The Journal of Clinical Endocrinology and Metabolism Journal Article

Inflammation and COVID-19 Mortality in Type 2 Diabetes

May 03, 2022

Jia Guo, Wen-Hsuan W Lin, Jason E Zucker, Renu Nandakumar, Anne-Catrin Uhlemann, Shuang Wang, Rupak Shivakoti
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 5, May 2022, Pages e1961–e1968
https://doi.org/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.