Virological and Serological Characterisation of SARS-CoV-2 Infections Diagnosed After mRNA BNT162b2 Vaccination Between December 2020 and March 2021

  1. Francesca Colavita
  2. Silvia Meschi
  3. Cesare Ernesto Maria Gruber
  4. Martina Rueca
  5. Francesco Vairo
  6. Giulia Matusali
  7. Daniele Lapa
  8. Emanuela Giombini
  9. Gabriella De Carli
  10. Martina Spaziante
  11. Francesco Messina
  12. Giulia Bonfiglio
  13. Fabrizio Carletti
  14. Eleonora Lalle
  15. Lavinia Fabeni
  16. Giulia Berno
  17. Vincenzo Puro
  18. Barbara Bartolini
  19. Antonino Di Caro
  20. Giuseppe Ippolito
  21. Maria Rosaria Capobianchi
  22. Concetta Castilletti

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Abstract

Vaccines for coronavirus disease 2019 (COVID-19) are proving to be very effective in preventing severe illness; however, although rare, post-vaccine infections have been reported. The present study focuses on virological and serological features of 94 infections that occurred in Lazio Region (Central Italy) between 27 December 2020, and 30 March 2021, after one or two doses of mRNA BNT162b2 vaccine.

Methods

We evaluated clinical features, virological (viral load; viral infectiousness; genomic characterisation), and serological (anti-nucleoprotein Ig; anti-Spike RBD IgG; neutralising antibodies, nAb) characteristics of 94 post-vaccine infections at the time of diagnosis. Nasopharyngeal swabs (NPSs) and serum samples were collected in the framework of the surveillance activities on SARS-CoV-2 variants established in Lazio Region (Central Italy) and analysed at the National Institute for Infectious Diseases “L. Spallanzani” in Rome.

Results

The majority (92.6%) of the post-vaccine infections showed pauci/asymptomatic or mild clinical course, with symptoms and hospitalisation rate significantly less frequent in patients infected after full vaccination course as compared to patients who received a single dose vaccine. Although differences were not statistically significant, viral loads and isolation rates were lower in NPSs from patients infected after receiving two vaccine doses as compared to patients with one dose. Most cases (84%) had nAb in serum at the time of infection diagnosis, which is a sub-group of vaccinees, were found similarly able to neutralise Alpha and Gamma variants. Asymptomatic individuals showed higher nAb titres as compared to symptomatic cases (median titre: 1:120 vs. 1:40, respectively). Finally, the proportion of post-vaccine infections attributed either to Alpha and Gamma variants was similar to the proportion observed in the contemporary unvaccinated population in the Lazio region, and mutational analysis did not reveal enrichment of a defined set of Spike protein substitutions depending on the vaccination status.

Conclusion

Our study conducted using real-life data, emphasised the importance of monitoring vaccine breakthrough infections, through the characterisation of virological, immunological, and clinical features associated with these events, in order to tune prevention measures in the next phase of the COVID-19 pandemic.

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  1. Version published to 10.3389/fmed.2021.815870
  2. ScreenIT

    SciScore for 10.1101/2021.09.21.21263882: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Use of laboratory and epidemiological records for research purpose has been approved by the INMI Ethical Committee (issue n. 214/20-11-2020), and the need of informed consent form was waived.
    Consent: Use of laboratory and epidemiological records for research purpose has been approved by the INMI Ethical Committee (issue n. 214/20-11-2020), and the need of informed consent form was waived.
    Sex as a biological variablenot detected.
    RandomizationSequencing data (n=1072) produced at INMI exclusively from randomly selected samples collected from unvaccinated individuals during the same study period and representing all the regional territory, were used to evaluate the prevalence of variants of concern (VOCs).
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological testing: Serological investigation included the detection of anti-N and anti-RBD Spike IgG using Abbott SARS-CoV-2 assay on Abbott ARCHITECT® i2000sr (Abbott Diagnostics, Chicago, IL, USA) and the evaluation of the neutralising antibodies (nAb) titres using SARS-CoV-2 microneutralization test (MNT) based on live virus 13.
    anti-N
    suggested: None
    anti-RBD
    suggested: None
    MNT
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Virus isolation: Viral culture was performed in a biosafety level 3 (BSL-3) laboratory at INMI on Vero E6/TMPRSS2 (kindly provided by Dr. Oeda S., National Institute of Infectious Diseases, Tokyo, Japan), as previously described 12.
    Vero E6/TMPRSS2
    suggested: None
    Software and Algorithms
    SentencesResources
    Serological testing: Serological investigation included the detection of anti-N and anti-RBD Spike IgG using Abbott SARS-CoV-2 assay on Abbott ARCHITECT® i2000sr (Abbott Diagnostics, Chicago, IL, USA) and the evaluation of the neutralising antibodies (nAb) titres using SARS-CoV-2 microneutralization test (MNT) based on live virus 13.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistics: Epidemiological and demographic data were extracted from the Regional Surveillance Information System established by the regional health authority and analyzed using the STATA 14 software.
    STATA
    suggested: (Stata, RRID:SCR_012763)
    Analyses were performed using GraphPad Prism version 8.00 (GraphPad Software, La Jolla California) and SPSS V.23 for Windows statistical software; p-value<0.05 was considered statistically significant.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    Our study presents some limitation that should be acknowledged. First, the study was an observational study based on real-life data obtained from pandemic surveillance activities, aimed not to establish vaccine efficacy compared to a matched unvaccinated control group, but, to report a virological characterization of those patients reported with SARS-CoV-2 infection despite being vaccinated. Therefore, our observation should be replicated and extended on larger cohorts established ad hoc and to other vaccine formulations. Furthermore, no follow-up samples were available for the post-vaccination infected individuals, so that it was not possible to monitor the viral loads and the shedding of infectious virus. In addition, as described above, pre-infection antibody status was only available for few patients. Finally, the evaluation of the cellular immune response would be of great interest to better understand the protection status in cases of vaccine breakthrough infections.

    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.

  3. Version published to 10.1101/2021.09.21.21263882v1 on medRxiv