Efficacy and safety of molnupiravir for the treatment of SARS-CoV-2 infection: a systematic review and meta-analysis

Abstract

Background: The role of molnupiravir for coronavirus disease 2019 (COVID-19) treatment is unclear.

Methods: We conducted a systematic review until 1 November 2022 searching for randomized controlled trials (RCTs) involving COVID-19 patients comparing molnupiravir [±standard of care (SoC)] versus SoC and/or placebo. Data were pooled in random-effects meta-analyses. Certainty of evidence was assessed according to the Grading of Recommendations, Assessment, Development and Evaluations approach.

Results: Nine RCTs were identified, eight investigated outpatients (29 254 participants) and one inpatients (304 participants). Compared with placebo/SoC, molnupiravir does not reduce mortality [risk ratio (RR) 0.27, 95% CI 0.07-1.02, high-certainty evidence] and probably does not reduce the risk for 'hospitalization or death' (RR 0.81, 95% CI 0.55-1.20, moderate-certainty evidence) by Day 28 in COVID-19 outpatients. We are uncertain whether molnupiravir increases symptom resolution by Day 14 (RR 1.20, 95% CI 1.02-1.41, very-low-certainty evidence) but it may make no difference by Day 28 (RR 1.05, 95% CI 0.92-1.19, low-certainty evidence). In inpatients, molnupiravir may increase mortality by Day 28 compared with placebo (RR 3.78, 95% CI 0.50-28.82, low-certainty evidence). There is little to no difference in serious adverse and adverse events during the study period in COVID-19 inpatients/outpatients treated with molnupiravir compared with placebo/SoC (moderate- to high-certainty evidence).

Conclusions: In a predominantly immunized population of COVID-19 outpatients, molnupiravir has no effect on mortality, probably none on 'hospitalization or death' and effects on symptom resolution are uncertain. Molnupiravir was safe during the study period in outpatients although a potential increase in inpatient mortality requires careful monitoring in ongoing clinical research. Our analysis does not support routine use of molnupiravir for COVID-19 treatment in immunocompetent individuals.

Figure 1.

Flow diagram for identification of eligible clinical trials. PR, press release.

Figure 2.

Association between molnupiravir and all-cause mortality by Day 28 in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 3.

Association between molnupiravir and hospitalization or death by Day 28 in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 4.

Association between molnupiravir and symptom resolution by Day 14 in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 5.

Association between molnupiravir and symptom resolution by Day 28 in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 6.

Association between molnupiravir and adverse events in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.

Figure 7.

Association between molnupiravir and serious adverse events in outpatients. MH, Mantel–Haenszel method. This figure appears in colour in the online version of JAC and in black and white in the print version of JAC.