Orlando Quintero, MD

All Publications

• Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19: The ACTIV-6 Randomized Clinical Trial. JAMA Stewart, T. G., Rebolledo, P. A., Mourad, A., Lindsell, C. J., Boulware, D. R., McCarthy, M. W., Thicklin, F., Garcia Del Sol, I. T., Bramante, C. T., Lenert, L. A., Lim, S., Williamson, J. C., Cardona, O. Q., Scott, J., Schwasinger-Schmidt, T., Ginde, A. A., Castro, M., Jayaweera, D., Sulkowski, M., Gentile, N., McTigue, K., Felker, G. M., DeLong, A., Wilder, R., Rothman, R. L., Collins, S., Dunsmore, S. E., Adam, S. J., Hanna, G. J., Shenkman, E., Hernandez, A. F., Naggie, S. 2023

  Abstract

  The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain.To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19.The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less.Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607).The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28.Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy = .40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy = .86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths.Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.ClinicalTrials.gov Identifier: NCT04885530.

  View details for DOI 10.1001/jama.2023.23363

  View details for PubMedID 37976072

• Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Holubar, M., Subramanian, A., Purington, N., Hedlin, H., Bunning, B., Walter, K. S., Bonilla, H., Boumis, A., Chen, M., Clinton, K., Dewhurst, L., Epstein, C., Jagannathan, P., Kaszynski, R. H., Panu, L., Parsonnet, J., Ponder, E. L., Quintero, O., Sefton, E., Singh, U., Soberanis, L., Truong, H., Andrews, J. R., Desai, M., Khosla, C., Maldonado, Y. 2022

  Abstract

  Favipiravir is an oral, RNA-dependent RNA polymerase inhibitor with in vitro activity against SARS-CoV2. Despite limited data, favipiravir is administered to patients with COVID-19 in several countries.We conducted a phase 2 double-blind randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV2 RT-PCR within 72 hours of enrollment. Participants were randomized 1: 1 to receive placebo or favipiravir (1800mg BID Day 1, 800 mg BID Days 2-10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir's impact on mutagenesis.From July 8, 2020 - March 23, 2021, we randomized 149 participants with 116 included in the mITT cohort. The participants' mean age was 43 years (SD 12.5) and 57 (49%) were women. We found no difference in time to shedding cessation by treatment arm overall (HR 0.76 favoring placebo, 95% confidence interval [CI] 0.48-1.20) or in sub-group analyses (age, sex, high-risk comorbidities, seropositivity or symptom duration at enrollment). We observed no difference in time to symptom resolution (initial: HR 0.84, 95% CI 0.54-1.29; sustained: HR 0.87, 95% CI 0.52-1.45). We detected no difference in accumulation of transition mutations in the viral genome during treatment.Our data do not support favipiravir use at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher doses of favipiravir are effective and safe for patients with COVID-19.

  View details for DOI 10.1093/cid/ciac312

  View details for PubMedID 35446944

• Invasive mold infection of the gastrointestinal tract - A case series of 22 immunocompromised patients from a single academic center. Medical mycology Quintero, O., Allard, L., Ho, D. 1800

  Abstract

  Invasive mold infection (IMI) of the gastrointestinal (GI) tract is a rare complication in immunocompromised patients that carries a high mortality rate. It is most often described in the setting of disseminated disease. Early diagnosis and treatment are critical in its management, but this is rarely obtained, leading to delayed therapy. To describe the clinical characteristics, treatment and outcomes of this infection, we reviewed all the cases of adult patients with histopathological findings from autopsy or surgical specimens that demonstrated fungal invasion into the GI tract at Stanford Hospital & Clinics from January 1997 to August 2020. Twenty-two patients that met criteria were identified and they were all immunocompromised, either due to their underlying medical conditions or the treatments that they received. The most common underlying disease was hematological malignancies (63.6%) and the most common symptoms were abdominal pain, GI bleeding and diarrhea. A majority of patients (72.7%) had disseminated invasive mold infection, while the rest had isolated GI tract involvement. In 2/3 of our cases the fungal genus or species was confirmed based on culture or PCR results. Given the very high mortality associated with GI mold infection, this diagnosis should be considered when evaluating immunocompromised patients with concerning GI signs and symptoms. A timely recognition of the infection, prompt initiation of appropriate antifungal therapy as well as surgical intervention if feasible, are key to improve survival from this devastating infection.

