Persistence of neutralizing antibodies a year after SARS‐CoV‐2 infection in humans

  1. Anu Haveri
  2. Nina Ekström
  3. Anna Solastie
  4. Camilla Virta
  5. Pamela Österlund
  6. Elina Isosaari
  7. Hanna Nohynek
  8. Arto A Palmu
  9. Merit Melin

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Abstract

Most subjects develop antibodies to SARS‐CoV‐2 following infection. In order to estimate the duration of immunity induced by SARS‐CoV‐2 it is important to understand for how long antibodies persist after infection in humans. Here, we assessed the persistence of serum antibodies following WT SARS‐CoV‐2 infection at 8 and 13 months after diagnosis in 367 individuals. The SARS‐CoV‐2 spike IgG (S‐IgG) and nucleoprotein IgG (N‐IgG) concentrations and the proportion of subjects with neutralizing antibodies (NAb) were assessed. Moreover, the NAb titers among a smaller subset of participants ( n = 78) against a WT virus (B) and variants of concern (VOCs): Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2) were determined. We found that NAb against the WT virus persisted in 89% and S‐IgG in 97% of subjects for at least 13 months after infection. Only 36% had N‐IgG by 13 months. The mean S‐IgG concentrations declined from 8 to 13 months by less than one third; N‐IgG concentrations declined by two‐thirds. Subjects with severe infection had markedly higher IgG and NAb levels and are expected to remain seropositive for longer. Significantly lower NAb titers against the variants compared to the WT virus, especially after a mild disease, suggests reduced protection against VOCs.

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  1. Version published to 10.1002/eji.202149535
  2. ScreenIT

    SciScore for 10.1101/2021.07.13.21260426: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: The study protocol was reviewed and approved by the ethical committee the Hospital District of Helsinki and Uusimaa (HUS) and registered under the Development of seroprevalence in Finland during the new coronavirus (SARS-CoV-2) epidemic – serological population study protocol HUS/1137/2020.
    Consent: Informed consent was obtained from all study subjects before sample collection.
    Sex as a biological variablenot detected.
    RandomizationA smaller subset of participants for the NAb titration: For comparison of NAb titers against a wild-type virus and variants of concern (Alpha, Beta and Delta), 80/536 twelve-month sera screened to have NAb positive (titer ≥6 against wild-type virus) were randomly selected as above mentioned.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Further, samples of subjects with ≥30% increase in IgG antibody concentration to both SARS-CoV-2 spike glycoprotein antigens (full-length spike protein (SFL) and receptor binding protein (RBD)) between six and twelve month blood sampling (n=29) were excluded from the analysis.
    SARS-CoV-2 spike glycoprotein antigens (full-length spike protein (SFL) and receptor binding protein (RBD)
    suggested: None
    Goat Anti-Human IgG detection antibody (Jackson Immuno Research) was added into the wells and incubated for 30 minutes before washing.
    Anti-Human IgG
    suggested: None
    A sample was considered positive for SARS-CoV-2 IgG antibodies (S-IgG) when SFL and RBD specific antibody concentrations were ≥0.089 and ≥0.13 BAU/ml, respectively.
    SARS-CoV-2 IgG
    suggested: None
    A sample was considered positive for nucleoprotein specific IgG antibodies (N-IgG) when N-IgG concentration was ≥0.58 BAU/ml.
    nucleoprotein specific IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus isolation and propagation was performed in Vero E6 cells (44).
    Vero E6
    suggested: RRID:CVCL_XD71)
    All variant viruses were isolated and propagated (passages 1-2) in VeroE6-TMPRSS2-H10 cells (46) and further propagated in Vero E6 cells (passage 3) for MNT.
    VeroE6-TMPRSS2-H10
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using SPSS v27 and R (v4.0.4) with Rstudio (v1.4.1106).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    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: We detected the following sentences addressing limitations in the study:
    We recognize certain limitations in our study. Due to high SARS-CoV-2 vaccine coverage in the older age groups (≥60 years of age) at the time of the study, only 11% of the participants of our study were ≥60 years of age, the age group with highest disease incidence and morbidity. Since the median age of study subjects was 50 years, our results may not necessarily apply to all age groups. The number of subjects selected to the NAb titer comparison was limited but the study subjects were matched by disease severity, age and gender and randomly selected from the participants. Previous studies have indicated that the presence of antibodies to SARS-CoV-2 was associated with a significantly reduced risk of SARS-CoV-2 reinfection among health-care workers for up to seven months after infection (21, 42). We observed that S-IgG antibodies and neutralizing antibodies persist at least a year after infection in the vast majority of individuals who have recovered from infection. This strongly suggests that protection against re-infection is long-lived, although antibody-mediated immunity may not persist equally well among elderly subjects. A previous study found that patients older than 60 years had fewer memory B cells secreting total IgG and RBD-specific IgG than patients under 60 years old nine months after infection (8). In this study we observed that IgG concentrations declined from six to twelve months more substantially in subjects ≥60 years compared to younger age groups. Similar ...

    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

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  3. Version published to 10.1101/2021.07.13.21260426v1 on medRxiv