Tocilizumab in addition to standard of care in the management of COVID-19: a meta-analysis of RCTs.

OBJECTIVE: We performed a systematic review and meta-analysis for exploring clinical benefits and safety of tocilizumab in addition to standard of care (SOC) in treating patients with coronavirus disease 2019 (COVID-19). METHODS: An electronic search was carried out in PubMed, EMBASE, Cochrane Library, and Science Direct, as well as in medRxiv preprint server, to identify eligible studies. Only randomized Controlled Trials (RCTs) that compared mortality events and/or adverse events between a tocilizumab + SOC group and a SOC-only control group were included. The primary outcome was 28-day mortality. Secondary outcomes include progression to severe disease, defined as need for mechanical ventilation (MV) or intensive care unit (ICU) admission, and adverse events (AE). RESULTS: A total of nine studies (6,490 participants) could be included in this meta-analysis, with 3,358 participants in the tocilizumab + SOC group and 3,132 participants in the SOC-only group. The overall mortality rate was lower in the tocilizumab group compared to the SOC-only group, though the difference was not statistically significant (odds ratio [OR], 0.87; 95% CI, 0.73-1.04; I2, 15%). This finding was unaffected by subgroup analyses based on initial use of steroids or mechanical ventilation at baseline. Patients receiving tocilizumab were 26% less likely to progress to MV, and this difference was statistically significant (OR, 0.74; 95% CI, 0.64-0.86; I2, 0%). Among patients who were not in ICU at randomization, the tocilizumab group had 34 % lower rate of ICU admission compared to the SOC-only group (OR, 0.66; 95% CI, 0.40-2.14; I2, 29%). The occurrence of serious infections was lower in the tocilizumab group (OR, 0.57; 95% CI, 0.36-0.89; I2, 21%). CONCLUSION: Tocilizumab is generally well-tolerated in COVID-19. Although this drug does not appear to have a significant benefits on survival, it may have a role in preventing progression to intensive care and MV.

Lymphopenia and neutrophilia at admission predicts severity and mortality in patients with COVID-19: a meta-analysis.

BACKGROUND: There is a compelling need to identify clinical and laboratory predictors of unfavorable clinical course and death in patients with coronavirus disease (COVID-19). A trend towards low lymphocyte count and high neutrophil counts in patients with poor outcomes has been reported by earlier studies. We aim to synthesize existing data evaluating the relationship between clinical outcomes and abnormal neutrophil and lymphocyte counts at admission in COVID-19 patients. METHODS: An electronic search was carried out in PubMed, China National Knowledge Infrastructure (CNKI) and Cochrane Central Register of Controlled Trials (CENTRAL) to identify eligible studies reporting frequency data on neutrophilia and lymphopenia at admission in hospitalization in COVID-19 patients. Pooled odds ratios of clinical outcomes for each parameter were calculated using Comprehensive Meta-Analysis. RESULTS: A total of 22 studies (4,969 patients) were included in this meta-analysis. Lymphopenia at admission was found to be significantly associated with increased odd of progression to severe disease (odds ratio [OR], 4.20; 95% confidence interval [95CI%], 3.46-5.09) and death (OR, 3.71; 95%CI, 1.63-8.44). Neutrophilia at admission was also found to be significantly associated with increased odd of progression to severe disease (OR, 7.99; 95%CI, 1.77-36.14) and death (OR, 7.87; 95%CI, 1.75-35.35). Subgroup analysis revealed that COVID-19 patients with severe lymphopenia (<0.5 x10×9/L) had 12-fold increased odds of in-hospital mortality. CONCLUSION: Admission lymphopenia and neutrophilia are associated with poor outcomes in patients with COVID-19. Regular monitoring and early and even more aggressive intervention shall hence be advisable in patients with low lymphocyte and high neutrophil counts. These variables may be useful in risk stratification models.