Metabolomics in the Diagnosis and Prognosis of COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) pandemic triggered an unprecedented global effort in developing rapid and inexpensive diagnostic and prognostic tools. Since the genome of SARS-CoV-2 was uncovered, detection of viral RNA by RT-qPCR has played the most significant role in preventing the spread of the virus through early detection and tracing of suspected COVID-19 cases and through screening of at-risk population. However, a large number of alternative test methods based on SARS-CoV-2 RNA or proteins or host factors associated with SARS-CoV-2 infection have been developed and evaluated. The application of metabolomics in infectious disease diagnostics is an evolving area of science that was boosted by the urgency of COVID-19 pandemic. Metabolomics approaches that rely on the analysis of volatile organic compounds exhaled by COVID-19 patients hold promise for applications in a large-scale screening of population in point-of-care (POC) setting. On the other hand, successful application of mass-spectrometry to detect specific spectral signatures associated with COVID-19 in nasopharyngeal swab specimens may significantly save the cost and turnaround time of COVID-19 testing in the diagnostic microbiology and virology laboratories. Active research is also ongoing on the discovery of potential metabolomics-based prognostic markers for the disease that can be applied to serum or plasma specimens. Several metabolic pathways related to amino acid, lipid and energy metabolism were found to be affected by severe disease with COVID-19. In particular, tryptophan metabolism via the kynurenine pathway were persistently dysregulated in several independent studies, suggesting the roles of several metabolites of this pathway such as tryptophan, kynurenine and 3-hydroxykynurenine as potential prognostic markers of the disease. However, standardization of the test methods and large-scale clinical validation are necessary before these tests can be applied in a clinical setting. With rapidly expanding data on the metabolic profiles of COVID-19 patients with varying degrees of severity, it is likely that metabolomics will play an important role in near future in predicting the outcome of the disease with a greater degree of certainty.

Does acute and persistent metabolic dysregulation in COVID-19 point to novel biomarkers and future therapeutic strategies?

“…The authors found consistent disruptions in glucose metabolism and dysregulation in the TCA and urea cycles which were identified as potential targets for therapeutic intervention ( figure 1a ). These metabolomics changes are consistent with metabolomics studies in other contexts and point to an underlying bioenergetic crisis as a key pathogenic feature of COVID-19 [ 5 ].…”

“…More recent studies have begun to associate metabolomics changes with symptoms representing specific organ system failures – for example, the acute delirium and post-recovery mental health issues of the nervous system and disruptions of the digestive system [ 6 , 7 ]. Dysregulation of the kynurenine pathway has been among the most consistent findings as reported in numerous, independent studies [ 5 ]. Of potential significance is that many of the metabolomics abnormalities in COVID-19 are similar to those found in sepsis and acute respiratory failure, suggesting a common mechanism leading to an acute bioenergetic crisis [ 8 , 9 ].…”

“…Despite the lack of therapeutic successes, we have gained unprecedented insight into the progression of the disease [ 4 ]. Among the vast amount of clinical and biological data published over the course of the pandemic, some of the most consistent and exciting results have come from metabolomics profiling of patient serum samples [ 5 ]. Metabolomics, a rapidly developing field of research in which metabolites present in tissue or fluids are comprehensively analysed, has deepened our understanding of the pathobiology of multiple disorders, identified predictive biomarkers, and highlighted potential novel therapeutic strategies.…”

Towards risk stratification and prediction of disease severity and mortality in COVID-19: Next generation metabolomics for the measurement of host response to COVID-19 infection

“…The results indicate that Covid 19 severity is associated with a decline in tryptophan (Trp) reflecting immune dysregulation. Early evidence that tryptophan metabolism regulated immunity (D) has more recently led to the observation that kynurenine/tryptophan ratios correlate with carbohydrate metabolism and cardio-metabolic risk [ 23 ] both associated with COVID-19 severity [ 24 ].…”

Increased Kynurenine Indicates a Fatal Course of COVID-19

“…Metabolomics in COVID-19 patients proofed the existence of a characteristic immune-metabolic signature [ 34 , 35 , 36 ] with marked alterations in nitrogen metabolism, amino acid homeostasis, catabolism, transamination, and carbon metabolism affecting glucose and free fatty acids levels [ 34 ]. The metabolites in these affected pathways correlated with the increased IL-6 and CRP concentrations [ 34 ].…”