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Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19

Stewart et al., JAMA, doi:10.1001/jama.2023.23363 (date from preprint), ACTIV-6, NCT04885530

Sep 2023

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Fluvoxamine

27th treatment shown to reduce risk in November 2021

^*, now with p = 0.00014 from 21 studies, recognized in 3 countries.

Lower risk for mortality, hospitalization, progression, recovery, and cases.

No treatment is 100% effective. Protocols combine treatments. ^* >10% efficacy, ≥3 studies.

5,000+ studies for 104 treatments. c19early.org

Late treatment low risk population RCT showing lower progression to hospitalization or urgent care/ER visits with fluvoxamine, without statistical significance.

There was no mortality and only three hospitalizations. Authors provide no details on the cause of hospitalization, but they appear to be unrelated to COVID-19. eFigure 5 shows no COVID-19 clinical progression to hospitalization (note that a hospitalization can be seen in the equivalent plot for the low dose arm), and the text indicates that the "COVID clinical progression scale simplified into a self-reported evaluation of home levels (limited vs not)".

Note that the urgent care/ER visit outcome is also likely diluted due to inclusion of all-cause events, and could be statistically significant for only COVID-19 events.

The sustained recovery outcome, which shows no difference, was a post-hoc creation used to hide efficacy for ivermectin, and is not logical for evaluating efficacy in this trial. The definition includes any minor symptom within a three day period - e.g., any minor cough, headache, body ache, or fatigue that occurs in a three day period, regardless of cause, results in the treatment being considered a failure. For example, late treatment that is effective at minimizing progression, but has no improvement in resolution of cough, would not be detected. (Authors even use the end of the three day period to further minimize efficacy).

Late treatment - median 5 days, 75% 4+ days, 25% 7+ days, up to 12 days.

Also see Naggie for many issues with this trial, and McCarthy for the lower dose arm.

Important missing comments or errors? Let us know.

risk of progression, 31.0% lower, RR 0.69, p = 0.34, treatment 14 of 589 (2.4%), control 21 of 586 (3.6%), NNT 83, adjusted per study, urgent or emergency care visits, hospitalizations, or death.

clinical progression, 34.0% lower, OR 0.66, p = 0.32, treatment 589, control 586, mid-recovery, day 14, RR approximated with OR.

clinical progression, 15.0% higher, OR 1.15, p = 0.68, treatment 589, control 586, day 7, RR approximated with OR.

clinical progression, 6.0% lower, OR 0.94, p = 0.90, treatment 589, control 586, day 28, RR approximated with OR.

recovery time, 1.5% lower, relative time 0.99, treatment 589, control 586, mean time unwell.

risk of no recovery, 1.0% higher, HR 1.01, p = 0.86, treatment 589, control 586, inverted to make HR<1 favor treatment, post-hoc primary outcome.

risk of hospitalization, 49.0% lower, RR 0.51, p = 0.59, treatment 1 of 589 (0.2%), control 2 of 586 (0.3%), NNT 583, non-COVID-19 hospitalization, day 28.

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Naggie et al., Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial, JAMA, doi:10.1001/jama.2022.18590.jamanetwork.com, doi.org.

2. McCarthy et al., Effect of Fluvoxamine vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19, JAMA, doi:10.1001/jama.2022.24100.jamanetwork.com, doi.org.

Stewart et al., 13 Sep 2023, Double Blind Randomized Controlled Trial, placebo-controlled, USA, peer-reviewed, 32 authors, study period 5 August, 2022 - 20 January, 2023, average treatment delay 5.0 days, trial NCT04885530 (history) (ACTIV-6). Contact: susanna.naggie@duke.edu.

