Characterization of cytokine expression in critically ill patients with COVID-19

ABSTRACT

INTRODUCTION: Early commentary on SARS-CoV-2 infection proposed a mechanism of cytokine release syndrome (CRS) to explain severe acute respiratory failure associated with COVID-19. Management strategies have included targeted immunomodulation with biologic agents. The role of IL-6 and other cytokines in the pathogenesis of COVID-19 is not well defined. Evidence for use of immunomodulators has been mixed and these agents may expose patients to harm. This study aims to characterize the expression of cytokines and their association with inflammatory biomarkers and outcomes in critically ill patients with COVID-19. METHODS: This was a single-center, retrospective analysis of critically ill patients with COVID-19 confirmed by PCR. Patients were included if they had a partial or full cytokine panel drawn while admitted. Descriptive statistics were used to assess demographics, outcomes, and relationships between cytokine levels and inflammatory markers. The Mann- Whitney U Test was used to compare IL-6 levels between survivors and nonsurvivors. RESULTS: Eighty-nine patients were included with 68 full cytokine panels and 108 IL-6 levels. Patients had a mean (range) of 10 ventilator-days (0-47), 15 ICU-days (1-60), 20 hospital-days (3-69) and a mortality rate of 31%. Cytokine levels were assessed a median of 10 days from symptom onset and 1 day from ICU admission. Levels of IL-1B, IL-2, IL-4, IL-5, IL-8, IL-12, IL-13, IL-17, IFN-G, and TNF-A were undetectable in at least 80% of patients, and expression did not correlate with other inflammatory biomarkers (CRP, ferritin), severity of illness (SOFA), or outcome. IL-2R levels were numerically elevated in most patients (n=68;median 1227, range 76-30670). IL-6 levels were mildly elevated (n=108;median 31, range 2-882, SD 150), and levels were statistically significantly higher in nonsurvivors (p = 0.002). CONCLUSIONS: Assessment of cytokine levels in critically ill patients with COVID-19 does not support a hypothesis of CRS. While IL-6 levels were numerically higher in nonsurvivors, the clinical significance of this finding is unknown. The role of IL-2R in the pathogenesis of COVID-19 remains unclear. Larger studies exploring the role of inflammatory mediators in pathogenesis and targeted immunomudulators in management of COVID-19 are warranted.