Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes

By D. Leisman, L. Ronner, R. Pinotti, Matthew D Taylor, P. Sinha, C. Calfee, A. Hirayama, Fiore Mastroiani, C. Turtle, M. Harhay and 2 more. The Lancet Respiratory Medicine, 2020

764 citations recorded by the source corpus.

The description of a so-called cytokine storm in patients with COVID-19 has prompted consideration of anti-cytokine therapies, particularly interleukin-6 antagonists. However, direct systematic comparisons of COVID-19 with other critical illnesses associated with elevated cytokine concentrations have not been reported. In this Rapid Review, we report the results of a systematic review and meta-analysis of COVID-19 studies published or posted as preprints between Nov 1, 2019, and April 14, 2020, in which interleukin-6 concentrations in patients with severe or critical disease were recorded. 25 COVID-19 studies (n=1245 patients) were ultimately included. Comparator groups included four trials each in sepsis (n=5320), cytokine release syndrome (n=72), and acute respiratory distress syndrome unrelated to COVID-19 (n=2767). In patients with severe or critical COVID-19, the pooled mean serum interleukin-6 concentration was 36·7 pg/mL (95% CI 21·6–62·3 pg/mL; I2=57·7%). Mean interleukin-6 concentrations were nearly 100 times higher in patients with cytokine release syndrome (3110·5 pg/mL, 632·3–15 302·9 pg/mL; p<0·0001), 27 times higher in patients with sepsis (983·6 pg/mL, 550·1–1758·4 pg/mL; p<0·0001), and 12 times higher in patients with acute respiratory distress syndrome unrelated to COVID-19 (460 pg/mL, 216·3–978·7 pg/mL; p<0·0001). Our findings question the role of a cytokine storm in COVID-19-induced organ dysfunction. Many questions remain about the immune features of COVID-19 and the potential role of anti-cytokine and immune-modulating treatments in patients with the disease.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/b0b1a80ca2eaeac2300577af0da2897c09805715

Citations in the corpus

• Synergism of TNF-α and IFN-γ Triggers Inflammatory Cell Death, Tissue Damage, and Mortality in SARS-CoV-2 Infection and Cytokine Shock Syndromes (2020, neutral): “Furthermore, some have questioned whether the phenomenon observed during COVID-19 truly constitutes a cytokine storm, as emerging evidence has shown that the levels of proinflammatory cytokines in these patients are much lower than in patients with other diseases previously associated with cytokine ”