This Paper Fluvoxamine All

Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19

PhD Thomas G Stewart, MD, MSc Paulina A Rebolledo, MD Ahmad Mourad, PhD Christopher J Lindsell, MD, MPH David R Boulware, MD Matthew W Mccarthy, Florence Thicklin, Idania T Garcia Del Sol, MD, MPH Carolyn T Bramante, MD Leslie A Lenert, MS Stephen Lim, MD; John C Williamson, Orlando Quintero Cardona, MD Jake Scott, MD Tiffany Schwasinger-Schmidt, PhD Adit A Ginde, MD, MPH Mario Castro, MD, MPH Dushyantha Jayaweera, MD Mark Sulkowski, MD Nina Gentile, MD Kathleen Mctigue, G Michael Felker, MD, MHS Allison Delong, BS Rhonda Wilder, MS Russell L Rothman, MD, MPP Sean Collins, MD, MSci Sarah E Dunsmore, PhD; Stacey J Adam, PhD; George J Hanna, MD Elizabeth Shenkman, PhD Adrian F Hernandez, MD, MHS Susanna Naggie, Ryan Fraser, Mark Ward, Jennifer Gamboa Jackman, M Patricia Mcadams, Julia Vail, Kayla Korzekwinski, Martina Oyelakin, Julie Chopp, Desmon Randle, Samantha Dockery, Rodney Adkins, Mathew Crow, Erin Nowell, Kadie Wells, Alicia Herbert, Allegra Stone, Heather Heavlin, Linley Brown, Tina Harding, Amanda Harrington, Meaghan Beauchaine, Kelly Lindblom, Andrea Burns, David Aamodt, Jess Collins, Sheri Dixon, Yue Gao, John Graves, James Grindstaff, Frank Harrell, Jessica Lai, Vicky Liao, Itzel Lopez, Elizabeth Manis, Kalley Mankowski, Jessica Marlin, Alyssa Merkel, Sam Nwosu, Savannah Obregon, Dirk Orozco, Nelson Prato, Max Rohde, Jana Shirey-Rice, Krista Vermillion, Jacob Smith, Hsi-Nien Tan, Meghan Vance, Maria Weir, William (kelly) Vincent, Raina Vincent, Ray Bianchi, Jen Premas, Diana Cordero-Loperena, Evelyn Rivera, Madhu Gupta, Greg Karawan, Joseph Arena, Sonaly Dealmeida, Soroush Ramin, Jaya Nataraj, Julien Dedier, Ana Maria Ramirez, Katherine Waite, Jason Okulicz, Joseph Marcus, Alexis Southwell, Genice Jacques, Cedar Sexton, David Miller, Ginger Brounce, Constance George-Adebayo, Adeolu Adebayo, Jose Zapatero, Julie Clement, Theresa Ronan, Ashley Woods, Christopher Gallegos, Tamara Flys, Olivia Sloan, Anthony Olofintuyi, Joshua Samraj, Jackelyn Samraj, Alma Vasbinder, Amaya Averett, Alex Slandzicki, Aaron Milstone, Jessica Wallan, Lindsey Robbs, Claudia Vogel, Sebastian Munoz, David Kavtaradze, Casandra Watson, David Singleton, Marcus Sevier, Maria Rivon, Arnold Del Pilar, Amber Spangler, Sohail Rao, Luis Cantu, Arvind Krishna, Heidi Daugherty, Brandi Kerr, Kathy Evans, Robert Spees, Mailyn Marta, Rowena Dolor, Lorraine Vergara, Jackie Jordan, Valencia Burruss, Terri Hurst, Igho Ofotokun, MD, MSc Paulina A Rebolledo, Cecilia Zhang, Veronica E Smith, Rajesh Prabhu, Krystal Klicka, Amber Lightfeather, Vickie James, Marcella Rogers, Pradeep Parihar, De'ambra Torress, Chukwuemeka Oragwu, Ngozi Oguego, Rajesh Pillai, Mustafa Juma, Ahab Gabriel, Emad Ghaly, Marian Michal, Michelle Vasquez, Angela Mamon, Michelle Sheets, Gammal Hassanien, Samah Ismail, Yehia Samir, Andrew Meltzer, Soroush Shahamatdar, Ryan S Heidish, Scott Brehaut, Angelina Roche, Manisha Mehta, Nicole Koppinger, Jose Baez, Ivone Pagan, Dallal Abdelsayed, Mina Aziz, Philip Robinson, Grace Lozinski, Julie Nguyen, Alvin Griffin, Michael Morris, Nicole Love, Bonnie Mattox, Raykel Martin, Victoria Pardue, Teddy Rowland, Juan Ruiz-Unger, Lionel Reyes, Yadira Zamora, Navila Bacallao, John Cienki, Jonathan Cohen, Ying Yuan, Jenny Li, Jeremy Szeto, MD Mark Sulkowski, Lauren Stelmash, Idania Garcia Del Sol, Ledular Morales Castillo, Anya Gutierrez, Sabrina Prieto, Arch Amon, Andrew Barbera, Andrew Bugajski, Walter Wills, Kellcee Jacklin, Deryl Lamb, Amron Harper, Elmer Stout, Katherine Weeks, Merischia Griffin, Nancy Pyram-Bernard, Arlen Quintero, Eftim Adhami, Giovanni Carrillo, Josette Maria, Diksha Paudel, Oksana Raymond, Jeffrey Summers, Tammy Turner, Ebony Panaccione, Elizabeth Szwast, Ahsan Abdulghani, Pravin Vasoya, Conrad Miller, Hawa Wiley, Austin Chan, Saadia Khizer, Nirav Shah, Oluwadamilola Adeyemi, Wei Ning Chi, July Chen, Melissa Morton-Jost, Julie Castex, Phillip Feliciano, Jacqueline Olivo, Maria Maldonado, Anthony Vecchiarelli, Diana Gaytan-Alvarez, Vijaya Cherukuri, Santia Lima, Radica Alicic, Allison A Lambert, Carissa Urbat, Joni Baxter, Ann Cooper, Dawn Linn, Laura Fisher, Vijay Patel

