Reduced numbers of T cells and B cells correlates with persistent SARS-CoV-2 presence in non-severe COVID-19 patients

  1. Bing Liu
  2. Junyan Han
  3. Xiaohuan Cheng
  4. Long Yu
  5. Li Zhang
  6. Wei Wang
  7. Lan Ni
  8. Chaojie Wei
  9. Yafei Huang
  10. Zhenshun Cheng

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Abstract

COVID-19 has been widely spreading. We aimed to examine adaptive immune cells in non-severe patients with persistent SARS-CoV-2 shedding. 37 non-severe patients with persistent SARS-CoV-2 presence that were transferred to Zhongnan hospital of Wuhan University were retrospectively recruited to the PP (persistently positive) group, which was further allocated to PPP group (n = 19) and PPN group (n = 18), according to their testing results after 7 days (N = negative). Epidemiological, demographic, clinical and laboratory data were collected and analyzed. Data from age- and sex-matched non-severe patients at disease onset (PA [positive on admission] patients, n = 37), and lymphocyte subpopulation measurements from matched 54 healthy subjects were extracted for comparison (HC). Compared with PA patients, PP patients had much improved laboratory findings. The absolute numbers of CD3 + T cells, CD4 + T cells, and NK cells were significantly higher in PP group than that in PA group, and were comparable to that in healthy controls. PPP subgroup had markedly reduced B cells and T cells compared to PPN group and healthy subjects. Finally, paired results of these lymphocyte subpopulations from 10 PPN patients demonstrated that the number of T cells and B cells significantly increased when the SARS-CoV-2 tests turned negative. Persistent SARS-CoV-2 presence in non-severe COVID-19 patients is associated with reduced numbers of adaptive immune cells. Monitoring lymphocyte subpopulations could be clinically meaningful in identifying fully recovered COVID-19 patients.

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  1. Version published to 10.1038/s41598-020-73955-8
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    SciScore for 10.1101/2020.03.26.20044768: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Participants, study design and definitions: This study was approved by Zhongnan Hospital of Wuhan University (ZHWU)’s ethical review board (No. 2020013).
    Consent: Written informed consent was waived by the Ethics Commission of the hospital for emerging infectious diseases
    RandomizationAge- and sex-matched healthy subjects and non-severe COVID-19 patients were randomly recruited into the HC group and the PA group, respectively.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Lymphocyte subpopulations were examined by FACS Aria III cytometer (BD bioscience, USA) and analyzed using Flowjo software v.10.2 (BD bioscience, USA).
    Flowjo
    suggested: (FlowJo, RRID:SCR_008520)
    Statistical Analysis: Data analysis was performed using SPSS (Statistical Package for the Social Sciences, version 23).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    Statistical Package for the Social Sciences
    suggested: (SPSS, RRID:SCR_002865)

    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: We detected the following sentences addressing limitations in the study:
    However, some limitations were noticed. First, the kinetics of SARS-CoV-2 shedding was different from that of SARS-CoV and MERS-CoV. RNA copies of SARS-CoV-2 were very high in nasopharyngeal swab during the first week of symptoms, with peak on day 4 post-onset, whereas the peak value appeared until 7-10 days post-onset with much lower RNA copies during SARS-CoV and MERS-CoV infection [6,18-20]. Second, the presence of virus RNA in lower respiratory tract (sputum or BALs), stool, and blood samples were reported, and the kinetics of virus shedding in these sites were distinct from that in throat [8-11]. Third, sampling error and the technical limitations of RT-PCR sometimes led to a false testing result [21]. With these limitations, it is not surprising that some patients who tested negative in two consecutively RT-PCR tests and were discharged from hospital had positive results 5 to 13 days later [21,22]. In together, these notions posed a great challenge to discharge management for COVID-19 patients, especially for non-severe cases having obtained clinical cure. Since the presence of viral RNA might come from fragments of dead virus, isolating live SARS-CoV-2 is therefore useful in determining viral infectivity [6]. However, this method is required to be performed in a biological safety level 3 (BSL-3) laboratory, which limited its application in clinical practice for discharge management. Indicators from the immune system are promising candidates in this regard. Detection fo...

    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: We did not find any issues relating to colormaps.

    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

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  3. Version published to 10.1101/2020.03.26.20044768v1 on medRxiv