Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19

  1. Jingyi Yang
  2. Maohua Zhong
  3. Ejuan Zhang
  4. Ke Hong
  5. Qingyu Yang
  6. Dihan Zhou
  7. Jianbo Xia
  8. Yao-Qing Chen
  9. Mingbo Sun
  10. Bali Zhao
  11. Jie Xiang
  12. Ying Liu
  13. Yang Han
  14. Mengxin Xu
  15. Xi Zhou
  16. Chaolin Huang
  17. You Shang
  18. Huimin Yan

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM−CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3−HLA-DR− lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that  severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.

Article activity feed

  1. Version published to 10.1093/jmcb/mjab014
  2. ScreenIT

    SciScore for 10.1101/2020.07.01.20144030: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was reviewed and approved by the Medical Ethical Committee of Wuhan Jinyintan hospital (approval number KY-2020-47·01).
    Consent: Written informed consent was obtained from the COVID-19 recovered individuals and the healthy donors.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableAfter exclusion, a cohort of fifty-five healthy donors (HD, 23 male and 32 female, mean age 49·1, median age 51) and a fifty-five clinical recovered COVID-19 cohort (CR, 21 male and 34 female, mean age 48·8, median age 51) were involved in the study (supplement table 1), except the cases for assay on Tfh, B cells and cytokines IL-2, in which a sub-cohort of only 36 clinical recovered individuals (14 male and 22 female, mean age 50·6, median age 52) was involved in due to lack of antibody reagents.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data was analyzed using FlowJo V7.0.
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical analysis was carried out with InStat, version 8·0 (GraphPad Software, La Jolla, CA, USA).
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: Please consider improving the rainbow (“jet”) colormap(s) used on page 21. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2020.07.01.20144030v1 on medRxiv