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medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.09.22.22280245


BackgroundImmune dysregulation contributes to poorer outcomes in severe Covid-19. Immunomodulators targeting various pathways have improved outcomes. We investigated whether infliximab provides benefit over standard of care. MethodsWe conducted a master protocol investigating immunomodulators for potential benefit in treatment of participants hospitalized with Covid-19 pneumonia. We report results for infliximab (single dose infusion) versus shared placebo both with standard of care. Primary outcome was time to recovery by day 29 (28 days after randomization). Key secondary endpoints included 14-day clinical status and 28-day mortality. ResultsA total of 1033 participants received study drug (517 infliximab, 516 placebo). Mean age was 54.8 years, 60.3% were male, 48.6% Hispanic or Latino, and 14% Black. No statistically significant difference in the primary endpoint was seen with infliximab compared with placebo (recovery rate ratio 1.13, 95% CI 0.99-1.29; p=0.063). Median (IQR) time to recovery was 8 days (7, 9) for infliximab and 9 days (8, 10) for placebo. Participants assigned to infliximab were more likely to have an improved clinical status at day 14 (OR 1.32, 95% CI 1.05-1.66). Twenty-eight-day mortality was 10.1% with infliximab versus 14.5% with placebo, with 41% lower odds of dying in those receiving infliximab (OR 0.59, 95% CI 0.39-0.90). No differences in risk of serious adverse events including secondary infections. ConclusionsInfliximab did not demonstrate statistically significant improvement in time to recovery. It was associated with improved 14-day clinical status and substantial reduction in 28- day mortality compared with standard of care. Trial (NCT04593940).

Pneumonia , COVID-19
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.06.15.21258928


Surveillance testing and quarantine have been effective measures for limiting SARS-CoV-2 transmission on university campuses. However, the importance of these measures needs to be re-evaluated in the context of a complex and rapidly changing environment that includes vaccines, variants, and waning immunity. Also, recent guidelines from the CDC suggest that vaccinated students do not need to participate in surveillance testing. We used an agent-based SEIR model to evaluate the utility of surveillance testing and quarantine in a fully vaccinated student population where vaccine effectiveness may be impacted by the type of vaccination, the presence of variants, and the loss of vaccine-induced or natural immunity over time. We found that weekly surveillance testing at 90% vaccine effectiveness only marginally reduces viral transmission as compared to no testing. However, at 50%-75% effectiveness, surveillance testing can provide over 10-fold reduction in the number of infections on campus over the course of the semester. We also show that a 10-day quarantine protocol for exposures has limited effect on infections until vaccine effectiveness drops to 50%, and that increased surveillance testing for exposures is at least as effective as quarantine at limiting infections. Together these findings provide a foundation for universities to design appropriate mitigation protocols for the 2021-2022 academic year.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.06.17.21258639


BackgroundEasily distributed oral antivirals are urgently needed to treat coronavirus disease-2019 (COVID-19), prevent progression to severe illness, and block transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We report the results of a Phase 2a trial evaluating the safety, tolerability, and antiviral efficacy of molnupiravir in the treatment of COVID-19 ( NCT04405570). MethodsEligible participants included outpatients with confirmed SARS-CoV-2 infection and symptom onset within 7 days. Participants were randomized 1:1 to 200 mg molnupiravir or placebo, or 3:1 to molnupiravir (400 or 800 mg) or placebo, twice-daily for 5 days. Antiviral activity was assessed as time to undetectable levels of viral RNA by reverse transcriptase polymerase chain reaction and time to elimination of infectious virus isolation from nasopharyngeal swabs. ResultsAmong 202 treated participants, virus isolation was significantly lower in participants receiving 800 mg molnupiravir (1.9%) versus placebo (16.7%) at Day 3 (p = 0.02). At Day 5, virus was not isolated from any participants receiving 400 or 800 mg molnupiravir, versus 11.1% of those receiving placebo (p = 0.03). Time to viral RNA clearance was decreased and a greater proportion overall achieved clearance in participants administered 800 mg molnupiravir versus placebo (p = 0.01). Molnupiravir was generally well tolerated, with similar numbers of adverse events across all groups. ConclusionsMolnupiravir is the first oral, direct-acting antiviral shown to be highly effective at reducing nasopharyngeal SARS-CoV-2 infectious virus and viral RNA and has a favorable safety and tolerability profile.

Severe Acute Respiratory Syndrome , Coronavirus Infections , HIV Infections , COVID-19