstractors simultaneously searched IIS, medical records, and other sources for vaccination information. To compare vaccination status by self-report and documentation, we estimated percent agreement and unweighted kappa with 95% confidence intervals (CIs). We then calculated VE in preventing COVID-19 hospitalization of full vaccination (2 doses of mRNA product ≥14days prior to illness onset) independently using data from self-report or source documentation.RESULTS: Of 2520 patients, 594 (24%) did not have self-reported vaccination information to assign vaccination group; these patients tended to be more severely ill. Among 1924 patients with both self-report and source documentation information, 95.0% (95% CI: 93.9-95.9%) agreement was observed, with a kappa of 0.9127 (95% CI: 0.9109-0.9145). VE was 86% (95% CI: 81-90%) by self-report data only and 85% (95% CI: 81-89%) by source documentation data only.CONCLUSIONS: Approximately one-quarter of hospitalized patients could not provide self-report COVID-19 vaccination status. Among patients with self-report information, there was high concordance with source documented status. Self-report may be a reasonable source of COVID-19 vaccination information for timely VE assessment for public health action.

  View details for DOI 10.1111/irv.13023

  View details for PubMedID 35818721

• COVID-19 Acute Respiratory Distress Syndrome: One Pathogen, Multiple Phenotypes. Critical care clinics Empson, S., Rogers, A. J., Wilson, J. G. 2022; 38 (3): 505-519

  Abstract

  Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome arising from multiple causes with a range of clinical severity. In recent years, the potential for prognostic and predictive enrichment of clinical trials has been increased with identification of more biologically homogeneous subgroups or phenotypes within ARDS. COVID-19 ARDS also exhibits significant clinical heterogeneity despite a single causative agent. In this review the authors summarize the existing literature on COVID-19 ARDS phenotypes, including physiologic, clinical, and biological subgroups as well as the implications for improving both prognostication and precision therapy.

  View details for DOI 10.1016/j.ccc.2022.02.001

  View details for PubMedID 35667740

• Effectiveness of the Ad26.COV2.S (Johnson & Johnson) COVID-19 Vaccine for Preventing COVID-19 Hospitalizations and Progression to High Disease Severity in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Lewis, N. M., Self, W. H., Gaglani, M., Ginde, A. A., Douin, D. J., Keipp Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., Ghamande, S. A., McNeal, T. A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, A. M., Martin, E. T., Monto, A. S., Khan, A., Busse, L. W., Ten Lohuis, C. C., Duggal, B., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Lauring, A. S., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Rhoads, J. P., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Adams, K., Patel, M. M., Tenforde, M. W. 2022

  Abstract

  Adults in the United States (US) began receiving the viral vector COVID-19 vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use.In a multicenter case-control analysis of US adults (≥18 years) hospitalized March 11-December 15, 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression.After excluding patients receiving mRNA vaccines, among 3,979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2.229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% CI: 63%-75%) overall, including 55% (29%-72%) among immunocompromised patients, and 72% (64%-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59%-82%]), 91-180 days (71% [60%-80%]), and 181-274 days (70% [54%-81%]) post-vaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18%-65%) among immunocompetent patients.The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months post-vaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

  View details for DOI 10.1093/cid/ciac439

  View details for PubMedID 35675695

• Protection of mRNA vaccines against hospitalized COVID-19 in adults over the first year following authorization in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Tenforde, M. W., Self, W. H., Zhu, Y., Naioti, E. A., Gaglani, M., Ginde, A. A., Jensen, K., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Ten Lohuis, C., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Botros, M. M., Lauring, A. S., Shapiro, N. I., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Turbyfill, C., Olson, S., Murray, N., Adams, K., Patel, M. M., Influenza and Other Viruses in the Acutely Ill (IVY) Network 2022

  Abstract

  BACKGROUND: COVID-19 mRNA vaccines were authorized in the United States in December 2020. Although vaccine effectiveness (VE) against mild infection declines markedly after several months, limited understanding exists on the long-term durability of protection against COVID-19-associated hospitalization.METHODS: Case control analysis of adults (≥18 years) hospitalized at 21 hospitals in 18 states March 11 - December 15, 2021, including COVID-19 case patients and RT-PCR-negative controls. We included adults who were unvaccinated or vaccinated with two doses of a mRNA vaccine before the date of illness onset. VE over time was assessed using logistic regression comparing odds of vaccination in cases versus controls, adjusting for confounders. Models included dichotomous time (<180 vs ≥180 days since dose two) and continuous time modeled using restricted cubic splines.RESULTS: 10,078 patients were included, 4906 cases (23% vaccinated) and 5172 controls (62% vaccinated). Median age was 60 years (IQR 46-70), 56% were non-Hispanic White, and 81% had ≥1 medical condition. Among immunocompetent adults, VE <180 days was 90% (95%CI: 88-91) vs 82% (95%CI: 79-85) at ≥180 days (p<0.001). VE declined for Pfizer-BioNTech (88% to 79%, p<0.001) and Moderna (93% to 87%, p<0.001) products, for younger adults (18-64 years) [91% to 87%, p=0.005], and for adults ≥65 years of age (87% to 78%, p<0.001). In models using restricted cubic splines, similar changes were observed.CONCLUSION: In a period largely pre-dating Omicron variant circulation, effectiveness of two mRNA doses against COVID-19-associated hospitalization was largely sustained through 9 months.

  View details for DOI 10.1093/cid/ciac381

  View details for PubMedID 35580849

• Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial LANCET INFECTIOUS DISEASES Self, W. H., Sandkovsky, U., Reilly, C. S., Vock, D. M., Gottlieb, R. L., Mack, M., Golden, K., Dishner, E., Vekstein, A., Ko, E. R., Der, T., Franzone, J., Almasri, E., Fayed, M., Filbin, M. R., Hibbert, K. A., Rice, T. W., Casey, J. D., Hayanga, J., Badhwar, V., Leshnower, B. G., Sharifpour, M., Knowlton, K. U., Peltan, I. D., Bakowska, E., Kowalska, J., Bowdish, M. E., Sturek, J. M., Rogers, A. J., Files, D., Mosier, J. M., Gong, M. N., Douin, D. J., Hite, R., Trautner, B. W., Jain, M. K., Gardner, E. M., Khan, A., Jensen, J., Matthay, M. A., Ginde, A. A., Brown, S. M., Higgs, E. S., Pett, S., Weintrob, A. C., Chang, C. C., Murrary, D. D., Gunthard, H. F., Moquete, E., Grandits, G., Engen, N., Grund, B., Sharma, S., Cao, H., Gupta, R., Osei, S., Margolis, D., Zhu, Q., Polizzotto, M. N., Babiker, A. G., Davey, V. J., Kan, V., Thompson, B., Gelijns, A. C., Neaton, J. D., Lane, H., Lundgren, J. D., ACTIV-3 Theropeutics Inpatients CO 2022; 22 (5): 622-635

  Abstract

  We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.US National Institutes of Health and Operation Warp Speed.

  View details for DOI 10.1016/S1473-3099(21)00751-9

  View details for Web of Science ID 000821471300027

  View details for PubMedID 34953520

  View details for PubMedCentralID PMC8700279

• Modeling clinical trajectory status of critically ill COVID-19 patients over time: A method for analyzing discrete longitudinal and ordinal outcomes JOURNAL OF CLINICAL AND TRANSLATIONAL SCIENCE Ward, M. J., Douin, D. J., Gong, W., Ginde, A. A., Hough, C. L., Exline, M. C., Tenforde, M. W., Stubblefield, W. B., Steingrub, J. S., Prekker, M. E., Khan, A., Files, D., Gibbs, K. W., Rice, T. W., Casey, J. D., Henning, D. J., Wilson, J. G., Brown, S. M., Patel, M. M., Self, W. H., Lindsell, C. J., Influenza Other Viruses Acutely Il 2022; 6 (1)

  View details for DOI 10.1017/cts.2022.393

  View details for Web of Science ID 000800145300001

• Modeling clinical trajectory status of critically ill COVID-19 patients over time: A method for analyzing discrete longitudinal and ordinal outcomes. Journal of clinical and translational science Ward, M. J., Douin, D. J., Gong, W., Ginde, A. A., Hough, C. L., Exline, M. C., Tenforde, M. W., Stubblefield, W. B., Steingrub, J. S., Prekker, M. E., Khan, A., Files, D. C., Gibbs, K. W., Rice, T. W., Casey, J. D., Henning, D. J., Wilson, J. G., Brown, S. M., Patel, M. M., Self, W. H., Lindsell, C. J. 2022; 6 (1): e61

  Abstract

  Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

  View details for DOI 10.1017/cts.2022.393

  View details for PubMedID 35720967

  View details for PubMedCentralID PMC9161049

• Primary palliative care recommendations for critical care clinicians. Journal of intensive care Ito, K., George, N., Wilson, J., Bowman, J., Aaronson, E., Ouchi, K. 2022; 10 (1): 20

  Abstract

  Palliative care is an interdisciplinary care to optimize physical, psychosocial, and spiritual symptoms of patients and their families whose quality of life is impaired by serious, life-limiting illness. In 2021, the importance of providing palliative care in the intensive care unit (ICU) is well recognized by various studies to alleviate physical symptoms due to invasive treatments, to set patient-centered goals of care, and to provide end-of-life care. This paper summarizes the evidence known to date on primary palliative care delivered in the ICU settings. We will then discuss the potential benefits and harms of primary palliative care so that critical care clinicians are better equipped to decide what services might best improve the palliative care needs in their ICUs.

  View details for DOI 10.1186/s40560-022-00612-9

  View details for PubMedID 35428371

• mRNA Vaccine Effectiveness Against COVID-19 Hospitalization Among Solid Organ Transplant Recipients. The Journal of infectious diseases Kwon, J. H., Tenforde, M. W., Gaglani, M., Talbot, H. K., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Caspers, S. D., Exline, M. C., Botros, M., Gong, M. N., Li, A., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Khan, A., Hough, C. L., Busse, L. W., Duggal, A., Wilson, J. G., Perez, C., Chang, S. Y., Mallow, C., Rovinski, R., Babcock, H. M., Lauring, A. S., Felley, L., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Womack, K. N., Lindsell, C. J., Hart, K. W., Baughman, A., Olson, S. M., Schrag, S., Kobayashi, M., Verani, J. R., Patel, M. M., Self, W. H., Influenza and Other Viruses in the Acutely Ill (IVY) Network 2022

  Abstract

  BACKGROUND: The study objective was to evaluate 2 and 3 dose COVID-19 mRNA vaccine effectiveness (VE) in preventing COVID-19 hospitalization among adult solid organ transplant (SOT) recipients.METHODS: 21-site case-control analysis of 10,425 adults hospitalized March-December 2021. Cases were hospitalized with COVID-19; controls were hospitalized for an alternative diagnosis (SARS-CoV-2 negative). Participants were classified as: SOT recipient (n=440), other immunocompromising condition (n=1684), or immunocompetent (n=8301). VE against COVID-19 associated hospitalization was calculated as 1-adjusted odds ratio of prior vaccination among cases compared with controls.RESULTS: Among SOT recipients, VE was 29% (95% CI: -19 to 58%) for 2 doses and 77% (95% CI: 48 to 90%) for 3 doses. Among patients with other immunocompromising conditions, VE was 72% (95% CI: 64 to 79%) for 2 doses and 92% (95% CI: 85 to 95%) for 3 doses. Among immunocompetent patients, VE was 88% (95% CI: 87 to 90%) for 2 doses and 96% (95% CI: 83 to 99%) for 3 doses.CONCLUSION: Effectiveness of COVID-19 mRNA vaccines was lower for SOT recipients than immunocompetent people and those with other immunocompromising conditions. Among SOT recipients, vaccination with 3 doses of an mRNA vaccine led to substantially greater protection than 2 doses.

  View details for DOI 10.1093/infdis/jiac118

  View details for PubMedID 35385875

• Effectiveness of mRNA Vaccination in Preventing COVID-19-Associated Invasive Mechanical Ventilation and Death - United States, March 2021-January 2022 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Self, W. H., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Shehu, A., Prekker, M. E., Frosch, A. E., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Botros, M., Lauring, A. S., Shapiro, N., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Adams, K., Surie, D., McMorrow, M. L., Patel, M. M., IVY Network 2022; 71 (12): 459-465

  Abstract

  COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) are effective at preventing COVID-19-associated hospitalization (1-3). However, how well mRNA vaccines protect against the most severe outcomes of these hospitalizations, including invasive mechanical ventilation (IMV) or death is uncertain. Using a case-control design, mRNA vaccine effectiveness (VE) against COVID-19-associated IMV and in-hospital death was evaluated among adults aged ≥18 years hospitalized at 21 U.S. medical centers during March 11, 2021-January 24, 2022. During this period, the most commonly circulating variants of SARS-CoV-2, the virus that causes COVID-19, were B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.529 (Omicron). Previous vaccination (2 or 3 versus 0 vaccine doses before illness onset) in prospectively enrolled COVID-19 case-patients who received IMV or died within 28 days of hospitalization was compared with that among hospitalized control patients without COVID-19. Among 1,440 COVID-19 case-patients who received IMV or died, 307 (21%) had received 2 or 3 vaccine doses before illness onset. Among 6,104 control-patients, 4,020 (66%) had received 2 or 3 vaccine doses. Among the 1,440 case-patients who received IMV or died, those who were vaccinated were older (median age = 69 years), more likely to be immunocompromised* (40%), and had more chronic medical conditions compared with unvaccinated case-patients (median age = 55 years; immunocompromised = 10%; p<0.001 for both). VE against IMV or in-hospital death was 90% (95% CI = 88%-91%) overall, including 88% (95% CI = 86%-90%) for 2 doses and 94% (95% CI = 91%-96%) for 3 doses, and 94% (95% CI = 88%-97%) for 3 doses during the Omicron-predominant period. COVID-19 mRNA vaccines are highly effective in preventing COVID-19-associated death and respiratory failure treated with IMV. CDC recommends that all persons eligible for vaccination get vaccinated and stay up to date with COVID-19 vaccination (4).

  View details for Web of Science ID 000778006200001

  View details for PubMedID 35324878

  View details for PubMedCentralID PMC8956334

• Selection bias in estimating the relationship between prolonged ED boarding and mortality in emergency critical care patients. Journal of the American College of Emergency Physicians open Gardner, K., Gordon, A. J., Shannon, B., Nesbitt, J., Wilson, J. G., Mitarai, T., Kohn, M. A. 2022; 3 (1): e12667

  Abstract

  Objectives: Studies have found that prolonged boarding time for intensive care unit (ICU) patients in the emergency department (ED) is associated with higher in-hospital mortality. However, these studies introduced selection bias by excluding patients with ICU admission orders who were downgraded and never arrived in the ICU. Consequently, they may overestimate mortality in prolonged ED boarders.Methods: This was a retrospective cohort study at a single center covering the period from August 14, 2015 to August 13, 2019. Adult ED patients with medical ICU admission orders and at least 6hours of subsequent critical care in either the ED or the ICU were included. Patients were classified as having either prolonged(>6hours) or non-prolonged (≤6hours) ED boarding. Downgraded patients were identified, and mortality was compared, both including and excluding downgraded patients.Results: Of 1862 patients, 612 (32.9%) had prolonged boarding; at 6hours after ICU admission order entry, they were still in the ED. The remaining 1250 (67.1%) had non-prolonged boarding; at 6hours after the ICU admission order entry, they were already in the ICU. In-hospital mortality in the non-prolonged boarding group was 18.9%. In the prolonged boarding group, 296 (48.4%) patients were downgraded in the ED and never arrived in the ICU. Including these ED downgrades, the mortality in the prolonged boarding group was 13.4% (risk difference -5.5%, 95% confidence interval [CI] -8.9% to -2.0%, P=0.0031). When we excluded downgrades, the mortality in the prolonged boarding group increased to 17.4% (risk difference -1.5%, 95% CI -6.2% to 3.2%, P=0.5720). The lower mortality in the prolonged group was attributable to lower severity of illness (mean emergency critical care SOFA [eccSOFA] difference: -0.8, 95% CI -1.1 to -0.4, P<0.0001).Conclusions: Excluding critical care patients who were downgraded in the ED leads to selection bias and overestimation of mortality among prolonged ED boarders.

  View details for DOI 10.1002/emp2.12667

  View details for PubMedID 35128534

• Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults - United States, August-December 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Patel, M. M., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Botros, M., Lauring, A. S., Shapiro, N., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Naioti, E. A., Adams, K., Lewis, N. M., Surie, D., McMorrow, M. L., Self, W. H., IVY Network 2022; 71 (4): 118-124

  Abstract

  COVID-19 mRNA vaccines (BNT162b2 [Pfizer-BioNTech] and mRNA-1273 [Moderna]) provide protection against infection with SARS-CoV-2, the virus that causes COVID-19, and are highly effective against COVID-19-associated hospitalization among eligible persons who receive 2 doses (1,2). However, vaccine effectiveness (VE) among persons with immunocompromising conditions* is lower than that among immunocompetent persons (2), and VE declines after several months among all persons (3). On August 12, 2021, the Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for a third mRNA vaccine dose as part of a primary series ≥28 days after dose 2 for persons aged ≥12 years with immunocompromising conditions, and, on November 19, 2021, as a booster dose for all adults aged ≥18 years at least 6 months after dose 2, changed to ≥5 months after dose 2 on January 3, 2022 (4,5,6). Among 2,952 adults (including 1,385 COVID-19 case-patients and 1,567 COVID-19-negative controls) hospitalized at 21 U.S. hospitals during August 19-December 15, 2021, effectiveness of mRNA vaccines against COVID-19-associated hospitalization was compared between adults eligible for but who had not received a third vaccine dose (1,251) and vaccine-eligible adults who received a third dose ≥7 days before illness onset (312). Among 1,875 adults without immunocompromising conditions (including 1,065 [57%] unvaccinated, 679 [36%] 2-dose recipients, and 131 [7%] 3-dose [booster] recipients), VE against COVID-19 hospitalization was higher among those who received a booster dose (97%; 95% CI = 95%-99%) compared with that among 2-dose recipients (82%; 95% CI = 77%-86%) (p <0.001). Among 1,077 adults with immunocompromising conditions (including 324 [30%] unvaccinated, 572 [53%] 2-dose recipients, and 181 [17%] 3-dose recipients), VE was higher among those who received a third dose to complete a primary series (88%; 95% CI = 81%-93%) compared with 2-dose recipients (69%; 95% CI = 57%-78%) (p <0.001). Administration of a third COVID-19 mRNA vaccine dose as part of a primary series among immunocompromised adults, or as a booster dose among immunocompetent adults, provides improved protection against COVID-19-associated hospitalization.