JAMA, doi:10.1001/jama.2023.23363

IMPORTANCE The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. OBJECTIVE To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. DESIGN, SETTING, AND PARTICIPANTS 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. INTERVENTIONS 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). MAIN OUTCOMES AND MEASURES 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. RESULTS 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. CONCLUSIONS AND RELEVANCE Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms.

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{ 'indexed': { 'date-parts': [[2023, 11, 18]], 'date-time': '2023-11-18T00:39:48Z', 'timestamp': 1700267988727}, 'reference-count': 19, 'publisher': 'American Medical Association (AMA)', 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': 'ImportanceThe effect of higher-dose fluvoxamine in ' 'reducing symptom duration among outpatients with mild to moderate COVID-19 remains ' 'uncertain.ObjectiveTo assess ' 'the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating ' 'mild to moderate COVID-19.Design, Setting, and ' 'ParticipantsThe 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.InterventionsParticipants ' 'were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice ' 'daily for 12 additional days (n\u2009=\u2009601), or placebo (n\u2009=\u2009' '607).Main Outcomes and ' 'MeasuresThe 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.ResultsAmong 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\u2009=\u2009.40]). ' '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\u2009=\u2009.86) There were 7 serious adverse events in 6 participants (2 with ' 'fluvoxamine and 4 with placebo) but no ' 'deaths.Conclusions and ' 'RelevanceAmong outpatients with mild to moderate COVID-19, treatment ' 'with fluvoxamine does not reduce duration of COVID-19 ' 'symptoms.Trial ' 'RegistrationClinicalTrials.gov Identifier: NCT04885530', 'DOI': '10.1001/jama.2023.23363', 'type': 'journal-article', 'created': { 'date-parts': [[2023, 11, 17]], 'date-time': '2023-11-17T16:31:12Z', 'timestamp': 1700238672000}, 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19', 'prefix': '10.1001', 'author': [ { 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'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Margaret', 'family': 'Powers-Fletcher', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Delia', 'family': 'Miller', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Sylvere', 'family': 'Mukunzi', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Brittney', 'family': 'Manning', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and 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'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Vanessa', 'family': 'Motel', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Neeta', 'family': 'Bhat', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Daniela', 'family': 'Parra', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Matthew', 'family': 'Pullen', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and 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'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Thomas F.', 'family': 'Patterson', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Robin', 'family': 