Circulatory Cytokines and Chemokines Profile in Human Coronaviruses: A systematic review and meta-analysis

Abstract

Background: SARS, MERS, and COVID-19 share similar characteristics as the genetic homology of SARS-CoV-2 compared to SARS-CoV and MERS-CoV is 80% and 50% respectively and cause similar clinical features. Uncontrolled release of proinflammatory mediators (cytokine storm) by activated immune cells in SARS, MERS, and COVID-19 leads to severe phenotype development. Aim: This systematic review and meta-analysis aimed to evaluate the inflammatory cytokines profile associated with severe human coronavirus diseases, including three stains: MERS-CoV, SARS-CoV SARS-CoV-2, in severe patients. Method: PubMed, Embase, and Cochrane Library databases were searched up to July 2020. Randomized and Observational studies reporting the inflammatory cytokines associated with severe and non-severe human coronavirus diseases, including MERS-CoV, SARS-CoV SARS-CoV-2 were included. Two reviewers independently screened articles, extracted data, and assessed the quality of included studies. Meta-analysis was performed using a random-effects model with a 95% confidence interval (CI) to estimate the pooled mean of inflammatory biomarkers. Results: A high level of circulating IL-6 could be associated with the severity of the three strains of coronaviruses infection. TNF, IL-10, and IL-8 is associated with the severity of COVID-19. Increased circulating levels of CXCL10/IP10 and CCL2/MCP-1 might also be related to the severity of MERS. Conclusion: This study suggests that the immune response and immunopathology in the three severe human coronavirus strains are similar to some extent. These findings highlight that nearly all studies reporting severe cases of SARS, MERS, and COVID-19 have been associated with elevated levels of IL-6, which could be used as a potential therapeutic target to improve patients outcomes in severe cases.