LAUSR

AIMS Endotoxemia commonly occurs in severe and fatal COVID-19 suggesting that concomitant bacterial stimuli may amplify the innate immune response induced by SARS-CoV-2. We previously demonstrated that endogenous GLP-1 system in conjunction with increased procalcitonin (PCT) is hyper-activated in patients with severe Gram-negative sepsis and modulated by T2D. We aimed to determine the association of COVID- 19 severity with endogenous GLP-1 activation upregulated by increased specific pro-inflammatory innate immune response in patients with and without T2D. MATERIALS AND METHODS Plasma levels of total GLP-1, IL-6 and PCT were estimated on admission and during hospitalization in 61 patients (17 with T2D) with non-severe and severe COVID-19. RESULTS COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless the disease severity. Increased admission GLP-1 levels (p=0.03) accompanied by two-fold increased PCT were found in severe as compared with non-severe patients. Moreover, GLP-1 and PCT levels were significantly increased in non-survived as compared with survived patients at admission (p=0.01 and p=0.001, respectively) and at 5-6 days of hospitalization (p=0.05). Both nondiabetic and T2D patients demonstrated positive correlation between GLP-1 and PCT response (r=0.33, p=0.03 and r=0.54, p=0.03, respectively), but intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. CONCLUSIONS The persistent joint increase of endogenous GLP-1 and PCT in severe and fatal COVID-19 suggests a role of concomitant bacterial infection in disease exacerbation. Early elevation of endogenous GLP-1 may serve as new biomarker of COVID-19 severity and fatal outcome. This article is protected by copyright. All rights reserved.