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Levy Library Blog

Article in the Spotlight - October 2020

by Kerry McKee on 2020-10-28T12:00:00-04:00 | Comments

Each month Levy Library showcases the achievements of Mount Sinai faculty and researchers by highlighting an article and its altmetrics. Altmetrics are alternative measures of impact that capture non-traditional data like abstract views, article downloads, and social media activity. Our altmetrics data is provided by the PlumX platform

This month we highlight a publication from a member of our Library team, Rachel Pinotti. Cytokine elevation in severe and critical COVID-19: a rapid systematic review, meta-analysis, and comparison with other inflammatory syndromes by , and .




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.


  • The systemic inflammatory profile of COVID-19 is distinct from that of non-COVID-19 ARDS, sepsis, and CAR T cell-induced cytokine release syndrome; applying the descriptor cytokine storm to COVID-19 might be particularly problematic
  • Inflammatory cytokine elevations in patients with severe and critical COVID-19, including elevations of interleukin-6, are profoundly lower than those reported in patients with acute respiratory distress syndrome (ARDS) unrelated to COVID-19, sepsis, and chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome
  • In contrast, several non-cytokine biomarkers, including D-dimer, C-reactive protein, and ferritin, are elevated to a similar or greater extent in patients with COVID-19 than in patients with these comparison disorders
  • As in other syndromes of critical illness, the role of inflammatory cytokine elevations in the pathobiology of COVID-19 remains unclear
  • Alternative models of organ dysfunction in COVID-19, such as endovasculitis, direct viral injury and lymphodepletion, or viral-induced immunosuppression, might be worth considering

View the PlumX profile to learn more about the metrics details of this publication. 
Read this publication in The Lancet Respiratory Medicine

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