Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers

  1. Pratibha Kale
  2. Ekta Gupta
  3. Chhagan Bihari
  4. Niharika Patel
  5. Sheetalnath Rooge
  6. Amit Pandey
  7. Meenu Bajpai
  8. Vikas Khillan
  9. Partha Chattopadhyay
  10. Priti Devi
  11. Ranjeet Maurya
  12. Neha Jha
  13. Priyanka Mehta
  14. Manish Kumar
  15. Pooja Sharma
  16. Sheeba Saifi
  17. Aparna Swaminathan
  18. Sarfaraz Alam
  19. Bharathram Uppili
  20. Mohammed Faruq
  21. Anurag Agrawal
  22. Rajesh Pandey
  23. Shiv Kumar Sarin

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Abstract

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

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  1. Version published to 10.3390/vaccines10010054
  2. ScreenIT

    SciScore for 10.1101/2021.06.28.21259546: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: The study had the approval of the Institutional Ethical Committee (IEC/2020/77/MA07) and was conducted following the Declaration of Helsinki.
    Sex as a biological variablenot detected.
    RandomizationSARS-CoV-2 Whole genome sequencing: Sequencing using Illumina MiSeq Platform: 46 RT-PCR positive samples (Ct value ≤ 20) were randomly selected from the Virology repository at -80°C and subjected to whole genome sequencing (WGS).
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    The SARS COV2 IgG antibodies were measured using the enhanced chemiluminescence method (Vitros ECi, Ortho Clinical Diagnostics, New Jersey, US).
    SARS COV2 IgG
    suggested: (EnCor Biotechnology Cat# RPCA-SARS-CoV2-bd, RRID:AB_2861175)
    Software and Algorithms
    SentencesResources
    SARS-CoV-2 Whole genome sequencing: Sequencing using Illumina MiSeq Platform: 46 RT-PCR positive samples (Ct value ≤ 20) were randomly selected from the Virology repository at -80°C and subjected to whole genome sequencing (WGS).
    WGS
    suggested: None
    Sequencing data analysis: MiSeq data analysis: FastQC v0.11.9 (http://www.bioinformatics.babraham.ac.uk/projects/fastqc) was used to check the Phred quality score for all sequences.
    MiSeq
    suggested: (A5-miseq, RRID:SCR_012148)
    FastQC
    suggested: (FastQC, RRID:SCR_014583)
    Phred
    suggested: (Phred, RRID:SCR_001017)
    Adapter trimming was performed using the Trim Galore tool v0.6.1 (https://www.bioinformatics.babraham.ac.uk/projects/trim_galore/) and alignment of sequences was performed using the HISAT2 [7] algorithm on human data build GRCh38.
    Trim Galore
    suggested: (Trim Galore, RRID:SCR_011847)
    HISAT2
    suggested: (HISAT2, RRID:SCR_015530)
    To remove any human sequences from the dataset, samtools v1.12 [8] were used to remove aligned sequences.
    samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    SARS-CoV-2 Phylogenetic and mutation analysis: We sequenced 46 vaccinated COVID-19 positive samples that were aligned to NC_045512 reference genome using MAFFT v7.475 [9] multiple alignment tool.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    The aligned sequences were trimmed to remove gaps and a phylogenetic tree was generated using the default model of the IQ-TREE tool v2.0.3 [10].
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)
    The tree was visualized using FigTree v1.4.4 [11].
    FigTree
    suggested: (FigTree, RRID:SCR_008515)
    The lollipop plot is generated in RStudio using g3viz, rtracklayer, and trackViewer packages followed by data visualization using the ggplot2 package.
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)
    All the figures were updated using Inkscape software [13].
    Inkscape
    suggested: (Inkscape, RRID:SCR_014479)
    The statistical analysis was done using SPSS software version 22.
    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: 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 10.1101/2021.06.28.21259546v1 on medRxiv