Extract
The concept of COVID-19 related cytokine storm syndrome (COVID-CSS) emerged early in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic to explain why some patients exposed to this virus become critically ill with acute respiratory distress syndrome, multi-organ failure, and death. A seminal study from Wuhan, China reported higher serum concentrations of inflammatory cytokines in patients requiring critical care compared to those with milder disease, and the authors postulated that “cytokine storm was associated with disease severity” [1]. COVID-19 hypercytokinemia initially invited comparisons to other respiratory viral infections that cause a dysregulated immune response, namely severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Subsequently, similarities between COVID-CSS and other cytokine storm syndromes such as hemophagocytic lymphohistiocytosis (HLH) [2], autoinflammatory syndromes, and chimeric antigen T-cell therapy cytokine release syndrome (CAR T-cell CRS) became apparent [3–5]. The proposition that hypercytokinemia is pathological in some patients with COVID-19 catalysed numerous clinical trials of immunomodulatory and cytokine-inhibitor therapy. However, critics contend that CSS is a misleading conceptual framework in COVID-19 and two prominent editorials have raised significant doubt about COVID-CSS [6, 7].
Abstract
Hypercytokinemic immune dysregulation in COVID-19 is known as cytokine storm syndrome. Interleukin-6 levels ≥80 pg×mL−1 predict an increased risk of respiratory failure and death, and immunomodulatory therapy is an area of urgent investigation
Acknowledgement
The authors thank Dr. Catherine Biggs for her critical review of the manuscript.
Footnotes
Contributorship: All authors contributed to the conception and drafting of the article and provided critical revision for important intellectual content and final approval.
Support statement: Dr. Chen is supported by the UBC Hematology Research Program. Dr. Sekhon is supported by the Vancouver Coastal Health Research Institute Clinician Scientist Award. Dr. Wellington is supported by grants from Canadian Institutes for Health Research, National Institutes of Health, Weston Brain Institute and Cure Alzheimer Fund. Cure Alzheimer's Fund; DOI: http://dx.doi.org/10.13039/100007625; Vancouver Coastal Health Research Institute; DOI: http://dx.doi.org/10.13039/501100008002; NIH Clinical Center; DOI: http://dx.doi.org/10.13039/100000098; Weston Brain Institute; DOI: http://dx.doi.org/10.13039/100012479; Canadian Institutes of Health Research; DOI: http://dx.doi.org/10.13039/501100000024.
Conflict of interest: Dr. Chen has nothing to disclose.
Conflict of interest: Dr. Hoiland has nothing to disclose.
Conflict of interest: Dr. Stukas has nothing to disclose.
Conflict of interest: Dr. Wellington has nothing to disclose.
Conflict of interest: Dr. Sekhon has nothing to disclose.
- Received August 2, 2020.
- Accepted August 24, 2020.
- Copyright ©ERS 2020
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