Abstract
Introduction: Increased COVID-19 disease severity is higher among patients with type 2 diabetes mellitus and hypertension. However, the metabolic pathways underlying this association are not fully characterized. This study aims to identify the metabolic signature associated with increased COVID-19 severity in patients with diabetes mellitus and hypertension.Methods: One hundred and fifteen COVID-19 patients were divided based on disease severity, diabetes status, and hypertension status. Targeted metabolomics of serum samples from all patients was performed using tandem mass spectrometry followed by multivariate and univariate models.Results: Reduced levels of various triacylglycerols were observed with increased disease severity in the diabetic patients, including those containing palmitic (C16:0), docosapentaenoic (C22:5, DPA), and docosahexaenoic (C22:6, DHA) acids (FDR < 0.01). Functional enrichment analysis revealed triacylglycerols as the pathway exhibiting the most significant changes in severe COVID-19 in diabetic patients (FDR = 7.1 × 10−27). Similarly, reduced levels of various triacylglycerols were also observed in hypertensive patients corresponding with increased disease severity, including those containing palmitic, oleic (C18:1), and docosahexaenoic acids. Functional enrichment analysis revealed long-chain polyunsaturated fatty acids (n-3 and n-6) as the pathway exhibiting the most significant changes with increased disease severity in hypertensive patients (FDR = 0.07).Conclusions: Reduced levels of triacylglycerols containing specific long-chain unsaturated, monounsaturated, and polyunsaturated fatty acids are associated with increased COVID-19 severity in diabetic and hypertensive patients, offering potential novel diagnostic and therapeutic targets.
Highlights
Increased COVID-19 disease severity is higher among patients with type 2 diabetes mellitus and hypertension
Identifying potential diagnostic biomarkers could further the understanding of the underlying molecular mechanisms responsible for increased risk of mortality in COVID-19 patients. This cohort study included 115 patients containing type 2 diabetic (n = 61, 53%) and non-diabetic (n = 54, 47%) patients diagnosed with COVID-19 at Hamad Medical Corporation (HMC) between July and December 2020
Protocols were approved by the Institutional Review Boards (IRBs) of HMC (MRC-01-20-145) and Qatar University (QU-IRB 1289-EA/20)
Summary
Increased COVID-19 disease severity is higher among patients with type 2 diabetes mellitus and hypertension. This study aims to identify the metabolic signature associated with increased COVID-19 severity in patients with diabetes mellitus and hypertension. Up to 20% of COVID19 patients develop interstitial pneumonia and respiratory failure that demands intensive care, especially among older individuals and those with chronic illnesses [3, 4]. Previous reports have shown that there is a high risk of lung infection in patients with type 2 diabetes mellitus (T2DM) [5]. Accumulating evidence suggests that COVID-19 is more prevalent among individuals suffering from T2DM and hypertension [6,7,8], with studies showing that treatment of these patients with angiotensinconverting enzyme 2 (ACE2)-increasing drugs could lead to a severe outcome [9]
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