  View details for Web of Science ID 000748639100001

  View details for PubMedID 35085218

• Effectiveness of a Third Dose of Pfizer-BioNTech and Moderna Vaccines in Preventing COVID-19 Hospitalization Among Immunocompetent and Immunocompromised Adults - United States, August-December 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Patel, M. M., Gaglani, M., Ginde, A. A., Douin, D. J., Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Duggal, A., Wilson, J. G., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Botros, M., Lauring, A. S., Shapiro, N., Halasa, N., Chappell, J. D., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Naioti, E. A., Adams, K., Lewis, N. M., Surie, D., McMorrow, M. L., Self, W. H., IVY Network 2022; 71 (4): 118-124

  View details for Web of Science ID 000931811300001

• Autoantibodies targeting cytokines and connective tissue disease autoantigens are common in acute non-SARS-CoV-2 infections. Research square Feng, A., Yang, E., Moore, A., Dhingra, S., Chang, S., Yin, X., Pi, R., Mack, E., Völkel, S., Geßner, R., Gundisch, M., Neubauer, A., Renz, H., Tsiodras, S., Fragkou, P., Asuni, A., Levitt, J., Wilson, J., Leong, M., Lumb, J., Mao, R., Pinedo, K., Roque, J., Richards, C., Stabile, M., Swaminathan, G., Salagianni, M., Triantafyllia, V., Bertrams, W., Blish, C., Carette, J., Frankovich, J., Meffre, E., Nadeau, K. C., Singh, U., Wang, T., Prak, E. L., Herold, S., Andreakos, E., Schmeck, B., Skevaki, C., Rogers, A., Utz, P. 2022

  Abstract

  The widespread presence of autoantibodies in acute infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is increasingly recognized, but the prevalence of autoantibodies in infections with organisms other than SARS-CoV-2 has not yet been reported. We used protein arrays to profile IgG autoantibodies from 317 samples from 268 patients across a spectrum of non-SARS-CoV-2 infections, many of whom were critically ill with pneumonia. Anti-cytokine antibodies (ACA) were identified in > 50% of patients infected with non-SARS-CoV-2 viruses and other pathogens, including patients with pneumonia attributed to bacterial causes. In cell-based functional assays, some ACA blocked binding to surface receptors for type I interferons (Type I IFN), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-6 (IL-6). Autoantibodies against traditional autoantigens associated with connective tissue diseases (CTDs) were also commonly observed in these cohorts, including newly-detected antibodies that emerged in longitudinal samples from patients infected with influenza. We conclude that autoantibodies, some of which are functionally active, may be much more prevalent than previously appreciated in patients who are symptomatically infected with diverse pathogens.

  View details for DOI 10.21203/rs.3.rs-1233038/v1

  View details for PubMedID 35075455

  View details for PubMedCentralID PMC8786233

• Clinical severity of, and effectiveness of mRNA vaccines against, covid-19 from omicron, delta, and alpha SARS-CoV-2 variants in the United States: prospective observational study. BMJ (Clinical research ed.) Lauring, A. S., Tenforde, M. W., Chappell, J. D., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Exline, M. C., Gong, M. N., Mohamed, A., Johnson, N. J., Srinivasan, V., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Halasa, N., Grijalva, C. G., Rice, T. W., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Adams, K., Schrag, S. J., Olson, S. M., Kobayashi, M., Verani, J. R., Patel, M. M., Self, W. H., Influenza and Other Viruses in the Acutely Ill (IVY) Network 2022; 376: e069761

  Abstract

  OBJECTIVES: To characterize the clinical severity of covid-19 associated with the alpha, delta, and omicron SARS-CoV-2 variants among adults admitted to hospital and to compare the effectiveness of mRNA vaccines to prevent hospital admissions related to each variant.DESIGN: Case-control study.SETTING: 21 hospitals across the United States.PARTICIPANTS: 11690 adults (≥18 years) admitted to hospital: 5728 with covid-19 (cases) and 5962 without covid-19 (controls). Patients were classified into SARS-CoV-2 variant groups based on viral whole genome sequencing, and, if sequencing did not reveal a lineage, by the predominant circulating variant at the time of hospital admission: alpha (11 March to 3 July 2021), delta (4 July to 25 December 2021), and omicron (26 December 2021 to 14 January 2022).MAIN OUTCOME MEASURES: Vaccine effectiveness calculated using a test negative design for mRNA vaccines to prevent covid-19 related hospital admissions by each variant (alpha, delta, omicron). Among patients admitted to hospital with covid-19, disease severity on the World Health Organization's clinical progression scale was compared among variants using proportional odds regression.RESULTS: Effectiveness of the mRNA vaccines to prevent covid-19 associated hospital admissions was 85% (95% confidence interval 82% to 88%) for two vaccine doses against the alpha variant, 85% (83% to 87%) for two doses against the delta variant, 94% (92% to 95%) for three doses against the delta variant, 65% (51% to 75%) for two doses against the omicron variant; and 86% (77% to 91%) for three doses against the omicron variant. In-hospital mortality was 7.6% (81/1060) for alpha, 12.2% (461/3788) for delta, and 7.1% (40/565) for omicron. Among unvaccinated patients with covid-19 admitted to hospital, severity on the WHO clinical progression scale was higher for the delta versus alpha variant (adjusted proportional odds ratio 1.28, 95% confidence interval 1.11 to 1.46), and lower for the omicron versus delta variant (0.61, 0.49 to 0.77). Compared with unvaccinated patients, severity was lower for vaccinated patients for each variant, including alpha (adjusted proportional odds ratio 0.33, 0.23 to 0.49), delta (0.44, 0.37 to 0.51), and omicron (0.61, 0.44 to 0.85).CONCLUSIONS: mRNA vaccines were found to be highly effective in preventing covid-19 associated hospital admissions related to the alpha, delta, and omicron variants, but three vaccine doses were required to achieve protection against omicron similar to the protection that two doses provided against the delta and alpha variants. Among adults admitted to hospital with covid-19, the omicron variant was associated with less severe disease than the delta variant but still resulted in substantial morbidity and mortality. Vaccinated patients admitted to hospital with covid-19 had significantly lower disease severity than unvaccinated patients for all the variants.

  View details for DOI 10.1136/bmj-2021-069761

  View details for PubMedID 35264324

• Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial. JAMA Berger, J. S., Kornblith, L. Z., Gong, M. N., Reynolds, H. R., Cushman, M., Cheng, Y., McVerry, B. J., Kim, K. S., Lopes, R. D., Atassi, B., Berry, S., Bochicchio, G., de Oliveira Antunes, M., Farkouh, M. E., Greenstein, Y., Hade, E. M., Hudock, K., Hyzy, R., Khatri, P., Kindzelski, A., Kirwan, B., Baumann Kreuziger, L., Lawler, P. R., Leifer, E., Lopez-Sendon Moreno, J., Lopez-Sendon, J., Luther, J. F., Nigro Maia, L., Quigley, J., Sherwin, R., Wahid, L., Wilson, J., Hochman, J. S., Neal, M. D., ACTIV-4a Investigators, Newman, J., Geraci, M., Maggioni, A., Kamel, H., Goligher, E. C., Zarychanski, R., Everett, B. M., van Diepen, S., Le Gal, G., Siegal, D. M., Galanaud, J., Hegde, S., Kim, Y., Rost, N. S., Singhal, A. B., Contreras, A., Mavromichalis, S., Iturrate, E., Gilsenan, M., Naumova, A., Roberts, A., Levine, J., Leeper, C. M., Angus, D. C., Martinez, M., Schreiber, J., Froess, J., Stehle, C. E., Vadlamudi, A. S., Sciurba, F., Morris, A., Music, E., de Brouwer, S., Perrin, E., Gombault, C., Bula, S., Nelson, M., Daelemans, C., Paraz, L., Detry, M. A., McGlothlin, A., Quintana, M., Crawford, A., Sin, D., Diene, E., Gwiszcz, E., Hogan, I., Holden, A., Ringwood, N., Fitzgerald, L., Morin, H., Nunez-Garcia, B., Kornblith, A. E., Hendrickson, C. M., Lee, D., Nguyen, V., Shelley, I., Broaddrick, S., Atal, N., Huang, D. T., Wunderly, R., Buxton, M., Roberts, T., Linstrum, K., McNamara, A., Weissman, A., Barbee, D., Berryman, E., Frasure, J., Sulken, A., Ianof, J. N., Mazza, L., Morata, J., Cafarella, C. M., Suiama, M. A., de Lima Franco, D., Escobedo, J., Martinez, A., Ohara, P., Assis, D., Manzalini, C., Corsi, S., Campo, G., Prieto, P., Prieto, R., Garg, S., Fonseco, R., Reese, S., Mohammed, O., Dolor, R., Ortel, T. L., Wolfe, C., Plump, M., Nair, R., Nkemdirim, W., Chen, J., Galen, B., Moskowitz, A., Keller, N., Yuriditsky, E., Horowitz, J., Hindenburg, A., Chkhikvadze, T., Bassoli, L., Costa, T., Lopez-Sendon Moreno, J. L., Rodriguez Jorge, F., Garcia Madrona, S., Morillo Guerrero, R., Alpanes Buesa, M., Nieto Royo, R., Besse Diaz, R., Diz Farina, S., Gonzalez Garcia, A., da Silva Junior, O., Pradela, C., Jorge, C., Buka, M., Costa, O., Frassatto, D., Vieira, J., Dutra, P., Moreira, L., da Silva, N., Prado, N., Martins, A., Centurione, A., de Matos Soeiro, A., Avancini Caramori, P. R., Coppola, N., Contoli, M., Lopez-de-Sa, E., Worner, F., Lopez-Bernus, A., Gonzalez Juanatey, J. R., Peteiro, J., Gandotra, S., Krishnan, V., Widmer, R., Satterwhite, L., Macchiavelli, A., Hanna, N., Patel, H., Lyubarova, R., Gashi, E., Alvaro, A., Pan, S., Vallurupalli, S., Iovine, N., Nair, R., Jathavedam, A., Shah, A., Duggal, A., Khan, A., Matthay, M. A., Prekker, M. E., Lim, G., Moore, S., Costantini, T. W., Kutcher, M. E., Joseph, B., Bromberg, M., Effron, M. B., Pishko, A., Sheehan, J. P., Gaddh, M., Rezai, K., Latorre, J. G., Liang, C., Ajani, Z., Guo, S., Whitson, M. 1800; 327 (3): 227-236

  Abstract

  Importance: Platelets represent a potential therapeutic target for improved clinical outcomes in patients with COVID-19.Objective: To evaluate the benefits and risks of adding a P2Y12 inhibitor to anticoagulant therapy among non-critically ill patients hospitalized for COVID-19.Design, Setting, and Participants: An open-label, bayesian, adaptive randomized clinical trial including 562 non-critically ill patients hospitalized for COVID-19 was conducted between February 2021 and June 2021 at 60 hospitals in Brazil, Italy, Spain, and the US. The date of final 90-day follow-up was September 15, 2021.Interventions: Patients were randomized to a therapeutic dose of heparin plus a P2Y12 inhibitor (n=293) or a therapeutic dose of heparin only (usual care) (n=269) in a 1:1 ratio for 14 days or until hospital discharge, whichever was sooner. Ticagrelor was the preferred P2Y12 inhibitor.Main Outcomes and Measures: The composite primary outcome was organ support-free days evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and, for those who survived to hospital discharge, the number of days free of respiratory or cardiovascular organ support up to day 21 of the index hospitalization (range, -1 to 21 days; higher scores indicate less organ support and better outcomes). The primary safety outcome was major bleeding by 28 days as defined by the International Society on Thrombosis and Hemostasis.Results: Enrollment of non-critically ill patients was discontinued when the prespecified criterion for futility was met. All 562 patients who were randomized (mean age, 52.7 [SD, 13.5] years; 41.5% women) completed the trial and 87% received a therapeutic dose of heparin by the end of study day 1. In the P2Y12 inhibitor group, ticagrelor was used in 63% of patients and clopidogrel in 37%. The median number of organ support-free days was 21 days (IQR, 20-21 days) among patients in the P2Y12 inhibitor group and was 21 days (IQR, 21-21 days) in the usual care group (adjusted odds ratio, 0.83 [95% credible interval, 0.55-1.25]; posterior probability of futility [defined as an odds ratio <1.2], 96%). Major bleeding occurred in 6 patients (2.0%) in the P2Y12 inhibitor group and in 2 patients (0.7%) in the usual care group (adjusted odds ratio, 3.31 [95% CI, 0.64-17.2]; P=.15).Conclusions and Relevance: Among non-critically ill patients hospitalized for COVID-19, the use of a P2Y12 inhibitor in addition to a therapeutic dose of heparin, compared with a therapeutic dose of heparin only, did not result in an increased odds of improvement in organ support-free days within 21 days during hospitalization.Trial Registration: ClinicalTrials.gov Identifier: NCT04505774.

  View details for DOI 10.1001/jama.2021.23605

  View details for PubMedID 35040887

• Effectiveness of mRNA vaccines in preventing COVID-19 hospitalization by age and burden of chronic medical conditions among immunocompetent US adults, March-August 2021. The Journal of infectious diseases Lewis, N. M., Naioti, E. A., Self, W. H., Ginde, A. A., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Gaglani, M., Ghamande, S. A., McNeal, T. A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Henning, D. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Hubel, K., Hough, C. L., Busse, L. W., Ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Rhoads, J. P., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Schrag, S. J., Kobayashi, M., Verani, J. R., Patel, M. M., Tenforde, M. W. 1800

  Abstract

  In a multi-state network, vaccine effectiveness (VE) against COVID-19 hospitalizations was evaluated among immunocompetent adults (≥18-years) during March-August 2021 using a case-control design. Among 1669 hospitalized COVID-19 cases (11% fully vaccinated) and 1950 RT-PCR-negative controls (54% fully vaccinated), VE was higher at 96% (95% CI: 93-98%) among patients with no chronic medical conditions than patients with ≥3 categories of conditions (83% [95% CI: 76-88%]). VE was similar between those aged 18-64 years vs ≥65 years (p>0.05). Vaccine effectiveness against severe COVID-19 was very high among adults without chronic conditions and lessened with increasing burden of comorbidities.

  View details for DOI 10.1093/infdis/jiab619

  View details for PubMedID 34932114

• Natural language processing of head CT reports to identify intracranial mass effect: CTIME algorithm. The American journal of emergency medicine Gordon, A. J., Banerjee, I., Block, J., Winstead-Derlega, C., Wilson, J. G., Mitarai, T., Jarrett, M., Sanyal, J., Rubin, D. L., Wintermark, M., Kohn, M. A. 2021; 51: 388-392

  Abstract

  BACKGROUND: The Mortality Probability Model (MPM) is used in research and quality improvement to adjust for severity of illness and can also inform triage decisions. However, a limitation for its automated use or application is that it includes the variable "intracranial mass effect" (IME), which requires human engagement with the electronic health record (EHR). We developed and tested a natural language processing (NLP) algorithm to identify IME from CT head reports.METHODS: We obtained initial CT head reports from adult patients who were admitted to the ICU from our ED between 10/2013 and 9/2016. Each head CT head report was labeled yes/no IME by at least two of five independent labelers. The reports were then randomly divided 80/20 into training and test sets. All reports were preprocessed to remove linguistic and style variability, and a dictionary was created to map similar common terms. We tested three vectorization strategies: Term Frequency-Inverse Document frequency (TF-IDF), Word2Vec, and Universal Sentence Encoder to convert the report text to a numerical vector. This vector served as the input to a classification-tree-based ensemble machine learning algorithm (XGBoost). After training, model performance was assessed in the test set using the area under the receiver operating characteristic curve (AUROC). We also divided the continuous range of scores into positive/inconclusive/negative categories for IME.RESULTS: Of the 1202 CT reports in the training set, 308 (25.6%) reports were manually labeled as "yes" for IME. Of the 355 reports in the test set, 108 (30.4%) were labeled as "yes" for IME. The TF-IDF vectorization strategy as an input for the XGBoost model had the best AUROC:-- 0.9625 (95% CI 0.9443-0.9807). TF-IDF score categories were defined and had the following likelihood ratios: "positive" (TF-IDF score>0.5) LR=24.59; "inconclusive" (TF-IDF 0.05-0.5) LR=0.99; and "negative" (TF-IDF<0.05) LR=0.05. 82% of reports were classified as either "positive" or "negative". In the test set, only 4 of 199 (2.0%) reports with a "negative" classification were false negatives and only 8 of 93 (8.6%) reports classified as "positive" were false positives.CONCLUSION: NLP can accurately identify IME from free-text reports of head CTs in approximately 80% of records, adequate to allow automatic calculation of MPM based on EHR data for many applications.

