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Risk of bias was extracted from COVID\u201019\u2010NMA, with odds ratio utilized for pooled comparison.\u00a0Searches identified 281 studies with 61 published RCTs for 33 diverse interventions analyzed. RCTs were largely unvaccinated cohorts with at least one COVID\u201019 hospitalization risk factor. Grouping by class, monoclonal antibodies (mAbs)\u00a0(OR\u2009=\u20090.31 [95% CI\u2009=\u20090.24\u22120.40]) had highest hospital reduction efficacy, followed by COVID\u201019 convalescent plasma\u00a0(CCP) (OR\u2009=\u20090.69 [95% CI\u2009=\u20090.53\u22120.90]), small molecule antivirals (OR\u2009=\u20090.78 [95% CI\u2009=\u20090.48\u22121.33]), and repurposed drugs (OR\u2009=\u20090.82 [95% CI: 0.72\u22120.93]). Earlier in disease onset interventions performed better than later. This meta\u2010analysis allows approximate head\u2010to\u2010head comparisons of diverse outpatient interventions.\u00a0Omicron sublineages (XBB and BQ.1.1) are resistant to mAbs\u00a0Despite trial heterogeneity, this pooled comparison by intervention class indicated oral antivirals are the preferred outpatient treatment where available, but intravenous interventions from convalescent plasma to remdesivir are also effective and necessary in constrained medical resource settings or for acute and chronic COVID\u201019 in the immunocompromised.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.29310","type":"journal-article","created":{"date-parts":[[2023,12,18]],"date-time":"2023-12-18T05:10:30Z","timestamp":1702876230000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Outpatient randomized controlled trials to reduce COVID\u201019 hospitalization: Systematic review and 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