Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. In this retrospective cohort study, nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and mortality associated with coronavirus disease 2019 (COVID-19).

2. Molnupiravir was also associated with a reduction in 30-day mortality associated with COVID-19.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Nirmatrelvir-ritonavir and molnupiravir received emergency use authorization from the United States Food and Drug Administration for the treatment of non-hospitalized patients with COVID-19 in 2021. However, there is a gap in knowledge as to the effectiveness of both nirmatrelvir-ritonavir and molnupiravir, as early clinical trials were conducted among unvaccinated participants before the emergence of the omicron variant. Prior randomized controlled trials did not directly compare the efficacy of antiviral agents, nor did they measure outcomes beyond 29 days after infection. Overall, this study found that nirmatrelvir-ritonavir seems to be an effective treatment for eligible patients with COVID-19 to reduce short-term outcomes such as hospitalization or death. This study was limited by comparators in this study potentially being asymptomatic persons or symptomatic persons whose diagnosis was delayed beyond the eligible treatment window. Nevertheless, these study’s findings are significant, as they demonstrate that nirmatrelvir-ritonavir can provide significant benefits for the treatment of COVID-19 and prevention of hospitalization and death.

In-Depth [retrospective cohort study]:

This retrospective cohort study was designed to emulate three target randomized controlled trials of COVID-19 antivirals. Patients who were Veteran’s Health Association (VHA) enrollees with a VHA primary care encounter in the 18 months preceding the test-positive date were eligible for the study. Patients who died or were hospitalized on or before their antiviral treatment date were excluded. The primary outcome measured was hospitalization or all-cause mortality through day 30 after the index date. Outcomes in the primary analysis were assessed via Kaplan-Meier curves with unadjusted risks, risk differences, and risk ratios. Based on the primary analysis, patients treated with nirmatrelvir–ritonavir had a lower 30-day risk for hospitalization (22.07 versus 30.32 per 1000 participants; risk difference [RD], -8.25; 95% Confidence Interval [CI], 12.27 to -4.23 per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22; 95% CI, -5.45 to -3.00 per 1000 participants). For patients alive at day 31, reductions were seen in 31- to the 180-day incidence of death (hazard ratio, 0.66; 95% CI, 0.49 to 0.89) but not hospitalization (subhazard ratio, 0.90; 95% CI, 0.79 to 1.02). Those who received molnupiravir had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42; 95% CI, -13.49 to -7.35 per 1000 participants; hazard ratio at 31 to 180 days, 0.67; 95% CI, 0.48 to 0.95) but not hospitalization. In summary, this study demonstrates that nirmatrelvir–ritonavir is effective in reducing 30-day hospitalization and death in patients with symptomatic COVID-19 infection, while molnupiravir is associated with a benefit in 30-day mortality.

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