  View details for DOI 10.1016/j.ajem.2021.11.001

  View details for PubMedID 34839182

• Association Between mRNA Vaccination and COVID-19 Hospitalization and Disease Severity. JAMA Tenforde, M. W., Self, W. H., Adams, K., Gaglani, M., Ginde, A. A., McNeal, T., Ghamande, S., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Exline, M. C., Gong, M. N., Mohamed, A., Henning, D. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., Ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Rhoads, J. P., Lindsell, C. J., Hart, K. W., Zhu, Y., Olson, S. M., Kobayashi, M., Verani, J. R., Patel, M. M., Influenza and Other Viruses in the Acutely Ill (IVY) Network 2021

  Abstract

  Importance: A comprehensive understanding of the benefits of COVID-19 vaccination requires consideration of disease attenuation, determined as whether people who develop COVID-19 despite vaccination have lower disease severity than unvaccinated people.Objective: To evaluate the association between vaccination with mRNA COVID-19 vaccines-mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech)-and COVID-19 hospitalization, and, among patients hospitalized with COVID-19, the association with progression to critical disease.Design, Setting, and Participants: A US 21-site case-control analysis of 4513 adults hospitalized between March 11 and August 15, 2021, with 28-day outcome data on death and mechanical ventilation available for patients enrolled through July 14, 2021. Date of final follow-up was August 8, 2021.Exposures: COVID-19 vaccination.Main Outcomes and Measures: Associations were evaluated between prior vaccination and (1) hospitalization for COVID-19, in which case patients were those hospitalized for COVID-19 and control patients were those hospitalized for an alternative diagnosis; and (2) disease progression among patients hospitalized for COVID-19, in which cases and controls were COVID-19 patients with and without progression to death or mechanical ventilation, respectively. Associations were measured with multivariable logistic regression.Results: Among 4513 patients (median age, 59 years [IQR, 45-69]; 2202 [48.8%] women; 23.0% non-Hispanic Black individuals, 15.9% Hispanic individuals, and 20.1% with an immunocompromising condition), 1983 were case patients with COVID-19 and 2530 were controls without COVID-19. Unvaccinated patients accounted for 84.2% (1669/1983) of COVID-19 hospitalizations. Hospitalization for COVID-19 was significantly associated with decreased likelihood of vaccination (cases, 15.8%; controls, 54.8%; adjusted OR, 0.15; 95% CI, 0.13-0.18), including for sequenced SARS-CoV-2 Alpha (8.7% vs 51.7%; aOR, 0.10; 95% CI, 0.06-0.16) and Delta variants (21.9% vs 61.8%; aOR, 0.14; 95% CI, 0.10-0.21). This association was stronger for immunocompetent patients (11.2% vs 53.5%; aOR, 0.10; 95% CI, 0.09-0.13) than immunocompromised patients (40.1% vs 58.8%; aOR, 0.49; 95% CI, 0.35-0.69) (P<.001) and weaker at more than 120 days since vaccination with BNT162b2 (5.8% vs 11.5%; aOR, 0.36; 95% CI, 0.27-0.49) than with mRNA-1273 (1.9% vs 8.3%; aOR, 0.15; 95% CI, 0.09-0.23) (P<.001). Among 1197 patients hospitalized with COVID-19, death or invasive mechanical ventilation by day 28 was associated with decreased likelihood of vaccination (12.0% vs 24.7%; aOR, 0.33; 95% CI, 0.19-0.58).Conclusions and Relevance: Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and disease progression to death or mechanical ventilation. These findings are consistent with risk reduction among vaccine breakthrough infections compared with absence of vaccination.

  View details for DOI 10.1001/jama.2021.19499

  View details for PubMedID 34734975

• Comparative Effectiveness of Moderna, Pfizer-BioNTech, and Janssen (Johnson & Johnson) Vaccines in Preventing COVID-19 Hospitalizations Among Adults Without Immunocompromising Conditions - United States, March-August 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Self, W. H., Tenforde, M. W., Rhoads, J. P., Gaglani, M., Ginde, A. A., Douin, D. J., Olson, S. M., Talbot, K., Casey, J. D., Mohr, N. M., Zepeski, A., McNeal, T., Ghamande, S., Gibbs, K. W., Files, D., Hager, D. N., Shchu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Henning, D. J., Steingrub, J. S., Peltan, I. D., ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Mills, L., Lester, S. N., Stumpf, M. M., Naioti, E. A., Kobayashi, M., Verani, J. R., Thornburg, N. J., Patel, M. M., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., IVY Network 2021; 70 (38): 1337-1343

  Abstract

  Three COVID-19 vaccines are authorized or approved for use among adults in the United States (1,2). Two 2-dose mRNA vaccines, mRNA-1273 from Moderna and BNT162b2 from Pfizer-BioNTech, received Emergency Use Authorization (EUA) by the Food and Drug Administration (FDA) in December 2020 for persons aged ≥18 years and aged ≥16 years, respectively. A 1-dose viral vector vaccine (Ad26.COV2 from Janssen [Johnson & Johnson]) received EUA in February 2021 for persons aged ≥18 years (3). The Pfizer-BioNTech vaccine received FDA approval for persons aged ≥16 years on August 23, 2021 (4). Current guidelines from FDA and CDC recommend vaccination of eligible persons with one of these three products, without preference for any specific vaccine (4,5). To assess vaccine effectiveness (VE) of these three products in preventing COVID-19 hospitalization, CDC and collaborators conducted a case-control analysis among 3,689 adults aged ≥18 years who were hospitalized at 21 U.S. hospitals across 18 states during March 11-August 15, 2021. An additional analysis compared serum antibody levels (anti-spike immunoglobulin G [IgG] and anti-receptor binding domain [RBD] IgG) to SARS-CoV-2, the virus that causes COVID-19, among 100 healthy volunteers enrolled at three hospitals 2-6 weeks after full vaccination with the Moderna, Pfizer-BioNTech, or Janssen COVID-19 vaccine. Patients with immunocompromising conditions were excluded. VE against COVID-19 hospitalizations was higher for the Moderna vaccine (93%; 95% confidence interval [CI] = 91%-95%) than for the Pfizer-BioNTech vaccine (88%; 95% CI = 85%-91%) (p = 0.011); VE for both mRNA vaccines was higher than that for the Janssen vaccine (71%; 95% CI = 56%-81%) (all p<0.001). Protection for the Pfizer-BioNTech vaccine declined 4 months after vaccination. Postvaccination anti-spike IgG and anti-RBD IgG levels were significantly lower in persons vaccinated with the Janssen vaccine than the Moderna or Pfizer-BioNTech vaccines. Although these real-world data suggest some variation in levels of protection by vaccine, all FDA-approved or authorized COVID-19 vaccines provide substantial protection against COVID-19 hospitalization.

  View details for Web of Science ID 000701940200005

  View details for PubMedID 34555004

  View details for PubMedCentralID PMC8459899

• Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Self, W. H., Naioti, E. A., Ginde, A. A., Douin, D. J., Olson, S. M., Talbot, H., Casey, J. D., Mohr, N. M., Zepeski, A., Gaglani, M., McNeal, T., Ghamande, S., Shapiro, N. I., Gibbs, K. W., Files, D., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Gong, M. N., Mohamed, A., Henning, D. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. L., Busse, L. W., ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A., Qadir, N., Chang, S. Y., Mallow, C., Rivas, C., Babcock, H. M., Kwon, J. H., Exline, M. C., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Stephenson, M., Schrag, S. J., Kobayashi, M., Verani, J. R., Patel, M. M., IVY Network Investigators 2021; 70 (34): 1156-1162

  Abstract

  Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.

  View details for Web of Science ID 000691315200005

  View details for PubMedID 34437524

• Tracheal aspirate RNA sequencing identifies distinct immunological features of COVID-19 ARDS. Nature communications Sarma, A., Christenson, S. A., Byrne, A., Mick, E., Pisco, A. O., DeVoe, C., Deiss, T., Ghale, R., Zha, B. S., Tsitsiklis, A., Jauregui, A., Moazed, F., Detweiler, A. M., Spottiswoode, N., Sinha, P., Neff, N., Tan, M., Serpa, P. H., Willmore, A., Ansel, K. M., Wilson, J. G., Leligdowicz, A., Siegel, E. R., Sirota, M., DeRisi, J. L., Matthay, M. A., COMET Consortium, Hendrickson, C. M., Kangelaris, K. N., Krummel, M. F., Woodruff, P. G., Erle, D. J., Calfee, C. S., Langelier, C. R., Abe-Jones, Y., Asthana, S., Beagle, A., Bhakta, T., Bhide, S., Cai, C., Caldera, S., Calfee, C., Calvo, M., Carrillo, S., Cattamanchi, A., Chak, S., Chan, V., Chew, N., Christenson, S., Collins, Z., Combes, A., Courau, T., Darmanis, S., Erle, D., Esmaili, A., Fragiadakis, G. K., Ghale, R., Giberson, J., Gonzalez, A., Serpa, P. H., Hendrickson, C., Hiam, K., Hu, K., Huang, B., Jauregui, A., Jones, C., Jones, N., Kangelaris, K., Krummel, M., Kumar, N., Kushnoor, D., Lea, T., Lee, D., Lee, D., Liu, K. D., Liu, Y., Mahboob, S., Matthay, M., Milush, J., Munoz-Sandoval, P., Nguyen, V., Ortiz, G., Parada, R., Phelps, M., Pierce, L., Prasad, P., Rao, A., Rashid, S., Reeder, G., Rodriguez, N., Samad, B., Scarlet, D., Shaw, C., Shen, A., Sigman, A., Spitzer, M., Sun, Y., Sunshine, S., Tang, K., Altamirano, L. T., Tsui, J., Tumurbaatar, E., Turner, K., Ward, A., Willmore, A., Wilson, M., Winkler, J., Withers, R., Wong, K., Woodruff, P., Ye, J., Yee, K., Yu, M., Zha, S., Zhan, J., Zhou, M., Zhu, W. S. 2021; 12 (1): 5152

  Abstract

  The immunological features that distinguish COVID-19-associated acute respiratory distress syndrome (ARDS) from other causes of ARDS are incompletely understood. Here, we report the results of comparative lower respiratory tract transcriptional profiling of tracheal aspirate from 52 critically ill patients with ARDS from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a "cytokine storm," we observe reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS is characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity. In silico analysis of gene expression identifies several candidate drugs that may modulate gene expression in COVID-19 ARDS, including dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 is characterized by impaired interferon-stimulated gene (ISG) expression. The relationship between SARS-CoV-2 viral load and expression of ISGs is decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients reveals distinct immunological features of COVID-19 ARDS.

  View details for DOI 10.1038/s41467-021-25040-5

  View details for PubMedID 34446707

• Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Tenforde, M. W., Patel, M. M., Ginde, A. A., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Gaglani, M., McNeal, T., Ghamande, S., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Exline, M. C., Gong, M. N., Mohamed, A., Henning, D. J., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. T., Busse, L., Ten Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Gershengorn, H. B., Babcock, H. M., Kwon, J. H., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Olson, S. M., Stephenson, M., Schrag, S. J., Kobayashi, M., Verani, J. R., Self, W. H., Influenza and Other Viruses in the Acutely Ill (IVY) Network 2021

  Abstract

  BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.METHODS: In a multicenter case-control analysis of US adults hospitalized March 11-May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.RESULTS: Among 1212 participants, including 593 cases and 619 controls, median age was 58 years, 22.8% were Black, 13.9% were Hispanic, and 21.0% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 (Alpha) was the most common variant (67.9% of viruses with lineage determined). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 8.2% of cases and 36.4% of controls. Overall vaccine effectiveness was 87.1% (95% CI: 80.7 to 91.3%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.4%; 95% CI: 79.3 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (62.9%; 95% CI: 20.8 to 82.6%) than without immunosuppression (91.3%; 95% CI: 85.6 to 94.8%).CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

  View details for DOI 10.1093/cid/ciab687

  View details for PubMedID 34358310

• Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19. The New England journal of medicine REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, Goligher, E. C., Bradbury, C. A., McVerry, B. J., Lawler, P. R., Berger, J. S., Gong, M. N., Carrier, M., Reynolds, H. R., Kumar, A., Turgeon, A. F., Kornblith, L. Z., Kahn, S. R., Marshall, J. C., Kim, K. S., Houston, B. L., Derde, L. P., Cushman, M., Tritschler, T., Angus, D. C., Godoy, L. C., McQuilten, Z., Kirwan, B., Farkouh, M. E., Brooks, M. M., Lewis, R. J., Berry, L. R., Lorenzi, E., Gordon, A. C., Berry, S. M., McArthur, C. J., Neal, M. D., Hochman, J. S., Webb, S. A., Zarychanski, R., Ahuja, T., Al-Beidh, F., Annane, D., Arabi, Y. M., Aryal, D., Baumann Kreuziger, L., Beane, A., Bhimani, Z., Bihari, S., Billett, H. H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L. A., Chekuri, S., Chen, J., Cheng, A. C., Chkhikvadze, T., Coiffard, B., Contreras, A., Costantini, T. W., de Brouwer, S., Detry, M. A., Duggal, A., Dzavik, V., Effron, M. B., Eng, H. F., Escobedo, J., Estcourt, L. J., Everett, B. M., Fergusson, D. A., Fitzgerald, M., Fowler, R. A., Froess, J. D., Fu, Z., Galanaud, J. P., Galen, B. T., Gandotra, S., Girard, T. D., Goodman, A. L., Goossens, H., Green, C., Greenstein, Y. Y., Gross, P. L., Haniffa, R., Hegde, S. M., Hendrickson, C. M., Higgins, A. M., Hindenburg, A. A., Hope, A. A., Horowitz, J. M., Horvat, C. M., Huang, D. T., Hudock, K., Hunt, B. J., Husain, M., Hyzy, R. C., Jacobson, J. R., Jayakumar, D., Keller, N. M., Khan, A., Kim, Y., Kindzelski, A., King, A. J., Knudson, M. M., Kornblith, A. E., Kutcher, M. E., Laffan, M. A., Lamontagne, F., Le Gal, G., Leeper, C. M., Leifer, E. S., Lim, G., Gallego Lima, F., Linstrum, K., Litton, E., Lopez-Sendon, J., Lother, S. A., Marten, N., Saud Marinez, A., Martinez, M., Mateos Garcia, E., Mavromichalis, S., McAuley, D. F., McDonald, E. G., McGlothlin, A., McGuinness, S. P., Middeldorp, S., Montgomery, S. K., Mouncey, P. R., Murthy, S., Nair, G. B., Nair, R., Nichol, A. D., Nicolau, J. C., Nunez-Garcia, B., Park, J. J., Park, P. K., Parke, R. L., Parker, J. C., Parnia, S., Paul, J. D., Pompilio, M., Quigley, J. G., Rosenson, R. S., Rost, N. S., Rowan, K., Santos, F. O., Santos, M., Santos, M. O., Satterwhite, L., Saunders, C. T., Schreiber, J., Schutgens, R. E., Seymour, C. W., Siegal, D. M., Silva, D. G., Singhal, A. B., Slutsky, A. S., Solvason, D., Stanworth, S. J., Turner, A. M., van Bentum-Puijk, W., van de Veerdonk, F. L., van Diepen, S., Vazquez-Grande, G., Wahid, L., Wareham, V., Widmer, R. J., Wilson, J. G., Yuriditsky, E., Zhong, Y., Manax, V., Connor, J., Bion, J., Gates, S., Reynolds, J., van der Poll, T., Al-Beidh, F., Angus, D., Annane, D., Arabi, Y., Beane, A., van Bentum-Pujik, W., Berry, S., Bhimani, Z., Bonten, M., Bradbury, C., Brunkhorst, F., Buxton, M., Cheng, A., Derde, L., Estcourt, L., Goossens, H., Gordon, A., Green, C., Haniffa, R., Lamontagne, F., Lawler, P., Linstrum, K., Litton, E., Marshall, J., McArthur, C., McAuley, D., McGuinness, S., McVerry, B., Montgomery, S., Mouncey, P., Murthy, S., Nichol, A., Parke, R., Parker, J., Rowan, K., Santos, M., Seymour, C., Turgeon, A., Turner, A., van de Veerdonk, F., Webb, S., Zarychanski, R., Campbell, L., Forbes, A., Gattas, D., Heritier, S., Kruger, P., Peake, S., Presneill, J., Seppelt, I., Trapani, T., Young, P., Cuthbertson, B., Fowler, R., Manoharan, V., Aryal, D., Dondrop, A. M., Hashmi, M., Jayakumar, D., Tolppa, T., Singh, V., Brillinger, N., Cecconi, M., Ermann, S., Francois, B., Hullegie, S., Markgraff, R., Pletz, M., Povoa, P., Rohde, G., Parker, L., Scheepstra-Beukers, I., Alexander, B., Basile, K., Girard, T., Horvat, C., Huang, D., Mayr, F., Beasley, R., Daneman, N., Fowler, R., McGloughlin, S., Morpeth, S., Paterson, D., Venkatesh, A. N., de Jong, M., Uyeki, T., Baillie, K., Duffy, E., Hills, T., Orr, K., Patanwala, A., Tong, S., Cooper, N., Cremer, O., Galea, J., King, A., Leavis, H., Netea, M., Ogungbenro, K., Patawala, A., Pettila, V., Rademaker, E., Saxena, M., Sligl, W., Tong, S., Youngstein, T., Seymour, C. W., Aryal, D. 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J., Nery, E., Saporito, W., Pereira, T., Mancini, B., Kowalski Neto, E., Andrade, B., Santos, J., Pompilio, M., Pompilio, R., Grava, S., Koga, K., Silva, M., Lemos, D., Villegas, B., Garcia, E. M., Cortes Vazquez, M. A., Perez Gonzalez, Y. S., Carreno Perez, P., Valenzuela, J., Santillan, J. A. 2021

  Abstract

  BACKGROUND: Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.METHODS: In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.RESULTS: The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation. Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis). The median value for organ support-free days was 1 (interquartile range, -1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, -1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%). The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11). Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.CONCLUSIONS: In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis. (REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.).

