Association of inflammatory markers with severity of disease and mortality in COVID-19 patients: a systematic review and meta-analysis

Khan, S.; Mishra, P.; Parveen, R.; Bajpai, R.; Khan, M. A.; Agarwal, N. B.

Purpose: Literature suggests association of inflammatory markers with the severity and mortality related to COVID-19, but there are varying conclusions available. We aimed to provide an overview of the association of inflammatory markers with the severity and mortality of COVID-19 patients. Methods: We searched Medline (via PubMed), Cochrane, Clinicaltrials.gov databases until Sept 1, 2020. Results: A total of 21 studies comprising 4023 patients with COVID-19 were included in our analysis. Levels of IL-6 (WMD=18.17 95%CI 3.38 to 32.96, p=0.016), IL-8 (WMD=12.09 95%CI 4.41 to 19.77, p=0.002), MCP-1 (WMD=146.66 95%CI 88.16 to 205.16, p<0.001), CRP (WMD=31.09 95%CI 10.08 to 52.10, p=0.004), PCT (WMD= -31.23 95%CI -37.70 to -24.76, p<0.001), IL-2R (WMD=861.93 95%CI 275.45 to 1448.41, p=0.004), ferritin (WMD= 1083.34 95%CI 431.99 to 1734.70, p=0.001) were found significantly higher in the severe group compared with the non-severe group of COVID-19 patients. Moreover, non-survivors had a higher levels of IL-2R (WMD= -666.06 95%CI -782.54 to -549.59, p<0.001), IL-8 (WMD= -26.63 95%CI -33.031 to -20.236, p<0.001), IL-10 (WMD= -7.60 95%CI -8.93 to -6.26, p<0.001), TNF- (WMD= -4.60 95%CI -5.71 to -3.48, p<0.001), IL- 1{beta} (WMD=22.66 95%CI 8.13 to 37.19, p=0.002), CRP (WMD= -96.40 95%CI -117.84 to -74.97, p<0.001), and ferritin (WMD= -937.60 95%CI -1084.15 to -791.065, p<0.001) when compared to the non-survivor group. Conclusion: This meta-analysis highlights the association of inflammatory markers with the severity and mortality of COVID-19 patients. Measurement of these inflammatory markers may assist clinicians to monitor and evaluate the severity and prognosis of COVID-19 thereby reducing the mortality rate. Keywords: inflammatory markers, cytokine storm, interleukin, disease severity, COVID-19