IL-17A in COVID-19: a meta-analysis
Abstract Numerous reviews, commentaries and opinion pieces have suggested targeting IL-17A as part of managing Coronavirus disease 2019 (COVID-19), the notorious pandemic caused by the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). IL-17A is a proinflammatory cytokine attributed with homeostatic roles but that is also involved in autoimmune disease pathogenesis. While some studies have reported an increase in IL-17A in subjects affected by COVID-19, no significant associations were found by others. Hence, we undertook this meta-analysis to examine whether serum IL-17A increases in COVID-19 patients. Multiple databases were systematically reviewed for literature published on the topic from January 1, 2020 to April 30, 2021. A random effects model was used to calculate weighted mean differences (WMDs) and 95% confidence interval (CIs) as well as the 𝜏2 and 𝐼2 statistics for heterogeneity analysis. We report that IL-17A increases in COVID-19 subjects irrespective of disease severity compared to controls [WMD=2.51 pg/ml (95% CI 1.73-3.28), p<0.00001]. It is also higher in patients with moderate disease compared to controls [WMD=2.41 pg/ml (95% CI:1.40-3.43), p<0.00001] as well as higher in patients with severe COVID-19 [WMD=4.13 pg/ml (95% CI:1.65-6.60), p=0.001]. While the increase in serum levels in subjects with severe disease over those with moderate disease was statistically significant, the association was not as robust as the other comparisons [WMD= 2.07 pg/ml (95% CI:0.20-3.95), p=0.03]. Variable heterogeneity was observed in the various analyses with no significant publication bias detected. Hence, IL-17A may be of relevance when considering management approaches to COVID-19.