  View details for DOI 10.1056/NEJMoa2103417

  View details for PubMedID 34351722

• Therapeutic Anticoagulation with Heparin in Noncritically Ill Patients with Covid-19. The New England journal of medicine ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, Lawler, P. R., Goligher, E. C., Berger, J. S., Neal, M. D., McVerry, B. J., Nicolau, J. C., Gong, M. N., Carrier, M., Rosenson, R. S., Reynolds, H. R., Turgeon, A. F., Escobedo, J., Huang, D. T., Bradbury, C. A., Houston, B. L., Kornblith, L. Z., Kumar, A., Kahn, S. R., Cushman, M., McQuilten, Z., Slutsky, A. S., Kim, K. S., Gordon, A. C., Kirwan, B., Brooks, M. M., Higgins, A. M., Lewis, R. J., Lorenzi, E., Berry, S. M., Berry, L. R., Angus, D. C., McArthur, C. J., Webb, S. A., Farkouh, M. E., Hochman, J. S., Zarychanski, R., Aday, A. W., Al-Beidh, F., Annane, D., Arabi, Y. M., Aryal, D., Baumann Kreuziger, L., Beane, A., Bhimani, Z., Bihari, S., Billett, H. H., Bond, L., Bonten, M., Brunkhorst, F., Buxton, M., Buzgau, A., Castellucci, L. A., Chekuri, S., Chen, J., Cheng, A. 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X., Brum, A., Procopio, A., Alves, M., Grumach, A., Bertolini, L., Porto, C., Oliveira, S., Burihan, M., Santos Delcio Silva, M. J., Nery, E., Saporito, W., Pereira, T., Mancini, B., Kowalski Neto, E., Andrade, B., Santos, J., Pompilio, M., Pompilio, R., Agostinho, T., Grava, S., Koga, K., Silva, M., Lemos, D., Villegas, B., Medina, O., Gudino, H., Borja, P., Mateos Garcia, E., Cortes Vazquez, M. A., Perez Gonzalez, Y. S., Carreno Perez, P., Santillan, J. A., Becker, R. C., Del Zoppo, G., Henke, P., Holubkov, R., Kerr, K., Lee, A., Lurie, F., Vesely, S. K., Hochman, J. S., Neal, M. D., Berger, J. S., Cushman, M., Baumann Kreuziger, L., Berry, S., Gong, M. N., Hudock, K., Kim, K. S., Kornblith, L. Z., Lawler, P. R., Leifer, E., McVerry, B. J., Reynolds, H. R., Wilson, J. G., Hochman, J., Berger, J., Reynolds, H., Bragat, A., Goldfeld, K., Hade, E., Contreras, A., Mavromichalis, S., Iturrate, E., Gilsenan, M., Naumova, A., Roberts, A., Neal, M., Wisniewski, S., Leeper, C., Angus, D., Eng, H., Linstrum, K., Seymour, C., Girard, T., Montgomery, S., Martinez, M., Schreiber, J., Froess, J., Fu, Z., Zhong, Y., Vadlamudi, A., Sciurba, F., Morris, A., Gombault, C., Bula, S., Nelson, M., Daelemans, C., Wegmuller, R., La Framboise, D., Hoots, W. K., Kindzelski, A., Mondoro, T., Punturieri, A., Weinmann, G., Troendle, J. F., Kendrick, A. S., Nolen, T. L., Thomas, S., Sin, D., Diene, E., Gwiszcz, E., Hogan, I., Holden, A., Gong, M., Ringwood, N., Fitzgerald, L., Sharer, J., Ceusters, D., Hintlian, C., Kornblith, L., Nunez-Garcia, B., Uribe, V., Hendrickson, C., Barua, C., Knudson, M. M., Park, J., Gonzalez, A., Lopez-Sendon, J., Moraga Alapont, P., Prieto, P., Hernandez, V., Broaddrick, S., Kim, K., Quigley, S., McVerry, B., Huang, D., Buxton, M., Roberts, T., Kamel, H., Khatri, P., Frasure, J., Silken, A., Lopez-Sendon Moreno, J. L., Morillo Guerrero, R., Garcia Madrona, S., Molinera, A., Navarro Carrion, O., Besse Diaz, R., Diz Farina, S., Hidalgo Salinas, F., Gonzalez Ferrandiz, P., Zhilina, S., Alpanes Buesa, M., Gonzalez Garcia, A., Marcos Martin, M., Sanchez, M., Hernandez, J., Alvarez Navid, F., Belhassen Garcia, M., Carbonell Munoz, C., Hernandez Perez, G., Lopez Bernus, A., Martin Oterino, J. A., Sanchez Fernandez, P. L., de Tapia Majado, B., Gonzalez Juanatey, J. R., Seijas, J., Dominguez Santallas, M. J., Pose Reino, A., Valdes Cuadrado, L., Rodriguez Nunez, N., Keller, N., Yuriditsky, E., Ahuja, T., Horowitz, J., Hindenburg, A., Chkhikvadze, T., Parnia, S., Moran, Z., Fadzan, M., Levine, J., Cobos, S., Roberts, A., Mamistvalova, L., Garabedian, M., Ahmed, F., Zapata, G., Robinson, M., Quigley, J., Jacobson, J., Atal, N., Amosu, O., Tzehaie, H., Nair, R., Lopez, B., Hache Marliere, M., Fein, D., Offor, O., Kiyatkin, M., Chekuri, S., Galen, B., Hambardzumyan, A., Desai, A., Akhter, M., Aleem, H., Virdi, S., Shah, R., Hope, A., Chen, J., Mohamed, A., Kornblith, A., Shelley, I., Ambachew, B., Bensen, N., Burbee, D., Richardson, A., McNamara, A., Stavor, D., Abaye, M., Scholl, D., Wunderley, R., Yang, A., Amin, S. S., Berryman, E., Gilliam, M., Basile, K., Clermont, G., Garrard, W., Horvat, C., Kalchthaler, K., King, A. J., Ricketts, D., Malakouti, S., Marroquin, O., Music, E., Quinn, K., Andreae, M., Bain, W., Barbash, I., Brant, E., Barton, D., Fitzpatrick, M., Franz, C. A., Haidar, G., Hussain, M., Kitsios, G. D., Mayr, F. B., Malley, B., McCreary, E., Moghbeli, K., Rosborough, B., Schoenling, A., Shah, F. A., Shetty, V. U., Suber, T., Talia, N., Weissman, A., Schaefer, C., Muir, M., Urbanek, K. L., Greenstein, Y., Teeter, R., Plump, M., Kovalenko, O., Obando, E., Taveras, Y., Fanka, B., Suri, N., Patel, S., Kaur, M., Hite, R., Roads, T., Gebremedhen, A., Kiran, S., More, H., Costantini, T., Curry, T., Trinidad, E., Tyler, M., Berndtson, A., Allison, M., Bhatia, H., Denenberg, J., Marsh-Armstrong, B., Verzhbinsky, I., Morris, T., Fernandes, T., Elliott, A., Eastman, A., Lim, G., Hendey, G., Chang, S., Qadir, N., Beutler, R., Agarwal, T., Vargas, J., Singer, J., Haase, D., Murphy, J., Brzezinski, A., Yap, A., Yao, D. H., Bolduc, C., Antonuk, C., Spungen, H., Vuong, A., Wilson, J., Rogers, A., Levitt, J., Vojnik, R., Roque, J., Perez, C., Khan, A., Krol, O., Mistry, K., Nguyen, K., Lu, Z., Jouzestani, M. 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D., Frolkis, C., Matthay, M., Kirsten, K., Kangelaris, K., Liu, K., Calfee, C., Zhuo, H., Daniel, B., Yee, K., Jauregui, A., Ghale, R., Chak, S., Wick, K., Siegel, E., Jones, C., Ashktorab, K., Satterwhite, L., Harris, P., Lovell, K., Mourad, M., Bengtson, C., Atieh, T., Brownback, K., Aguiar, C., White, M., Deculus, K., Scott, L., English, L., Greer, S., Murry, S., Woodring, L., Nazir, U., Truong, A., Mallett, N., Williams, S., Hellwig, H., Burton, M., Pandey, A., Bates, C., Lewis, B., Tarbutton, J., Kondamudi, N., Huet, R. G., Xu, X., Berger-Nagele, M., Molina, E., Duggal, A., Mucha, S., Mehkri, O., King, A., Poynter, B., Ashok, K., Thiruchelvam, N., Sahoo, D., Goyanes, A., Siuba, M., Sunderkrishnan, R., Minear, S., Hernandez-Montfort, J., Mehta, J., McWilliams, C., Anekwe, C., Van, A., Calderon, A., Arazo, L., Nasim, S. S., De Carvalho Teixeira, C., Zelaya, D., Malhotra, S., Nedeltcheva, A., Rezai, K., Hoffman, M., Hernandez Acosta, R., Sarmiento, J., Uday, S., Hanna, N., Malik, A., Merritt, S., Davenport, J., Mears, K., Bryce, J., Arnold, M., Norwood, J., Urias, C., Kutcher, M., Galbraith, J., Jones, A., Nandi, U., Garla, V., Peacock, R., Davis, J., Grenn, E., Shaw, T., Moore, M., Prekker, M., Puskarich, M., Driver, B., Baker, J., Frosch, A., Kolb, A., Hubbard, L., Dunn, A., Hendrickson, A., Maruggi, E., Andersen, T., Miller, W., Raiter, A., Edpuganti, R., Ehlen, Q., Leland, G., Roth, M., Scharber, T., Tordsen, W., Reing, M., Isaksen, A., Erickson, H., Sheehan, J., Stewart, S., Kumfer, K., Veintimilla, R., Roginski, C., Bonk, N., Ensminger, S., Munir, M. S., Octain, J., Sheehy, A., Waters, A., Wilson, S., Hamburg, N., Minetti, E. 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M., Hashmi, M., Jayakumar, D., Tolppa, T., Singh, V., Brillinger, N., Cecconi, M., Ermann, S., Francois, B., Hullegie, S., Markgraff, R., Pletz, M., Povoa, P., Rohde, G., Parker, L., Scheepstra-Beukers, I., Alexander, B., Mayr, F., Beasley, R., Daneman, N., Fowler, R., McGloughlin, S., Morpeth, S., Paterson, D., Venkatesh, B., de Jong, M., Uyeki, T., Baillie, K., Duffy, E., Hills, T., Orr, K., Patanwala, A., Tong, S., Cooper, N., Cremer, O., Galea, J., King, A., Leavis, H., Netea, M., Ogungbenro, K., Patawala, A., Pettila, V., Rademaker, E., Saxena, M., Sligl, W., Tong, S., Youngstein, T., Seymour, C. W., Bihari, S., Hunt, B., Jayakumar, D., Laffan, M., Lother, S., Middeldorp, S., McQuilten, Z., Schutgens, R., Stanworth, S., Adhikari, N., Anstey, M., de Man, A., Lamonagne, F., Masse, M., Udy, A., Arnold, D., Begin, P., Charlewood, R., Chasse, M., Coyne, M., Cooper, J., Daly, J., Gosbell, I., Harvala-Simmonds, H., Hills, T., MacLennan, S., Menon, D., McDyer, J., Pridee, N., Roberts, D., Thomas, H., Tinmouth, A., Triulzi, D., Walsh, T., Wood, E., O'Kane, C., Shyamsundar, M., Sinha, P., Thompson, T., Young, I., Lawless, P., Ferguson, N., Hodgson, C., Laffey, J., Orford, N., Neto, A., Baron, R., Epelman, S., Frankfurter, C., Gommans, F., Kim, E., Leaf, D., Vaduganathan, M., van Kimmenade, R., Sanil, A., Berry, L., Lorenzi, E., Buzgau, A., Higgins, A., Zammit, C., Groeneveld, E., Peters, S., Okundaye, C., van Hout, D., Smit, A., Rikkert, L., Bari, S., Raymakers, K., Kwakkenbos-Craanen, M., Post, S., Schreuder, G., Markgraf, R., Ainscough, K., Brickell, K., Doran, P., Anjum, A., Lane, J., Fagbodun, E., Miller, L., Parry-Billings, K., Peters, S., Richards-Belle, A., Saull, M., Sprinckmoller, S., Wiley, D., van Beurden, M., Effelaar, E., Schotsman, J., Boyd, C., Harland, C., Shearer, A., Wren, J., Quinn, K., Attanayaka, U., Darshana, S., Ishani, P., Jawad, I., Pabasara, U., Udayanga, I., Gilmour, K., Pearson, K., Siewerski, C., Hurford, S., Marsh, E., Campbell, D., Williams, P., Shirley, K., Logan, M., Hanson, J., Dilley, B., Phillips, L., Oliver, A., Sutu, M., Murphy, S., Aravindan, L., Collins, J., Monaghan, H., Unsworth, A., Beddows, S., Dawson, L. 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T., McCracken, P., Young, M., Board, J., Martin, E., El-Khawas, K., Richardson, A., Hill, D., Commons, R. J., Abdelkharim, H., Knott, C., Smith, J., Boschert, C., Affleck, J., Apte, Y., Subbanna, U., Bartholdy, R., Frakking, T., Keat, K., Bhonagiri, D., Sanghavi, R., Nema, J., Ford, M., Parikh, H. G., Avard, B., Nourse, M., Cheung, W., Kol, M., Wong, H., Shah, A., Wagh, A., Simpson, J., Duke, G., Chan, P., Carter, B., Hunter, S., Laver, R. D., Shrestha, T., Jin, X., Regli, A., Pellicano, S., Palermo, A., Eroglu, E., French, C., Bates, S., Towns, M., Yang, Y., McGain, F., McCullough, J., Tallott, M., Kumar, N., Panwar, R., Brinkerhoff, G., Koppen, C., Cazzola, F., Brain, M., Mineall, S., Fischer, R., Biradar, V., Soar, N., White, H., Estensen, K., Morrison, L., Sutton, J., Cooper, M., Shehabi, Y., Al-Bassam, W., Hulley, A., Kadam, U., Sathianathan, K., Whitehead, C., Lowrey, J., Gresham, R., Masters, K., Walsham, J., Meyer, J., Harward, M., Venz, E., Brady, K., Vale, C., Shekar, K., Lavana, J., Parmar, D., Williams, P., Kurenda, C., Miles, H., Attokaran, A., Gluck, S., O'Connor, S., Chapman, M., Glasby, K., Smyth, K., Phillips, M., Barge, D., Byrne, K., Driscoll, A., Fortune, L., Janin, P., Yarad, E., Bass, F., Hammond, N., O'Connor, A., Waterson, S., McNamara, R., Buhr, H., Coles, J., Schweikert, S., Wibrow, B., Rauniyar, R., Deshpande, K., Konecny, P., Miller, J., Kintono, A., Tung, R., Fysh, E., Dawda, A., Mevavala, B., De Keulenaer, A. R., Litton, E., Ferrier, J., Nair, P., Buscher, H., Reynolds, C., Newman, S., Santamaria, J., Barbazza, L., Homes, J., Smith, R., Garrett, P., Murray, L., Brailsford, J., Forbes, L., Maguire, T., Fennessy, G., Mulder, J., Morgan, R., McEldrew, R., Naeem M, A., Fagan, L., Ryan, E., Mariappa, V., Smith, J., Simpson, S., Maiden, M., Bone, A., Horton, M., Salerno, T., Sterba, M., Geng, W., Depuydt, P., Waele, J. D., De Bus, L., Fierens, J., Bracke, S., Vermassen, J., Vermeiren, D., Reeve, B., Dechert, W., Chasse, M., Carrier, F. M., Boumahni, D., Benettaib, F., Ghamraoui, A., Couillard-Chenard, E., Lauzier, F., Francoeur, C., Lamontagne, F., D'Aragon, F., Carbonneau, E., Leblond, J., Vazquez-Grande, G., Liu, T., Siddiqui, A., Wilson, M., Albert, M., Serri, K., Cavayas, A., Duplaix, M., Williams, V., Rochwerg, B., Karachi, T., Oczkowski, S., Centofanti, J., Millen, T., Khwaja, K., Campisi, J., Duan, E., Tsang, J., Patterson, L., Sy, E., Gupta, C., Kassir, S. S., Kutsogiannis, D., Thompson, P., Kamra, M., Marinoff, N., Cook, D., Clarke, F., Kruisselbrink, R., Brochard, L., Burns, K., Sandhu, G., Khalid, I., English, S., Miezitis, S., McIntyre, L., Wilcox, E., Del Sorbo, L., Abdelhady, H., Romagnuolo, T., Baig, N., Rewa, O., Bagshaw, S., Binnie, A., Powell, E., McMillan, A., Luk, T., Aref, N., Pratheema, R., Babu, S., Vignesh, C., Kumar, B., Ramakrishnan, N., James, A., Elvira, E., Ebenezer, R., Krishnaoorthy, S., Ranganathan, L., Shree, M. M., Mani, A. K., Mathew, M., Khanal, R. S., Amatya, S., Paneru, H. R., Koirala, S., Paudel, P., Koirala, K., Rai, N., Luitel, S., Bhattarai, B., Hashmi, M., Panjwani, A., Umrani, Z. 