ABSTRACT
Background: Hyperglycemia worsens the prognosis and severity in Covid-19 patients. Objective: To assess the impact of glycemic control on COVID-19 severity. Methods and Findings: Data from 460 individuals collected in Spain between April and July 2020 was analyzed in a cross-sectional study: healthy, Sars-Cov-2 negative (group 0, N = 197), Sars-Cov-2 positive, with mild COVID-19 symptoms (group 1, N = 113), Sars-Cov-2 positive, with severe COVID-19 symptoms who required hospitalization (group 2, N = 150) at Hospital Universitario Cruces in Bilbao, Spain. Fasting blood glucose, HbA1c and serum 1,5-anhydroglucitol (1,5-AG, indicator of hyperglycemic excursions over the prior 1-2 weeks) were measured. Differences in 1,5-AG (normal range >10µg/mL) were observed between all three groups (mean 1,5-AG of 21.19, 18.99, 14.64 µg/mL, respectively) when compared by an unpaired t-test. 1,5-AG levels across groups decreased with increasing severity, with the hospitalized patients (group 2) showing the greatest difference when compared to healthy individuals, p value < 0.0001. Logistic regression analysis showed that 1,5-AG had a mild positive association with increased COVID-19 severity (group 0 vs. group 2: AUC = 0.69, p value < 0.0001). A previous T2D diagnosis did not show association with COVID-19 severity (group 0 vs. group 2: AUC = 0.58, p value < 0.0001). Analysis of patients with a previous diagnosis of T2D showed a robust positive association between 1,5-AG and COVID-19 (group 0 vs. group 2, AUC = 0.79, p value 0.008). There was no association between HbA1c or fasting glucose with severity. Combination of 1,5-AG and HbA1c was similar than 1,5-AG alone (AUC = 0.80, p value 0.028). Conclusions: Glycemic fluctuations in T2D patients may contribute to severe COVID-19. Measurement of serum 1,5-AG in T2D patients might help clinicians quickly identify diabetes patients at risk of severe COVID-19. These patients may benefit from more intensive management, treatment and vaccine prioritization.
ABSTRACT
COVID-19 is a systemic infection that exerts significant impact on the metabolism. Yet, there is little information on how SARS-CoV-2 affects metabolism. Using NMR spectroscopy, we measured the metabolomic and lipidomic serum profile from 263 (training cohort) + 135 (validation cohort) symptomatic patients hospitalized after positive PCR testing for SARS-CoV-2 infection. We also established the profiles of 280 persons collected before the coronavirus pandemic started. Principal-component analysis discriminated both cohorts, highlighting the impact that the infection has on overall metabolism. The lipidomic analysis unraveled a pathogenic redistribution of the lipoprotein particle size and composition to increase the atherosclerotic risk. In turn, metabolomic analysis reveals abnormally high levels of ketone bodies (acetoacetic acid, 3-hydroxybutyric acid, and acetone) and 2-hydroxybutyric acid, a readout of hepatic glutathione synthesis and marker of oxidative stress. Our results are consistent with a model in which SARS-CoV-2 infection induces liver damage associated with dyslipidemia and oxidative stress.