Evaluation of COVID-19 vaccine breakthrough infections among immunocompromised patients fully vaccinated with BNT162b2

  1. Manuela Di Fusco
  2. Mary M Moran
  3. Alejandro Cane
  4. Daniel Curcio
  5. Farid Khan
  6. Deepa Malhotra
  7. Andy Surinach
  8. Amanda Miles
  9. David Swerdlow
  10. John M McLaughlin
  11. Jennifer L Nguyen

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Abstract

Objective

To evaluate COVID-19 vaccine breakthrough infections among immunocompromised (IC) individuals.

Methods

Individuals vaccinated with BNT162b2 were selected from the US HealthVerity database (12/10/2020-7/8/2021). COVID-19 vaccine breakthrough infections were examined in fully vaccinated (≥14 days after 2 nd dose) IC individuals (IC cohort), 12 mutually exclusive IC condition groups, and a non-IC cohort. IC conditions were identified using an algorithm based on diagnosis codes and immunosuppressive (IS) medication usage.

Results

Of 1,277,747 individuals ≥16 years of age who received 2 BNT162b2 doses, 225,796 (17.7%) were identified as IC (median age: 58 years; 56.3% female). The most prevalent IC conditions were solid malignancy (32.0%), kidney disease (19.5%), and rheumatologic/inflammatory conditions (16.7%). Among the fully vaccinated IC and non-IC cohorts, a total of 978 breakthrough infections were observed during the study period; 124 (12.7%) resulted in hospitalization and 2 (0.2%) were inpatient deaths. IC individuals accounted for 38.2% (N=374) of all breakthrough infections, 59.7% (N=74) of all hospitalizations, and 100% (N=2) of inpatient deaths. The proportion with breakthrough infections was 3 times higher in the IC cohort compared to the non-IC cohort (N=374 [0.18%] vs. N=604 [0.06%]; unadjusted incidence rates were 0.89 and 0.34 per 100 person-years, respectively. Organ transplant recipients had the highest incidence rate; those with >1 IC condition, antimetabolite usage, primary immunodeficiencies, and hematologic malignancies also had higher incidence rates compared to the overall IC cohort. Incidence rates in older (≥65 years old) IC individuals were generally higher versus younger IC individuals (<65).

Limitations

This retrospective analysis relied on coding accuracy and had limited capture of COVID-19 vaccine receipt.

Conclusions

COVID-19 vaccine breakthrough infections are rare but are more common and severe in IC individuals. The findings from this large study support FDA authorization and CDC recommendations to offer a 3 rd vaccine dose to increase protection among IC individuals.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.12.21264707: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was deemed exempt from Institutional Review Board (IRB) review pursuant to the terms of the US Department of Health and Human Service’s Policy for Protection of Human Research Subjects at 45 C.F.R. 46.104(d); category 4 exemption (Sterling IRB, Boston, Maine waived ethical approval for this work).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, North Carolina).
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)
    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:
    The findings of this study should be interpreted in the context of its limitations. First, COVID-19 vaccination status captured in administrative claims-based data sources may not be comprehensive and some BNT162b2 vaccinated individuals may have been missed, especially with the code-specific definitions of vaccination status utilized in this study. Furthermore, an unvaccinated study group was not included in the analyses, because people who are unvaccinated could not be reliably identified in the administrative claims-based data source. We utilized the ICD-10 code U071 on a healthcare claim to identify a breakthrough infection, and thus asymptomatic/minimally symptomatic breakthrough infection cases that may have been only identified with a RT-PCR test may have been missed, in addition to those individuals who did not seek care for COVID-19 illness. Although we included multiple types of IC conditions in this study, the sample sizes of some IC condition groups were small, especially bone marrow transplant recipients. Additionally, the broad algorithm used to identify individuals with IC conditions may have led to some individuals being categorized as IC when they actually were not. Laboratory test results, if they were available in the data source, may have helped in identifying more precisely individuals who were IC and further study is warranted using other data sources that contain such information. The majority of the study period encompassed the time prior to the domina...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT05020145Active, not recruitingCOVID-19 Vaccination and Breakthrough Infections Among Perso…

    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.

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  2. Version published to 10.1101/2021.10.12.21264707 on medRxiv
  3. Version published to 10.1080/13696998.2021.2002063