tetano
Editor, Senior Moderator
BMC Infect Dis
. 2026 Jul 23;26(1):1829.
doi: 10.1186/s12879-026-13901-7.
Banafshe Hosseini 1 2 3 , Lesley Anne Pablo 1 , Jolanta Piszczek 4 , Yoav Keynan 5 6 , Peter Daley 7 , Becky Skidmore 8 , Andrew D Pinto 9 10 11 12
Affiliations Expand
Background: Outpatient therapeutics for SARS-CoV-2 remain critical to reducing disease severity, preventing hospitalization, and mitigating long-term complications, yet evidence across trials has been fragmented and evolving.
Objective: To systematically identify and evaluate the effectiveness of oral or inhaled pharmaceutical treatments, including repurposed and antiviral therapies, for acute SARS-CoV-2 infection in adult patients managed in outpatient settings.
Methods: Comprehensive peer-reviewed searches were conducted in several databases for studies published by March 2024. We included randomized controlled trials evaluating oral or inhaled therapeutics administered to adults with acute SARS-CoV-2 infection in outpatient settings and excluded non-randomized and observational studies. Outcomes of interest included severe clinical outcomes. Random-effects meta-analyses were performed where feasible.
Results: A total of 124 randomized controlled trials evaluating 137 therapeutics across 35 countries were included. Most interventions were repurposed agents (n = 88), with 33 antiviral and three combination regimens. Molnupiravir shortened time to recovery and reduced hospitalization in a subgroup pool of unvaccinated, higher-risk outpatients (OR 0.68, 95% CI 0.52-0.89), although this effect attenuated when mostly vaccinated patients was included (OR 0.83, 95% CI 0.58-1.19). Inhaled budesonide and metformin showed modest or setting-specific benefits, while most repurposed drugs, including fluvoxamine, ivermectin, and hydroxychloroquine, had no consistent clinical impact. Safety profiles were class-typical with no new signals identified.
Conclusions: Most repurposed and antiviral therapies evaluated in outpatient COVID-19 trials showed no consistent benefit for severe clinical outcomes. Modest or setting-specific effects were observed for inhaled budesonide, metformin, and molnupiravir, with molnupiravir's effect on hospitalization most evident in unvaccinated, higher-risk outpatients and unreplicated for mortality.
Clinical trial number: Not applicable.
Keywords: Antivirals; COVID-19; Drug repurposing; Outpatient therapeutics; Randomized controlled trials; SARS-CoV-2; Systematic review.
. 2026 Jul 23;26(1):1829.
doi: 10.1186/s12879-026-13901-7.
Effectiveness of oral and inhaled repurposed and antiviral pharmaceutical treatments for acute SARS-CoV-2 in outpatient settings: a systematic review of 124 randomized trials
Banafshe Hosseini 1 2 3 , Lesley Anne Pablo 1 , Jolanta Piszczek 4 , Yoav Keynan 5 6 , Peter Daley 7 , Becky Skidmore 8 , Andrew D Pinto 9 10 11 12
Affiliations Expand
- PMID: 42902159
- PMCID: PMC13682097
- DOI: 10.1186/s12879-026-13901-7
Abstract
Background: Outpatient therapeutics for SARS-CoV-2 remain critical to reducing disease severity, preventing hospitalization, and mitigating long-term complications, yet evidence across trials has been fragmented and evolving.
Objective: To systematically identify and evaluate the effectiveness of oral or inhaled pharmaceutical treatments, including repurposed and antiviral therapies, for acute SARS-CoV-2 infection in adult patients managed in outpatient settings.
Methods: Comprehensive peer-reviewed searches were conducted in several databases for studies published by March 2024. We included randomized controlled trials evaluating oral or inhaled therapeutics administered to adults with acute SARS-CoV-2 infection in outpatient settings and excluded non-randomized and observational studies. Outcomes of interest included severe clinical outcomes. Random-effects meta-analyses were performed where feasible.
Results: A total of 124 randomized controlled trials evaluating 137 therapeutics across 35 countries were included. Most interventions were repurposed agents (n = 88), with 33 antiviral and three combination regimens. Molnupiravir shortened time to recovery and reduced hospitalization in a subgroup pool of unvaccinated, higher-risk outpatients (OR 0.68, 95% CI 0.52-0.89), although this effect attenuated when mostly vaccinated patients was included (OR 0.83, 95% CI 0.58-1.19). Inhaled budesonide and metformin showed modest or setting-specific benefits, while most repurposed drugs, including fluvoxamine, ivermectin, and hydroxychloroquine, had no consistent clinical impact. Safety profiles were class-typical with no new signals identified.
Conclusions: Most repurposed and antiviral therapies evaluated in outpatient COVID-19 trials showed no consistent benefit for severe clinical outcomes. Modest or setting-specific effects were observed for inhaled budesonide, metformin, and molnupiravir, with molnupiravir's effect on hospitalization most evident in unvaccinated, higher-risk outpatients and unreplicated for mortality.
Clinical trial number: Not applicable.
Keywords: Antivirals; COVID-19; Drug repurposing; Outpatient therapeutics; Randomized controlled trials; SARS-CoV-2; Systematic review.