Delayed neutralizing antibody response in the acute phase correlates with severe progression of COVID-19

  1. Hitoshi Kawasuji
  2. Yoshitomo Morinaga
  3. Hideki Tani
  4. Miyuki Kimura
  5. Hiroshi Yamada
  6. Yoshihiro Yoshida
  7. Yusuke Takegoshi
  8. Makito Kaneda
  9. Yushi Murai
  10. Kou Kimoto
  11. Akitoshi Ueno
  12. Yuki Miyajima
  13. Koyomi Kawago
  14. Yasutaka Fukui
  15. Ippei Sakamaki
  16. Yoshihiro Yamamoto

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Adaptive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) dynamics remain largely unknown. The neutralizing antibody (NAb) levels in patients with coronavirus disease 2019 (COVID-19) are helpful for understanding the pathology. Using SARS-CoV-2 pseudotyped virus, serum sample neutralization values in symptomatic COVID-19 patients were measured using the chemiluminescence reduction neutralization test (CRNT). At least two sequential serum samples collected during hospitalization were analyzed to assess NAbs neutralizing activity dynamics at different time points. Of the 11 patients, four (36.4%), six (54.5%), and one (9.1%) had moderate, severe, and critical disease, respectively. Fifty percent neutralization (N50%-CRNT) was observed upon admission in 90.9% (10/11); all patients acquired neutralizing activity 2–12 days after onset. In patients with moderate disease, neutralization was observed at earliest within two days after symptom onset. In patients with severe-to-critical disease, neutralization activity increased, plateauing 9–16 days after onset. Neutralization activity on admission was significantly higher in patients with moderate disease than in patients with severe-to-critical disease (relative % of infectivity, 6.4% vs. 41.1%; P  = .011). Neutralization activity on admission inversely correlated with disease severity. The rapid NAb response may play a crucial role in preventing the progression of COVID-19.

Article activity feed

  1. Version published to 10.1038/s41598-021-96143-8
  2. ScreenIT

    SciScore for 10.1101/2021.02.06.21251246: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approval: This study was performed in accordance with the Helsinki Declaration and was approved by the ethical review board of the University of Toyama (approval No.: R2019167).
    Consent: Written informed consent was obtained from all patients.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Briefly, Vero cells were treated with two hundred-fold dilutions of sera from in-hospital patients with COVID-19 and then inoculated with pseudotyped VSVs bearing the S protein, the 19-amino acid-truncated S protein of SARS-CoV-2 or VSV-G.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    Data were analyzed using JMP Pro version 15.0.0 software (SAS Institute Inc.
    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:
    This study had several limitations. First, the number of involved patients was very small and selected using consecutive instead of random sampling. Thus, representativeness is relatively insufficient, and the samples could only represent the general situation to a certain extent. Second, the subjects mainly had moderate and severe disease, and only one critically ill patient was included. The NAb response in asymptomatic infections and mild patients requires further exploration. Third, the meaning of the quantitative values of CRNT results remains controversial. To make the value clinically meaningful, continuous improvement of our method and comparison with clinical findings are required.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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

    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 10.1101/2021.02.06.21251246v1 on medRxiv