'Tragus', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Bridgette T.', 'family': 'Soileau', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'given': 'Patrick E.H.', 'family': 'Jackson', 'sequence': 'additional', 'affiliation': [ { 'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines 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'name': 'for the Accelerating COVID-19 Therapeutic Interventions and ' 'Vaccines (ACTIV)-6 Study Group and Investigators'}]}, { 'name': 'Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV)-6 Study Group ' 'and Investigators', 'sequence': 'additional', 'affiliation': []}], 'member': '10', 'published-online': {'date-parts': [[2023, 11, 17]]}, 'reference': [ { 'issue': '7', 'key': 'joi230138r1', 'doi-asserted-by': 'publisher', 'DOI': '10.1016/S2213-2600(21)00270-8', 'article-title': 'Repurposing drugs for treatment of COVID-19.', 'volume': '9', 'author': 'Venkatesan', 'year': '2021', 'journal-title': 'Lancet Respir Med'}, { 'issue': '7', 'key': 'joi230138r2', 'doi-asserted-by': 'publisher', 'first-page': '599', 'DOI': '10.1056/NEJMoa2201662', 'article-title': 'Randomized trial of metformin, ivermectin, and fluvoxamine for ' 'Covid-19.', 'volume': '387', 'author': 'Bramante', 'year': '2022', 'journal-title': 'N Engl J Med'}, { 'key': 'joi230138r3', 'doi-asserted-by': 'publisher', 'DOI': '10.3389/fphar.2021.652688', 'article-title': 'Fluvoxamine: a review of its mechanism of action and its role in ' 'COVID-19.', 'volume': '12', 'author': 'Sukhatme', 'year': '2021', 'journal-title': 'Front Pharmacol'}, { 'issue': '22', 'key': 'joi230138r5', 'doi-asserted-by': 'publisher', 'first-page': '2292', 'DOI': '10.1001/jama.2020.22760', 'article-title': 'Fluvoxamine vs placebo and clinical deterioration in outpatients with ' 'symptomatic COVID-19: a randomized clinical trial.', 'volume': '324', 'author': 'Lenze', 'year': '2020', 'journal-title': 'JAMA'}, { 'issue': '1', 'key': 'joi230138r6', 'doi-asserted-by': 'publisher', 'first-page': 'e42', 'DOI': '10.1016/S2214-109X(21)00448-4', 'article-title': 'Effect of early treatment with fluvoxamine on risk of emergency care ' 'and hospitalisation among patients with COVID-19: the TOGETHER ' 'randomised, platform clinical trial.', 'volume': '10', 'author': 'Reis', 'year': '2022', 'journal-title': 'Lancet Glob Health'}, { 'issue': '4', 'key': 'joi230138r7', 'doi-asserted-by': 'publisher', 'first-page': '296', 'DOI': '10.1001/jama.2022.24100', 'article-title': 'Effect of fluvoxamine vs placebo on time to sustained recovery in ' 'outpatients with mild to moderate COVID-19: a randomized clinical ' 'trial.', 'volume': '329', 'author': 'McCarthy', 'year': '2023', 'journal-title': 'JAMA'}, { 'issue': '5', 'key': 'joi230138r8', 'doi-asserted-by': 'publisher', 'first-page': '667', 'DOI': '10.7326/M22-3305', 'article-title': 'Oral fluvoxamine with inhaled budesonide for treatment of early-onset ' 'COVID-19: a randomized platform trial.', 'volume': '176', 'author': 'Reis', 'year': '2023', 'journal-title': 'Ann Intern Med'}, { 'issue': '16', 'key': 'joi230138r9', 'doi-asserted-by': 'publisher', 'first-page': '1595', 'DOI': '10.1001/jama.2022.18590', 'article-title': 'Effect of ivermectin vs placebo on time to sustained recovery in ' 'outpatients with mild to moderate COVID-19: a randomized clinical ' 'trial.', 