SARS-CoV-2 antibodies remain detectable 12 months after infection and antibody magnitude is associated with age and COVID-19 severity

  1. Eric D. Laing
  2. Nusrat J. Epsi
  3. Stephanie A. Richard
  4. Emily C. Samuels
  5. Wei Wang
  6. Russell Vassell
  7. Daniel F. Ewing
  8. Rachel Herrup
  9. Spencer L. Sterling
  10. David A Lindholm
  11. Eugene V. Millar
  12. Ryan C. Maves
  13. Derek T. Larson
  14. Rhonda E. Colombo
  15. Sharon Chi
  16. Cristian Madar
  17. Tahaniyat Lalani
  18. Anuradha Ganesan
  19. Anthony Fries
  20. Christopher J. Colombo
  21. Katrin Mende
  22. Mark P. Simons
  23. Kevin L. Schully
  24. Carol D. Weiss
  25. David R. Tribble
  26. Brian K. Agan
  27. Simon D. Pollett
  28. Christopher C. Broder
  29. Timothy H. Burgess
  30. for the EPICC Study team

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Abstract

Importance

The persistence of SARS-CoV-2 antibodies may be a predictive correlate of protection for both natural infections and vaccinations. Identifying predictors of robust antibody responses is important to evaluate the risk of re-infection / vaccine failure and may be translatable to vaccine effectiveness.

Objective

To 1) determine the durability of anti-SARS-CoV-2 IgG and neutralizing antibodies in subjects who experienced mild and moderate to severe COVID-19, and 2) to evaluate the correlation of age and IgG responses to both endemic human seasonal coronaviruses (HCoVs) and SARS-CoV-2 according to infection outcome.

Design

Longitudinal serum samples were collected from PCR-confirmed SARS-CoV-2 positive participants (U.S. active duty service members, dependents and military retirees, including a range of ages and demographics) who sought medical treatment at seven U.S. military hospitals from March 2020 to March 2021 and enrolled in a prospective observational cohort study.

Results

We observed SARS-CoV-2 seropositivity in 100% of inpatients followed for six months (58/58) to one year (8/8), while we observed seroreversion in 5% (9/192) of outpatients six to ten months after symptom onset, and 18% (2/11) of outpatients followed for one year. Both outpatient and inpatient anti-SARS-CoV-2 binding-IgG responses had a half-life ( T 1/2 ) of >1000 days post-symptom onset. The magnitude of neutralizing antibodies (geometric mean titer, inpatients: 378 [246-580, 95% CI] versus outpatients: 83 [59-116, 95% CI]) and durability (inpatients: 65 [43-98, 95% CI] versus outpatients: 33 [26-40, 95% CI]) were associated with COVID-19 severity. Older age was a positive correlate with both higher IgG binding and neutralizing antibody levels when controlling for COVID-19 hospitalization status. We found no significant relationships between HCoV antibody responses and COVID-19 clinical outcomes, or the development of SARS-CoV-2 neutralizing antibodies.

Conclusions and Relevance

This study demonstrates that humoral responses to SARS-CoV-2 infection are robust on longer time-scales, including those arising from milder infections.

However, the magnitude and durability of the antibody response after natural infection was lower and more variable in younger participants who did not require hospitalization for COVID-19. These findings support vaccination against SARS-CoV-2 in all suitable populations including those individuals that have recovered from natural infection.

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  1. ScreenIT

    SciScore for 10.1101/2021.04.27.21256207: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
    Consent: The protocol was approved by the Uniformed Services University Institutional Review Board (IDCRP-085), and all subjects or their legally authorized representative provided informed consent to participate.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The antibody dilution causing a 50% and 80% reduction (inhibitory concentration, IC) of vector-expressed luciferase compared to control (IC50- and IC80-neutralizing antibody titer, respectively) was calculated with nonlinear regression using GraphPad Prism.
    IC80-neutralizing
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Additional details are provided in the (eMethods), briefly, pseudovirus titers were measured by infecting 293T-ACE2.TMPRSS2 cells.
    293T-ACE2.TMPRSS2
    suggested: None
    SARS-CoV-2 (USA WA1/2020, BEI Resources cat # NR-52281) and serum samples were incubated for one hour then incubated with Vero-81 cells (ATCC cat NoCRL-1587).
    Vero-81
    suggested: None
    Software and Algorithms
    SentencesResources
    Figures were generated and statistical analyses were performed in GraphPad Prism version 9.0.2 and RStudio version 4.0.2 software (R Foundation for Statistical Computing)43.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    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.

  2. Version published to 10.1101/2021.04.27.21256207v1 on medRxiv