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

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)-alpha 2, IFN-gamma, interleukin (IL)-1 alpha, IL-1 beta, IL-6, IL-8/CXCL8, IFN gamma-induced protein 10 (IP10)/CXCL10 and tumor necrosis factor alpha (TNF-alpha) 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.

Automated summary

In this study, elevated serum levels of IL-6, IL-8, and IP10 were significantly associated with mortality in COVID-19 hospitalized patients, with this association observed within each strata of diabetes as well. The findings suggest that interventions targeting these innate immune pathways could potentially benefit patients with diabetes.