Abstract
Background
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 differed by strata of type 2 diabetes status. We hypothesized that the association of inflammation with mortality was different by 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 eight 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% confidence intervals (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 (PC) with loadings reflecting similarities among these three 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.
Conclusions
We show that mortality in COVID19 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.