The Clinical Efficacy and Safety of Anti-Viral Agents for Non-Hospitalized Patients with COVID-19: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials

Abstract

This network meta-analysis compared the clinical efficacy and safety of anti-viral agents for the prevention of disease progression among non-hospitalized patients with COVID-19. PubMed, Embase, Web of Science, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform were searched from their inception to 28 May 2022. Only randomized controlled trials (RCTs) that investigated the clinical efficacy of anti-viral agents for non-hospitalized patients with COVID-19 were included. Three RCTs involving 4241 patients were included. Overall, anti-viral agents were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo (OR, 0.23; 95% CI: 0.06–0.96; p = 0.04). Compared with the placebo, patients receiving nirmatrelvir plus ritonavir had the lowest risk of hospitalization or death (OR, 0.12; 95% CI: 0.06–0.24), followed by remdesivir (OR, 0.13; 95% CI: 0.03–0.57) and then molnupiravir (OR, 0.67; 95% CI: 0.46–0.99). The rank probability for each treatment calculated using the P-score revealed that nirmatrelvir plus ritonavir was the best anti-viral treatment, followed by remdesivir and then molnupiravir. Finally, anti-viral agents were not associated with an increased risk of adverse events compared with the placebo. For non-hospitalized patients with COVID-19 who are at risk of disease progression, the currently recommended three anti-viral agents, nirmatrelvir plus ritonavir, molnupiravir and remdesivir, should continue to be recommended for the prevention of disease progression. Among them, oral nirmatrelvir plus ritonavir and intravenous remdesivir seem to be the better choice, followed by molnupiravir, as determined by this network meta-analysis. Additionally, these three anti-viral agents were shown to be as tolerable as the placebo in this clinical setting.

Real-World Study on Effectiveness of Molnupiravir and Nirmatrelvir–Ritonavir in Unvaccinated Patients with Chronic Respiratory Diseases with Confirmed SARS-CoV-2 Infection Managed in Out-Patient Setting

“…Both clinical trials and real-world study suggest the benefits of both oral antivirals in reducing hospitalization and mortality [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. In a systemic review and meta-analysis, treatment with both NMV-r and MOV were associated with a significantly lower risk of COVID-19 related hospitalization or death compared with the placebo, with the benefits being more pronounced for NMV-r than MOV [ 20 ]. A real-world study in Italy suggested both NMV-r and MOV to be effective, while patients treated with NMV-r had lower risk of hospitalizations and earlier recovery, though the age, body mass index and underlying co-morbidities differed in the NMV-r and MOV groups, as in our study as well as other real-world studies [ 21 ].…”

The Potential of Nanobodies for COVID-19 Diagnostics and Therapeutics

“…Notably, molnupiravir, nirmatrelvir, remdesivir, and paxlovid have demonstrated neutralizing activity against variants, including Omicron [ 6 , 45 ]. Lai et al reviewed and analyzed data from RCTs to determine the clinical efficacy and safety of antiviral drugs for non-hospitalized COVID-19 patients [ 47 ]. Their results indicated that antiviral drugs were related to a significantly lower risk of hospitalization/death [ 47 ].…”

“…Lai et al reviewed and analyzed data from RCTs to determine the clinical efficacy and safety of antiviral drugs for non-hospitalized COVID-19 patients [ 47 ]. Their results indicated that antiviral drugs were related to a significantly lower risk of hospitalization/death [ 47 ]. Additionally, nirmatrelvir plus RTV was the best antiviral treatment with the lowest hospitalization/death risk, followed by remdesivir and molnupiravir [ 47 ].…”

“…Their results indicated that antiviral drugs were related to a significantly lower risk of hospitalization/death [ 47 ]. Additionally, nirmatrelvir plus RTV was the best antiviral treatment with the lowest hospitalization/death risk, followed by remdesivir and molnupiravir [ 47 ].…”

Multi-Targeting Approach in Selection of Potential Molecule for COVID-19 Treatment

“…As per the studies, oral nirmatrelvir plus ritonavir and intravenous remdesivir is reported to be the better choice, followed by molnupiravir. However, most of these drugs just target the early steps of the life cycle or the early phase of infection, and there are no excellent drugs that provide a long-lasting suppression of viral replication [ 13 , 14 ].…”