OBJECTIVE: This study aimed to determine the association of early use of oral antiviral drugs (including nirmatrelvir-ritonavir and molnupiravir) with the risk of post COVID-19 condition (PCC) and compare the possible efficacy of nirmatrelvir-ritonavir and molnupiravir.
METHODS: PubMed, Web of Science, Embase, Cochrane, MedRxiv, and Psycinfo were searched from inception until November 1, 2023. We included studies that assessed the effect of oral antiviral drugs on the incidence of PCC. Pairwise and network meta-analyses were conducted using a random-effects model. Risk ratios (RRs) for oral antiviral drugs were calculated with a confidence interval (CI).
RESULTS: Nine observational studies containing 866,066 patients were included. Nirmatrelvir-ritonavir and molnupiravir were evaluated in eight and two studies respectively, with both drugs evaluated in one study. Pair-wise meta-analysis showed that early oral antiviral drugs reduced PCC risk (RR 0.77, 95% CI 0.68-0.88). Network meta-analysis showed that nirmatrelvir-ritonavir may perform better than molnupiravir (surface under the cumulative ranking curve: 95.5% vs. 31.6%) at reducing PCC risk.
CONCLUSIONS: Early use of oral antiviral drugs may potentially protect against developing PCC in non-hospitalized patients with COVID-19. These findings support the standardized administration of oral antiviral drugs in patients during the acute phase of COVID-19 according to the guidelines.

BACKGROUND: Molnupiravir (MOV) is an oral antiviral for the treatment of individuals with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Our objective was to conduct a systematic literature review (SLR) of evidence on the effectiveness of MOV in reducing the risk of severe COVID-19 outcomes in real-world outpatient settings.
METHODS: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and using pre-determined population, intervention, comparison, outcome, time, and study design inclusion criteria. Eligible studies were published between January 1, 2021, and March 10, 2023, and evaluated the real-world effectiveness of MOV compared to no treatment in reducing the risk of severe COVID-19 outcomes among outpatients ≥ 18 years of age with a laboratory-confirmed diagnosis of SARS-CoV-2 infection.
RESULTS: Nine studies from five countries were included in the review. The size of the MOV-treated group ranged from 359 to 7818 individuals. Omicron variants of SARS-CoV-2 were dominant in all study periods. Most studies noted differences in the baseline characteristics of the MOV-treated and untreated control groups, with the treated groups generally being older and with more comorbidities. Eight studies reported that treatment with MOV was associated with a significantly reduced risk of at least one severe COVID-19 outcome in at least one age group, with greater benefits consistently observed among older age groups.
CONCLUSIONS: In this SLR study, treatment with MOV was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the MOV-treated and control groups may have led to underestimation of the effectiveness of MOV in many observational studies. Real-world studies published to date thus provide additional evidence supporting the continued benefits of MOV in non-hospitalized adults with COVID-19.
COVID-19 continues to be a major source of morbidity and mortality. Throughout the pandemic, many countries authorized various therapies for the treatment of individuals presenting with mild-to-moderate COVID-19 and at high risk of progression to severe disease. Some of these therapies have since been rendered ineffective due to the emergence of Omicron variants in late 2021. The objective of the current study was to conduct a systematic literature review to assess real-world evidence on the effectiveness of molnupiravir, including effectiveness against COVID-19 caused by Omicron variants, to supplement the findings of the MOVe-OUT clinical trial and further inform on the potential clinical benefit and utility of this antiviral agent. Nine studies were included in the systematic literature review. We found that treatment with molnupiravir was effective in reducing the risk of severe outcomes from COVID-19 caused by Omicron variants, especially for older individuals. Differences in the ages and baseline comorbidities of the molnupiravir-treated and control groups may have led to underestimation of the effectiveness of molnupiravir in many observational studies. In summary, real-world effectiveness studies provide additional evidence supporting the continued benefits of molnupiravir in non-hospitalized adults with COVID-19.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the effectiveness and safety of molnupiravir and sotrovimab in the treatment of patients with coronavirus disease 2019 (COVID-19).
METHODS: Cochrane Library, Web of Science, PubMed, medRxiv, and Google Scholar were systematically searched to identify relevant evidence up to December 2023. The risk of bias was assessed using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis (CMA).
RESULTS: Our search identified and included 13 studies involving 16166 patients. The meta-analysis revealed a significant difference between the molnupiravir and sotrovimab groups in terms of the mortality rate (odds ratio [OR] = 2.07, 95% confidence interval [CI]: 1.16, 3.70). However, no significant difference was observed between the two groups in terms of hospitalization rate (OR = 0.71, 95% CI: 0.47, 1.06), death or hospitalization rate (OR = 1.51, 95% CI: 0.81, 2.83), and intensive care unit admission (OR = 0.59, 95% CI: 0.07, 4.84). In terms of safety, molnupiravir was associated with a higher incidence of adverse events (OR = 1.67, 95% CI: 1.21, 2.30).
CONCLUSIONS: The current findings indicate that sotrovimab may be more effective than molnupiravir in reducing the mortality rate in COVID-19 patients. However, no statistical difference was observed between the two treatments for other effectiveness outcomes. The certainty of evidence for these findings was rated as low or moderate. Further research is required to provide a better comparison of these interventions in treating COVID-19 patients.

Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication of SARS-CoV-2. Following PRISMA guidelines, a thorough literature search was performed on electronic and medical databases from December 2022 till January 2023. Molnupiravir 800 mg showed significance in creating viral RNA error rate at Day 5 (WMD: 4.91; 95% CI; [1.19, 8.63] p = 0.01; I2  = 0%). Similarly, at 400 mg, Molnupiravir creates an RNA error rate (WMD: 2.27; 95% CI; 2.27 [0.50, 4.65] p = 0.02; I2  = 0%). Furthermore, exhibit a significant outcome for mean change in SARS-CoV-2 RNA viral load from baseline in nasopharyngeal sample at 800 mg Molnupiravir on Day 3 (WMD: -0.22; 95% CI; [-0.35, -0.08] p = 0.002; I2  = 0%), Day 5 (WMD: -0.32; 95% CI; [-0.53, -0.11] p = 0.003; I2  = 24%) and overall pooled analysis (WMD: -0.17; 95% CI; [-0.29, 0.33] p = 0.003; I2  = 32%). Moreover, Molnupiravir 400 mg significantly reduced the incidence of death compared to the placebo group (RR: 0.17; 95% CI; [0.07, 0.43] p = 0.0002; I2  = 0%). Molnupiravir effectively treats SARS-CoV-2 patients by eliminating the virus from the host.

Vaccines remain the cornerstone of medical prevention and are highly effective in reducing the risk of severe disease and death due to coronavirus disease 2019 (COVID-19). In the context of expanding the therapeutic armamentarium against COVID-19, molnupiravir (Lagevrio) and ritonavir-boosted nirmatrelvir (Paxlovid) were developed, constituting the first effective oral treatments against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this narrative review, we retrospectively inquired into the clinical trials and real-world studies investigating the efficacy of these agents. Overall, clinical trials and real-world studies have demonstrated the efficacy of both agents in reducing hospitalization and death rates in COVID-19 patients. As per current recommendations, their use is suggested in patients with mild to moderate symptoms who are at high risk of developing severe disease. Nevertheless, limited data exist regarding their efficacy in specific subpopulations, such as immunocompromised patients, those with severe kidney disease, pregnant women, and children.

This study aimed to compare the efficacy and safety of nirmatrelvir/ritonavir (Paxlovid) with molnupiravir in the treatment of coronavirus disease 2019 (COVID-19). To end this, PubMed, Cochrane Library, Web of Science, medRxiv, and Google Scholar were systematically searched to collect relevant evidence up to February 15, 2023. The risk of bias was evaluated using the risk of bias in nonrandomized studies of interventions tool. Data were analyzed using Comprehensive Meta-Analysis software. Eighteen studies involving 57 659 patients were included in the meta-analysis. The meta-analysis showed a significant difference between nirmatrelvir/ritonavir and molnupiravir in terms of all-cause mortality rate (odds ratio [OR] = 0.54, 95% confidence interval [CI]: 0.44-0.67), all-cause hospitalization rate (OR = 0.61, 95% CI: 0.54-0.69), death or hospitalization rate (OR = 0.61, 95% CI: 0.38-0.99), and negative polymerase chain reaction conversion time (mean difference = -1.55, 95% CI: -1.74 to -1.37). However, no significant difference was observed between the two groups in terms of COVID-19 rebound (OR = 0.87, 95% CI: 0.71-1.07). In terms of safety, although the incidence of any adverse events was higher in the nirmatrelvir/ritonavir group (OR = 2.52, 95% CI: 1.57-4.06), no significant difference was observed between the two treatments in terms of adverse events leading to treatment discontinuation (OR = 1.18, 95% CI: 0.69-2.00). The present meta-analysis demonstrated the significant superiority of nirmatrelvir/ritonavir over molnupiravir in improving clinical efficacy in COVID-19 patients during the prevalence of Omicron variant. These findings, however, need to be further confirmed.

BACKGROUND: There are currently some differences in the research results of molnupiravir. This study aimed to evaluate the efficacy and safety of molnupiravir in the treatment of COVID-19.
METHODS: PubMed, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), ClinicalTrials.gov, ICTRP (International Clinical Trials Registry Platform) and medRxiv were searched to identify relevant randomised controlled trials (RCTs) from inception to 1 January 2023. The Cochrane risk of bias tool for randomised trials was used to assess the bias risk of the included studies. Revman 5.4 software was used for meta-analysis.
RESULTS: Nine RCTs were included, including 31 573 COVID-19 patients, of whom 15 846 received molnupiravir. The meta-analysis results showed that the molnupiravir group had a higher proportion in terms of clinical improvement (Day 5 RR 2.41, 95% CI 1.18-4.92; Day 10 RR 1.45, 95% CI 1.04-2.01) and real-time polymerase chain reaction negativity (Day 5 RR 2.78, 95% CI 1.38-5.62; Day 10 RR 1.18, 95% CI 1.07-1.31). However, no significant difference was observed between the two groups in terms of mortality, hospitalisation, adverse events and serious adverse events.
CONCLUSIONS: Molnupiravir can accelerate the rehabilitation of COVID-19 patients, but it does not significantly reduce mortality and hospitalisation.

