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

Educational Objective
To understand how cytokine levels in critically ill patients with COVID-19 can help us manage the pandemic
1 Credit CME

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.

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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.

Article Information

Corresponding Author: Peter Pickkers, MD, PhD, Radboud University Medical Center, Postbus 9101, 6500 HB, Nijmegen, the Netherlands (peter.pickkers@radboudumc.nl).

Accepted for Publication: August 20, 2020.

Published Online: September 3, 2020. doi:10.1001/jama.2020.17052

Author Contributions: Dr Kox had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kox, Pickkers.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kox, Waalders, Pickkers.

Critical revision of the manuscript for important intellectual content: Kooistra, Gerretsen, Pickkers.

Statistical analysis: Kox, Waalders.

Administrative, technical, or material support: Waalders, Kooistra, Pickkers.

Supervision: Pickkers.

Conflict of Interest Disclosures: None reported.

References
1.
Tisoncik  JR , Korth  MJ , Simmons  CP , Farrar  J , Martin  TR , Katze  MG .  Into the eye of the cytokine storm.   Microbiol Mol Biol Rev. 2012;76(1):16-32. doi:10.1128/MMBR.05015-11PubMedGoogle ScholarCrossref
2.
Sinha  P , Matthay  MA , Calfee  CS .  Is a “cytokine storm” relevant to COVID-19?   JAMA Intern Med. Published online June 30, 2020. doi:10.1001/jamainternmed.2020.3313PubMedGoogle Scholar
3.
Khan  SS , Smith  MS , Reda  D , Suffredini  AF , McCoy  JP  Jr .  Multiplex bead array assays for detection of soluble cytokines: comparisons of sensitivity and quantitative values among kits from multiple manufacturers.   Cytometry B Clin Cytom. 2004;61(1):35-39. doi:10.1002/cyto.b.20021PubMedGoogle ScholarCrossref
4.
Habes  QLM , van Ede  L , Gerretsen  J , Kox  M , Pickkers  P .  Norepinephrine contributes to enterocyte damage in septic shock patients: a prospective cohort study.   Shock. 2018;49(2):137-143. doi:10.1097/SHK.0000000000000955PubMedGoogle ScholarCrossref
5.
Timmermans  K , Kox  M , Vaneker  M ,  et al.  Plasma levels of danger-associated molecular patterns are associated with immune suppression in trauma patients.   Intensive Care Med. 2016;42(4):551-561. doi:10.1007/s00134-015-4205-3PubMedGoogle ScholarCrossref
6.
Timmermans  K , Kox  M , Gerretsen  J ,  et al.  The involvement of danger-associated molecular patterns in the development of immunoparalysis in cardiac arrest patients.   Crit Care Med. 2015;43(11):2332-2338. doi:10.1097/CCM.0000000000001204PubMedGoogle ScholarCrossref
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