Longitudinal Analysis of SARS-CoV-2 Vaccine Breakthrough Infections Reveals Limited Infectious Virus Shedding and Restricted Tissue Distribution

  1. Ruian Ke
  2. Pamela P Martinez
  3. Rebecca L Smith
  4. Laura L Gibson
  5. Chad J Achenbach
  6. Sally McFall
  7. Chao Qi
  8. Joshua Jacob
  9. Etienne Dembele
  10. Camille Bundy
  11. Lacy M Simons
  12. Egon A Ozer
  13. Judd F Hultquist
  14. Ramon Lorenzo-Redondo
  15. Anita K Opdycke
  16. Claudia Hawkins
  17. Robert L Murphy
  18. Agha Mirza
  19. Madison Conte
  20. Nicholas Gallagher
  21. Chun Huai Luo
  22. Junko Jarrett
  23. Abigail Conte
  24. Ruifeng Zhou
  25. Mireille Farjo
  26. Gloria Rendon
  27. Christopher J Fields
  28. Leyi Wang
  29. Richard Fredrickson
  30. Melinda E Baughman
  31. Karen K Chiu
  32. Hannah Choi
  33. Kevin R Scardina
  34. Alyssa N Owens
  35. John Broach
  36. Bruce Barton
  37. Peter Lazar
  38. Matthew L Robinson
  39. Heba H Mostafa
  40. Yukari C Manabe
  41. Andrew Pekosz
  42. David D McManus
  43. Christopher B Brooke

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Abstract

Background

The global effort to vaccinate people against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during an ongoing pandemic has raised questions about how vaccine breakthrough infections compare with infections in immunologically naive individuals and the potential for vaccinated individuals to transmit the virus.

Methods

We examined viral dynamics and infectious virus shedding through daily longitudinal sampling in 23 adults infected with SARS-CoV-2 at varying stages of vaccination, including 6 fully vaccinated individuals.

Results

The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases.

Conclusions

Vaccination shortens the duration of time of high transmission potential, minimizes symptom duration, and may restrict tissue dissemination.

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  1. Version published to 10.1093/ofid/ofac192
  2. ScreenIT

    SciScore for 10.1101/2021.08.30.21262701: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Western Institutional Review Board, and all participants provided informed consent.
    Consent: This study was approved by the Western Institutional Review Board, and all participants provided informed consent.
    Sex as a biological variablenot detected.
    RandomizationSample collection: Each day, participants were remotely observed by trained study staff collecting: The order of nostrils (left vs. right) used for the two different swabs was randomized.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus culture from nasal swabs: Vero-TMPRSS2 cells were grown in complete medium (CM) consisting of DMEM with 10% fetal bovine serum (Gibco), 1 mM glutamine (Invitrogen), 1 mM sodium pyruvate (Invitrogen), 100 U/ml of penicillin (Invitrogen), and 100 μg/ml of streptomycin (Invitrogen)17.
    Vero-TMPRSS2
    suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)
    Software and Algorithms
    SentencesResources
    Swift v2 primer sequences were trimmed prior to variant analysis from iVar version 1.3.1 (https://genomebiology.biomedcentral.com/articles/10.1186/s13059-018-1618-7) retaining all calls with a minimum allele frequency of 0.01 and higher.
    iVar
    suggested: None

    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.

    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 10.1101/2021.08.30.21262701v1 on medRxiv