Plasma Metabolomic Profiles and Clinical Features in Recovered COVID-19 Patients Without Previous Underlying Diseases 3 Months After Discharge

Knowing the residual and future effect of SARS-CoV-2 on recovered COVID-19 patients is critical for optimized long-term patient management. Recent studies focus on the symptoms and clinical indices of recovered patients, but the pathophysiological change is still unclear. To address this question, we examined the metabolomic profiles of recovered asymptomatic (RA), moderate (RM) and severe and critical (RC) patients without previous underlying diseases discharged from the hospital for 3 months, along with laboratory and CT findings. We found that the serum metabolic profiles in recovered COVID-19 patients still conspicuously differed from that in healthy control (HC), especially in the RM, and RC patients. Additionally, these changes bore close relationship with the function of pulmonary, renal, hepatic, microbial and energetic metabolism and inflammation. These findings suggested that RM and RC patients sustained multi-organ and multi-system damage and these patients should be followed up on regular basis for possible organ and system damage.

[1]  Xuedong Zhou,et al.  The microbial coinfection in COVID-19 , 2020, Applied Microbiology and Biotechnology.

[2]  Eike Nagel,et al.  Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19) , 2020, JAMA cardiology.

[3]  Zigui Chen,et al.  Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19 , 2020, Gut.

[4]  Yu Fang,et al.  Pulmonary fibrosis in critical ill patients recovered from COVID-19 pneumonia: Preliminary experience , 2020, The American Journal of Emergency Medicine.

[5]  Dong Men,et al.  SARS-CoV-2 proteome microarray for global profiling of COVID-19 specific IgG and IgM responses , 2020, Nature Communications.

[6]  Feng Wu,et al.  Fasting blood glucose at admission is an independent predictor for 28-day mortality in patients with COVID-19 without previous diagnosis of diabetes: a multi-centre retrospective study , 2020, Diabetologia.

[7]  J. Ayres,et al.  A metabolic handbook for the COVID-19 pandemic , 2020, Nature metabolism.

[8]  N. Xiong,et al.  Olfactory Dysfunction in Recovered Coronavirus Disease 2019 (COVID‐19) Patients , 2020, Movement Disorders.

[9]  Gek Huey Chua,et al.  Omics-Driven Systems Interrogation of Metabolic Dysregulation in COVID-19 Pathogenesis , 2020, Cell Metabolism.

[10]  X. Tang,et al.  Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections , 2020, Nature Medicine.

[11]  É. Azoulay,et al.  Acute kidney injury in critically ill patients with COVID-19 , 2020, Intensive Care Medicine.

[12]  Hesong Zeng,et al.  Cardiac Involvement in Patients Recovered From COVID-2019 Identified Using Magnetic Resonance Imaging , 2020, JACC: Cardiovascular Imaging.

[13]  C. Camargo,et al.  Respiratory viruses are associated with serum metabolome among infants hospitalized for bronchiolitis: A multicenter study , 2020, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[14]  M. Netea,et al.  Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection , 2020, Cell.

[15]  Fang Lei,et al.  Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes , 2020, Cell Metabolism.

[16]  Fu-Sheng Wang,et al.  Characteristics and prognostic factors of disease severity in patients with COVID-19: The Beijing experience , 2020, Journal of Autoimmunity.

[17]  Chang Hu,et al.  Clinical features and short-term outcomes of 221 patients with COVID-19 in Wuhan, China , 2020, Journal of Clinical Virology.

[18]  Huanhuan Gao,et al.  Proteomic and Metabolomic Characterization of COVID-19 Patient Sera , 2020, Cell.

[19]  Hong Wang,et al.  Plasma metabolomic and lipidomic alterations associated with COVID-19 , 2020, medRxiv.

[20]  P. Naquet,et al.  Regulation of coenzyme A levels by degradation: the 'Ins and Outs'. , 2020, Progress in lipid research.

[21]  Wei Wang,et al.  Comorbidity and its impact on 1590 patients with COVID-19 in China: a nationwide analysis , 2020, European Respiratory Journal.

[22]  Heshui Shi,et al.  Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study , 2020, The Lancet Infectious Diseases.

[23]  Zunyou Wu,et al.  Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. , 2020, JAMA.

[24]  X. Shu,et al.  Associations of choline-related nutrients with cardiometabolic and all-cause mortality: results from 3 prospective cohort studies of blacks, whites, and Chinese. , 2020, The American journal of clinical nutrition.

[25]  R. Du,et al.  Metabolic characteristics of large and small extracellular vesicles from pleural effusion reveal biomarker candidates for the diagnosis of tuberculosis and malignancy , 2020, Journal of extracellular vesicles.

[26]  Yongmei Cao,et al.  Metabolomics Analysis of the Renal Cortex in Rats With Acute Kidney Injury Induced by Sepsis , 2019, Frontiers in Molecular Biosciences.

[27]  M. Cheng,et al.  Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice , 2019, Respiratory Research.

