Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento

  1. Paola Stefanelli
  2. Antonino Bella
  3. Giorgio Fedele
  4. Stefano Fiore
  5. Serena Pancheri
  6. Eleonora Benedetti
  7. Concetta Fabiani
  8. Pasqualina Leone
  9. Paola Vacca
  10. Ilaria Schiavoni
  11. Arianna Neri
  12. Anna Carannante
  13. Maurizio Simmaco
  14. Iolanda Santino
  15. Maria Grazia Zuccali
  16. Giancarlo Bizzarri
  17. Rosa Magnoni
  18. Pier Paolo Benetollo
  19. Silvio Brusaferro
  20. Giovanni Rezza
  21. Antonio Ferro

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Abstract

Background

There are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before.

Methods

All individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID 50 ) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA).

Findings

Overall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity.

Interpretation

A decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.

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  1. Version published to 10.1101/2020.11.11.20229062v2 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2020.11.11.20229062: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the Ethical Committee of the ISS (Prot.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The Department of Prevention of the Azienda Provinciale per i Servizi Sanitari (APSS) sent a letter of invitation to participate at a second study to all the citizens who resulted to be positive for anti-SARS-CoV-2 antibodies in the serosurvey conducted 4 months before, between May 5 and 15, 2020.
    anti-SARS-CoV-2
    suggested: None
    The analyser automatically calculates SARS-CoV-2 NC IgG antibody concentration expressed as an index value.
    NC IgG
    suggested: None
    The DiaSorin SARS-CoV-2 IgG assay is also a two-step CLIA assay for the detection of IgG antibodies against S1/S2 antigens of SARS-CoV-2.
    S1/S2
    suggested: None
    The analyser automatically calculates SARS-CoV-2 S1/S2 IgG antibody concentrations expressed as arbitrary units (AU/mL).
    S1/S2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    A known amount of SARS-CoV-2 (code 77III, isolated and cultivated at ISS, titre 1×105,4; GISAID accession ID: EPI_ISL_412973) was incubated with different dilutions of the serum sample to determine the dilution at which cytopathic effect on Vero E6 cells (ATCC® CRL-1586) is observed in 50% of infected wells (MN 50%).
    Vero E6
    suggested: None
    Software and Algorithms
    SentencesResources
    Serum preparation and storage: Blood samples (5 ml) were collected in Serum Separator Tubes (BD Diagnostic Systems, Franklin Lakes, NJ, USA) and centrifuged at room temperature at 1600 rpm for 10 min.
    BD Diagnostic Systems
    suggested: None
    In particular, all the serum samples were evaluated by using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, Chicago, IL, USA); sera resulting negative were retested using the DiaSorin Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis was performed by the STATA version 16.1 (STATA Corp., College Station, Texas, USA).
    STATA
    suggested: (Stata, RRID:SCR_012763)

    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.

    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 10.1101/2020.11.11.20229062v1 on medRxiv