Early use of oral antiviral drugs and the risk of post COVID-19 syndrome: A systematic review and network meta-analysis.

OBJECTIVES: 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.

Efficacy of the oral nucleoside prodrug GS-5245 (Obeldesivir) against SARS-CoV-2 and coronaviruses with pandemic potential.

Despite the wide availability of several safe and effective vaccines that can prevent severe COVID-19 disease, the emergence of SARS-CoV-2 variants of concern (VOC) that can partially evade vaccine immunity remains a global health concern. In addition, the emergence of highly mutated and neutralization-resistant SARS-CoV-2 VOCs such as BA.1 and BA.5 that can partially or fully evade (1) many therapeutic monoclonal antibodies in clinical use underlines the need for additional effective treatment strategies. Here, we characterize the antiviral activity of GS-5245, Obeldesivir (ODV), an oral prodrug of the parent nucleoside GS-441524, which targets the highly conserved RNA-dependent viral RNA polymerase (RdRp). Importantly, we show that GS-5245 is broadly potent in vitro against alphacoronavirus HCoV-NL63, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-related Bat-CoV RsSHC014, Middle East Respiratory Syndrome coronavirus (MERS-CoV), SARS-CoV-2 WA/1, and the highly transmissible SARS-CoV-2 BA.1 Omicron variant in vitro and highly effective as antiviral therapy in mouse models of SARS-CoV, SARS-CoV-2 (WA/1), MERS-CoV and Bat-CoV RsSHC014 pathogenesis. In all these models of divergent coronaviruses, we observed protection and/or significant reduction of disease metrics such as weight loss, lung viral replication, acute lung injury, and degradation in pulmonary function in GS-5245-treated mice compared to vehicle controls. Finally, we demonstrate that GS-5245 in combination with the main protease (Mpro) inhibitor nirmatrelvir had increased efficacy in vivo against SARS-CoV-2 compared to each single agent. Altogether, our data supports the continuing clinical evaluation of GS-5245 in humans infected with COVID-19, including as part of a combination antiviral therapy, especially in populations with the most urgent need for more efficacious and durable interventions.

Efficacy of oral antiviral drugs to prevent mother-to-child transmission of hepatitis B virus: a network meta-analysis.

BACKGROUND: Hepatitis B is a serious global health problem. Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is a major risk factor in the endemicity of HBV infection. Oral antiviral drugs are recommended to highly viremic mothers to decrease MTCT of HBV. The present network analysis compared the efficacy of available treatments to prevent the MTCT of HBV. METHODS: The electronic databases of PubMed, Embase, Web of Science, Scopus, and Wanfang data were searched for eligible studies. Pair-wise meta-analysis and Bayesian network analysis were applied to compare the efficacy of antiviral drugs. RESULTS: Seventy-five studies involving 12,740 pregnant females were eligible for analysis. On pair-wise analysis, lamivudine (OR 0.15, 95% CI 0.09-0.25, I-squared = 0%), telbivudine (OR 0.07, 95% CI 0.05-0.10, I-squared = 0%) and tenofovir (OR 0.07, 95% CI 0.04-0.13, I-squared = 0%) significantly decreased the MTCT rate. Results of multiple comparisons with ranking probability based on Bayesian analysis showed that tenofovir (SUCRA = 96.83%) appeared more effective than the two other drugs. CONCLUSION: In addition to active and passive immunoprophylaxis, lamivudine, telbivudine and tenofovir in highly viremic mothers can further decrease MTCT of HBV. Based on direct and indirect evidence, tenofovir appears to be more effective than the two other drugs in the prevention of HBV MTCT.