SARS-CoV-2 induces a durable and antigen specific humoral immunity after asymptomatic to mild COVID-19 infection

  1. Sebastian Havervall
  2. August Jernbom Falk
  3. Jonas Klingström
  4. Henry Ng
  5. Nina Greilert-Norin
  6. Lena Gabrielsson
  7. Ann-Christin Salomonsson
  8. Eva Isaksson
  9. Ann-Sofie Rudberg
  10. Cecilia Hellström
  11. Eni Andersson
  12. Jennie Olofsson
  13. Lovisa Skoglund
  14. Jamil Yousef
  15. Elisa Pin
  16. Wanda Christ
  17. Mikaela Olausson
  18. My Hedhammar
  19. Hanna Tegel
  20. Sara Mangsbo
  21. Mia Phillipson
  22. Anna Månberg
  23. Sophia Hober
  24. Peter Nilsson
  25. Charlotte Thålin

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Abstract

Current SARS-CoV-2 serological assays generate discrepant results, and the longitudinal characteristics of antibodies targeting various antigens after asymptomatic to mild COVID-19 are yet to be established. This longitudinal cohort study including 1965 healthcare workers, of which 381 participants exhibited antibodies against the SARS-CoV-2 spike antigen at study inclusion, reveal that these antibodies remain detectable in most participants, 96%, at least four months post infection, despite having had no or mild symptoms. Virus neutralization capacity was confirmed by microneutralization assay in 91% of study participants at least four months post infection. Contrary to antibodies targeting the spike protein, antibodies against the nucleocapsid protein were only detected in 80% of previously anti-nucleocapsid IgG positive healthcare workers. Both anti-spike and anti-nucleocapsid IgG levels were significantly higher in previously hospitalized COVID-19 patients four months post infection than in healthcare workers four months post infection (p = 2*10 −23 and 2*10 −13 respectively). Although the magnitude of humoral response was associated with disease severity, our findings support a durable and functional humoral response after SARS-CoV-2 infection even after no or mild symptoms. We further demonstrate differences in antibody kinetics depending on the antigen, arguing against the use of the nucleocapsid protein as target antigen in population-based SARS-CoV-2 serological surveys.

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  1. Version published to 10.1371/journal.pone.0262169
  2. Version published to 10.1101/2021.01.03.21249162v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.01.03.21249162: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: The study was approved by the Swedish Ethical Review Authority (dnr 2020-01653), and informed consent was obtained from all study participants.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    Although this study is strengthened by the large sample size and the longitudinal design with close to complete follow-up, there are certain limitations worth noting. Study inclusion took place simultaneously for HCW and hospitalized COVID-19 patients, regardless of whether and when HCW had symptoms compatible with COVID-19. A relatively large portion of seropositive HCW furthermore reported to have had no symptoms. Although the time window of infection is quite narrow in this group, considering that study inclusion started early in the Swedish pandemic, the precise time of infection remains uncertain. A direct comparison of antibody levels between HCW and hospitalized COVID-19 patients at study inclusion was therefore not appropriate. However, the levels and efficacy of neutralizing antibodies at follow-up, which was within 4-5 months post infection in both the patient and HCW groups, are more indicative of a persistent measurable humoral immunity than the dynamics between initial sampling and follow-up. Taken together, our findings imply a strong and long-lasting humoral immune response against SARS-CoV-2, even after asymptomatic or mild infection. We furthermore reveal different patterns of acute and convalescent anti-spike IgG and anti-nucleocapsid IgG responses, and show that anti-spike IgG remain detectable in 98% of individuals while anti-nucleocapsid IgG declined to undetectable levels in 32% of the study group with mild infection. These findings have high relevance i...

    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.

  4. Version published to 10.1101/2021.01.03.21249162v1 on medRxiv