SARS-CoV-2 seroprevalence trends in healthy blood donors during the COVID-19 Milan outbreak

  1. Luca Valenti
  2. Annalisa Bergna
  3. Serena Pelusi
  4. Federica Facciotti
  5. Alessia Lai
  6. Maciej Tarkowski
  7. Alessandra Berzuini
  8. Flavio Caprioli
  9. Luigi Santoro
  10. Guido Baselli
  11. Carla Della Ventura
  12. Elisa Erba
  13. Silvano Bosari
  14. Massimo Galli
  15. Gianguglielmo Zehender
  16. Daniele Prati

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Abstract

Background&Aims: The Milan metropolitan area in Northern Italy was among the most severely hit by the SARS-CoV-2 outbreak. The aim of this study was to examine the seroprevalence trends of SARS-CoV-2 in healthy asymptomatic adults, the risk factors, and laboratory correlates. Methods: We conducted a cross-sectional study in a random sample of blood donors since the start of the outbreak (February 24th to April 8th 2020, n=789). Presence of IgM/IgG antibodies against the SARS-CoV-2-Nucleocapsid protein was assessed by a lateral flow immunoassay. Results: The test had a 100/98.3 sensitivity/specificity, and for IgG+ was validated in a subset by an independent ELISA against the Spike protein (N=34, P<0.001). At the outbreak start, the overall adjusted seroprevalence of SARS-CoV-2 was 2.7%, 95% c.i. 0.3-6% (P<0.0001 vs. 120 historical controls). During the study period characterized by a gradual implementation of social distancing measures, there was a progressive increase in adjusted seroprevalence to 5.2%, 95% c.i. 2.4-9.0, due to a rise in IgG+ tests to 5%, 95%CI 2.8-8.2 (P=0.004 for trend, adjusted weekly increase 2.7+/-1.3%), but not of IgM+ (P=NS). At multivariate logistic regression analysis, seroconversion to IgG+ was more frequent in younger (P=0.043), while recent infections (IgM+) in older individuals (P=0.002). IgM+ was independently associated with higher triglycerides, eosinophils, and lymphocytes (P<0.05). Conclusions: SARS-CoV-2 infection was already circulating in Milan at the outbreak start. Social distancing may have been more effective in younger individuals, and by the end of April 2.4-9.0% of healthy adults had evidence of seroconversion. Asymptomatic infection may affect lipid profile and blood count.

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    SciScore for 10.1101/2020.05.11.20098442: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study protocol complies with Good Clinical Practice (GCP) rules, Declaration of Helsinki, European clinical practice, international guidelines and national law regulation in Italy, and was approved by the Ethical Committee of the Fondazione IRCCS Ca’ Granda (“COVID-19 Donors Study”, CoDS), n.334-2020 on 03/04/2020.
    Consent: The study participants were involved in the research at the time when the study was presented and informed consent signed.
    RandomizationAmong the 3,586 individuals who donated blood during the study period, we randomly selected 20 per each day to assess SARS-CoV-2 seroprevalence, whose clinical features were representative of the overall population (not shown).
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTo gain further insight into the epidemiological trends before the outbreak, we also examined anonymized samples of 184 individuals, who presented for blood donation between December 2019 and March 2020 and were included in a screening program for metabolic disorders (Bible study, mean age 54.7±6.4, 89.6% of male sex, body mass index (BMI) 28.8±3.4 Kg/m2).

    Table 2: Resources

    Antibodies
    SentencesResources
    Evaluation of anti-SARS-CoV-antibodies: The presence of IgM/IgG against SARS-CoV-2 were determined on plasma samples (20 μl) by a lateral flow immunoassay against the Nucleocapsid protein (COVID-19 IgG/IgM Rapid Test, Prima Lab, Balerna, CH).
    anti-SARS-CoV-antibodies
    suggested: None
    SARS-CoV-2
    suggested: None
    COVID-19 IgG/IgM Rapid Test, Prima Lab, Balerna, CH).
    suggested: None
    Software and Algorithms
    SentencesResources
    The study protocol complies with Good Clinical Practice (GCP) rules, Declaration of Helsinki, European clinical practice, international guidelines and national law regulation in Italy, and was approved by the Ethical Committee of the Fondazione IRCCS Ca’ Granda (“COVID-19 Donors Study”, CoDS), n.334-2020 on 03/04/2020.
    CoDS
    suggested: None
    Statistical analysis was carried out using the JMP Pro 14.0 Statistical Analysis Software (SAS Institute, Cary, NC), and R statistical analysis software version 3.5.2 (http://www.R-project.org/).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    This study has other limitations. Lateral flow immunoassays may have limited accuracy, although they showed adequate performance for epidemiological studies [18]. Although follow-up data are not yet available, the test we used showed was validated in a subset of cases by ELISA. In addition, an overestimation of the sensitivity of the test may have led to a modest underestimation of the true prevalence of SARS-CoV-2 infection, but the adjusted rate of IgG+ increase during the study was less likely affected. Blood donors are generally healthier than the general population, therefore they might have a higher number of social interactions than other groups. Furthermore, they do not include extreme age groups, at different risk of severe COVID-19. In conclusion, SARS-CoV-2 infection was already circulating in Milan at the start of COVID-19 outbreak. Social distancing may have been more effective in younger individuals, and by April 8th 2020 2.4-9.0% of healthy adults had evidence of seroconversion. Asymptomatic infection may have an impact on laboratory tests.

    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.

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  2. Version published to 10.1101/2020.05.11.20098442v2 on medRxiv
  3. Version published to 10.1101/2020.05.11.20098442v1 on medRxiv