Severe and fatal COVID-19 is characterised by increased circulating glucagon like peptide 1 and procalcitonin modulated by type 2 diabetes.

Abstract

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 the endogenous glucagon like peptide 1 (GLP-1) system in conjunction with increased procalcitonin (PCT) is hyperactivated in patients with severe Gram-negative sepsis and modulated by type 2 diabetes (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 withoutT2D. Plasma levels of total GLP-1, IL-6, and PCT were estimated on admission and during hospitalisation in 61 patients (17 with T2D) with non-severe and severe COVID-19. COVID-19 patients demonstrated ten-fold increase of IL-6 levels regardless of 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 to 6days of hospitalisation (p=0.05). Both non-diabetic and T2D patients demonstrated a positive correlation between GLP-1 and PCT response (r=0.33, p=0.03, and r=0.54, p=0.03, respectively), but the intensity of this joint pro-inflammatory/GLP-1 response was modulated by T2D. In addition, hypoxaemia down-regulated GLP-1 response only in T2D patients with bilateral lung damage. 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 a new biomarker of COVID-19 severity and fatal outcome.