Abstract
COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.
Highlights
As a new pandemic disease, coronavirus disease 2019 (COVID19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhu et al, 2020)
Five ornithine cycle-related metabolites highly correlated with “cytokine storms” and coagulation index. These results suggest that ornithine cycle dysregulation may be a potential pathogenetic factor of COVID-19, and may serve as an important target for regulating metabolic disorders in COVID19 patients
An untargeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) was used to observe the dynamic metabolic profile of COVID-19 patients and identify the metabolic characteristics associated with severe disease
Summary
As a new pandemic disease, coronavirus disease 2019 (COVID19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhu et al, 2020). SARS-CoV-2 mainly infects the lower respiratory tract and lungs; many other organs, including liver, kidney, muscle, and lymph nodes, as well as gastrointestinal organs and central nervous system organs, have been found or proposed to be attacked by this virus. The disease is associated with multiple symptoms, including fever, persistent dry cough, shortness of breath, chills, muscle pain, headache, loss of taste or smell, and gastrointestinal symptoms (Laing et al, 2020; Wu and McGoogan, 2020). About 19% of confirmed patients develop severe pneumonia or multiple organ failure with high mortality (Wu and McGoogan, 2020)
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