Plasma Metabolomic Profiling of Patients Recovered From Coronavirus Disease 2019 (COVID-19) With Pulmonary Sequelae 3 Months After Discharge

Abstract

Background Elucidation of the molecular mechanisms involved in the pathogenesis of coronavirus disease (COVID-19) may help to discover therapeutic targets. Methods To determine the metabolomic profile of circulating plasma from COVID-19 survivors with pulmonary sequelae 3 months after discharge, a random, outcome-stratified case-control sample was analyzed. We enrolled 103 recovered COVID-19 patients as well as 27 healthy donors, and performed pulmonary function tests, computerized tomography (CT) scans, laboratory examinations, and liquid chromatography-mass spectrometry. Results Plasma metabolite profiles of COVID-19 survivors with abnormal pulmonary function were evidently different from those of healthy donors or subjects with normal pulmonary function. These alterations were associated with disease severity and mainly involved amino acid, and glycerophospholipid metabolic pathways. Furthermore, increased levels of triacylglycerols, phosphatidylcholines, prostaglandin E2, arginine, and decreased levels of betain and adenosine were associated with pulmonary CO diffusing capacity and total lung capacity. The global plasma metabolomic profile differed between subjects with abnormal and normal pulmonary function. Conclusions Further metabolite-based analysis may help to identify the mechanisms underlying pulmonary dysfunction in COVID-19 survivors, and provide potential therapeutic targets in the future.

Plasma Metabolomic Profiles in Recovered COVID-19 Patients without Previous Underlying Diseases 3 Months After Discharge

“… 54 Moreover, taurine depletion can lead to pancreatic β-cell malfunction, which may reduce plasma insulin levels. 55 In our study, taurine was reduced in the recovered COVID-19 patients, which has also been validated in our another cohort study (another five representative metabolites [arginine, indoleacetic acid, uric acid, pyroglutamic acid and PE 40:8] also have been validated) 20 ( Supplementary Figure 2 ). The relationship between taurine and α-HBDH was reversed from a positive correlation in the HCs to a negative one in the RMs ( Figure 6D ), indicating that the cardiovascular function might be affected by the abnormally reduced taurine in recovered COVID-19 patients.…”

“… 18 , 19 In addition, we recently found that discharged patients with pulmonary sequelae also had disordered plasma metabolite profiles. 20 Therefore, understanding the metabolomic changes of discharged COVID-19 patients who lack a previous underlying disease after several months of recovery may help us find clues to the physiological and pathophysiological processes during recovery and better manage these patients.…”

Immunological profiling of COVID-19 patients with pulmonary sequelae

“…Emerging evidence suggests that COVID-19 survivors have impaired lung function, with the development of pulmonary fibrosis(2, 14). Tissue-resident CD8 + T cells drive age-associated chronic lung sequelae after viral pneumonia(45).…”

“…Our findings are in line with published papers(42)(43)(44).SARS-CoV-2 infection may induce a cytotoxic response, characterized by simultaneous production of GZMB and perforin in T cells, NK cells and γδ T cells inPPSs. Excessive activation of cytotoxic T, NK and γδ T cells is not protective but rather drives pulmonary damage after SARS-CoV-2 infection.Emerging evidence suggests that COVID-19 survivors have impaired lung function, with the development of pulmonary fibrosis(2,14). Tissue-resident CD8 + T cells drive age-associated chronic lung sequelae after viral pneumonia(45).Besides, clonally expanded tissue-resident memory-like Th17 cells may interact with pro-fibrotic macrophages and cytotoxic CD8+ T cells leading to the formation of pulmonary fibrosis(4).…”

Introductory Chapter: A Tool for Aided Advanced Diagnostics and Deep View into Biological Sample

“…A number of analytical methods for mass spectrometry in clinical laboratories were developed during the recent past, and the development gains additional momentum as the CoVID-19 pandemics holds the mankind in grip and methods for fast HPLC-MS have been developed and applied [6][7][8][9][10][11][12][13][14][15].…”