The Levy Library Blog

Article in the Spotlight - October 2020

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:

SUMMARY

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.

KEY MESSAGES

• 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