Cross-Neutralizing Activity Against SARS-CoV-2 Variants in COVID-19 Patients: Comparison of 4 Waves of the Pandemic in Japan

  1. Koichi Furukawa
  2. Lidya Handayani Tjan
  3. Silvia Sutandhio
  4. Yukiya Kurahashi
  5. Sachiyo Iwata
  6. Yoshiki Tohma
  7. Shigeru Sano
  8. Sachiko Nakamura
  9. Mitsuhiro Nishimura
  10. Jun Arii
  11. Tatsunori Kiriu
  12. Masatsugu Yamamoto
  13. Tatsuya Nagano
  14. Yoshihiro Nishimura
  15. Yasuko Mori

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Abstract

Background

As of March 2021, Japan is facing a fourth wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To prevent further spread of infection, sera cross-neutralizing activity of patients previously infected with conventional SARS-CoV-2 against novel variants is important but has not been firmly established.

Methods

We investigated the neutralizing potency of 81 coronavirus disease 2019 (COVID-19) patients’ sera from the first to fourth waves of the pandemic against SARS-CoV-2 D614G, B.1.1.7, P.1, and B.1.351 variants using their authentic viruses.

Results

Most sera had neutralizing activity against all variants, showing similar activity against B.1.1.7 and D614G, but lower activity especially against B.1.351. In the fourth wave, sera-neutralizing activity against B.1.1.7 was significantly higher than that against any other variants, including D614G. The sera-neutralizing activity in less severe patients was lower than that of more severe patients for all variants.

Conclusions

The cross-neutralizing activity of convalescent sera was effective against all variants but was potentially weaker for B.1.351. The high neutralizing activity specific to B.1.1.7 in the fourth wave suggests that mutations in the virus might cause conformational change of its spike protein, which affects immune recognition of D614G. Our results indicate that individuals who recover from COVID-19 could be protected from the severity caused by infection with newly emerging variants.

Article activity feed

  1. Version published to 10.1093/ofid/ofab430
  2. ScreenIT

    SciScore for 10.1101/2021.06.10.21258682: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: This study was a retrospective observational investigation and was carried out after written consent was obtained from the subjects or by the opt-out method when it was difficult to get written consent due to the disease severity.
    IRB: Ethical approval: This study was approved by the ethical committees of Kobe University Graduate School of Medicine (approval code: B200200) and Hyogo Prefectural Kakogawa Medical Center.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Vero E6 (TMPRSS2) cells were used [22].
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Statistical analysis: GraphPad Prism software (ver. 8.4.3) was used for the statistical analysis and preparation of figures.
    GraphPad Prism
    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: 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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.06.10.21258682 on medRxiv