Seropositivity in blood donors and pregnant women during the first year of SARS‐CoV‐2 transmission in Stockholm, Sweden

  1. X. Castro Dopico
  2. S. Muschiol
  3. M. Christian
  4. L. Hanke
  5. D. J. Sheward
  6. N. F. Grinberg
  7. J. Rorbach
  8. G. Bogdanovic
  9. G. M. Mcinerney
  10. T. Allander
  11. C. Wallace
  12. B. Murrell
  13. J. Albert
  14. G. B. Karlsson Hedestam

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Abstract

Background

In Sweden, social restrictions to contain SARS‐CoV‐2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS‐CoV‐2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women ( n  = 5,100) were sampled at random between 14 March 2020 and 28 February 2021.

Methods

In this cross‐sectional prospective study, otherwise‐healthy blood donors ( n  = 2,600) and pregnant women ( n =  2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls ( n  = 595) were screened for IgG responses against stabilized trimers of the SARS‐CoV‐2 spike (S) glycoprotein and the smaller receptor‐binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut‐off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time.

Setting

Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020–01807.

Participants

No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants.

Results

Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened ( n  = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS‐CoV‐2 spike mRNA vaccination, supporting that mild infection engenders a competent B‐cell response.

Conclusions

These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.

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  1. Version published to 10.1111/joim.13304
  2. Version published to 10.1101/2020.12.24.20248821v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.12.24.20248821: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationHuman samples and ethical declaration: Anonymized samples from blood donors (n=100/sampling week) and pregnant women (n=100/sampling week) were randomly selected from their respective pools by the department of Clinical Microbiology, Karolinska University Hospital.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableHuman samples and ethical declaration: Anonymized samples from blood donors (n=100/sampling week) and pregnant women (n=100/sampling week) were randomly selected from their respective pools by the department of Clinical Microbiology, Karolinska University Hospital.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Secondary HRP-conjugated anti-human antibodies were diluted in blocking buffer and incubated with samples for 1 hour at room temperature.
    anti-human
    suggested: None
    Secondary antibodies (from Southern Biotech) and dilutions used: goat anti-human IgG (2014-05) at 1:10,000.
    anti-human IgG
    suggested: (SouthernBiotech Cat# 2014-05, RRID:AB_2795580)
    Briefly, we used a logistic regression over anti-RBD and -S training data (from n=595 historical blood donor controls and n=138 SARS-CoV-2 PCR+ individuals across the clinical spectrum) to model the relationship between the ELISA measurements and the probability that a sample is antibody-positive.
    anti-RBD
    suggested: None
    antibody-positive
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The RBD domain (RVQ – QFG) of SARS-CoV-2 was cloned upstream of a Sortase A recognition site (LPETG) and a 6xHIS tag, and expressed in 293F cells as described above.
    293F
    suggested: RRID:CVCL_D615)
    In vitro virus neutralisation assay: Pseudotyped viruses were generated by the co-transfection of HEK293T cells with plasmids encoding the SARS-CoV-2 spike protein harboring an 18 amino acid truncation of the cytoplasmic tail2; a plasmid encoding firefly luciferase; a lentiviral packaging plasmid (Addgene 8455) using Lipofectamine 3000 (Invitrogen).
    HEK293T
    suggested: None
    Pseudotyped neutralisation assays were adapted from protocols validated to characterize the neutralization of HIV, but with the use of HEK293T-ACE2 cells.
    HEK293T-ACE2
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.

    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.

  4. Version published to 10.1101/2020.12.24.20248821v1 on medRxiv