Diboun, I.I.DibounCyprian, F.S.F.S.CyprianAnwardeen, N.R.N.R.AnwardeenYassine, H.M.H.M.YassineElrayess, M.A.M.A.ElrayessRahmoon, S.M.S.M.RahmoonSayed, S.K.S.K.SayedSchuchardt, SvenSvenSchuchardtKhatib, M.M.KhatibBansal, D.D.BansalFarag, E.A.B.A.E.A.B.A.FaragEmara, M.M.M.M.EmaraAbdallah, A.M.A.M.Abdallah2022-12-192022-12-192022https://publica.fraunhofer.de/handle/publica/43017510.3389/fcimb.2022.9296892-s2.0-8513544514035937683Severe 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.enbiomarkersCOVID-19 disease severitymetabolomicspost-tuberculosis long-term consequencestuberculosisjournal article