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D., Malfroy, S., Mezher, C., Bourgoin, C., Moneger, G., Bouvier, E., Megarbane, B., Voicu, S., Deye, N., Malissin, I., Sutterlin, L., Mrad, A., Pepin Lehalleur, A., Naim, G., Nguyen, P., Ekherian, J., Boue, Y., Sideris, G., Vodovar, D., Guerin, E., Grant, C., Guitton, C., Darreau, C., Landais, M., Chudeau, N., Robert, A., Tirot, P., Callahan, J. C., Saint Martin, M., Le Moal, C., Marnai, R., Leroyer, M. H., Moine, P., Heming, N., Maxime, V., Bossard, I., Nicholier, T. B., Clair, B., Orlikowski, D., Bounab, R., Abdeladim, L., Colin, G., Zinzoni, V., Maquigneau, N., Henri-Lagarrigue, M., Pouplet, C., Soukup, J., Wetzold, R., Lobel, M., Ing, D., Starke, L., Grimm, P., Finn, A., KreSS, G., Hoff, U., Hinrichs, C. F., Nee, J., Pletz, M. W., Hagel, S., Ankert, J., Kolanos, S., Bloos, F., Nickoleit-Bitzenberger, D., Schaaf, B., Meermeier, W., Prebeg, K., Azzaui, H. S., Hower, M., Brieger, K., Elender, C., Sabelhaus, T., Riepe, A., Akamp, C., Kremling, J., Klein, D., Landsiedel-Mechenbier, E., Petros, S., Kunz, K., Schutze, B., Kluge, S., Nierhaus, A., Jarczak, D., Roedl, K., Ulrich Rohde, G. G., Grunewaldt, A., Bojunga, J., Weismann, D., Frey, A., Drayss, M., Goebeler, M. E., Flor, T., Fragner, G., Wahl, N., Totzke, J., Sayehli, C., Reill, L., Distler, M., Maselli, A., Belteczki, J., Magyar, I., Fazekas, A., Kovacs, S., Szoke, V., Szigligeti, G., Leszkoven, J., Collins, D., Reid, L., Smyth, M., Breen, P., Spain, S., Curley, G., McEvoy, N., Geoghegan, P., Clarke, J., Laffeyirbre McNicholas, J., Scully, M., Casey, S., Kernan, M., Brennan, A., Rangan, R., Tully, R., Corbett, S., McCarthy, A., Duffy, O., Burke, D., Hayes, L., Murphy, L., Neill, A., Reidy, B., O'Dwyer, M., Ryan, D., Hoiting, O., Peters, M., Rengers, E., Evers, M., Prinssen, A., van den Oever, H. L., Kruisdijk-Gerritsen, A., Simons, K., van Zuylen, T., Bouman, A., van Gulik, L., Schouten, J., Pickkers, P., Roovers, N., Klop-Riehl, M., van der Eng, H., Jonge, E. d., Wigbers, J., Del Prado, M., Haitsma Mulier, J., Peters, A. L., Romberg, B., van Bree, S., Bouw-Ruiterrbara Festen, M., van Gelder, F., van Iperen, M., Osinga, M., Schellaars, R., Tjan, D., van der Wekken, R., Melchers, M., van Zanten, A., van Nieuwkoop, K., Ottens, T., Visser, Y., Juffermans, N., Koopmans, M., Guilder, E., Butler, M., Cowdrey, K., Woollett, M., Newby, L., Chen, Y., Simmonds, C., McConnochie, R., O'Connor, C., Carter, J. R., Henderson, S., Van Der Heyden, K., Mehrtens, J., Morris, A., Morgan, S., Williams, T., Kazemi, A., Song, R., Lai, V., Girijadevi, D., Everitt, R., Russell, R., Hackin, D., Buehner, U., Williams, E., Browne, T., Grimwade, K., Goodson, J., Keet, O., Callender, O., Martynoga, R., Trask, K., Butler, A., Young, C., Lesona, E., Olatunji, S., Navarra, L., Sol Cruz, R., Perry, K., Fuchs, R., Lambert, B., Albrett, J., Jackson, C., Kirkham, S., Amaro Dos Santos Catorze, N. J., Lima Pereira, T. N., Castro Ferreira, R. M., Pereira Sousa Bastos, J. M., Oliveira Batista, T. M., Florescu, S. A., Stanciu, D., Zaharia, M. F., Kosa, A. G., Codreanu, D., Arabi, Y. M., Qasim, E. A., Tlayjeh, H., Alswaidan, L., Naidu, B., Munoz-Bermudez, R., Marin-Corral, J., Salazar Degracia, A., Parrilla Gomez, F., Mateo Lopez, M. I., Lopez, R. L., Rodriguez, J., Carcel, S., Carmona, R., de la Fuente, C., Rodriguez, M., Kaye, C., Allan, A., Summers, C., Polgarova, P., McWilliam, S. J., Hawcutt, D. B., Rad, L., O'Malley, L., Whitbread, J., Kelsall, O., Cowley, N., Wild, L., Thrush, J., Wood, H., Austin, K., Donnelly, A., Kelly, M., Smyth, N., O'Kane, S., McClintock, D., Warnock, M., Campbell, R., McCallion, E., Johnson, P., McKenna, S., Hanley, J., Currierbara Allen, A., McGoldrick, C., McMaster, M., Jha, R., Kalogirou, M., Ellis, C., Krishnamurthy, V., Deelchand, V., O'Connor, A., Silversides, J., McGuigan, P., Ward, K., O'Neill, A., Finn, S., Phillips, B., Ortiz-Ruiz de Gordoa, L., Bewley, J., Thomas, M., Sweet, K., Grimmer, L., Johnson, R., Pinnell, J., Robinson, M., Gledhill, L., Wood, T., Morgan, M., Cole, J., Hill, H., Davies, M., Williams, A., Thomas, E., Davies, R., Wise, M., Antcliffe, D., Templeton, M., Rojo, R., Coghlan, P., Smee, J., Mackay, E., Cort, J., Whileman, A., Spencer, T., Spittle, N., Beavis, S., Padmakumar, A., Dale, K., Hawes, J., Moakes, E., Gascoyne, R., Pritchard, K., Stevenson, L., Cooke, J., Nemeth-Roszpopa, K., Kasipandian, V., Patel, A., Allibone, S., Mary-Genetu, R., Ramali, M., Ghosh, A., Osagie, R., Jayasinghe Arachchige, M., Hartley, M., Bamford, P., London, E., Cawley, K., Faulkner, M., Jeffrey, H., Sundar Raj, A., Tsinaslanidis, G., Nair Khade, R., Nwajei Agha, G., Nalumansi Sekiwala, R., Smith, T., Brewer, C., Gregory, J., Limb, J., Cowton, A., O'Brien, J., Postlethwaite, K., Nikitas, N., Wells, C., Lankester, L., McMillan, H., Pulletz, M., Birch, J., Wiseman, S., Horton, S., Alegria, A., Turki, S., Elsefi, T., Crisp, N., Allen, L., Smith, M., Chukkambotla, S., Goddard, W., Duberley, S., McCullagh, I. J., Robinson, P., Patel, B., Kelly, S., Touma, O., Holland, S., Hodge, C., Taylor, H., Alderman, M., Barnes, N., Da Rocha, J., Smith, C., Brooks, N., Weerasinghe, T., Sinclair, J., Abusamra, Y., Doherty, R., Cudlipp, J., Singh, R., Yu, H., Daebis, A., Ng, C., Kendrick, S., Saran, A., Makky, A., Greener, D., Rowe-Leete, L., Edwards, A., Bland, Y., Dolman, R., Foster, T., Linnett, V., Sanderson, A., Ritzema, J., Wild, H., Khare, D., Pinder, M., Selvamoni, S., Gopinath, A., Pugh, R., Menzies, D., Lean, R., Qiu, X., Scanlon, J. J., Puxty, K., Cathcart, S., McGovern, C., Carmichael, S., Rimmer, D., Yusuff, H., Isgro, G., Brightling, C., Bourne, M., Craner, M., Boyles, R., Szakmany, T., Cherian, S., Williams, G., James, C., Waters, A., Watters, M., Prout, R., Davies, L., Pegler, S., Kyeremeh, L., Mian, A., Ostermann, M., Marotti, M., Grau Novellas, N., Bociek, A., Brett, S., Sousa Arias, S., Hall, R. E., Jain, S., Gupta, A., Holbrook, C., Henning, J., Bonner, S., Hugill, K., Cirstea, E., Wilkinson, D., Jones, J., Karlikowski, M., Sutherland, H., Wilhelmsen, E., Woods, J., North, J., Sundaran, D., Hollos, L., Coburn, S., Williams, A., Saunders, S., Hopkins, P., Smith, J., Noble, H., Depante, M. T., Clarey, E., Laha, S., Verlander, M., Williams, A., Paramasivam, E., Wilby, E., Ogg, B., Howcroft, C., Aspinwall, A., Charlton, S., Gould, R., Mistry, D., Awan, S., Bedford, C., Hall, A., Cooke, J., Gardiner-Hill, C., Maloney, C., Brunskill, N., QureshiI, H. R., Flint, N., Nicholson, S., Southin, S., Nicholson, A., Ghattaoraya, A., Harding, D., O'Halloran, S., Collins, A., Smith, E., Trues, E., Borgatta, B., Turner-Bone, I., Reddy, A., Wilding, L., Wilson, C., Surti, Z., Chamara Warnapura, L., Agno, R., Sathianathan, P., Shaw, D., Ijaz, N., Burns, D., Nisar, M., Quick, V., Alexander, C., Patel, S., Hussain, N., Croucher, Y., Langnu Rudran, E., Gilani, S., Wieder, T., Tate, M. L., Golden, D., Davey, M., Seaman, R., Felton, T., Bannard-Smith, J., Henry, J., Clark, R., Birchall, K., Pomeroy, F., Quayle, R., Wylie, K., Sukuraman, A., McNamarra, J., Makowski, A., Misztal, B., Ahmed, I., Neicker, K., Millington, S., Squires, R., Phulpoto, M., Stewart, R., Mwaura, E., Mew, L. E., Wren, L., Willams, F., Oborska, A., Maeda, R., Kalchko-Veyssal, S., Orat Prabakaran, R., Hadebe, B., Makmur, E., Nicholls, G., Innes, R., Doble, P., Graham, L., Shovelton, C., Hamlyn, V., Hawkins, N., Roynon-Reed, A., Cutler, S., Lewis, S., Lazaro, J. M., Newman, T., Austin, P., Chapman, S., Cabrelli, L., Fletcher, S., Nortje, J., Fottrell-Gould, D., Randell, G., Stammers, K., Zaman, M., Elmahi, E., Jones, A., Hall, K., Mills, G. H., Ryalls, K., Harrington, K., Bowler, H., Sall, J., Bourne, R., Borrill, Z., Duncan, T., Lamb, T., Shaw, J., Fox, C., Smith, K., Holland, S., Blackledge, B., McMorrow, L., Durrans, L., Harris, J., Moreno Cuesta, J., Xavier, K., Purohit, D., Elhassan, M., Haldeos, A., Vincent, R., Abdelrazik, M., Jenkins, S., Ganesan, A., Kumar, R., Carter, D., Bakthavatsalam, D., Rowland, M., Hutton, P., Bashyal, A., Davidson, N., Hird, C., Beer, S., Chhablani, M., Phalod, G., Kirkby, A., Archer, S., Netherton, K., Philips, B., Mullan, D., Skinner, D., Gaylard, J., Newman, J., Sathe, S. A., Roche, L., Davies, E., Turner, K., Reschreiter, H., Camsooksai, J., Patch, S., Jenkins, S., Humphrey, C., Pogson, D., Rose, S., Daly, Z., Brimfield, L., Nown, A., Parekh, D., Bergin, C., Bates, M., McGhee, C., Lynch, D., Bhandal, K., Tsakiridou, K., Bamford, A., Cooper, L., Whitehouse, T., Veenith, T., Sim, M. A., Kennedy Hay, S., Henderson, S., Nygren, M., Valentine, E., Katary, A., Bell, G., Wilcox, L., English, K., Adams, A., Phull, M., Zaidi, A., Pogreban, T., Rosaroso, L. P., Harvey, D., Lowe, B., Meredith, M., Ryan, L., Hormis, A., Walker, R., Collier, D., Kimpton, S., Oakley, S., Rooney, K., Rodden, N., Hughes, E., Thomson, N., McGlynn, D., Clark, C., Clark, P., Walden, A., Keating, L., Frise, M., Okeke, T., Jacques, N., Coles, H., Tilney, E., Vowell, E., Schuster-Bruce, M., Pitts, S., Miln, R., Purandare, L., Vamplew, L., Patel, B., Dempster, D., Gummadi, M., Dormand, N., Wang, S. F., Spivey, M., Bean, S., Burt, K., Moore, L., Day, C., Gibson, C., Gordon, E., Zitter, L., Keenan, S., Singh, J., Lynch, C., Mikusek, J., Deacon, B., Baker, E., Hickey, J., Champanerkar, S., Aitken, L., Lewis Prosser, L., Raithatha, A., Bauchmuller, K., Ahmad, N., Wiles, M., Willson, J., Grecu, I., Martin, J., Wrey Brown, C., Arias, A., Bevan, E., Craven, T. H., Hope, D., Singleton, J., Clark, S., McCulloch, C., Welters, I. D., Hamilton, D. O., Williams, K., Waugh, V., Shaw, D., Mulla, S., Waite, A., Fernandez Roman, J., Lopez Martinez, M., Puthucheary, Z., Martin, T., Santos, F., Uddin, R., Fernandez, M., Seidu, F., Somerville, A., Pakats, M. L., Dias, P., Begum, S., Shahid, T., Bhagani, S., De Neef, M., Filipe, H., Mingos, S., Maharajh, A., Pakou, G., Nandani, A., Tatham, K. C., Jhanji, S., Blackurs, E., Dela Rosaurs, A., Howle, R., Baikady, R. R., Tully, R. P., Drummond, A., Dearden, J., Philbin, J. E., Munt, S., Gopal, S., Pooni, J., Ganguly, S., Smallwood, A., Metherell, S., Vuylsteke, A., Chan, C., Victor, S., Hospital, P., Matsa, R., Gellamucho, M., Creagh-Brown, B., Tooley, J., Montague, L., De Beaux, F., Bullman, L., Kerslake, I., Demetriou, C., Mitchard, S., Ramos, L., White, K., Reay, M., Jenkins, S., Tuckwell, C., Watts, A., Traverse, E., Jennings, S., Donnison, P., Johns, M., Casey, R., Mattocks, L., Salisbury, S., Dark, P., Harvey, A., Reece, R., Doonan, D., Knowles, K., Hulme, J., Kannan, S., Joseph, S., Kinney, F., Senya, H. J., Ratnam, V., Gill, M., Kirk, J., Shelton, S., Frey, C., Scano, R., McKee, M., Murphy, P., Thomas, M., Worner, R., Faulkner, B., Gendall, E., Hayes, K., Hayley, H., Blakemore, B., Borislavova, B., Hamilton-Davies, C., Chan, C., Mfuko, C., Abbass, H., Mandadapu, V., Leaver, S., Patel, K., Farnell-Ward, S., Pepermans Saluzzio, R., Rawlins, J., Banach, D., Fernandez de Pinedo Artaraz, Z., Cabreros, L., White, I., Croft, M., Holland, N., Pereira, R., Zaki, A., Johnson, D., Jackson, M., Garrard, H., Juhaz, V., Brown, L., Roy, A., Rostron, A., Woods, L., Cornell, S., Pillai, S., Harford, R., Ivatt, H., Evans, D., Richards, S., Roberts, E., Bowen, J., Ainsworth, J., Clark, T., Foulds, A., Atkins, S., Lee, K., Barber, R., Hilldrith, A., Hewitt, C., Bremmer, P., Ward, G., Bassford, C., Brohi, F., Jagannath, V., Clark, M., Purvis, S., Wetherill, B., Dushianthan, A., Cusack, R., de Courcy-Golder, K., Salmon, K., Burnish, R., Smith, S., Jackson, S., Ruiz, W., Duke, Z., Johns, M., Male, M., Gladas, K., Virdee, S., Swabe, J., Tomlinson, H., Attwood, B., Parsons, P., Campbell, B., Smith, A., Page, V. J., Zhao, X. B., Oza, D., Abrahamson, G., Sheath, B., Ellis, C., Rhodes, J., Anderson, T., Morris, S., Xia Le Tai, C., Thomas, A., Keen, A., Tridente, A., Shuker, K., Anders, J., Greer, S., Scott, P., Millington, A., Buchanan, P., Kirk, J., Denmade, C., Sadera, G., Jacob, R., Jones, C., Hughes, D., Digby, S., Southern, D., Reddy, H., Hulse, S., Campbell, A., Garton, M., Watkins, C., Smuts, S., Quinn, A., Simpson, B., McMillan, C., Finch, C., Hill, C., Cooper, J., Budd, J., Small, C., O'Leary, R., Birch, J., Collins, E., Alexander, P. D., Ferguson, S., Sellers, K., Bradley-Potts, J., Yates, D., Birkinshaw, I., Kell, K., Scott, Z., Pearson, H., Adams, P., Vita, T., Buhay, M., Winters, J., Doherty, K., Ghaffari, M., Bagavathy, K., Donadee, C., Bryan-Morris, K., Arnold, J., Reynolds, B., Beard, G., McAdams, D., Walker, G., Gingo, M., Dunsavage, D., Saiyed, S., Hernandez, E., Goldman, J., Brown, C., Comp, S., Raczek, J., Morris, J. L., Vargas, J. J., Weiss, D., Hensley, J. W., Kochert, E., Wnuk, C., Nemeth, C., Mowery, B., Hutchinson, C., Winters, L., Martin, E., Bariola, R., Viehman, A., Daley, J., Lopus, A., Schmidhofer, M., Sackrowitz, R., Skrtich, A., Minnier, T., Wisniewski, M. K., Mayak, K., Ambrosino, R., Keen, S., Della Toffalo, S., Stambaugh, M., Trimmer, K., Perri, R., Casali, S., Medva, R., Massar, B., Beyerl, A., Burkey, J., Keeler, S., Lowery, M., Oncea, L., Daugherty, J., Sevilla, C., Woelke, A., Dice, J., Weber, L., Roth, J., Ferringer, C., Beer, D. 2021