  View details for DOI 10.1093/mmy/myac007

  View details for PubMedID 35092429

• Peginterferon Lambda-1a for treatment of outpatients with uncomplicated COVID-19: a randomized placebo-controlled trial. Nature communications Jagannathan, P. n., Andrews, J. R., Bonilla, H. n., Hedlin, H. n., Jacobson, K. B., Balasubramanian, V. n., Purington, N. n., Kamble, S. n., de Vries, C. R., Quintero, O. n., Feng, K. n., Ley, C. n., Winslow, D. n., Newberry, J. n., Edwards, K. n., Hislop, C. n., Choong, I. n., Maldonado, Y. n., Glenn, J. n., Bhatt, A. n., Blish, C. n., Wang, T. n., Khosla, C. n., Pinsky, B. A., Desai, M. n., Parsonnet, J. n., Singh, U. n. 2021; 12 (1): 1967

  Abstract

  Type III interferons have been touted as promising therapeutics in outpatients with coronavirus disease 2019 (COVID-19). We conducted a randomized, single-blind, placebo-controlled trial (NCT04331899) in 120 outpatients with mild to moderate COVID-19 to determine whether a single, 180 mcg subcutaneous dose of Peginterferon Lambda-1a (Lambda) within 72 hours of diagnosis could shorten the duration of viral shedding (primary endpoint) or symptoms (secondary endpoint). In both the 60 patients receiving Lambda and 60 receiving placebo, the median time to cessation of viral shedding was 7 days (hazard ratio [HR] = 0.81; 95% confidence interval [CI] 0.56 to 1.19). Symptoms resolved in 8 and 9 days in Lambda and placebo, respectively, and symptom duration did not differ significantly between groups (HR 0.94; 95% CI 0.64 to 1.39). Both Lambda and placebo were well-tolerated, though liver transaminase elevations were more common in the Lambda vs. placebo arm (15/60 vs 5/60; p = 0.027). In this study, a single dose of subcutaneous Peginterferon Lambda-1a neither shortened the duration of SARS-CoV-2 viral shedding nor improved symptoms in outpatients with uncomplicated COVID-19.

  View details for DOI 10.1038/s41467-021-22177-1

  View details for PubMedID 33785743

• Chagas Disease in the New York City Metropolitan Area OPEN FORUM INFECTIOUS DISEASES Zheng, C., Quintero, O., Revere, E. K., Oey, M. B., Espinoza, F., Puius, Y. A., Ramirez-Baron, D., Salama, C. R., Hidalgo, L. F., Machado, F. S., Saeed, O., Shin, J., Patel, S. R., Coyle, C. M., Tanowitz, H. B. 2020; 7 (5): ofaa156

  Abstract

  Chagas disease, caused by the parasite Trypanosoma cruzi, once considered a disease confined to Mexico, Central America, and South America, is now an emerging global public health problem. An estimated 300 000 immigrants in the United States are chronically infected with T. cruzi. However, awareness of Chagas disease among the medical community in the United States is poor.We review our experience managing 60 patients with Chagas disease in hospitals throughout the New York City metropolitan area and describe screening, clinical manifestations, EKG findings, imaging, and treatment.The most common country of origin of our patients was El Salvador (n = 24, 40%), and the most common detection method was by routine blood donor screening (n = 21, 35%). Nearly half of the patients were asymptomatic (n = 29, 48%). Twenty-seven patients were treated with either benznidazole or nifurtimox, of whom 7 did not complete therapy due to side effects or were lost to follow-up. Ten patients had advanced heart failure requiring device implantation or organ transplantation.Based on our experience, we recommend that targeted screening be used to identify at-risk, asymptomatic patients before progression to clinical disease. Evaluation should include an electrocardiogram, echocardiogram, and chest x-ray, as well as gastrointestinal imaging if relevant symptoms are present. Patients should be treated if appropriate, but providers should be aware of adverse effects that may prevent patients from completing treatment.

