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Deciphering the COVID‐19 cytokine storm: Systematic review and meta‐analysis
Author(s) -
Mulchandani Rubina,
Lyngdoh Tanica,
Kakkar Ashish Kumar
Publication year - 2021
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/eci.13429
Subject(s) - meta analysis , cytokine storm , medicine , covid-19 , web of science , cytokine , cd8 , ards , immune system , immunology , disease , lung , infectious disease (medical specialty)
The coronavirus pandemic has affected more than 20 million people so far. Elevated cytokines and suppressed immune responses have been hypothesized to set off a cytokine storm, contributing to ARDS, multiple‐organ failure and, in the most severe cases, death. We aimed to quantify the differences in the circulating levels of major inflammatory and immunological markers between severe and nonsevere COVID‐19 patients. Methods Relevant studies were identified from PubMed, EMBASE, Web of Science, SCOPUS and preprint servers. Risk of bias was assessed for each study, using appropriate checklists. All studies were described qualitatively and a subset was included in the meta‐analysis, using forest plots. Results Based on 23 studies, mean cytokine levels were significantly higher (IL‐6: MD, 19.55 pg/mL; CI, 14.80, 24.30; IL‐8: MD, 19.18 pg/mL; CI, 2.94, 35.43; IL‐10: MD, 3.66 pg/mL; CI, 2.41, 4.92; IL‐2R: MD, 521.36 U/mL; CI, 87.15, 955.57; and TNF‐alpha: MD, 1.11 pg/mL; CI, 0.07, 2.15) and T‐lymphocyte levels were significantly lower (CD4+ T cells: MD, −165.28 cells/µL; CI, −207.58, −122.97; CD8+ T cells: MD, −106.51 cells/µL; CI, −128.59, −84.43) among severe cases as compared to nonsevere ones. There was heterogeneity across studies due to small sample sizes and nonuniformity in outcome assessment and varied definitions of disease severity. The overall quality of studies was sub‐optimal. Conclusion Severe COVID‐19 is characterized by significantly increased levels of pro‐inflammatory cytokines and reduced T lymphocytes. Well‐designed and adequately powered prospective studies are needed to amplify the current evidence and provide definitive answers to dilemmas regarding timing and type of anti‐COVID‐19 therapy particularly in severe patients.