  Abstract

  BACKGROUND: Thrombosis and inflammation may contribute to the risk of death and complications among patients with coronavirus disease 2019 (Covid-19). We hypothesized that therapeutic-dose anticoagulation may improve outcomes in noncritically ill patients who are hospitalized with Covid-19.METHODS: In this open-label, adaptive, multiplatform, controlled trial, we randomly assigned patients who were hospitalized with Covid-19 and who were not critically ill (which was defined as an absence of critical care-level organ support at enrollment) to receive pragmatically defined regimens of either therapeutic-dose anticoagulation with heparin or usual-care pharmacologic thromboprophylaxis. The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of -1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge. This outcome was evaluated with the use of a Bayesian statistical model for all patients and according to the baseline d-dimer level.RESULTS: The trial was stopped when prespecified criteria for the superiority of therapeutic-dose anticoagulation were met. Among 2219 patients in the final analysis, the probability that therapeutic-dose anticoagulation increased organ support-free days as compared with usual-care thromboprophylaxis was 98.6% (adjusted odds ratio, 1.27; 95% credible interval, 1.03 to 1.58). The adjusted absolute between-group difference in survival until hospital discharge without organ support favoring therapeutic-dose anticoagulation was 4.0 percentage points (95% credible interval, 0.5 to 7.2). The final probability of the superiority of therapeutic-dose anticoagulation over usual-care thromboprophylaxis was 97.3% in the high d-dimer cohort, 92.9% in the low d-dimer cohort, and 97.3% in the unknown d-dimer cohort. Major bleeding occurred in 1.9% of the patients receiving therapeutic-dose anticoagulation and in 0.9% of those receiving thromboprophylaxis.CONCLUSIONS: In noncritically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin increased the probability of survival to hospital discharge with reduced use of cardiovascular or respiratory organ support as compared with usual-care thromboprophylaxis. (ATTACC, ACTIV-4a, and REMAP-CAP ClinicalTrials.gov numbers, NCT04372589, NCT04505774, NCT02735707, and NCT04359277.).

  View details for DOI 10.1056/NEJMoa2105911

  View details for PubMedID 34351721

• Prospective validation of an 11-gene mRNA host response score for mortality risk stratification in the intensive care unit. Scientific reports Moore, A. R., Roque, J., Shaller, B. T., Asuni, T., Remmel, M., Rawling, D., Liesenfeld, O., Khatri, P., Wilson, J. G., Levitt, J. E., Sweeney, T. E., Rogers, A. J. 2021; 11 (1): 13062

  Abstract

  Several clinical calculators predict intensive care unit (ICU) mortality, however these are cumbersome and often require 24h of data to calculate. Retrospective studies have demonstrated the utility of whole blood transcriptomic analysis in predicting mortality. In this study, we tested prospective validation of an 11-gene messenger RNA (mRNA) score in an ICU population. Whole blood mRNA from 70 subjects in the Stanford ICU Biobank with samples collected within 24h of Emergency Department presentation were used to calculate an 11-gene mRNA score. We found that the 11-gene score was highly associated with 60-day mortality, with an area under the receiver operating characteristic curve of 0.68 in all patients, 0.77 in shock patients, and 0.98 in patients whose primary determinant of prognosis was acute illness. Subjects with the highest quartile of mRNA scores were more likely to die in hospital (40% vs 7%, p<0.01) and within 60days (40% vs 15%, p=0.06). The 11-gene score improved prognostication with a categorical Net Reclassification Improvement index of 0.37 (p=0.03) and an Integrated Discrimination Improvement index of 0.07 (p=0.02) when combined with Simplified Acute Physiology Score 3 or Acute Physiology and Chronic Health Evaluation II score. The test performed poorly in the 95 independent samples collected>24h after emergency department presentation. Tests will target a 30-min turnaround time, allowing for rapid results early in admission. Moving forward, this test may provide valuable real-time prognostic information to improve triage decisions and allow for enrichment of clinical trials.

  View details for DOI 10.1038/s41598-021-91201-7

  View details for PubMedID 34158514

• Adults Hospitalized with COVID-19 -United States, March-June and October-December 2020: Implications for the Potential Effects of COVID-19 Tier-1 Vaccination on Future Hospitalizations and Outcomes. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Sami, S., Tenforde, M. W., Talbot, H. K., Lindsell, C. J., Steingrub, J. S., Shapiro, N. I., Ginde, A. A., Douin, D. J., Prekker, M. E., Erickson, H. L., Brown, S. M., Peltan, I. D., Gong, M. N., Khan, A., Exline, M. C., Files, D. C., Gibbs, K. W., Rice, T. W., Casey, J. D., Grijalva, C. G., Stubblefield, W. B., Womack, K. N., Hager, D. N., Qadir, N., Chang, S. Y., Henning, D. J., Wilson, J. G., Self, W. H., Patel, M. M., IVY Network Investigators 2021

  Abstract

  BACKGROUND: Because of the increased risk for severe coronavirus disease 2019 (COVID-19), the Advisory Committee on Immunization Practices (ACIP) initially prioritized COVID-19 vaccination for persons in long-term care facilities (LTCF), persons aged ≥65 years, and persons aged 16-64 years with high-risk medical conditions when there is limited vaccine supply. We compared characteristics and severe outcomes of hospitalized patients with COVID-19 in the United States between early and later in the pandemic categorized by groups at higher risk of severe COVID-19.METHODS: Observational study of sampled patients aged ≥18 years who tested positive for SARS-CoV-2 and admitted to one of 14 academic hospitals in the United States during March-June and October-December 2020. Demographic and clinical information were gathered from electronic health record data.RESULTS: Among 647 patients, 91% met ≥1 of the following risk factors for severe COVID-19 [91% March-June (n=434); 90% October-December (n=213)]; 19% were LTCF residents, 45% were aged ≥65-years, and 84% had ≥1 high-risk condition. The proportion of patients who resided in a LTCF declined significantly (25% vs. 6%) from early to later pandemic periods. Compared with patients at lower risk for severe COVID-19, in-hospital mortality was higher among patients at high risk for severe COVID-19 (20% vs. 7%); these differences were consistently observed between March-June and October-December.CONCLUSIONS: Most adults hospitalized with COVID-19 were those recommended to be prioritized for vaccination based on risk for developing severe COVID-19. These findings highlight the urgency to vaccinate patients at high risk for severe COVID-19 and monitor vaccination impact on hospitalizations and outcomes.

  View details for DOI 10.1093/cid/ciab319

  View details for PubMedID 33977301

• Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Among Hospitalized Adults Aged >= 65 Years - United States, January-March 2021 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Olson, S. M., Self, W. H., Talbot, H., Lindsell, C. J., Steingrub, J. S., Shapiro, N., Ginde, A. A., Douin, D. J., Prekker, M. E., Brown, S. M., Peltan, I. D., Gong, M. N., Mohamed, A., Khan, A., Aline, M. C., Files, D., Gibbs, K. W., Stubblefield, W. B., Casey, J. D., Rice, T. W., Grijalva, C. G., Hager, D. N., Shehu, A., Qadir, N., Chang, S. Y., Wilson, J. G., Gaglani, M., Murthy, K., Calhoun, N., Monto, A. S., Martin, E. T., Malani, A., Zimmerman, R. K., Silveira, F. P., Middleton, D. B., Zhu, Y., Wyatt, D., Stephenson, M., Baughman, A., Womack, K. N., Hart, K. W., Kobayashi, M., Verani, J. R., Patel, M. M., IVY Network, HAIVEN Invest 2021; 70 (18): 674–79

  Abstract

  Adults aged ≥65 years are at increased risk for severe outcomes from COVID-19 and were identified as a priority group to receive the first COVID-19 vaccines approved for use under an Emergency Use Authorization (EUA) in the United States (1-3). In an evaluation at 24 hospitals in 14 states,* the effectiveness of partial or full vaccination† with Pfizer-BioNTech or Moderna vaccines against COVID-19-associated hospitalization was assessed among adults aged ≥65 years. Among 417 hospitalized adults aged ≥65 years (including 187 case-patients and 230 controls), the median age was 73 years, 48% were female, 73% were non-Hispanic White, 17% were non-Hispanic Black, 6% were Hispanic, and 4% lived in a long-term care facility. Adjusted vaccine effectiveness (VE) against COVID-19-associated hospitalization among adults aged ≥65 years was estimated to be 94% (95% confidence interval [CI] = 49%-99%) for full vaccination and 64% (95% CI = 28%-82%) for partial vaccination. These findings are consistent with efficacy determined from clinical trials in the subgroup of adults aged ≥65 years (4,5). This multisite U.S. evaluation under real-world conditions suggests that vaccination provided protection against COVID-19-associated hospitalization among adults aged ≥65 years. Vaccination is a critical tool for reducing severe COVID-19 in groups at high risk.

  View details for Web of Science ID 000647643800003

  View details for PubMedID 33956782

• COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and is modified by dexamethasone. Research square Sarma, A., Christenson, S., Mick, E., Deiss, T., DeVoe, C., Pisco, A., Ghale, R., Jauregui, A., Byrne, A., Moazed, F., Spottiswoode, N., Sinha, P., Zha, B., Neff, N., Tan, M., Serpa, P. H., Ansel, K. M., Wilson, J., Leligdowicz, A., Seigel, E., Sirota, M., DeRisi, J., Matthay, M., Consortium, C., Hendrickson, C., Kangelaris, K., Krummel, M., Woodruff, P., Erle, D., Calfee, C., Langelier, C. 2021

  Abstract

  We performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with the acute respiratory distress syndrome (ARDS) from COVID-19 or from other etiologies, as well as controls without ARDS. In contrast to a cytokine storm, we observed reduced proinflammatory gene expression in COVID-19 ARDS when compared to ARDS due to other causes. COVID-19 ARDS was characterized by a dysregulated host response with increased PTEN signaling and elevated expression of genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone and granulocyte colony stimulating factor. Compared to ARDS due to other types of viral pneumonia, COVID-19 was characterized by impaired interferon-stimulated gene expression (ISG). We found that the relationship between SARS-CoV-2 viral load and expression of ISGs was decoupled in patients with COVID-19 ARDS when compared to patients with mild COVID-19. In summary, assessment of host gene expression in the lower airways of patients with COVID-19 ARDS did not demonstrate cytokine storm but instead revealed a unique and dysregulated host response predicted to be modified by dexamethasone.

  View details for DOI 10.21203/rs.3.rs-141578/v1

  View details for PubMedID 33469573

  View details for PubMedCentralID PMC7814832

• Symptoms and recovery among adult outpatients with and without COVID-19 at 11 healthcare facilities-July 2020, United States. Influenza and other respiratory viruses Fisher, K. A., Olson, S. M., Tenforde, M. W., Self, W. H., Wu, M., Lindsell, C. J., Shapiro, N. I., Files, D. C., Gibbs, K. W., Erickson, H. L., Prekker, M. E., Steingrub, J. S., Exline, M. C., Henning, D. J., Wilson, J. G., Brown, S. M., Peltan, I. D., Rice, T. W., Hager, D. N., Ginde, A. A., Talbot, H. K., Casey, J. D., Grijalva, C. G., Flannery, B., Patel, M. M., Feldstein, L. R. 2021

  Abstract

  BACKGROUND: Symptoms of mild COVID-19 illness are non-specific and may persist for prolonged periods. Effects on quality of life of persistent poor physical or mental health associated with COVID-19 are not well understood.METHODS: Adults aged ≥18years with laboratory-confirmed COVID-19 and matched control patients who tested negative for SARS-CoV-2 infection at outpatient facilities associated with 11 medical centers in the United States were interviewed to assess symptoms, illness duration, and health-related quality of life. Duration of symptoms, health-related quality of life measures, and days of poor physical health by symptoms experienced during illness were compared between case patients and controls using Wilcoxon rank-sum tests. Symptoms associated with COVID-19 case status were evaluated by multivariable logistic regression.RESULTS: Among 320 participants included, 157 were COVID-19 cases and 163 were SARS-CoV-2 negative controls. Loss of taste or smell was reported by 63% of cases and 6% of controls and was strongly associated with COVID-19 in logistic regression models (adjusted odds ratio [aOR]=32.4; 95% confidence interval [CI], 12.6-83.1). COVID-19 cases were more likely than controls to have experienced fever, body aches, weakness, or fatigue during illness, and to report ≥1 persistent symptom more than 14days after symptom onset (50% vs 32%, P<.001). Cases reported significantly more days of poor physical health during the past 14days than controls (P<.01).CONCLUSIONS: Differentiating COVID-19 from other acute illnesses will require widespread diagnostic testing, especially during influenza seasons. Persistent COVID-19-related symptoms may negatively affect quality of life, even among those initially presenting with mild illness.

  View details for DOI 10.1111/irv.12832

  View details for PubMedID 33405338

• Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States. medRxiv : the preprint server for health sciences Tenforde, M. W., Patel, M. M., Ginde, A. A., Douin, D. J., Talbot, H. K., Casey, J. D., Mohr, N. M., Zepeski, A., Gaglani, M., McNeal, T., Ghamande, S., Shapiro, N. I., Gibbs, K. W., Files, D. C., Hager, D. N., Shehu, A., Prekker, M. E., Erickson, H. L., Exline, M. C., Gong, M. N., Mohamed, A., Henning, D. J., Steingrub, J. S., Peltan, I. D., Brown, S. M., Martin, E. T., Monto, A. S., Khan, A., Hough, C. T., Busse, L., Lohuis, C. C., Duggal, A., Wilson, J. G., Gordon, A. J., Qadir, N., Chang, S. Y., Mallow, C., Gershengorn, H. B., Babcock, H. M., Kwon, J. H., Halasa, N., Chappell, J. D., Lauring, A. S., Grijalva, C. G., Rice, T. W., Jones, I. D., Stubblefield, W. B., Baughman, A., Womack, K. N., Lindsell, C. J., Hart, K. W., Zhu, Y., Olson, S. M., Stephenson, M., Schrag, S. J., Kobayashi, M., Verani, J. R., Self, W. H. 2021

  Abstract

  As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes.In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2.Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%).During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population.

  View details for DOI 10.1101/2021.07.08.21259776

  View details for PubMedID 34268515

  View details for PubMedCentralID PMC8282104

• Point-of-Care Lung Ultrasound Pattern in Healthy Parturients: Prevalence of Pulmonary Interstitial Syndrome Following Vaginal Delivery, Elective and Unplanned Intrapartum Cesarean Delivery. Anesthesia and analgesia Macias, P. n., Wilson, J. G., Austin, N. S., Guo, N. n., Carvalho, B. n., Ortner, C. M. 2021

  Abstract

  Pregnancy-related cardiovascular physiologic changes increase the likelihood of pulmonary edema, with the risk of fluid extravasating into the pulmonary interstitium being potentially at a maximum during the early postpartum period. Data on the impact of labor and peripartum hemodynamic strain on lung ultrasound (LUS) are limited, and the prevalence of subclinical pulmonary interstitial syndrome in peripartum women is poorly described. The primary aim of this exploratory study was to estimate the prevalence of pulmonary interstitial syndrome in healthy term parturients undergoing vaginal (VD), elective (eCD), and unplanned intrapartum cesarean deliveries (uCD). Secondary aims were to estimate the prevalence of positive lung regions (≥3 B-lines on LUS per region) and to assess the associations between positive lung regions and possible contributing factors.In this prospective observational cohort study, healthy women at term undergoing VD, eCD, or uCD were enrolled. Following international consensus recommendations, a LUS examination was performed within 4 hours after delivery applying an 8-region technique. Pulmonary interstitial syndrome was defined by the presence of 2 or more positive lung regions per hemithorax. Ultrasound studies were reviewed by 2 blinded reviewers and assessed for interobserver reliability.Seventy-five women were assessed (n = 25 per group). No pulmonary interstitial syndrome was found in the VD and eCD groups (each 0 of 25; 0%, 95% confidence interval [CI], 0-13.7). Pulmonary interstitial syndrome was found in 2 of 25 (8%, 95% CI, 1-26) women undergoing an uCD (P = .490 for VD versus uCD and P = .490 for eCD versus uCD). In 1 woman, this correlated clinically with the development of pulmonary edema. One or more positive lung regions were present in 5 of 25 (20%), 6 of 25 (24%), and 11 of 25 (44%) parturients following VD, eCD, and uCD, respectively (P = .136). Positive lung regions were predominantly found in lateral lung regions. The number of positive lung regions showed a weak correlation with patient age (r = 0.25, 95% CI, 0.05-0.47; P = .033). No significant association was found between LUS pattern and parity, duration of labor, labor augmentation, labor induction, estimated total intravenous fluid intake, or net intravenous fluid intake.Although many focal areas of increased extravascular lung water (20%-44% prevalence) can be identified on LUS, the overall prevalence of pulmonary interstitial syndrome was 2.7% (2 of 75; 95% CI, 0.3-9.3) among healthy term parturients soon after delivery. Focal areas of positive lung water regions were weakly correlated with maternal age.