  View details for DOI 10.1093/ofid/ofaa156

  View details for Web of Science ID 000553470400042

  View details for PubMedID 32500090

  View details for PubMedCentralID PMC7255644

• Moving towards an Induction-Free Era: Short-Term Renal and Infectious Outcomes Moayedi, Y., Henricksen, E. J., Lafreniere-Roula, M., Fan, C. S., Multani, A., Puing, A., Couture-Cosette, A., Quintero, O., Han, J., Feng, K. Y., Lee, R., Duclos, S., Lyapin, A., Purewal, S., Subramanian, A., Ross, H. J., Hiesinger, W., Khush, K. K., Teuteberg, J. J. ELSEVIER SCIENCE INC. 2020: S274–S275

  View details for Web of Science ID 000522637202019

• 6-month vs 12-month CMV Prophylaxis for CMV-Mismatched Heart Transplant Recipients Puing, A., Couture-Cosette, A., Quintero, O., Multani, A., Henricksen, E., Lee, R., Foroutan, F., Moayedi, Y., Teuteberg, J., Subramanian, A. ELSEVIER SCIENCE INC. 2020: S204–S205

  View details for Web of Science ID 000522637201177

• Methenamine hippurate may have particular benefit in preventing recurrent urinary tract infections in diabetic renal transplant recipients TRANSPLANT INFECTIOUS DISEASE Quintero Cardona, O., Hemmige, V. S., Puius, Y. A. 2020: e13247

  View details for DOI 10.1111/tid.13247

  View details for Web of Science ID 000509794000001

  View details for PubMedID 31957150

• Influence of Immunosuppression on Seroconversion Against SARS-Cov-2 in Two Kidney Transplant Recipients. Transplant infectious disease : an official journal of the Transplantation Society Wang, A. X., Quintero Cardona, O. n., Ho, D. Y., Busque, S. n., Lenihan, C. R. 2020: e13423

  Abstract

  Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of Coronavirus Disease 2019 (COVID-19) in United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-Cov-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-Cov-2 antibodies.

  View details for DOI 10.1111/tid.13423

  View details for PubMedID 32701196

• Characteristics and outcomes of coronavirus disease patients under nonsurge conditions, northern California, USA, March–April 2020 Emerging Infectious Diseases Ferguson, J., Rosser, J., Quintero, O., Scott, J., Subramanian, A., Gumma, M., Rogers, A., Kappagoda, S. 2020

  Abstract

  Limited data are available on the clinical presentation and outcomes of coronavirus disease (COVID-19) patients in the United States hospitalized under normal-caseload or nonsurge conditions. We retrospectively studied 72 consecutive adult patients hospitalized with COVID-19 in 2 hospitals in the San Francisco Bay area, California, USA, during March 13-April 11, 2020. The death rate for all hospitalized COVID-19 patients was 8.3%, and median length of hospitalization was 7.5 days. Of the 21 (29% of total) intensive care unit patients, 3 (14.3% died); median length of intensive care unit stay was 12 days. Of the 72 patients, 43 (59.7%) had underlying cardiovascular disease and 19 (26.4%) had underlying pulmonary disease. In this study, death rates were lower than those reported from regions of the United States experiencing a high volume of COVID-19 patients.

  View details for DOI 10.3201/eid2608.201776

• Risk factors of laryngeal cryptococcosis: A case report MEDICAL MYCOLOGY CASE REPORTS Quintero, O., Trachuk, P., Lerner, M. Z., Sarungbam, J., Pirofski, L., Park, S. O. 2019; 24: 82–85

  Abstract

  Cryptococcal infections are acquired by inhalation of encapsulated yeast cells or basidiospores. While Cryptococcus has a propensity to invade the lungs and central nervous system, other sites can be affected. Laryngeal cryptococcosis is rare with less than 30 previously reported cases, which commonly occurred in apparently immunocompetent hosts on inhaled corticosteroids. We present a case of laryngeal cryptococcosis with a long-term inhaled corticosteroid use, co-infection of pulmonary Mycobacterium avium-intracellulare, and mannose-binding lectin deficiency.

  View details for DOI 10.1016/j.mmcr.2019.04.009

  View details for Web of Science ID 000468128500023

  View details for PubMedID 31080714

  View details for PubMedCentralID PMC6506557