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.
12 affiliations
- 1Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada.
- 2Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
- 3Division of Clinical Public Health & Institute for Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
- 4Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada.
- 5Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
- 6Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada.
- 7Division of Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland and Labrador, Canada.
- 8Independent Information Specialist, Ottawa, ON, Canada.
- 9Upstream Lab, MAP Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Unity Health Toronto, Toronto, ON, Canada. [email protected].
- 10Department of Family and Community Medicine, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada. [email protected].
- 11Division of Clinical Public Health & Institute for Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada. [email protected].
- 12Department of Family and Community Medicine, St. Michael's Hospital, Toronto, ON, Canada. [email protected].
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.
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BibTeX
@article{hosseini2026effectiveness,
title = {{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.}},
author = {Banafshe Hosseini and Lesley Anne Pablo and Jolanta Piszczek and Yoav Keynan and Peter Daley and Becky Skidmore and Andrew D Pinto},
journal = {BMC infectious diseases},
year = {2026},
month = jul,
doi = {10.1186/s12879-026-13901-7},
url = {https://europepmc.org/article/MED/42902159},
note = {CC BY},
}
RIS
TY - JOUR
TI - 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.
AU - Banafshe Hosseini
AU - Lesley Anne Pablo
AU - Jolanta Piszczek
AU - Yoav Keynan
AU - Peter Daley
AU - Becky Skidmore
AU - Andrew D Pinto
PY - 2026
DA - 2026/07/01
JO - BMC infectious diseases
DO - 10.1186/s12879-026-13901-7
UR - https://europepmc.org/article/MED/42902159
AB - 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.
SN - 1471-2334
ER -