'volume': '328', 'author': 'Naggie', 'year': '2022', 'journal-title': 'JAMA'}, { 'key': 'joi230138r12', 'article-title': 'Bayesian survival analysis using the rstanarm R package.', 'author': 'Brilleman', 'year': '2020', 'journal-title': 'arXiv'}, { 'key': 'joi230138r15', 'doi-asserted-by': 'publisher', 'article-title': 'Impact of molnupiravir treatment on patient-reported coronavirus ' 'disease 2019 (COVID-19) symptoms in the phase 3 MOVe-OUT trial: a ' 'randomized, placebo-controlled trial.', 'author': 'Guan', 'year': '2023', 'journal-title': 'Clin Infect Dis', 'DOI': '10.1093/cid/ciad409'}, { 'issue': '4', 'key': 'joi230138r16', 'doi-asserted-by': 'publisher', 'first-page': '1898', 'DOI': '10.1038/s41380-021-01432-3', 'article-title': 'Mechanisms of action of fluvoxamine for COVID-19: a historical review.', 'volume': '27', 'author': 'Hashimoto', 'year': '2022', 'journal-title': 'Mol Psychiatry'}, { 'issue': '8', 'key': 'joi230138r18', 'doi-asserted-by': 'publisher', 'first-page': '719', 'DOI': '10.1001/jama.2020.26443', 'article-title': 'Racial and ethnic health disparities related to COVID-19.', 'volume': '325', 'author': 'Lopez', 'year': '2021', 'journal-title': 'JAMA'}, { 'issue': '10', 'key': 'joi230138r19', 'doi-asserted-by': 'publisher', 'DOI': '10.1001/jamanetworkopen.2021.30479', 'article-title': 'Racial and ethnic disparities in rates of COVID-19-associated ' 'hospitalization, intensive care unit admission, and in-hospital death ' 'in the united states from March 2020 to February 2021.', 'volume': '4', 'author': 'Acosta', 'year': '2021', 'journal-title': 'JAMA Netw Open'}, { 'key': 'joi230138r10', 'volume-title': 'R: A Language and Environment for Statistical Computing', 'author': 'R Core Team', 'year': '2023'}, {'key': 'joi230138r11', 'author': 'Goodrich', 'year': '2023'}, { 'key': 'joi230138r13', 'volume-title': 'Bayesian Regression Modeling Strategies [R Package Rmsb]', 'author': 'Harrell', 'year': '2022'}, { 'key': 'joi230138r14', 'volume-title': 'Survival Analysis [R Package Survival]', 'author': 'Therneau', 'year': '2023'}, { 'key': 'joi230138r4', 'unstructured': 'COVID-19 Treatment Guidelines. National Institutes of Health. Accessed ' 'September 5, 2023. https://www.covid19treatmentguidelines.nih.gov/'}, { 'key': 'joi230138r17', 'unstructured': 'COVID-19 provisional counts: health disparities. Centers for Disease ' 'Control and Prevention. Accessed September 5, 2023. ' 'https://www.cdc.gov/nchs/nvss/vsrr/covid19/health_disparities.htm'}], 'container-title': 'JAMA', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://jamanetwork.com/journals/jama/articlepdf/2812204/jama_stewart_2023_oi_230138_1700012803.18294.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 17]], 'date-time': '2023-11-17T16:31:17Z', 'timestamp': 1700238677000}, 'score': 1, 'resource': {'primary': {'URL': 'https://jamanetwork.com/journals/jama/fullarticle/2812204'}}, 'subtitle': ['The ACTIV-6 Randomized Clinical Trial'], 'short-title': [], 'issued': {'date-parts': [[2023, 11, 17]]}, 'references-count': 19, 'URL': 'http://dx.doi.org/10.1001/jama.2023.23363', 'relation': {}, 'ISSN': ['0098-7484'], 'subject': ['General Medicine'], 'container-title-short': 'JAMA', 'published': {'date-parts': [[2023, 11, 17]]}}

Late treatment
is less effective

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