Seven-month kinetics of SARS-CoV-2 antibodies and role of pre-existing antibodies to human coronaviruses

  1. Natalia Ortega
  2. Marta Ribes
  3. Marta Vidal
  4. Rocío Rubio
  5. Ruth Aguilar
  6. Sarah Williams
  7. Diana Barrios
  8. Selena Alonso
  9. Pablo Hernández-Luis
  10. Robert A. Mitchell
  11. Chenjerai Jairoce
  12. Angeline Cruz
  13. Alfons Jimenez
  14. Rebeca Santano
  15. Susana Méndez
  16. Montserrat Lamoglia
  17. Neus Rosell
  18. Anna Llupià
  19. Laura Puyol
  20. Jordi Chi
  21. Natalia Rodrigo Melero
  22. Daniel Parras
  23. Pau Serra
  24. Edwards Pradenas
  25. Benjamin Trinité
  26. Julià Blanco
  27. Alfredo Mayor
  28. Sonia Barroso
  29. Pilar Varela
  30. Anna Vilella
  31. Antoni Trilla
  32. Pere Santamaria
  33. Carlo Carolis
  34. Marta Tortajada
  35. Luis Izquierdo
  36. Ana Angulo
  37. Pablo Engel
  38. Alberto L. García-Basteiro
  39. Gemma Moncunill
  40. Carlota Dobaño

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Abstract

Unraveling the long-term kinetics of antibodies to SARS-CoV-2 and the individual characteristics influencing it, including the impact of pre-existing antibodies to human coronaviruses causing common cold (HCoVs), is essential to understand protective immunity to COVID-19 and devise effective surveillance strategies. IgM, IgA and IgG levels against six SARS-CoV-2 antigens and the nucleocapsid antigen of the four HCoV (229E, NL63, OC43 and HKU1) were quantified by Luminex, and antibody neutralization capacity was assessed by flow cytometry, in a cohort of health care workers followed up to 7 months ( N  = 578). Seroprevalence increases over time from 13.5% (month 0) and 15.6% (month 1) to 16.4% (month 6). Levels of antibodies, including those with neutralizing capacity, are stable over time, except IgG to nucleocapsid antigen and IgM levels that wane. After the peak response, anti-spike antibody levels increase from ~150 days post-symptom onset in all individuals (73% for IgG), in the absence of any evidence of re-exposure. IgG and IgA to HCoV are significantly higher in asymptomatic than symptomatic seropositive individuals. Thus, pre-existing cross-reactive HCoVs antibodies could have a protective effect against SARS-CoV-2 infection and COVID-19 disease.

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  1. Version published to 10.1038/s41467-021-24979-9
  2. ScreenIT

    SciScore for 10.1101/2021.02.22.21252150: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Written informed consent was obtained from all study participants prior to study initiation.
    IRB: The study was approved by the Ethics Committee at HCB (Ref number: HCB/2020/0336).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Quantification of antibodies to SARS-CoV-2: IgM, IgG and IgA antibodies to the full length SARS-CoV-2 S protein, its subregions S1 and S2, RBD that lies within the S1 region, the N full length protein and its specific C-terminal region, and the full length N protein of the HCoVs HKU1, 229E, OC43 and NL63, were measured by Luminex (Supplementary Information) based on a previously described protocol49.
    SARS-CoV-2: IgM, IgG
    suggested: None
    IgA
    suggested: None
    NL63
    suggested: None
    Neutralizing antibodies: Percentage of inhibition of RBD binding to ACE2 by plasma was analyzed through a flow cytometric-based in vitro assay as detailed in the Supplementary Information.
    ACE2
    suggested: None
    Statistical data analysis: Prevalence of SARS-CoV-2 antibodies or SARS-CoV-2 infection confirmed by rRT-PCR, and cumulative prevalence of past or current infection (positive SARS-CoV-2 rRT-PCR and/or antibody seropositivity at any time point) were calculated as proportions with 95% CI.
    SARS-CoV-2
    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:
    The main limitations of this study are that our cohort had few participants with severe disease, and that we only assessed the impact of anti-HCoV N antibodies on SARS-CoV-2 response, while anti-N antibodies are not expected to have neutralizing capacity. However, it is likely that sera with high levels of N HCoV antibodies would also have high levels of antibodies targeting S antigens and B and T cells specific to HCoV, which could explain the potential association with a protective effect. All together, further studies will be needed to elucidate the potential role of prior HCoV infections in the spectrum of COVID-19 severity, as well as the temporal relevance of HCoV exposure and the possible impact on vaccine responses. In conclusion, antibody levels and neutralizing capacity are generally maintained up to 7.7 months, and in a substantial number of individuals antibody levels increase after some months PSO. Further studies are needed to elucidate the mechanisms and nature of these increases and their implications for virus shedding and disease progression. Importantly, previous exposure to HCoVs could have a protective effect against SARS-CoV-2 infection and symptoms development, and may explain in part the differential susceptibility to disease in the population. Additional work focusing on prospective cohorts would allow the assessment of mechanisms and confirm causality in anti-HCoV antibodies on SARS-CoV-2 acquisition, disease progression, immune response maintenance ...

    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.

    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 10.1101/2021.02.22.21252150 on medRxiv