Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts.