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June 30, 2020 Is a “Cytokine Storm” Relevant to COVID-19?

Discussion in 'Immunology and Rheumatology' started by Valery1957, Jul 10, 2020.

  1. Valery1957

    Valery1957 Famous Member

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    June 30, 2020
    Is a “Cytokine Storm” Relevant to COVID-19?
    Pratik Sinha, MB, ChB, PhD1,2; Michael A. Matthay, MD1,2,3; Carolyn S. Calfee, MD, MAS1,2,3
    Article Information
    JAMA Intern Med. Published online June 30, 2020. doi:10.1001/jamainternmed.2020.3313
    COVID-19 Resource Center

    1,2 Although the mechanisms of COVID-19–induced lung injury are still being elucidated, the term cytokine storm has become synonymous with its pathophysiology, both in scientific publications and the media. Absent convincing data of their effectiveness in COVID-19, drugs such as tocilizumab and sarilumab, which are monoclonal antibodies targeting interleukin (IL)-6 activity, are being used to treat patients; trials of these agents typically cite the cytokine storm as their rationale (NCT04306705, NCT04322773). A critical evaluation of the term cytokine storm and its relevance to COVID-19 is warranted.

    3 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 Table summarizes reported IL-6 levels in 5 cohorts of patients with COVID-19,1,2,4-6 each with more than 100 patients, and 3 cohorts of patients with ARDS.7-9 Although the median values 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.7-9 The hyperinflammatory phenotype of ARDS is characterized by elevated proinflammatory cytokines, an increased incidence of shock, and adverse clinical outcomes.7-9 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 (Table).
     

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