Is a “Cytokine Storm” Relevant to COVID-19?: A JAMA Review
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Cytokine storm has no definition. Broadly speaking, it denotes a hyperactive immune response characterized by the release of interferons, interleukins, tumor-necrosis factors, chemokines, and several other mediators. These mediators are part of a well-conserved innate immune response necessary for efficient clearance of infectious agents. Cytokine storm implies that the levels of released cytokines are injurious to host cells.

Why has the “cytokine storm” been so closely associated with COVID-19?

-- During the SARS epidemic caused by SARS-CoV-1, the term cytokine storm was described as a feature and associated with adverse outcomes.
-- Several early case series in COVID-19 reported levels of some plasma cytokines elevated above the normal range. In most cases, however, they are lower than plasma levels in previous cohorts of patients with ARDS.
-- Interleukin-6, a proinflammatory cytokine, is a key mediator in the acute inflammatory response and the purported cytokine storm.
-- The reported IL-6 levels in 5 cohorts of patients with COVID-19 each with more than 100 patients, and 3 cohorts of patients with ARDS are above the normal range in many (but not all) cases, they are lower than the median values typically reported in ARDS.
-- The median values in randomized clinical trials conducted by the National Heart, Lung and Blood Institute’s ARDS Network are approximately 10- to 40-fold higher, even when only patients with severe COVID-19 are considered.
-- The hyperinflammatory phenotype of ARDS is characterized by elevated proinflammatory cytokines, an increased incidence of shock, and adverse clinical outcomes.
-- The characteristics of this phenotype could be considered as most consistent with those expected with the cytokine storm. However, median IL-6 levels in patients with the hyperinflammatory phenotype of ARDS are 10- to 200-fold higher than levels in patients with severe COVID-19.

For these reasons, the term cytokine storm may be misleading in COVID-19 ARDS. Incorporating a poorly defined pathophysiological entity lacking a firm biological diagnosis may only further increase uncertainty about how best to manage this heterogeneous population of patients.

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Interesting read !
Jul 3, 2020Like1