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

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Abstract

Background

It remains unclear whether discharged COVID-19 patients have fully recovered from severe complications, including the differences in the post-infection metabolomic profiles of patients with different disease severities.

Methods

COVID-19-recovered patients, who had no previous underlying diseases and were discharged from Wuhan Union Hospital for 3 months, and matched healthy controls (HCs) were recruited in this prospective cohort study. We examined the blood biochemical indicators, cytokines, lung computed tomography scans, including 39 HCs, 18 recovered asymptomatic (RAs), 34 recovered moderate (RMs), and 44 recovered severe/ critical patients (RCs). A liquid chromatography-mass spectrometry-based metabolomics approach was employed to profile the global metabolites of fasting plasma of these participants.

Results

Clinical data and metabolomic profiles suggested that RAs recovered well, but some clinical indicators and plasma metabolites in RMs and RCs were still abnormal as compared with HCs, such as decreased taurine, succinic acid, hippuric acid, some indoles, and lipid species. The disturbed metabolic pathway mainly involved the tricarboxylic cycle, purine, and glycerophospholipid metabolism. Moreover, metabolite alterations differ between RMs and RCs when compared with HCs. Correlation analysis revealed that many differential metabolites were closely associated with inflammation and the renal, pulmonary, heart, hepatic, and coagulation system functions.

Conclusion

We uncovered metabolite clusters pathologically relevant to the recovery state in discharged COVID-19 patients which may provide new insights into the pathogenesis of potential organ damage in recovered patients.

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Most cited references 59

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A new equation to estimate glomerular filtration rate.

Andrew Levey, Lesley Stevens, Christopher H Schmid … (2009)

Equations to estimate glomerular filtration rate (GFR) are routinely used to assess kidney function. Current equations have limited precision and systematically underestimate measured GFR at higher values. To develop a new estimating equation for GFR: the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Cross-sectional analysis with separate pooled data sets for equation development and validation and a representative sample of the U.S. population for prevalence estimates. Research studies and clinical populations ("studies") with measured GFR and NHANES (National Health and Nutrition Examination Survey), 1999 to 2006. 8254 participants in 10 studies (equation development data set) and 3896 participants in 16 studies (validation data set). Prevalence estimates were based on 16,032 participants in NHANES. GFR, measured as the clearance of exogenous filtration markers (iothalamate in the development data set; iothalamate and other markers in the validation data set), and linear regression to estimate the logarithm of measured GFR from standardized creatinine levels, sex, race, and age. In the validation data set, the CKD-EPI equation performed better than the Modification of Diet in Renal Disease Study equation, especially at higher GFR (P < 0.001 for all subsequent comparisons), with less bias (median difference between measured and estimated GFR, 2.5 vs. 5.5 mL/min per 1.73 m(2)), improved precision (interquartile range [IQR] of the differences, 16.6 vs. 18.3 mL/min per 1.73 m(2)), and greater accuracy (percentage of estimated GFR within 30% of measured GFR, 84.1% vs. 80.6%). In NHANES, the median estimated GFR was 94.5 mL/min per 1.73 m(2) (IQR, 79.7 to 108.1) vs. 85.0 (IQR, 72.9 to 98.5) mL/min per 1.73 m(2), and the prevalence of chronic kidney disease was 11.5% (95% CI, 10.6% to 12.4%) versus 13.1% (CI, 12.1% to 14.0%). The sample contained a limited number of elderly people and racial and ethnic minorities with measured GFR. The CKD-EPI creatinine equation is more accurate than the Modification of Diet in Renal Disease Study equation and could replace it for routine clinical use. National Institute of Diabetes and Digestive and Kidney Diseases.

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Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

Heshui Shi, Xiaoyu Han, Nanchuan Jiang … (2020)