  View details for DOI 10.1213/ANE.0000000000005464

  View details for PubMedID 33721873

• ICU Bed Utilization During the Coronavirus Disease 2019 Pandemic in a Multistate Analysis-March to June 2020. Critical care explorations Douin, D. J., Ward, M. J., Lindsell, C. J., Howell, M. P., Hough, C. L., Exline, M. C., Gong, M. N., Aboodi, M. S., Tenforde, M. W., Feldstein, L. R., Stubblefield, W. B., Steingrub, J. S., Prekker, M. E., Brown, S. M., Peltan, I. D., Khan, A. n., Files, D. C., Gibbs, K. W., Rice, T. W., Casey, J. D., Hager, D. N., Qadir, N. n., Henning, D. J., Wilson, J. G., Patel, M. M., Self, W. H., Ginde, A. A. 2021; 3 (3): e0361

  Abstract

  Given finite ICU bed capacity, knowledge of ICU bed utilization during the coronavirus disease 2019 pandemic is critical to ensure future strategies for resource allocation and utilization. We sought to examine ICU census trends in relation to ICU bed capacity during the rapid increase in severe coronavirus disease 2019 cases early during the pandemic.Observational cohort study.Thirteen geographically dispersed academic medical centers in the United States.We obtained daily ICU censuses from March 26 to June 30, 2020, as well as prepandemic ICU bed capacities. The primary outcome was daily census of ICU patients stratified by coronavirus disease 2019 and mechanical ventilation status in relation to ICU capacity.None.Prepandemic overall ICU capacity ranged from 62 to 225 beds (median 109). During the study period, the median daily coronavirus disease 2019 ICU census per hospital ranged from 1 to 84 patients, and the daily ICU census exceeded overall ICU capacity for at least 1 day at five institutions. The number of critically ill patients exceeded ICU capacity for a median (interquartile range) of 17 (12-50) of 97 days at these five sites. All 13 institutions experienced decreases in their noncoronavirus disease ICU population, whereas local coronavirus disease 2019 cases increased. Coronavirus disease 2019 patients reached their greatest proportion of ICU capacity on April 12, 2020, when they accounted for 44% of ICU patients across all participating hospitals. Maximum ICU census ranged from 52% to 289% of overall ICU capacity, with three sites less than 80%, four sites 80-100%, five sites 100-128%, and one site 289%.From March to June 2020, the coronavirus disease 2019 pandemic led to ICU censuses greater than ICU bed capacity at fives of 13 institutions evaluated. These findings demonstrate the short-term adaptability of U.S. healthcare institutions in redirecting limited resources to accommodate a public health emergency.

  View details for DOI 10.1097/CCE.0000000000000361

  View details for PubMedID 33786437

  View details for PubMedCentralID PMC7994039

• Effect of emergency critical care nurses and emergency department boarding time on in-hospital mortality in critically ill patients. The American journal of emergency medicine Nesbitt, J., Mitarai, T., Chan, G. K., Wilson, J. G., Niknam, K., Nudelman, M. J., Cinkowski, C., Kohn, M. A. 2020; 41: 120–24

  Abstract

  STUDY HYPOTHESIS: We hypothesized that establishing a program of specialized emergency critical care (ECC) nurses in the ED would improve mortality of ICU patients boarding in the ED.METHODS: This was a retrospective before-after cohort study using electronic health record data at an academic medical center. We compared in-hospital mortality between the pre- and post-intervention periods and between non-prolonged (≤6h) boarding time and prolonged (>6h) boarding time. In-hospital mortality was stratified by illness severity (eccSOFA category) and adjusted using logistic regression.RESULTS: Severity-adjusted in-hospital mortality decreased from 12.8% pre-intervention to 12.3% post-intervention (-0.5% (95% CI, -3.1% to 2.1%), which was not statistically significant. This was despite a concurrent increase in ED and hospital crowding. The proportion of ECC patients downgraded to a lower level of care while still in the ED increased from 6.4% in the pre-intervention period to 17.0% in the post-intervention period. (+10.6%, 8.2% to 13.0%, p<0.001). Severity-adjusted mortality was 12.8% in the non-prolonged group vs. 11.3% in the prolonged group (p=0.331).CONCLUSIONS: During the post-intervention period, there was a significant increase in illness severity, hospital congestion, ED boarding time, and downgrades in the ED, but no significant change in mortality. These findings suggest that ECC nurses may improve the safety of boarding ICU patients in the ED. Longer ED boarding times were not associated with higher mortality in either the pre- or post-intervention periods.

  View details for DOI 10.1016/j.ajem.2020.12.067

  View details for PubMedID 33421675

• Community and Close Contact Exposures Associated with COVID-19 Among Symptomatic Adults >= 18Years in 11 Outpatient Health Care Facilities - United States, July 2020 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Fisher, K. A., Tenforde, M. W., Feldstein, L. R., Lindsell, C. J., Shapiro, N., Files, D., Gibbs, K. W., Erickson, H. L., Prekker, M. E., Steingrub, J. S., Exline, M. C., Henning, D. J., Wilson, J. G., Brown, S. M., Peltan, I. D., Rice, T. W., Hager, D. N., Ginde, A. A., Talbot, K., Casey, J. D., Grijalva, C. G., Flannery, B., Patel, M. M., Self, W. H., IVY Network Investigators, CDC COVID-19 Response Team 2020; 69 (36): 1258–64

  Abstract

  Community and close contact exposures continue to drive the coronavirus disease 2019 (COVID-19) pandemic. CDC and other public health authorities recommend community mitigation strategies to reduce transmission of SARS-CoV-2, the virus that causes COVID-19 (1,2). Characterization of community exposures can be difficult to assess when widespread transmission is occurring, especially from asymptomatic persons within inherently interconnected communities. Potential exposures, such as close contact with a person with confirmed COVID-19, have primarily been assessed among COVID-19 cases, without a non-COVID-19 comparison group (3,4). To assess community and close contact exposures associated with COVID-19, exposures reported by case-patients (154) were compared with exposures reported by control-participants (160). Case-patients were symptomatic adults (persons aged ≥18 years) with SARS-CoV-2 infection confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing. Control-participants were symptomatic outpatient adults from the same health care facilities who had negative SARS-CoV-2 test results. Close contact with a person with known COVID-19 was more commonly reported among case-patients (42%) than among control-participants (14%). Case-patients were more likely to have reported dining at a restaurant (any area designated by the restaurant, including indoor, patio, and outdoor seating) in the 2 weeks preceding illness onset than were control-participants (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI] = 1.5-3.8). Restricting the analysis to participants without known close contact with a person with confirmed COVID-19, case-patients were more likely to report dining at a restaurant (aOR = 2.8, 95% CI = 1.9-4.3) or going to a bar/coffee shop (aOR = 3.9, 95% CI = 1.5-10.1) than were control-participants. Exposures and activities where mask use and social distancing are difficult to maintain, including going to places that offer on-site eating or drinking, might be important risk factors for acquiring COVID-19. As communities reopen, efforts to reduce possible exposures at locations that offer on-site eating and drinking options should be considered to protect customers, employees, and communities.

  View details for Web of Science ID 000568709500005

  View details for PubMedID 32915165

  View details for PubMedCentralID PMC7499837

• Cytokine profile in plasma of severe COVID-19 does not differ from ARDS and sepsis. JCI insight Wilson, J. G., Simpson, L. J., Ferreira, A., Rustagi, A., Roque, J. A., Asuni, A., Ranganath, T., Grant, P. M., Subramanian, A. K., Rosenberg-Hasson, Y., Maecker, H., Holmes, S., Levitt, J. E., Blish, C., Rogers, A. J. 2020

  Abstract

  BACKGROUND: Elevated levels of inflammatory cytokines have been associated with poor outcomes among COVID-19 patients. It is unknown, however, how these levels compare to those observed in critically ill patients with ARDS or sepsis due to other causes.METHODS: We used a luminex assay to determine expression of 76 cytokines from plasma of hospitalized COVID-19 patients and banked plasma samples from ARDS and sepsis patients. Our analysis focused on detecting statistical differences in levels of 6 cytokines associated with cytokine storm (IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha) between patients with moderate COVID-19, severe COVID-19, and ARDS or sepsis.RESULTS: 15 hospitalized COVID-19 patients, 9 of whom were critically ill, were compared to critically ill patients with ARDS (n = 12) or sepsis (n = 16). There were no statistically significant differences in baseline levels of IL-1b, IL-1RA, IL-6, IL-8, IL-18, and TNFalpha between patients with COVID-19 and critically ill controls with ARDS or sepsis.CONCLUSIONS: Levels of inflammatory cytokines were not higher in severe COVID-19 patients than in moderate COVID-19 or critically ill patients with ARDS or sepsis in this small cohort. Broad use of immunosuppressive therapies in ARDS has failed in numerous Phase 3 studies; use of these therapies in unselected patients with COVID-19 may be unwarranted.FUNDING: A.J.R.: Stanford ICU Biobank NHLBI K23 HL125663. C.A.B.: Burroughs Wellcome Fund Investigators in the Pathogenesis of Infectious Diseases #1016687; NIH/NIAID U19AI057229-16 (PI MM Davis); Stanford Maternal Child Health Research Institute; Chan Zuckerberg Biohub.

  View details for DOI 10.1172/jci.insight.140289

  View details for PubMedID 32706339

• Characteristics of Adult Outpatients and Inpatients with COVID-19-11 Academic Medical Centers, United States, March-May 2020 MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT Tenforde, M. W., Rose, E., Lindsell, C. J., Shapiro, N., Files, D., Gibbs, K. W., Prekker, M. E., Steingrub, J. S., Smithline, H. A., Gong, M. N., Aboodi, M. S., Exline, M. C., Henning, D. J., Wilson, J. G., Khan, A., Qadir, N., Stubblefield, W. B., Patel, M. M., Self, W. H., Feldstein, L. R., CDC COVID-19 Response Team 2020; 69 (26): 841–46

  Abstract

  Descriptions of coronavirus disease 2019 (COVID-19) in the United States have focused primarily on hospitalized patients. Reports documenting exposures to SARS-CoV-2, the virus that causes COVID-19, have generally been described within congregate settings, such as meat and poultry processing plants (1) and long-term care facilities (2). Understanding individual behaviors and demographic characteristics of patients with COVID-19 and risks for severe illness requiring hospitalization can inform efforts to reduce transmission. During April 15-May 24, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had positive reverse transcription-polymerase chain reaction (RT-PCR) test results for SARS-CoV-2 in outpatient and inpatient settings at 11 U.S. academic medical centers in nine states. Respondents were contacted 14-21 days after SARS-CoV-2 testing and asked about their demographic characteristics, underlying chronic conditions, symptoms experienced on the date of testing, and potential exposures to SARS-CoV-2 during the 2 weeks before illness onset (or the date of testing among those who did not report symptoms at the time of testing). Among 350 interviewed patients (271 [77%] outpatients and 79 [23%] inpatients), inpatients were older, more likely to be Hispanic and to report dyspnea than outpatients. Fewer inpatients (39%, 20 of 51) reported a return to baseline level of health at 14-21 days than did outpatients (64%, 150 of 233) (p = 0.001). Overall, approximately one half (46%) of patients reported known close contact with someone with COVID-19 during the preceding 2 weeks. This was most commonly a family member (45%) or a work colleague (34%). Approximately two thirds (64%, 212 of 333) of participants were employed; only 35 of 209 (17%) were able to telework. These findings highlight the need for screening, case investigation, contact tracing, and isolation of infected persons to control transmission of SARS-CoV-2 infection during periods of community transmission. The need for enhanced measures to ensure workplace safety, including ensuring social distancing and more widespread use of cloth face coverings, are warranted (3).

  View details for Web of Science ID 000545314500007

  View details for PubMedID 32614810

  View details for PubMedCentralID PMC7332092

• ARDS Subphenotypes: Understanding a Heterogeneous Syndrome. Critical care (London, England) Wilson, J. G., Calfee, C. S. 2020; 24 (1): 102

  Abstract

  This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2020. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2020. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.

  View details for DOI 10.1186/s13054-020-2778-x

  View details for PubMedID 32204722

• eccSOFA: SOFA illness severity score adapted to predict in-hospital mortality in emergency critical care patients. The American journal of emergency medicine Niknam, K. n., Nesbitt, J. n., Mitarai, T. n., Nudelman, M. J., Gordon, A. J., Wilson, J. G., Kohn, M. A. 2020; 41: 145–51

  Abstract

  Boarding of ICU patients in the ED is increasing. Illness severity scores may help emergency physicians stratify risk to guide earlier transfer to the ICU and assess pre-ICU interventions by adjusting for baseline mortality risk. Most existing illness severity scores are based on data that is not available at the time of the hospital admission decision or cannot be extracted from the electronic health record (EHR). We adapted the SOFA score to create a new illness severity score (eccSOFA) that can be calculated at the time of ICU admission order entry in the ED using EHR data. We evaluated this score in a cohort of emergency critical care (ECC) patients at a single academic center over a period of 3 years.This was a retrospective cohort study using EHR data to assess predictive accuracy of eccSOFA for estimating in-hospital mortality risk. The patient population included all adult patients who had a critical care admission order entered while in the ED of an academic medical center between 10/24/2013 and 9/30/2016. eccSOFA's discriminatory ability for in-hospital mortality was assessed using ROC curves.Of the 3912 patients whose in-hospital mortality risk was estimated, 2260 (57.8%) were in the low-risk group (scores 0-3), 1203 (30.8%) in the intermediate-risk group (scores 4-7), and 449 (11.5%) in the high-risk group (scores 8+). In-hospital mortality for the low-, intermediate, and high-risk groups was 4.2% (95%CI: 3.4-5.1), 15.5% (95% CI 13.5-17.6), and 37.9% (95% CI 33.4-42.3) respectively. The AUROC was 0.78 (95%CI: 0.75-0.80) for the integer score and 0.75 (95% CI: 0.72-0.77) for the categorical eccSOFA.As a predictor of in-hospital mortality, eccSOFA can be calculated based on variables that are commonly available at the time of critical care admission order entry in the ED and has discriminatory ability that is comparable to other commonly used illness severity scores. Future studies should assess the calibration of our absolute risk predictions.

  View details for DOI 10.1016/j.ajem.2020.12.018

  View details for PubMedID 33453549

• Telework Before Illness Onset Among Symptomatic Adults Aged ≥18 Years With and Without COVID-19 in 11 Outpatient Health Care Facilities - United States, July 2020. MMWR. Morbidity and mortality weekly report Fisher, K. A., Olson, S. M., Tenforde, M. W., Feldstein, L. R., Lindsell, C. J., Shapiro, N. I., Files, D. C., Gibbs, K. W., Erickson, H. L., Prekker, M. E., Steingrub, J. S., Exline, M. C., Henning, D. J., Wilson, J. G., Brown, S. M., Peltan, I. D., Rice, T. W., Hager, D. N., Ginde, A. A., Talbot, H. K., Casey, J. D., Grijalva, C. G., Flannery, B. n., Patel, M. M., Self, W. H. 2020; 69 (44): 1648–53

  Abstract

  Since March 2020, large-scale efforts to reduce transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), have continued. Mitigation measures to reduce workplace exposures have included work site policies to support flexible work site options, including telework, whereby employees work remotely without commuting to a central place of work.* Opportunities to telework have varied across industries among U.S. jobs where telework options are feasible (1). However, little is known about the impact of telework on risk for SARS-CoV-2 infection. A case-control investigation was conducted to compare telework between eligible symptomatic persons who received positive SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) test results (case-patients, 153) and symptomatic persons with negative test results (control-participants, 161). Eligible participants were identified in outpatient health care facilities during July 2020. Among employed participants who reported on their telework status during the 2 weeks preceding illness onset (248), the percentage who were able to telework on a full- or part-time basis was lower among case-patients (35%; 42 of 120) than among control-participants (53%; 68 of 128) (p<0.01). Case-patients were more likely than were control-participants to have reported going exclusively to an office or school setting (adjusted odds ratio [aOR] = 1.8; 95% confidence interval [CI] = 1.2-2.7) in the 2 weeks before illness onset. The association was also observed when further restricting to the 175 participants who reported working in a profession outside the critical infrastructure† (aOR = 2.1; 95% CI = 1.3-3.6). Providing the option to work from home or telework when possible, is an important consideration for reducing the risk for SARS-CoV-2 infection. In industries where telework options are not available, worker safety measures should continue to be scaled up to reduce possible worksite exposures.

  View details for DOI 10.15585/mmwr.mm6944a4

  View details for PubMedID 33151918

• Symptom Duration and Risk Factors for Delayed Return to Usual Health Among Outpatients with COVID-19 in a Multistate Health Care Systems Network - United States, March-June 2020. MMWR. Morbidity and mortality weekly report Tenforde, M. W., Kim, S. S., Lindsell, C. J., Billig Rose, E. n., Shapiro, N. I., Files, D. C., Gibbs, K. W., Erickson, H. L., Steingrub, J. S., Smithline, H. A., Gong, M. N., Aboodi, M. S., Exline, M. C., Henning, D. J., Wilson, J. G., Khan, A. n., Qadir, N. n., Brown, S. M., Peltan, I. D., Rice, T. W., Hager, D. N., Ginde, A. A., Stubblefield, W. B., Patel, M. M., Self, W. H., Feldstein, L. R. 2020; 69 (30): 993–98

  Abstract

  Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.

