Background: Coagulopathy and thromboembolic events are common in patients and are poor prognostic factors. Controversy exists regarding the potential of anticoagulation (AC) to reduce mortality and incidence of thromboembolic events in Covid-19 patients. The current systematic review and meta-analysis investigated the association between anticoagulants and mortality in adult hospitalized COVID-19 patients using the available published non-randomized studies. Methods: Google Scholar, PubMed, Scopus, the Cochrane Library and Clinical Trials.gov were searched for relevant studies. A meta-analysis of adjusted and unadjusted estimates was performed. The relative risk was used as a measure of effect. The random-effects model was used to pool estimates using the generic inverse variance method.Results: Sixteen studies were included in the quantitative data synthesis. Results showed a statistically significant association between AC and mortality (RR ¼ 0.56, 95% CI 0.36; 0.92, p ¼ 0.02). Both therapeutic (Relative risk [RR] ¼ 0.4, 95% CI 0.27; 0.57) and prophylactic AC (RR ¼ 0.54, 95% CI 0.41; 0.71) were associated with lower risk of mortality. Pre-admission AC was not associated with mortality (RR ¼ 0.84, 95% CI 0.49; 1.43, p > 0.05) while prophylactic AC was associated with higher risk of mortality compared to therapeutic AC (RR ¼ 1.58, 95% CI 1.34; 1.87, p < 0.001). Conclusion: Findings support the association of AC with mortality in Covid-19 patients. The results, synthesized from mostly low-quality studies, show that prophylactic and therapeutic AC might reduce mortality in Covid-19 patients.Findings suggest that therapeutic doses might be associated with better survival compared to prophylactic doses.

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Summary Azithromycin (AZM) is commonly used in Covid‐19 patients based on low‐quality evidence, increasing the risk of developing adverse events and antimicrobial resistance. The current systematic review and meta‐analysis investigated the safety and efficacy of AZM in treating Covid‐19 patients using published randomized controlled trials. Google Scholar, PubMed, Scopus, Cochrane Library, Clinical Trials.gov, MEDLINE, bioRxiv and medRxiv were searched for relevant studies. The random‐effects model was used to pool estimates using the Paule–Mandel estimate for heterogeneity. The odds ratio and raw difference in medians were used for dichotomous and continuous outcomes, respectively. The analysis included seven studies with 8822 patients (median age, 55.8 years; 61% males). The risk of bias was assessed as ‘low’ for five of the seven mortality results and as ‘some concerns’ and ‘high’ in one trial each. There were 657/3100 (21.2%) and 1244/5654 (22%) deaths among patients randomized to AZM and standard of care, respectively. The use of AZM was not associated with mortality in Covid‐19 patients (OR = 0.96, 95% CI 0.88–1.05, p = 0.317 based on the random‐effect meta‐analysis). The use of AZM was not associated with need for invasive mechanical ventilation (OR = 0.96, 95% CI 0.49–1.87, p = 0.85) and length of stay ( Δ = 1.11, 95% CI −2.08 to 4.31, p = 0.49). The results show that using AZM as routine therapy in Covid‐19 patients is not justified due to lack of efficacy and potential risk of bacterial resistance that is not met by an increased clinical benefit.

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