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Objectives: Examining the cumulative evidence from randomized controlled trials (RCTs), evaluating the use of pharmacological agents for the treatment of COVID‐19 infections in patients with critical illness. Data Sources: Databases Medline, Embase, Web of Science, Scopus, CINAHL, and Cochrane. Study Selection: Inclusion criteria were RCTs that enrolled patients with confirmed or suspected COVID‐19 infection who are critically ill. Only RCTs that examined therapeutic agents against one another or no intervention, placebo, or standard of care, were included. Data Extraction: Pairs of reviewers extracted data independently. Outcomes of interest included the overall reported mortality defined as either the ICU mortality, hospital mortality, mortality within 28 days or mortality within 90 days. Data Synthesis: A total of 40 studies (11,613 patients) evaluated 50 therapeutic intervention arms divided into five main therapy categories; steroids, antiviral medications, immunomodulators, plasma therapies [intravenous immunoglobulins (IVIG), convalescent plasma and/or, therapeutic plasma exchange], and therapeutic anticoagulation. Immunomodulators was the only group with possible mortality benefit, risk ratio (RR) 0.83 (95% CI 0.73; 0.95), with nonsignificant heterogeneity (I2 = 8%, p = 0.36). In contrast, the other therapy groups showed no significant impact on mortality, as indicated by their respective pooled RRs: steroids [RR 0.91 (95% CI 0.82; 1.01), I2 = 31%], antiviral medications [RR 1.11 (95% CI 0.82; 1.49), I2 = 57%], plasma therapies [RR 0.77 (95% CI 0.58; 1.01), I2 = 36%], and anticoagulation [RR 1.06 (95% CI 0.95; 1.18), I2 = 0%]. Conclusions: This meta‐analysis highlights both the heterogeneity and a lack of benefit from therapies evaluated during the COVID‐19 pandemic. Many of the RCTs were developed based on limited observational data. Future RCTs investigating pharmaceutical interventions in critically ill patients during pandemics need to be designed based on better evidence. [ABSTRACT FROM AUTHOR]

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