IgG antibody seroconversion and the clinical progression of COVID-19 pneumonia: A retrospective, cohort study

  1. Kazuyoshi Kurashima
  2. Naho Kagiyama
  3. Takashi Ishiguro
  4. Yotaro Takaku
  5. Hiromi Nakajima
  6. Shun Shibata
  7. Yuma Matsui
  8. Kenji Takano
  9. Taisuke Isono
  10. Takashi Nishida
  11. Eriko Kawate
  12. Chiaki Hosoda
  13. Yoichi Kobayashi
  14. Noboru Takayanagi
  15. Tsutomu Yanagisawa

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Abstract

Background

Coronavirus Disease 2019 (COVID-19) causes severe acute respiratory failure. Antibody-dependent enhancement (ADE) is known as the mechanism for severe forms of other coronavirus diseases. The clinical progression of COVID-19 before and after IgG antibody seroconversion was investigated.

Methods

Fifty-three patients with reverse transcriptase PCR (RT-PCT)-confirmed COVID-19 viral pneumonia with or without respiratory failure were retrospectively investigated. The timing of the first IgG antibody against SARS-CoV-2-positive date, as well as changes of C-reactive protein (CRP) as an inflammatory marker and blood lymphocyte numbers, was assessed using serial preserved blood samples.

Findings

Ten patients recovered without oxygen therapy (mild/moderate group), 32 patients had hypoxemia and recovered with antiviral drugs (severe/non-ICU group), and 11 patients had severe respiratory failure and were treated in the ICU (6 of them died; critical/ICU group). The first IgG-positive date (day 0) was observed from 5 to 18 days from the onset of disease. At day 0, a CRP peak was observed in the severe and critical groups, whereas there was no synchronized CRP peak on day 0 in the mild/moderate group. In the severe/non-ICU group, the blood lymphocyte number increased (P=0.0007) and CRP decreased (P=0.0007) after day 0, whereas CRP did not decrease and the blood lymphocyte number further decreased (P=0.0370) in the critical/ICU group.

Interpretation

The respiratory failure due to COVID-19 viral pneumonia observed in week 2 may be related to an antibody-related mechanism rather than uncontrolled viral replication. In the critical form of COVID-19, inflammation was sustained after IgG seroconversion.

Funding

none

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  1. ScreenIT

    SciScore for 10.1101/2020.07.16.20154088: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Methods: The study was approved by the ethics committee of Saitama Cardiovascular and Respiratory Center.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Of the 74 patients, serial preserved blood-test samples could be examined for anti-SARS-CoV-2 IgG antibody in 53 patients.
    anti-SARS-CoV-2 IgG
    suggested: None
    IgG seroconversion was observed during the course in 27 of the patients, and IgG antibody was positive on admission in 26 patients.
    IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    JMP Ver.13, (SAS Institute Japan Ltd, Tokyo, Japan) was used for statistical analyses.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    There are several limitations that should be noted. First, because of the retrospective nature of the study, not all data points were collected. However, the times of seroconversion were consistent among the groups and with the results of previous reports. In addition, the rapid exacerbations that occurred around day 10 from onset could be traced. Second, the present findings provide only indirect evidence for ADE. Necrotic lymph nodes and atrophic spleens reported in COVID-19 patients1 also suggest significant apoptosis of lymphocytes, but more clinical and laboratory data are needed to establish the ADE process in COVID-19. Third, the bias of treatment should be assessed. All patients were treated with anti-viral drugs soon after admission in the severe and critical groups. The drugs were not different between the groups. In addition, the timing of the start of treatment and the timing of peak CRP were not consistent in the two groups. In conclusion, the results of the present study suggest that severe COVID-19 pneumonia is related to antibody-dependent inflammation. Multiple factors determine whether an antibody neutralizes a virus or causes ADE.24 These include the specificity, concentration, affinity, and isotype of the antibody. To elucidate a mechanism for the different clinical courses after seroconversion may help to develop drugs or vaccines against SARS-CoV-2. The safety of and the potentially harmful responses to vaccines to develop ADE antibodies should be carefu...

    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.
    • Thank you for including a protocol registration statement.

    About SciScore

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  2. Version published to 10.1101/2020.07.16.20154088v1 on medRxiv