BACKGROUND: The effects of molnupiravir in treating patients with non-severe COVID-19 remain uncertain.
OBJECTIVE: To evaluate the efficacy and safety of molnupiravir in adult patients with mild or moderate COVID-19.
METHODS: PubMed, Embase, CENTRAL, Web of Science, and WHO COVID-19 database up to 27 December 2022.
METHODS: Randomized controlled trials with no language restrictions.
METHODS: Adults with mild or moderate COVID-19.
METHODS: Molnupiravir against standard care or placebo.
UNASSIGNED: We used a revision of RoB-2 criteria.
UNASSIGNED: Outcomes were mortality, hospital admission, viral clearance, time to viral clearance, time to symptom resolution or clinical improvement, any adverse events, and serious adverse events. We performed DerSimonian-Laird random-effects meta-analyses to summarize the evidence and evaluated the certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.
RESULTS: Nine randomized controlled trials enrolling 30 472 patients proved eligible. Majority of patients were outpatients, with a mean age ranging from 35 to 56.6 years. In adult patients with mild or moderate COVID-19, molnupiravir probably reduces mortality (relative risk [RR], 0.43; 95% CI, 0.20-0.94; risk difference [RD], 0.1% fewer; moderate certainty) and the risk of hospital admission (RR, 0.67; 95% CI, 0.45-0.99; RD, 1.4% fewer; moderate certainty) and may reduce time to viral clearance (mean difference, -1.81 days; 95% CI, -3.31 to -0.31; low certainty) and time to symptom resolution or clinical improvement (mean difference, -2.39 days; 95% CI, -3.71 to -1.07; low certainty). Molnupiravir probably increases the rate of viral clearance (RR, 3.47; 95% CI, 2.43-4.96; RD 16.1% more; moderate certainty) at 7 days (±3 days) and likely does not increase serious adverse events (RR, 0.84; 95% CI, 0.61-1.15; RD 0.1% fewer; moderate certainty).
CONCLUSIONS: In adult patients with mild or moderate COVID-19, molnupiravir likely reduces mortality and risk of hospital admission probably without increasing serious adverse events.

The efficacy of molnupiravir in treating patients with coronavirus disease 2019 (COVID-19) has been inconsistent across randomized controlled trials (RCTs). Thus, this meta-analysis was conducted to clarify the literature. A literature search of electronic databases-PubMed, Embase, and Cochrane Library-was performed to identify relevant articles published up to December 31, 2022. Only RCTs that investigated the clinical efficacy and safety of molnupiravir for patients with COVID-19 were included. The primary outcome was all-cause mortality at 28-30 days. This pooled analysis of nine RCTs did not reveal a significant difference in all-cause mortality between molnupiravir and control groups (risk ratio [RR], 0.43; 95% confidence interval [CI], 0.10-1.77) for overall patients. However, the risks of mortality and hospitalization were lower in the molnupiravir group than in the control group (mortality: RR, 0.28; 95% CI, 0.10-0.79; hospitalization: RR, 0.67; 95% CI, 0.45-0.99) among nonhospitalized patients. In addition, molnupiravir use was associated with a borderline higher virological eradication rate relative to the control (RR, 1.05; 95% CI, 1.00-1.11). Finally, no significant difference in adverse event risk was discovered between the groups (RR, 0.98; 95% CI, 0.89-1.08). The findings reveal the clinical benefits of molnupiravir for nonhospitalized patients with COVID-19. However, molnupiravir may not improve the clinical outcomes of hospitalized patients. These findings support the recommended use of molnupiravir for treating nonhospitalized patients with COVID-19 but not for hospitalized patients.

UNASSIGNED: Liver involvement in COVID-19 is multifactorial, and the three potential mechanisms are direct hepatocyte viral damage, vascular or cellular damage during the cytokine storm of severe COVID-19 and drug-induced liver injury. To date, three antivirals are licensed for the treatment of COVID-19 by most guidelines: remdesivir, molnupiravir, and ritonavir-boosted nirmatrelvir.
UNASSIGNED: We performed a narrative review about the hepatic safety profile of the three antivirals licensed for COVID-19 treatment. We used data about hepatobiliary adverse events from English-language randomized clinical trials (RCTs).
UNASSIGNED: Remdesivir was found to be potentially hepatotoxic, and liver biochemistry abnormalities were common (2-34%) but mild and reversible. Molnupiravir exhibits a favorable safety profile and the increase in aminotransferases was usually mild and reversible (up to 11% of patients in one study). Ritonavir-boosted nirmatrelvir is potentially hepatotoxic, but in the only phase 3 RCT there were no safety issues and aspartate aminotransferase/alanine aminotransferase levels increase did not exceed 2.4% of patients. All antivirals have a favorable safety profile, but they are not sufficiently studied in patients with underlying chronic kidney or liver disease. In this special populations, antivirals should be used with caution and careful monitoring during treatment should be pursued on a case-by-case basis.