Mucosal Antibody Response to SARS-CoV-2 in Paediatric and Adult Patients: A Longitudinal Study

  1. Renee W. Y. Chan
  2. Kate C. C. Chan
  3. Grace C. Y. Lui
  4. Joseph G. S. Tsun
  5. Kathy Y. Y. Chan
  6. Jasmine S. K. Yip
  7. Shaojun Liu
  8. Michelle W. L. Yu
  9. Rita W. Y. Ng
  10. Kelvin K. L. Chong
  11. Maggie H. Wang
  12. Paul K. S. Chan
  13. Albert M. Li
  14. Hugh Simon Lam

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Abstract

Background: SARS-CoV-2 enters the body through inhalation or self-inoculation to mucosal surfaces. The kinetics of the ocular and nasal mucosal-specific-immunoglobulin A(IgA) responses remain under-studied. Methods: Conjunctival fluid (CF, n = 140) and nasal epithelial lining fluid (NELF, n = 424) obtained by paper strips and plasma (n = 153) were collected longitudinally from SARS-CoV-2 paediatric (n = 34) and adult (n = 47) patients. The SARS-CoV-2 spike protein 1(S1)-specific mucosal antibody levels in COVID-19 patients, from hospital admission to six months post-diagnosis, were assessed. Results: The mucosal antibody was IgA-predominant. In the NELF of asymptomatic paediatric patients, S1-specific IgA was induced as early as the first four days post-diagnosis. Their plasma S1-specific IgG levels were higher than in symptomatic patients in the second week after diagnosis. The IgA and IgG levels correlated positively with the surrogate neutralization readout. The detectable NELF “receptor-blocking” S1-specific IgA in the first week after diagnosis correlated with a rapid decline in viral load. Conclusions: Early and intense nasal S1-specific IgA levels link to a rapid decrease in viral load. Our results provide insights into the role of mucosal immunity in SARS-CoV-2 exposure and protection. There may be a role of NELF IgA in the screening and diagnosis of SARS-CoV-2 infection.

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  1. Version published to 10.3390/pathogens11040397
  2. ScreenIT

    SciScore for 10.1101/2021.09.27.21264219: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 27 The study was approved by the Joint Chinese University of Hong Kong – New Territories East Cluster Clinical Research Ethics Committee (CREC: 2020.076 and 2020.4421).
    Field Sample Permit: All strips were collected and transferred in a dry sterile collection tube and eluted within 24h after collection.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical tests were performed using Graphpad version 9.1.2 for macOS SPSS version 25.
    Graphpad
    suggested: (GraphPad, RRID:SCR_000306)
    SPSS
    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:
    One of the major limitations of this study was that we determined the SARS-CoV-2 S1-specific antibody only in its IgA and IgG isotypes. The diversity of the antibody responses to other SARS-CoV-2 viral antigens (e.g. nucleocapsid, open reading frame (ORF)8 and ORF3b) were not evaluated. These non-neutralizing antibodies are found to be detectable in COVID-19 patients plasma early in the disease course and serve crucial functions to counteract the viral inhibition on host antiviral effects.35 It would be of exceptional importance to characterize the antibody diversity in the mucosal fluids, so as to better determine its immunological involvement of differing disease outcomes. Moreover, the limited number of severe & critically ill patients limited the statistical power of the analysis. Another limitation of our study was the lack of a cell-based neutralization test or plaque reduction assay, which required Biosafety level 3 facilities. In addition, the direct measurement of S1-specific antibody might not confer immunity, while the surrogate neutralization assay is expensive and not affordable if the number of samples to be tested is enormous. Here, we derived a threshold of S1-specific IgA levels which is predicted to have the ‘neutralizing’ potency. We applied this threshold to the rest of the NELF S1-specific IgA measurements and converted it to a biologically rational observation. Patients with ‘neutralizing’ NELF within the first 7 days of diagnosis had a more rapid declin...

    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.

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

    About SciScore

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  3. Version published to 10.1101/2021.09.27.21264219v1 on medRxiv