Even though COVID-19 is a respiratory disease caused by the SARS-Cov-2, it can also affect other organs, leading to neurologic, renal, hepatic, and vascular damage. In the most severe cases, it frequently results in multi-organ damage. Early studies have shown dysregulation of coagulative and proinflammatory pathways, with COVID-19 patients displaying distinct metabolic profiles compared with healthy controls; this includes markers associated with atherosclerotic and hepatic damage.
However, there has been limited research in this area and because previous studies compared COVID-19 patients to healthy controls, it is not clear if these metabolic profiles are specific to COVID-19 or a consequence of critical illness more generally. Specific markers for COVID-19 disease severity could allow COVID-19 patients to be stratified based on metabolic profiling and the early identification of those most at risk from severe disease.
To explore this, researchers from the University of Lübeck in Germany analyzed multiple serum samples taken from five severely ill COVID-19 patients and 11 patients with cardiogenic shock, which were also being treated within the same intensive care unit, who tested negative for SARS-CoV-2. For this study, 58 healthy controls were also included. NMR metabolomics and lipidomics were performed using a Bruker Avance III HD 600 spectrometer equipped with a TXI probe.
In the untargeted NMR metabolomics and lipidomics analyses, the metabolic profiles of COVID-19 patients differed significantly not just from healthy controls but also cardiogenic shock patients. Targeted analyses enabled the quantification of metabolites and lipoproteins from the NMR spectra, revealing those providing the greatest discrimination between the COVID-19 patients and healthy and cardiogenic shock patients. These analyses allowed an almost complete separation of COVID-19 patients from cardiogenic shock patients and healthy controls.
Pairwise analysis of metabolites and lipoproteins provided greater detail into the metabolic effects of COVID-19, revealing changes consistent with disturbed energy status, hepatic damage, and dyslipidemia.
Several key metabolic characteristics were distinct for COVID-19 patients compared with both healthy controls and cardiogenic shock patients, i.e., low glutamine/glutamate ratio due to increased glutamine consumption in a catabolic disease state. This is a common feature of severe infectious diseases. COVID-19 patients also exhibited raised phenylalanine levels, which indicates hepatic dysfunction. Although the lipoprotein profile of COVID-19 patients was severely disturbed indicating an elevated cardiovascular risk, it was distinct from that of cardiogenic shock patients.
COVID-19 patients also had markers for disturbed energy metabolism, such as elevated glucose and lactic acid. However, these variations were similar in cardiogenic shock patients, suggesting that they are not specific for COVID-19.
Moreover, the study investigated the metabolic profiles of asymptomatic individuals or those who had mild disease. In this evaluation, 34 serum samples from 18 individuals with anti-coronavirus antibodies were analyzed and compared with age- and sex-matched controls without anti-coronavirus antibodies. Neither group tested positive for acute coronavirus infection.
The metabolite and lipoprotein profiles were similar among the two groups, indicating no consistent changes to the overall serum profile. However, correlations were found between antibody titers and some markers for metabolic health in patients with mild COVID-19. This included lipoprotein profile characteristics, such as cholesterol, phospholipids, and glycine, which is considered a marker for metabolic health.
According to the researchers, these findings suggest that metabolic profiles of COVID-19 patients are highly disrupted. Interestingly, after mild infection with SARS-Cov-2, antibody titers were correlated with markers of metabolic health.
Overall, this study indicates that NMR metabolomics can be applied to early identification and potentially stratification of COVID-19 patients. Moreover, it can further be used to predict the disease severity.
*Bruker NMR Instruments are for Research Use Only. Not for use in clinical diagnostic procedures.
- Schmelter F, Foeh B, Mallagaray A et al. (2021) Metabolic markers distinguish COVID-19 from other intensive care patients and show potential to stratify for disease risk. medRxiv preprint. doi: https://doi.org/10.1101/2021.01.13.21249645.
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