Human seasonal coronavirus neutralization and COVID‐19 severity

  1. David A. Wells
  2. Diego Cantoni
  3. Martin Mayora‐Neto
  4. Cecilia Di Genova
  5. Alexander Sampson
  6. Matteo Ferrari
  7. George Carnell
  8. Angalee Nadesalingam
  9. Peter Smith
  10. Andrew Chan
  11. Gianmarco Raddi
  12. Javier Castillo‐Olivares
  13. Helen Baxendale
  14. Nigel Temperton
  15. Jonathan L. Heeney

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Abstract

The virus severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), responsible for the global coronavirus disease‐2019 (COVID‐19) pandemic, spread rapidly around the world causing high morbidity and mortality. However, there are four known, endemic seasonal coronaviruses in humans (HCoVs), and whether antibodies for these HCoVs play a role in severity of COVID‐19 disease has generated a lot of interest. Of these seasonal viruses NL63 is of particular interest as it uses the same cell entry receptor as SARS‐CoV‐2. We use functional, neutralizing assays to investigate cross‐reactive antibodies and their relationship with COVID‐19 severity. We analyzed the neutralization of SARS‐CoV‐2, NL63, HKU1, and 229E in 38 COVID‐19 patients and 62 healthcare workers, and a further 182 samples to specifically study the relationship between SARS‐CoV‐2 and NL63. We found that although HCoV neutralization was very common there was little evidence that these antibodies neutralized SARS‐CoV‐2. Despite no evidence in cross‐neutralization, levels of NL63 neutralizing antibodies become elevated after exposure to SARS‐CoV‐2 through infection or following vaccination.

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  1. Version published to 10.1002/jmv.27937
  2. ScreenIT

    SciScore for 10.1101/2021.09.29.21264328: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Following informed consent, staff were invited to complete a questionnaire to clarify whether they had swab PCR confirmed SARS-CoV-2 infection (routine swabbing was not available at that time and there was limited access to swabbing when symptomatic) and whether they had experienced symptoms that they felt may have been consistent with COVID-19 since January 2020.
    IRB: The study was approved by Research Ethics Committee
    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
    Target cells for SARS-CoV-2 and NL63 PVs were HEK293T cells pre-transfected with ACE-2 and TMPRSS-2 (23), and CHO cells were used as target cells for HKU1 PVs.
    CHO
    suggested: CLS Cat# 603479/p746_CHO, RRID:CVCL_0213)
    Pre-transfected HEK293T target cells were seeded at 1×104 cells per well in plates containing either SARS-CoV-2 or NL63 PVs, Huh-7 cells were seeded at 1×104 cells per well in plates containing 229E PVs and CHO cells were seeded at 1×104 cells per well in plates containing HKU1 PVs.
    HEK293T
    suggested: None
    Huh-7
    suggested: None
    Recombinant DNA
    SentencesResources
    The seropositive cutoff for pMN was the 95% upper confidence interval of pre-pandemic samples in previous work (18).
    pMN
    suggested: RRID:Addgene_18785)
    Plasmids bearing the Spike of either SARS-CoV-2, NL63, HKU1, and 229E in the vector pcDNA3.1+, were mixed with the plasmids p8.91 lentiviral Gag-pol (21) and pCSFLW luciferase reporter gene (22) in Opti-MEM solution.
    pcDNA3.1+
    suggested: RRID:Addgene_117272)
    p8.91
    suggested: None
    pCSFLW
    suggested: None

    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:
    One limitation of this study is the lack of paired samples immediately before and after infection to measure the effect of SARS-CoV-2 infection on NL63 neutralisation directly. If moderate to severe COVID-19 disease causes an increase in NL63 neutralisation it would explain the observed relationship between COVID-19 severity and NL63 neutralisation. The increase in NL63 neutralisation after vaccination suggests the possibility that SARS-CoV-2 vaccination may also provide protection against the common cold caused by NL63. Spike protein binding was highly correlated between the HCoVs, however; there was relatively little correlation between HCoVs and SARS-CoV-2. If the correlation between HCoV binding was driven by cross reactive antibodies we would also expect them to correlate with SARS-CoV-2 as it is more closely related to the betacoronavirus HCoVs than 229E and NL63 are. We interpret the lack of correlation in spike binding between SARS-CoV-2 as evidence that HCoV spike antibodies are likely not cross reactive but co-occurring, i.e. people who are exposed to one of the HCoVs are likely to be exposed to other HCoVs (28). We found that SARS-CoV-2 neutralisation does not correlate with neutralisation of any HCoV we tested. At first this seems to contradict several studies reporting cross-reactive binding and neutralisation (7,8); however, these studies found only a very small proportion of people not exposed to SARS-CoV-2 displayed cross-reactive antibodies. Ng et al 2020 fou...

    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.

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  3. Version published to 10.1101/2021.09.29.21264328v1 on medRxiv