Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials

Abstract

BackgroundFew randomized trials evaluated the effect of combination therapy of Sofosbuvir-based direct-acting antivirals on mortality risk in patients with COVID-19. Therefore, we aimed to summarize the overall evidence in the form of a systematic review and meta-analysis. MethodsA systematic literature search with no language restriction was performed in electronic databases and preprint repositories to identify eligible randomized trials published up to July 8, 2021. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest using sofosbuvir combined with direct-acting antiviral agents relative to non-use of sofosbuvir-based direct-acting antiviral agents at 95% confidence intervals (CI). ResultsThe estimated effect of sofosbuvir-based direct-acting antiviral agents on the mortality risk indicated a significantly reduced risk (pooled odds ratio = 0.59; 95% confidence interval 0.36 to 0.99) with inadequate evidence against our model hypothesis of no significant difference at the current sample size. However, no statistically significant difference in the odds of development of composite endpoint of severe illness (pooled odds ratio = 0.79; 95% confidence interval 0.43 to 1.44), with the administration of a combination of sofosbuvir-based direct-acting antiviral agents among patients with COVID-19, relative to nonadministration of sofosbuvir-based direct-acting antiviral agents. ConclusionThe sofosbuvir-based direct-acting antiviral agents have no protective effects against the development of severe illness in patients with COVID-19 with the current dosing regimen. Whether sofosbuvir-based direct-acting antiviral agents could offer mortality benefits would require further investigations.

Impact of COVID-19 on the liver and on the care of patients with chronic liver disease, hepatobiliary cancer, and liver transplantation: An updated EASL position paper

“…However, interpretations are limited by small sample size and lack of adjustment for the presence of cirrhosis. The repurposing of DAA therapy for use against COVID-19 has been investigated but results remain contentious (discussed below) [ [100] , [101] , [102] ].

EASL position Patients with chronic viral hepatitis (HBV or HCV) without cirrhosis do not appear to have an increased risk of SARS-CoV-2 infection or COVID-19 related mortality.

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“…There are no reported concerns about DAA therapy in patients with COVID-19. Small clinical studies and one meta-analysis initially suggested that sofosbuvir-based therapies may even have clinical benefit in the case of COVID-19 [ 102 ], although this has not been replicated in other systematic analyses [ 101 ].

EASL position Following SARS-CoV-2 infection, planned initiation of DAA therapy can be postponed until after COVID-19 has resolved.

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“…However, interpretations are limited by small sample size and lack of adjustment for the presence of cirrhosis. The repurposing of DAA therapy for use against COVID-19 has been investigated but results remain contentious (discussed below) [100][101][102].…”

Small molecules in the treatment of COVID-19

“… 312 However, according to a meta-analysis by Kow et al, sofosbuvir-based direct-acting antiviral agents have no protective effects against the development of severe illness in patients with COVID-19 with the current dosing regimen. 313 In a previous study, sofosbuvir demonstrated higher anti-viral efficiency against West Nile virus in hepatic cells than in lung cells. 314 This liver-targeting characteristic of sofosbuvir raises concerns for its use in treating SARS-CoV-2.…”

Bacterial Proteases as Potentially Exploitable Modulators of SARS-CoV-2 Infection: Logic from the Literature, Informatics, and Inspiration from the Dog

“…Further development of safe and reliable treatment strategies for people who fall ill is thus required for full and concerted pandemic response. Much effort has been devoted to designing [14][15][16][17][18] or repurposing [19,20] drugs for SARS-CoV-2 targets, but such pursuits have not yet produced breakthrough success. Such disappointment is not surprising, given the historical challenges of developing antiviral therapeutics [21], but it is imperative to persevere and to innovate.…”