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Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals.

ABSTRACT: Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states.

SUBMITTER: Lim J

PROVIDER: S-EPMC8640498 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals.

Lim Jackwee J Puan Kia Joo KJ Wang Liang Wei LW Teng Karen Wei Weng KWW Loh Chiew Yee CY Tan Kim Peng KP Carissimo Guillaume G Chan Yi-Hao YH Poh Chek Meng CM Lee Cheryl Yi-Pin CY Fong Siew-Wai SW Yeo Nicholas Kim-Wah NK Chee Rhonda Sin-Ling RS Amrun Siti Naqiah SN Chang Zi Wei ZW Tay Matthew Zirui MZ Torres-Ruesta Anthony A Leo Fernandez Norman N How Wilson W Andiappan Anand Kumar AK Lee Wendy W Duan Kaibo K Tan Seow-Yen SY Yan Gabriel G Kalimuddin Shirin S Lye David Chien DC Leo Yee-Sin YS Ong Sean W X SWX Young Barnaby E BE Renia Laurent L Ng Lisa F P LFP Lee Bernett B Rötzschke Olaf O

Frontiers in immunology 20211119

Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, ...[more]

PMID: 34867943

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Project description:BackgroundPost-COVID-19 respiratory sequelae often involve lung damage, which is called residual lung abnormalities, and potentially lead to chronic respiratory issues. The adaptive immune response, involving T-cells and B-cells, plays a critical role in pathogen control, inflammation, and tissue repair. However, the link between immune dysregulation and the development of residual lung abnormalities remains unclear.Methods109 patients discharged with residual lung abnormalities after a critical COVID-19 were followed for 12 months and divided as full recovery patients (FRG, n = 88) and persistent lung abnormalities (PLAG, n = 21). Cell profiling analysis was done using flow cytometry at 24 h of not antigen-specific in vitro stimulation. Plasma or supernatant levels of IFN-g, IL-4, IL-10, IgM, and IgG were assessed, and 10 patients (5 FRG, 5 PLAG) were randomly selected for detailed immune cell phenotyping and functional analysis of peripheral blood mononuclear cells using flow cytometry.ResultsCompared to the FRG group, PLAG exhibited an increase of unswitched (p = 0.0159) and decreased double-negative activated B-cells (p = 0.0317), systemic IL-10 levels were lower, displayed reduced frequency of total B-cells, and impaired spontaneous IgM (p = 0.0357) and IgG (p = 0.0079) release in culture. Regarding T-cells, PLAG patients showed a reduction in effector memory CD4 + cells (p = 0.0159) and an increase in CD4 + TEMRA cells (p = 0.0079) following in vitro stimulation. Notably, the PLAG group also exhibited higher frequencies of central memory CD4 + Th2 (GATA3+) T-cells in response to activation than the FRG group (p = 0.0079).ConclusionsPatients with residual lung abnormalities 12 months post-critical COVID-19 exhibit impaired B-cell function, increased unswitched B-cells, and higher frequencies of CD4 + TEMRA T-cells following in vitro activation. These immune imbalances may contribute to ongoing lung dysfunction and warrant further investigation as a potential mechanism in residual lung abnormalities. Larger studies are necessary to confirm these findings.

Dataset Information

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals.

Publications

Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals.

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