Summary Background A cluster of patients with coronavirus disease 2019 (COVID-19) pneumonia caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were successively reported in Wuhan, China. We aimed to describe the CT findings across different timepoints throughout the disease course. Methods Patients with COVID-19 pneumonia (confirmed by next-generation sequencing or RT-PCR) who were admitted to one of two hospitals in Wuhan and who underwent serial chest CT scans were retrospectively enrolled. Patients were grouped on the basis of the interval between symptom onset and the first CT scan: group 1 (subclinical patients; scans done before symptom onset), group 2 (scans done ≤1 week after symptom onset), group 3 (>1 week to 2 weeks), and group 4 (>2 weeks to 3 weeks). Imaging features and their distribution were analysed and compared across the four groups. Findings 81 patients admitted to hospital between Dec 20, 2019, and Jan 23, 2020, were retrospectively enrolled. The cohort included 42 (52%) men and 39 (48%) women, and the mean age was 49·5 years (SD 11·0). The mean number of involved lung segments was 10·5 (SD 6·4) overall, 2·8 (3·3) in group 1, 11·1 (5·4) in group 2, 13·0 (5·7) in group 3, and 12·1 (5·9) in group 4. The predominant pattern of abnormality observed was bilateral (64 [79%] patients), peripheral (44 [54%]), ill-defined (66 [81%]), and ground-glass opacification (53 [65%]), mainly involving the right lower lobes (225 [27%] of 849 affected segments). In group 1 (n=15), the predominant pattern was unilateral (nine [60%]) and multifocal (eight [53%]) ground-glass opacities (14 [93%]). Lesions quickly evolved to bilateral (19 [90%]), diffuse (11 [52%]) ground-glass opacity predominance (17 [81%]) in group 2 (n=21). Thereafter, the prevalence of ground-glass opacities continued to decrease (17 [57%] of 30 patients in group 3, and five [33%] of 15 in group 4), and consolidation and mixed patterns became more frequent (12 [40%] in group 3, eight [53%] in group 4). Interpretation COVID-19 pneumonia manifests with chest CT imaging abnormalities, even in asymptomatic patients, with rapid evolution from focal unilateral to diffuse bilateral ground-glass opacities that progressed to or co-existed with consolidations within 1–3 weeks. Combining assessment of imaging features with clinical and laboratory findings could facilitate early diagnosis of COVID-19 pneumonia. Funding None.

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Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

Quan-Xin Long, Xiao-Jun Tang, Qiu-Lin Shi … (2020)

The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.

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Author and article information

Journal

Journal ID (nlm-ta): J Inflamm Res

Journal ID (iso-abbrev): J Inflamm Res

Journal ID (publisher-id): jir

Journal ID (pmc): jinres

Title: Journal of Inflammation Research

Publisher: Dove

ISSN (Electronic): 1178-7031

Publication date (Electronic): 07 September 2021

Publication date Collection: 2021

Volume: 14

Pages: 4485-4501

Affiliations

[1 ]Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[2 ]Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[3 ]Department of Translational Medicine Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[4 ]Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[5 ]Health Checkup Department, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[6 ]Department of Scientific Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei, 430022, People’s Republic of China

[7 ]School of Public Health, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, 430030, Hubei, People’s Republic of China

Author notes

Correspondence: Yang Jin Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , 1277 Jiefang Avenue, Wuhan, Hubei, 430022, People’s Republic of China Email whuhjy@126.com

[*]

These authors contributed equally to this work

Author information

Fan Yang http://orcid.org/0000-0001-5718-9420

Yang Jin http://orcid.org/0000-0003-2409-7073

Article

Publisher ID: 325853

DOI: 10.2147/JIR.S325853

PMC ID: 8434912

PubMed ID: 34522117

SO-VID: 9e286891-52b0-46e0-9f07-2ef5b3879be3

License:

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

History

Date received : 25 June 2021

Date accepted : 24 August 2021

Page count

Figures: 7, Tables: 6, References: 60, Pages: 17

Funding

Funded by: National Natural Science Foundation of China, open-funder-registry 10.13039/501100001809;

Funded by: Major Projects of the National Science and Technology;

Funded by: Ministry of Science and Technology of the People’s Republic of China;

Funded by: Natural Science Foundation of Hubei Province, China;

Funded by: Fundamental Research Funds for the Central Universities, HUST;

This work was supported by the National Natural Science Foundation of China [82041018, 81802113]; Major Projects of the National Science and Technology [2019ZX09301001]; Ministry of Science and Technology of the People’s Republic of China [2020YFC0844300]; the Natural Science Foundation of Hubei Province, China [2020CFB809] and the Fundamental Research Funds for the Central Universities, HUST [2020kfyXGYJ011]. The research sponsors were not involved in research design, data collection, analysis, or interpretation. They did not participate in the writing of the manuscript, nor did they participate in the decision to submit the manuscript.

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

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Abstract

Background

Methods

Results

Conclusion

Related collections

Novel Coronavirus Disease COVID-19

Most cited references 59

A new equation to estimate glomerular filtration rate.

Radiological findings from 81 patients with COVID-19 pneumonia in Wuhan, China: a descriptive study

Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections

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