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Objective:   To conduct a systematic review on the effectiveness and safety of pharmacological and nonpharmacological interventions, in the ambulatory setting, aimed at preventing severe disease in patients with COVID-19.Data Sources:   Electronic databases (PubMed, EMBASE, and EuropePMC) were searched on January 6, 2021.Study Selection and Data Extraction:   A systematic review was conducted, adhering to PRISMA guidelines. The quality of individual trials was assessed using the Cochrane Risk-of-Bias Tool 2, and the certainty of evidence was assessed using GRADE.Data Synthesis:   The collective search retrieved 3818 citations. Eight trials relating to 9 pharmacological interventions were identified. No evidence for nonpharmacological interventions was identified. Low certainty evidence of effectiveness in preventing severe disease was found for fluvoxamine (absolute difference: −8.7%; 95% CI: −1.8% to −16.4%) and bamlanivimab plus etesevimab (absolute difference: −4.9%; 95% CI: −0.8% to −8.9%). Both trials were limited by small sample sizes and short durations of follow-up. In addition, very low certainty evidence of effect was found for ivermectin plus doxycycline and sulodexide. Based on published data, insufficient evidence of effect was found for bamlanivimab (monotherapy), casirivimab plus imdevimab, ivermectin (monotherapy), nitazoxanide, and peginterferon lambda.Relevance to Patient Care and Clinical Practice:   This review assessed all ambulatory treatments for COVID-19 that may improve patient outcomes and reduce hospitalizations.Conclusion:   Recent trials have shown promising results for a number of pharmacological agents to treat COVID-19 in the ambulatory setting. However, larger, more robust trials are needed to support the routine use of these agents outside of monitored clinical trials.

Interventions in an Ambulatory Setting to Prevent Progression to Severe Disease in Patients With COVID-19: A Systematic Review