Inflammation and Mortality in COVID-19 Hospitalized Patients With and Without Type 2 Diabetes

J Clin Endocrinol Metab. 2022 Apr 19;107(5):e1961-e1968. doi: 10.1210/clinem/dgac003.

Abstract

Context: COVID-19 mortality is increased in patients with diabetes. A common hypothesis is that the relationship of inflammation with COVID-19 mortality differs by diabetes status.

Objective: The aim of this study was to determine the relationship of inflammation with mortality in COVID-19 hospitalized patients and to assess if the relationship differs by strata of type 2 diabetes status.

Methods: A case-control (died-survived) study of 538 COVID-19 hospitalized patients, stratified by diabetes status, was conducted at Columbia University Irving Medical Center. We quantified the levels of 8 cytokines and chemokines in serum, including interferon (IFN)-α2, IFN-γ, interleukin (IL)-1α, IL-1β, IL-6, IL-8/CXCL8, IFNγ-induced protein 10 (IP10)/CXCL10 and tumor necrosis factor α (TNF-α) using immunoassays. Logistic regression models were used to model the relationships of log-transformed inflammatory markers (or their principal components) and mortality.

Results: In multiple logistic regression models, higher serum levels of IL-6 (adjusted odds ratio [aOR]:1.74, 95% CI [1.48, 2.06]), IL-8 (aOR: 1.75 [1.41, 2.19]) and IP10 (aOR: 1.36 [1.24, 1.51]), were significantly associated with mortality. This association was also seen in second principal component with loadings reflecting similarities among these 3 markers (aOR: 1.88 [1.54-2.31]). Significant positive association of these same inflammatory markers with mortality was also observed within each strata of diabetes.

Conclusion: We show that mortality in COVID-19 patients is associated with elevated serum levels of innate inflammatory cytokine IL-6 and inflammatory chemokines IL-8 and IP10. This relationship is consistent across strata of diabetes, suggesting interventions targeting these innate immune pathways could potentially also benefit patients with diabetes.

Keywords: CXCL10; IL-6 inhibitor; SARS-CoV-2; chemokines; cytokine storm; death; innate immunity; type 2 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • COVID-19*
  • Chemokine CXCL10
  • Cytokines
  • Diabetes Mellitus, Type 2* / complications
  • Humans
  • Inflammation
  • Interleukin-6
  • Interleukin-8
  • SARS-CoV-2

Substances

  • Biomarkers
  • Chemokine CXCL10
  • Cytokines
  • Interleukin-6
  • Interleukin-8