Antibody kinetics to SARS-CoV-2 at 13.5 months, by disease severity

  1. Concepción Violán
  2. Pere Torán
  3. Bibiana Quirant
  4. Noemi Lamonja-Vicente
  5. Lucía A. Carrasco-Ribelles
  6. Carla Chacón
  7. Josep Maria Manresa-Dominguez
  8. Francesc Ramos-Roure
  9. Albert Roso-Llorach
  10. Aleix Pujol
  11. Dan Ouchi
  12. Mónica Monteagudo
  13. Pilar Montero
  14. Rosa Garcia-Sierra
  15. Fernando Arméstar
  16. Rosalia Dacosta-Aguayo
  17. Maria Doladé
  18. Nuria Prat
  19. Josep Maria Bonet
  20. Bonaventura Clotet
  21. Ignacio Blanco
  22. Julia G Prado
  23. Eva María Martínez Cáceres
  24. for the ProHEpiC-19 Investigators

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Abstract

Background

Understanding humoral responses and seroprevalence in SARS-CoV-2 infection is essential for guiding vaccination strategies in both infected and uninfected individuals.

Methods

We determine the kinetics of IgM against the nucleocapsid (N) and IgG against the spike (S) and N proteins of SARS-CoV-2 in a cohort of 860 health professionals (healthy and infected) in northern Barcelona. We model the kinetics of IgG and IgM at nine time points over 13.5 months from infection, using non-linear mixed models by sex and clinical disease severity.

Results

Of the 781 participants who were followed up, 478 (61.2%) became infected with SARS-CoV-2. Significant differences were found for the three antibodies by disease severity and sex. At day 270 after diagnosis, median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease, while IgG(N, S) levels remained positive to days 360 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay whose rate depended on disease severity. IgG(S) levels increased at day 15 and remained relatively constant over time.

Conclusions

We describe kinetic models of IgM(N) and IgG(N, S) SARS-CoV-2 antibodies at 13.5 months from infection and disease spectrum. Our analyses delineate differences in the kinetics of IgM and IgG over a year and differences in the levels of IgM and IgG as early as 15 days from symptoms onset in severe cases. These results can inform public health policies around vaccination criteria.

Funded by the regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478 )

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  1. ScreenIT

    SciScore for 10.1101/2021.09.10.21262527: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The ethics committees of the IDIAPJGol Foundation (ref. 20/067) and IGTP Health Institute (ref.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisSample size: Sample size calculation for healthy and infected cohorts can be found in the supplementary protocol.

    Table 2: Resources

    Antibodies
    SentencesResources
    The analysis reported in this work includes only participants with SARS-CoV-2 antibodies.
    SARS-CoV-2
    suggested: None
    Participants with positive anti-N serology or/and RT-PCR were also tested for antibodies against the spike (S) subunit of SARS-CoV-2 by means of an enzyme immunoassay (ELISA) for the quantitative determination of IgG class antibodies using DECOV1901.
    anti-N
    suggested: None
    DECOV1901
    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:
    Semi-quantitative tests have some limitations, especially at the upper threshold, where further dilutions may be necessary. The limited availability of quantitative in vitro diagnostic techniques at the beginning of the pandemic necessitated the use of semi-quantitative techniques. Also, given the rapid development of diagnostic tests and the lack of information on them, we had to conduct an ELISA evaluation study prior to this work. In May 2020, when the study began, the techniques for measuring antibodies to SARS-CoV-2 were qualitative or semi-quantitative, so once the WHO international standard for quantification of IgG(S) antibodies was established we retrospectively analyzed a measurement of IgG spike S1 using a quantitative technique. The follow-up of IgG(S) levels stopped as participants were vaccinated, while the IgM(N) and IgG(N) continued. Key questions remain unanswered, such as whether these models kinetics will be valid in vaccinated individuals; if the kinetics and duration of anti-S antibodies are similar in natural infection and vaccination; and whether previously infected and uninfected patients will show the same kinetics after vaccination. Epidemiological modelling studies, including long-term immune monitoring, will be crucial in the case of SARS CoV-2 but also to evaluate the interactions with other coronaviruses for accurate predictions in the case of other viral coinfections (e.g. flu, other coronavirus, HIV-1) 22, 23 To conclude, we monitored three ant...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04885478RecruitingProfessional's Health in Epidemiological Crisis Covid-19

    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

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  2. Version published to 10.1101/2021.09.10.21262527v1 on medRxiv