Breakthrough SARS‐CoV‐2 infection outcomes in vaccinated patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study

  1. Jin Ge
  2. Jean C. Digitale
  3. Mark J. Pletcher
  4. Jennifer C. Lai
  5. for the N3C Consortium

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Abstract

Outcomes of breakthrough SARS‐CoV‐2 infections have not been well characterized in non‐veteran vaccinated patients with chronic liver diseases (CLD). We used the National COVID Cohort Collaborative (N3C) to describe these outcomes.

Approach and Results:

We identified all CLD patients with or without cirrhosis who had SARS‐CoV‐2 testing in the N3C Data Enclave as of January 15, 2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all‐cause mortality at 30 days among infected CLD patients. We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of 43,079 vaccinated patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) with cirrhosis. Breakthrough infection incidences were 5.4 and 4.9 per 1000 person‐months for fully vaccinated CLD patients without cirrhosis and with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis, 15% and 3.7%, respectively, developed SARS‐CoV‐2 infection. The 30‐day outcome of mechanical ventilation or death after SARS‐CoV‐2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34‐times adjusted hazard of death at 30 days.

Conclusions:

In this N3C study, breakthrough infection rates were similar among CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all‐cause mortality for breakthrough infection among CLD patients with cirrhosis. These results provide an additional impetus for increasing vaccination uptake in CLD populations.

Article activity feed

  1. Version published to 10.1002/hep.32780
  2. Version published to 10.1101/2022.02.25.22271490v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.02.25.22271490: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Institutional Review Board Oversight: Submission of data from individual centers to N3C are governed by a central institutional review board (IRB) protocol #IRB00249128 hosted at Johns Hopkins University School of Medicine via the SMART IRB40 Master Common Reciprocal reliance agreement.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data queries, extractions, and transformations of OMOP data elements and concepts in the N3C Data Enclave were conducted using the Palantir Foundry implementations of Spark-Python, version 3.6, and Spark-SQL, version 3.0.
    Spark-Python
    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: We detected the following sentences addressing limitations in the study:
    While this study is one of the first on the impact of SARS-CoV-2 vaccinations in a large, gender-balanced, and diverse population of patients with CLD, there are several limitations that have been previously described in our works utilizing the N3C Data Enclave. Limitations due to the use of N3C Data Enclave include overrepresentation of tertiary academic medical centers, selection bias due to derivation of SARS-CoV-2 negative and positive populations based on testing, systematic missingness of certain variables due to data heterogeneity, and likely misclassification between patients with alcohol-associated liver disease and non-alcoholic fatty liver disease.10 These inherent limitations likely selected for a more clinically ill patient population than the general CLD and cirrhosis patient populations. There are also several limitations specific to this particular study. First, the underlying vaccination data is based on recorded medication exposures at each of the data partner sites. This data may not include vaccinations administered at mass vaccination sites, local pharmacies, “pop-up” vaccination sites, and other venues. Therefore, there may be a significant proportion of false-negatives for detection of vaccine doses (patients who actually received a vaccination not recorded as such in the N3C Data Enclave). Second, while the N3C Data Enclave had additional or “booster” dose information in the recorded medication exposures at data partner sites, we were not able to estim...

    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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  4. Version published to 10.1101/2022.02.25.22271490v1 on medRxiv