  View details for DOI 10.15585/mmwr.mm6930e1

  View details for PubMedID 32730238

• Retrospective Analysis of Peri-Intubation Hypoxemia During the Coronavirus Disease 2019 Epidemic Using a Protocol for Modified Airway Management. A&A practice Madhok, J. n., Vogelsong, M. A., Lee, T. C., Wilson, J. G., Mihm, F. n. 2020; 14 (14): e01360

  Abstract

  This single-center retrospective study evaluated a protocol for the intubation of patients with confirmed or suspected coronavirus disease 2019 (COVID-19). Twenty-one patients were intubated, 9 of whom were found to have COVID-19. Adherence to the airway management protocol was high. COVID-19 patients had lower peripheral capillary oxygen saturation by pulse oximetry (Spo2) nadirs during intubation (Spo2, 73% [72%-77%] vs 89% [86%-94%], P = .024), and a greater percentage experienced severe hypoxemia defined as Spo2 ≤80% (89% vs 25%, P = .008). The incidence of severe hypoxemia in COVID-19 patients should be considered in the development of guidelines that incorporate high-flow nasal cannula and noninvasive positive pressure ventilation.

  View details for DOI 10.1213/XAA.0000000000001360

  View details for PubMedID 33449537

• Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients. The New England journal of medicine National Heart, L., Ginde, A. A., Brower, R. G., Caterino, J. M., Finck, L., Banner-Goodspeed, V. M., Grissom, C. K., Hayden, D., Hough, C. L., Hyzy, R. C., Khan, A., Levitt, J. E., Park, P. K., Ringwood, N., Rivers, E. P., Self, W. H., Shapiro, N. I., Thompson, B. T., Yealy, D. M., Talmor, D. 2019

  Abstract

  BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study.METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality.RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level, <20 ng per milliliter [50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P=0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality.CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. (Funded by the National Heart, Lung, and Blood Institute; VIOLET ClinicalTrials.gov number, NCT03096314.).

  View details for DOI 10.1056/NEJMoa1911124

  View details for PubMedID 31826336

• End-of-Life Care, Palliative Care Consultation, and Palliative Care Referral in the Emergency Department: A Systematic Review. Journal of pain and symptom management Wilson, J. G., English, D. P., Owyang, C. G., Chimelski, E. A., Grudzen, C. R., Wong, H., Aslakson, R. A. 2019

  Abstract

  CONTEXT: There is growing interest in providing palliative care (PC) in the emergency department (ED), but relatively little is known about the efficacy of ED-based PC interventions. A 2016 systematic review on this topic found no evidence that ED-based PC interventions affect patient outcomes or healthcare utilization, but new research has emerged since the publication of that review.OBJECTIVE: This systematic review provides a concise summary of current literature addressing the impact of ED-based PC interventions on patient- or family-reported outcomes, healthcare utilization, and survival.METHODS: We searched Pubmed, Embase, Web of Science, Scopus and CINAHL from inception until September 1, 2018 and reviewed references. Eligible articles evaluated the effects of PC interventions in the ED on patient- or family-reported outcomes, healthcare utilization, or survival.RESULTS: We screened 3091 abstracts and 98 full text articles with 13 articles selected for final inclusion. Two articles reported the results of a single RCT, while the remaining 11 studies were descriptive or quasi-experimental cohort studies. Over half of the included articles were published after the previous systematic review on this topic. Populations studied included older adults, patients with advanced malignancy, and ED patients screening positive for unmet palliative care needs. Most interventions involved referral to hospice or PC, or PC provided directly in the ED. Compared to usual care, ED-PC interventions improved quality of life, though this improvement was not observed when comparing ED-PC to inpatient-PC. ED-PC interventions expedited PC consultation; most studies reported a concomitant reduction in hospital length-of-stay and increase in hospice utilization, but some data were conflicting. Short-term mortality rates were high across all studies, but ED-PC interventions did not decrease survival time compared to usual care.CONCLUSION: Existing data support that PC in the ED is feasible, may improve quality of life, and does not appear to affect survival.

  View details for DOI 10.1016/j.jpainsymman.2019.09.020

  View details for PubMedID 31586580

• Mechanical Ventilation in Hypoxemic Respiratory Failure. Emergency medicine clinics of North America Kapil, S., Wilson, J. G. 2019; 37 (3): 431–44

  Abstract

  Acute hypoxemic respiratory failure (AHRF) is a common challenge in emergency medicine. Patient outcomes depend on interventions performed during preintubation, intubation, and postintubation. The article presents recommendations for evidence-based practice to optimally manage patients with AHRF and the acute respiratory distress syndrome.

  View details for DOI 10.1016/j.emc.2019.04.005

  View details for PubMedID 31262413

• Metagenomic comparison of tracheal aspirate and mini-bronchial alveolar lavage for assessment of respiratory microbiota AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY Kalantar, K. L., Moazed, F., Christenson, S. C., Wilson, J., Deiss, T., Belzer, A., Vessel, K., Caldera, S., Jauregui, A., Bolourchi, S., DeRisi, J. L., Calfee, C. S., Langelier, C. 2019; 316 (3): L578–L584

  View details for DOI 10.1152/ajplung.00476.2018

  View details for Web of Science ID 000582272800001

• Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial LANCET RESPIRATORY MEDICINE Matthay, M. A., Calfee, C. S., Zhuo, H., Thompson, B., Wilson, J. G., Levitt, J. E., Rogers, A. J., Gotts, J. E., Wiener-Kronish, J. P., Bajwa, E. K., Donahoe, M. P., McVerry, B. J., Ortiz, L. A., Exline, M., Christman, J. W., Abbott, J., Delucchi, K. L., Caballero, L., McMillan, M., McKenna, D. H., Liu, K. D. 2019; 7 (2): 154–62

  View details for DOI 10.1016/S2213-2600(18)30418-1

  View details for Web of Science ID 000457172000025

• Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Langelier, C., Kalantar, K. L., Moazed, F., Wilson, M. R., Crawford, E. D., Deiss, T., Belzer, A., Bolourchi, S., Caldera, S., Fung, M., Jauregui, A., Malcolm, K., Lyden, A., Khan, L., Vessel, K., Quan, J., Zinter, M., Chiu, C. Y., Chow, E. D., Wilson, J., Miller, S., Matthay, M. A., Pollard, K. S., Christenson, S., Calfee, C. S., DeRisi, J. L. 2018; 115 (52): E12353–E12362

  View details for DOI 10.1073/pnas.1809700115

  View details for Web of Science ID 000454302600029

• Critical Care Ultrasound: A Review for Practicing Nephrologists ADVANCES IN CHRONIC KIDNEY DISEASE Wilson, J. G., Breyer, K. E. 2016; 23 (3): 141-145

  Abstract

  The use of point-of-care ultrasound in the intensive care unit, both for diagnostic and procedural purposes, has rapidly proliferated, and evidence supporting its use is growing. Conceptually, critical care ultrasound (CCUS) should be considered an extension of the physical examination and should not be considered a replacement for formal echocardiography or radiology-performed ultrasound. Several CCUS applications are of particular relevance to nephrologists, including focused renal ultrasound in patients at high risk for urinary tract obstruction, real-time ultrasound guidance and verification during the placement of central venous catheters, and ultrasound-augmented assessment of shock and volume status. Each of these applications has the capacity to improve outcomes in patients with acute kidney injury. Although robust evidence regarding long-term outcomes is lacking, existing data demonstrate that CCUS has the potential to improve diagnostic accuracy, expedite appropriate management, and increase safety for critically ill patients across a spectrum of pathologies.

  View details for DOI 10.1053/j.ackd.2016.01.015

  View details for Web of Science ID 000375348600004

  View details for PubMedID 27113689

• Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. The Lancet. Respiratory medicine Wilson, J. G., Liu, K. D., Zhuo, H., Caballero, L., McMillan, M., Fang, X., Cosgrove, K., Vojnik, R., Calfee, C. S., Lee, J., Rogers, A. J., Levitt, J., Wiener-Kronish, J., Bajwa, E. K., Leavitt, A., McKenna, D., Thompson, B. T., Matthay, M. A. 2015; 3 (1): 24-32

  Abstract

  No effective pharmacotherapy for acute respiratory distress syndrome (ARDS) exists, and mortality remains high. Preclinical studies support the efficacy of mesenchymal stem (stromal) cells (MSCs) in the treatment of lung injury. We aimed to test the safety of a single dose of allogeneic bone marrow-derived MSCs in patients with moderate-to-severe ARDS.The STem cells for ARDS Treatment (START) trial was a multicentre, open-label, dose-escalation, phase 1 clinical trial. Patients were enrolled in the intensive care units at University of California, San Francisco, CA, USA, Stanford University, Stanford, CA, USA, and Massachusetts General Hospital, Boston, MA, USA, between July 8, 2013, and Jan 13, 2014. Patients were included if they had moderate-to-severe ARDS as defined by the acute onset of the need for positive pressure ventilation by an endotracheal or tracheal tube, a PaO2:FiO2 less than 200 mm Hg with at least 8 cm H2O positive end-expiratory airway pressure (PEEP), and bilateral infiltrates consistent with pulmonary oedema on frontal chest radiograph. The first three patients were treated with low dose MSCs (1 million cells/kg predicted bodyweight [PBW]), the next three patients received intermediate dose MSCs (5 million cells/kg PBW), and the final three patients received high dose MSCs (10 million cells/kg PBW). Primary outcomes included the incidence of prespecified infusion-associated events and serious adverse events. The trial is registered with ClinicalTrials.gov, number NCT01775774.No prespecified infusion-associated events or treatment-related adverse events were reported in any of the nine patients. Serious adverse events were subsequently noted in three patients during the weeks after the infusion: one patient died on study day 9, one patient died on study day 31, and one patient was discovered to have multiple embolic infarcts of the spleen, kidneys, and brain that were age-indeterminate, but thought to have occurred before the MSC infusion based on MRI results. None of these severe adverse events were thought to be MSC-related.A single intravenous infusion of allogeneic, bone marrow-derived human MSCs was well tolerated in nine patients with moderate to severe ARDS. Based on this phase 1 experience, we have proceeded to phase 2 testing of MSCs for moderate to severe ARDS with a primary focus on safety and secondary outcomes including respiratory, systemic, and biological endpoints.The National Heart, Lung, and Blood Institute.

  View details for DOI 10.1016/S2213-2600(14)70291-7

  View details for PubMedID 25529339

• Biomarkers in acute respiratory distress syndrome: from pathobiology to improving patient care EXPERT REVIEW OF RESPIRATORY MEDICINE Walter, J. M., Wilson, J., Ware, L. B. 2014; 8 (5): 573-586

  Abstract

  Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by alveolar flooding with protein-rich pulmonary edema fluid. Despite an improved understanding of ARDS pathogenesis, our ability to predict the development of ARDS and risk-stratify patients with the disease remains limited. Biomarkers may help identify patients at highest risk of developing ARDS, assess response to therapy, predict outcome, and optimize enrollment in clinical trials. This review begins with a general description of biomarker use in clinical medicine. We then review evidence that supports the value of various ARDS biomarkers organized by the cellular injury processes central to ARDS development: endothelial injury, epithelial injury, disordered inflammation and coagulation, fibrosis, and apoptosis. Finally, we summarize the growing contributions of genomic and proteomic research and suggest ways in which the field may evolve in the coming years.

  View details for DOI 10.1586/17476348.2014.924073

  View details for Web of Science ID 000342062700007

  View details for PubMedID 24875533

• Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia THORAX Asmussen, S., Ito, H., Traber, D. L., Lee, J. W., Cox, R. A., Hawkins, H. K., McAuley, D. F., McKenna, D. H., Traber, L. D., Zhuo, H., Wilson, J., Herndon, D. N., Prough, D. S., Liu, K. D., Matthay, M. A., Enkhbaatar, P. 2014; 69 (9): 819-825

  Abstract

  Human bone marrow-derived mesenchymal stem (stromal) cells (hMSCs) improve survival in mouse models of acute respiratory distress syndrome (ARDS) and reduce pulmonary oedema in a perfused human lung preparation injured with Escherichia coli bacteria. We hypothesised that clinical grade hMSCs would reduce the severity of acute lung injury (ALI) and would be safe in a sheep model of ARDS.Adult sheep (30-40 kg) were surgically prepared. After 5 days of recovery, ALI was induced with cotton smoke insufflation, followed by instillation of live Pseudomonas aeruginosa (2.5×10(11) CFU) into both lungs under isoflurane anaesthesia. Following the injury, sheep were ventilated, resuscitated with lactated Ringer's solution and studied for 24 h. The sheep were randomly allocated to receive one of the following treatments intravenously over 1 h in one of the following groups: (1) control, PlasmaLyte A, n=8; (2) lower dose hMSCs, 5×10(6) hMSCs/kg, n=7; and (3) higher-dose hMSCs, 10×10(6) hMSCs/kg, n=4.By 24 h, the PaO2/FiO2 ratio was significantly improved in both hMSC treatment groups compared with the control group (control group: PaO2/FiO2 of 97±15 mm Hg; lower dose: 288±55 mm Hg (p=0.003); higher dose: 327±2 mm Hg (p=0.003)). The median lung water content was lower in the higher-dose hMSC-treated group compared with the control group (higher dose: 5.0 g wet/g dry [IQR 4.9-5.8] vs control: 6.7 g wet/g dry [IQR 6.4-7.5] (p=0.01)). The hMSCs had no adverse effects.Human MSCs were well tolerated and improved oxygenation and decreased pulmonary oedema in a sheep model of severe ARDS.NCT01775774 for Phase 1. NCT02097641 for Phase 2.

  View details for DOI 10.1136/thoraxjnl-2013-204980

  View details for Web of Science ID 000340239900009

  View details for PubMedID 24891325

  View details for PubMedCentralID PMC4284068

• Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome ANNALS OF INTENSIVE CARE Liu, K. D., Wilson, J. G., Zhuo, H., Caballero, L., McMillan, M. L., Fang, X., Cosgrove, K., Calfee, C. S., Lee, J., Kangelaris, K. N., Gotts, J. E., Rogers, A. J., Levitt, J. E., Wiener-Kronish, J. P., Delucchi, K. L., Leavitt, A. D., McKenna, D. H., Thompson, B. T., Matthay, M. A. 2014; 4

  View details for DOI 10.1186/s13613-014-0022-z

  View details for Web of Science ID 000345167000001

• OBLIQUE-AXIS VS. SHORT-AXIS VIEW IN ULTRASOUND-GUIDED CENTRAL VENOUS CATHETERIZATION JOURNAL OF EMERGENCY MEDICINE Wilson, J. G., Berona, K. M., Stein, J. C., Wang, R. 2014; 47 (1): 45-50

  Abstract

  Ultrasound (US) guidance during central venous catheterization (CVC) reduces complications and improves success rates compared to landmark-guided techniques. A novel "oblique view" (US transducer held at approximately 45° with respect to the target vessel) has been suggested to be superior to the standard short-axis approach usually used during US-guided CVC.The purpose of this study was to compare the rates of posterior vessel wall puncture (PVWP) between the short-axis and oblique-axis approaches to US-guided CVC.This was a prospective observational trial of emergency medicine residents and attending physicians, using gelatin models to simulate short-axis and oblique-axis US-guided CVC. Participants were blinded to the primary outcome of PVWP. Data collected included year in training/practice, number of central lines placed, time to successful "flash," and self-reported confidence of needle tip position using a Likert scale. After CVC simulation, models were deconstructed and inspected for PVWP.The rate of PVWP was 14.7% using short axis vs. 2.9% using oblique axis, resulting in a difference of 11.8% (95% confidence interval [CI] -4.7-28.3%, p = 0.10) and an odds ratio of 0.2 (95% CI 0.004-1.79). This difference was not statistically significant (p = 0.10). Mean time to flash was 11.9 s using short axis, and 15.4 s using oblique axis (p = 0.14). Confidence in needle tip location was 3.63 using short axis, and 4.58 using oblique axis (p < 0.001).We found decreased PVWP using the oblique axis approach, though the difference was not statistically significant, and participants felt more confident in their needle tip location using the oblique axis view. Further research into the potential benefits of the oblique axis approach is warranted.

  View details for DOI 10.1016/j.jemermed.2013.11.080

  View details for Web of Science ID 000338476500017

  View details for PubMedID 24685453

• Evolving practices in critical care and their influence on acute kidney injury CURRENT OPINION IN CRITICAL CARE Wilson, J. G., Butcher, B. W., Liu, K. D. 2013; 19 (6): 523-530

  Abstract

  This review highlights the principal advances in critical care over the past year, and discusses the impact of these advances on the diagnosis and management of acute kidney injury (AKI).Recent literature has focused on assessment of volume status and fluid management, particularly in the setting of respiratory and cardiac failure. Other critical care topics are reviewed using a system-based approach.The incidence of AKI appears to be increasing, and despite advances in the provision of critical care and renal replacement therapies, there has been little improvement in its associated morbidity and mortality. Nonetheless, recent advances in critical care will impact the diagnosis and management of AKI, as well as shape the future research agenda. Continued work in the fields of critical care and nephrology will undoubtedly be centered on improved biomarkers for the detection of AKI, specific therapies to mitigate or reverse AKI, and techniques to prevent the development of AKI in the critically ill population.

  View details for DOI 10.1097/MCC.0000000000000040

  View details for Web of Science ID 000330358100001

  View details for PubMedID 24240818

• Cardiac tamponade. The western journal of emergency medicine Wilson, J. G., Epstein, S. M., Wang, R., Kanzaria, H. K. 2013; 14 (2): 152-?

  View details for DOI 10.5811/westjem.2012.8.12919

  View details for PubMedID 23599855

  View details for PubMedCentralID PMC3628467