[28]  P. Meikle,et al.  Complement C5a Induces Renal Injury in Diabetic Kidney Disease by Disrupting Mitochondrial Metabolic Agility , 2019, Diabetes.

[29]  D. Choi,et al.  Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms , 2019, Redox biology.

[30]  P. Elliott,et al.  Serum metabolic signatures of coronary and carotid atherosclerosis and subsequent cardiovascular disease , 2019, European heart journal.

[31]  B. Wieringa,et al.  The Role of Lipids in Parkinson’s Disease , 2019, Cells.

[32]  M. Tan,et al.  Diverse Roles of Mitochondria in Immune Responses: Novel Insights Into Immuno-Metabolism , 2018, Front. Immunol..

[33]  Harry Sokol,et al.  Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. , 2018, Cell host & microbe.

[34]  M. Wingfield,et al.  IMA Genome-F 9 , 2018, IMA fungus.

[35]  Yulong Yin,et al.  Impact of the Gut Microbiota on Intestinal Immunity Mediated by Tryptophan Metabolism , 2018, Front. Cell. Infect. Microbiol..

[36]  Xin Lu,et al.  A Large‐scale, multicenter serum metabolite biomarker identification study for the early detection of hepatocellular carcinoma , 2018, Hepatology.

[37]  S. Tannenbaum,et al.  Serum metabolome changes in adult patients with severe dengue in the critical and recovery phases of dengue infection , 2018, PLoS neglected tropical diseases.

[38]  Kristin E. Burnum-Johnson,et al.  Multi-platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis. , 2017, Cell host & microbe.

[39]  B. Kestenbaum,et al.  Metabolomics and Gene Expression Analysis Reveal Down-regulation of the Citric Acid (TCA) Cycle in Non-diabetic CKD Patients , 2017, EBioMedicine.

[40]  Y. Li,et al.  Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection , 2017, Scientific Reports.

[41]  H. Vogel,et al.  Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia , 2017, Critical Care.

[42]  I. Rosenberg,et al.  Choline and its metabolites are differently associated with cardiometabolic risk factors, history of cardiovascular disease, and MRI-documented cerebrovascular disease in older adults. , 2017, The American journal of clinical nutrition.

[43]  Hanns-Ulrich Marschall,et al.  Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism. , 2016, Cell metabolism.

[44]  J. Chen,et al.  Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study , 2016, Hypertension.

[45]  P. Hylemon,et al.  Consequences of bile salt biotransformations by intestinal bacteria , 2016, Gut microbes.

[46]  H. Ho,et al.  Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. , 2015, Journal of the American College of Cardiology.

[47]  N. Berliner,et al.  How we evaluate and treat neutropenia in adults. , 2014, Blood.

[48]  Andrew Rowland,et al.  The UDP-glucuronosyltransferases: their role in drug metabolism and detoxification. , 2013, The international journal of biochemistry & cell biology.

[49]  A. Peters,et al.  Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach , 2013, Diabetes.

[50]  P. Neumann,et al.  Lipoteichoic Acid from Staphylococcus aureus Induces Lung Endothelial Cell Barrier Dysfunction: Role of Reactive Oxygen and Nitrogen Species , 2012, PloS one.

[51]  Karen Blyth,et al.  Serine starvation induces stress and p53 dependent metabolic remodeling in cancer cells , 2012, Nature.

[52]  Raymond Vanholder,et al.  Normal and pathologic concentrations of uremic toxins. , 2012, Journal of the American Society of Nephrology : JASN.

[53]  Joshua D. Knowles,et al.  Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry , 2011, Nature Protocols.

[54]  Y. Toda,et al.  Prevention of neointima formation by taurine ingestion after carotid balloon injury. , 2010, Vascular pharmacology.

[55]  C. Cuttitta,et al.  Taurine regulates insulin release from pancreatic beta cell lines , 2010, Journal of Biomedical Science.

[56]  P. Wookey,et al.  High Dietary Taurine Reduces Apoptosis and Atherosclerosis in the Left Main Coronary Artery: Association With Reduced CCAAT/Enhancer Binding Protein Homologous Protein and Total Plasma Homocysteine but not Lipidemia , 2009, Hypertension.

[57]  Johan Auwerx,et al.  Targeting bile-acid signalling for metabolic diseases , 2008, Nature Reviews Drug Discovery.

[58]  M. Ikawa,et al.  Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. , 2008, Journal of molecular and cellular cardiology.

[59]  N. Müller,et al.  Fleischner Society: glossary of terms for thoracic imaging. , 2008, Radiology.

[60]  A. Smilde,et al.  Fusion of mass spectrometry-based metabolomics data. , 2005, Analytical chemistry.

[61]  F. Lu,et al.  Roles of oxygen radicals and elastase in citric acid‐induced airway constriction of guinea‐pigs , 1999, British journal of pharmacology.

[62]  E. Alexander,et al.  Choline, an essential nutrient for humans , 1991, Nutrition.

[63]  J. Blusztajn,et al.  Choline and human nutrition. , 1994, Annual review of nutrition.