Decreased mortality and increased side effects in COVID-19 patients treated with IL-6 receptor antagonists: systematic review and meta-analysis.

There is controversy whether IL-6 (receptor) antagonists are beneficial in treating COVID-19 patients. We therefore update our systematic review to answer the following research questions: (1) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have lower mortality compared to standard of care? (2) Do patients hospitalized for COVID-19 treated with IL-6 (receptor) antagonists have more side effects compared to standard of care? The following databases were search up to December 1st 2020: PubMed, PMC PubMed Central, MEDLINE, WHO COVID-19 Database, Embase, Web-of-Science, COCHRANE LIBRARY, Emcare and Academic Search Premier. In order to pool the risk ratio (RR) and risk difference of individual studies we used random effects meta-analysis. The search strategy retrieved 2975 unique titles of which 71 studies (9 RCTs and 62 observational) studies comprising 29,495 patients were included. Mortality (RR 0.75) and mechanical ventilation (RR 0.78) were lower and the risk of neutropenia (RR 7.3), impaired liver function (RR 1.67) and secondary infections (RR 1.26) were higher for patients treated with IL-6 (receptor) antagonists compared to patients not treated with treated with IL-6 (receptor) antagonists. Our results showed that IL-6 (receptor) antagonists are effective in reducing mortality in COVID-19 patients, while the risk of side effects was higher. The baseline risk of mortality was an important effect modifier: IL-6 (receptor) antagonists were effective when the baseline mortality risk was high (e.g. ICU setting), while they could be harmful when the baseline mortality risk was low.