Drug treatments for covid-19 : living systematic review and network meta-analysis Siemieniuk, Reed A. C.; Bartoszko, Jessica J.; Ge, Long; Zeraatkar, Dena; Izcovich, Ariel; Kum, Elena; Pardo-Hernandez, Hector; Rochwerg, Bram; Lamontagne, Francois; Han, Mi Ah; et al.
Objective To compare the effects of treatments for coronavirus disease 2019 (covid-19). Design Living systematic review and network meta-analysis. Data sources US Centers for Disease Control and Prevention COVID-19 Research Articles Downloadable Database, which includes 25 electronic databases and six additional Chinese databases to 10 August 2020. Study selection Randomised clinical trials in which people with suspected, probable, or confirmed covid-19 were randomised to drug treatment or to standard care or placebo. Pairs of reviewers independently screened potentially eligible articles. Methods After duplicate data abstraction, a Bayesian network meta-analysis was conducted. Risk of bias of the included studies was assessed using a modification of the Cochrane risk of bias 2.0 tool, and the certainty of the evidence using the grading of recommendations assessment, development and evaluation (GRADE) approach. For each outcome, interventions were classified in groups from the most to the least beneficial or harmful following GRADE guidance. Results 35 trials with 16 588 patients met inclusion criteria; 12 (24.3%) trials and 6853 (41.3%) patients are new from the previous iteration. Twenty-seven randomised controlled trials were included in the analysis performed on 29 July 2020. Compared with standard care, glucocorticoids probably reduce death (risk difference 31 fewer per 1000 patients, 95% credible interval 55 fewer to 5 fewer, moderate certainty), mechanical ventilation (28 fewer per 1000 patients, 45 fewer to 9 fewer, moderate certainty), and duration of hospitalisation (mean difference −1.0 day, −1.4 to −0.6 days moderate certainty). The impact of remdesivir on mortality, mechanical ventilation, and length of hospital stay is uncertain, but it probably reduces duration of symptoms (−2.6 days −4.3 to −0.6 days, moderate certainty) and probably does not substantially increase adverse effects leading to drug discontinuation (3 more per 1000, 7 fewer to 43 more, moderate certainty). Hydroxychloroquine may not reduce risk of death (13 more per 1000, 15 fewer to 43 more, low certainty) or mechanical ventilation (19 more per 1000, 4 fewer to 45 more, moderate certainty). The certainty in effects for all other interventions was low or very low certainty. Co nclusion Glucocorticoids probably reduce mortality and mechanical ventilation in patients with covid-19 compared with standard care, whereas hydroxychloroquine may not reduce either. The effectiveness of most interventions is uncertain because most of the randomised controlled trials so far have been small and have important limitations. Systematic review registration This review was not registered. The protocol is included as a supplement. Readers’ note This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication. This version is update 1 of the original article published on 30 July 2020 (BMJ 2020;370:m2980), and previous versions can be found as data supplements. When citing this paper please consider adding the update number and date of access for clarity.
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