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    Research Letter
    September 3, 2020

    Cytokine Levels in Critically Ill Patients With COVID-19 and Other Conditions

    Author Affiliations
    • 1Department of Intensive Care Medicine, Radboud University Medical Center, Nijmegen, the Netherlands
    JAMA. 2020;324(15):1565-1567. doi:10.1001/jama.2020.17052

    An abnormally strong proinflammatory response known as “cytokine storm” may play an important role in the pathophysiology of coronavirus disease 2019 (COVID-19), although cytokine storm remains ill defined.1 Sinha and colleagues2 reported that although IL-6 levels are elevated in severe COVID-19, they are lower than levels usually observed in (non–COVID-19) acute respiratory distress syndrome (ARDS). However, this comparison is limited by the use of different assays, which are not well standardized.3 We compared cytokine levels in critically ill patients with COVID-19 vs levels in patients with other critical illnesses.

    All patients in this study were admitted to the intensive care unit (ICU) of Radboud University Medical Center. Plasma concentrations of the proinflammatory cytokines tumor necrosis factor (TNF), IL-6, and IL-8 were determined in consecutive mechanically ventilated patients with COVID-19 with ARDS (partial pressure of oxygen/fraction of inspired oxygen ratio <300; sampled within 48 hours after ICU admission), bacterial septic shock with or without ARDS (sampled within 24 hours after septic shock diagnosis), out-of-hospital cardiac arrest (OHCA; sampled within 24 hours after ICU admission), and multiple traumas (sampled within 24 hours after trauma). The patients with sepsis and trauma are part of larger published cohorts,4,5 whereas data of 14 patients with OHCA were previously published.6 Sampling occurred between 2010 and 2020 (Table). Patients with immunological insufficiencies were excluded, defined as chronic/concomitant use of immunosuppressive medication, chemotherapy/radiotherapy in the last year or in the past for (non-)Hodgkin lymphoma, or humoral/cellular deficiencies. Cytokines in all cohorts were determined using the same methodology (Milliplex assay, Millipore, on a MAGPIX instrument, Luminex Corporation) by the same technician using the same protocol.

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