Stratification of hypertensive COVID-19 patients by quantitative NMR spectroscopy of serum metabolites, lipoproteins and inflammation markers

Background: The exact pathophysiology of humans suffering from the multifaceted SARS-CoV-2 infection is not yet conclusively understood and risk stratification is needed. Novel diagnostic approaches like the nuclear magnetic resonance spectroscopy (NMR) based quantification of metabolites, lipoproteins, and inflammation markers has helped to identify typical alterations in the blood serum of COVID-19 patients. However, important confounders such as age, sex, and comorbidities, which strongly influence the metabolome, were often not considered. Therefore, the aim of this NMR study was to consider gender, as well as arterial hypertension (AHT) which affects more than 1.2 billion people worldwide, when investigating COVID-19-positive serum samples in a large age-matched cohort. As AHT is a risk factor for severe COVID-19 disease, this study focuses on comparing metabolomic characteristics of COVID-19 patients with and without AHT. Methods and Findings: NMR serum data from 329 COVID-19 patients were compared with 305 individuals from a healthy age and sex-matched control cohort. 134 of the 329 COVID-19 patients were affected by AHT. These were analyzed together with NMR data from 58 hypertensives without COVID-19. In addition to metabolite, lipoprotein, and glycoprotein data from NMR, common laboratory parameters were considered. Statistical comparison of the COVID-19 cohort with the control cohort reproduced results of previous studies. However, several differences emerged when AHT was considered. Especially, the previously described triglyceride-rich lipoprotein profile was no longer observed in COVID-19 patients, nor was an increase in ketone bodies. Typical metabolic changes that were apparent in COVID-19 patients in both sexes and with AHT were an increase in C- reactive protein (CRP) and the ratio of total glycoprotein (Glyc) to supramolecular phospholipids composite (SPC) which is an inflammatory NMR parameter. Further alterations were a decrease in glutamine, leucine, isoleucine, and lysine, citric acid, HDL-4 particles, and total cholesterol. Typical metabolic cardiovascular risk markers could be detected in hypertensive COVID-19 patients, as well as higher inflammatory NMR parameters than in normotensive COVID-19 patients. Conclusion: We could show that a more precise picture of COVID-19 blood serum parameters emerge when AHT is considered which accordingly should be included in future studies and would help for a refined patient stratification.