Combination therapy of high-dose intravenous anakinra and baricitinib in patients with critical COVID-19: Promising results from retrospective observational study

•No safety signal was observed with high-dose anakinra plus baricitinib treatment.•Anakinra plus baricitinib tended to reduce mortality in critical COVID-19.•Combined therapy was considered as a reasonable option in critical COVID-19. In this study, we aimed to evaluate the safety and efficacy of combination treatment of high-dose intravenous anakinra and baricitinib in patients with critically ill COVID-19. This retrospective observational study was conducted in a tertiary center with diagnosis of COVID-19 patients.Study population consisted of patients with positive polymerase chain reaction and computer tomography findings compatible with COVID-19 as well as critical illness. Data of 15 patients in combination group and 43 patients in control group were evaluated and included into the study. Overall mortality was 46.7 % (n = 7) in combination arm and 69.8 % (n = 30) in control group although it was not statistically significant (p = 0.1). Similarly, need of intubation was also lower in combination arm (46.7 %) compared to control group (69.8 %), it was not significantly different (p = 0.1). ICU admission was significantly lower in combination (46.7 %, n = 7) arm than control group (76.7 %, n = 33) (p = 0.03, Odds ratio [OR]:4.7). Development of severe infection (20 %, n = 3 vs 25 %, n = 9/36), pulmonary embolism (6.7 %, n = 1 vs 0), myocardial infarction (6.7 %, n = 1 vs 2.6 %, n = 1/38) and pneumothorax (13.3 %, n = 2 vs 2.6 %, n = 1/38) were not different between two groups (p = 0.7, p = 0.3, p = 0.5 and p = 0.2). In multivariable analysis only cHIS score was associated with high mortality (p = 0.018, OR:2.8, [95 % confidence interval: 1.2–6.6]). In survival analysis, mortality rate was significantly lower in combination arm than control group (Log-Rank:p = 0.04). Combination therapy of high-dose anakinra and baricitinib may be an adequate treatment option in patients with COVID-19 who had critical disease and has acceptable safety profile.