Prevalence of indeterminate tuberculosis interferon-gamma release assays in COVID-19 patients: Systematic review and meta-analysis

Health Sci Rep. 2023 Dec 20;6(12):e1695. doi: 10.1002/hsr2.1695. eCollection 2023 Dec.

Abstract

Background and aims: The reliability of interferon-gamma-release-assays (IGRAs) for tuberculosis (TB) testing in coronavirus disease 2019 (COVID-19) patients is unknown. This study aimed to systematically review the prevalence of indeterminate TB-IGRA following SARS-CoV-2 infection or vaccination and to review associated factors.

Methods: This systematic literature review was guided according to the PRISMA guidelines by searching PubMed, Scopus, Web of Science, Clinicalkey, and Cochrane Library. Studies reporting results of TB-IGRA tests (QuantiFERON [QFT]-TB, T-SPOT.TB) in COVID-19 patients or vaccines were included. The random effects model was used to assess the prevalence of indeterminate IGRA results. Heterogeneity was evaluated using the Τ 2 and 95% predictive interval.

Results: Of the 273 citations screened, 12 articles were included in the final analysis including a total of 2107 patients. The overall pooled effect size proportion of indeterminate QFT-TB results, estimated in eight studies using the QFT-TB Plus assay, was 0.26 (95% CI: 0.205-0.324, Τ 2 = 0.158). The mean true effect size was 0.26 (95% predictive interval: [0.110-0.500]). A subgroup analysis was not undertaken due to the small number of studies. Indeterminate QFT-TB rates were associated with COVID-19 severity, steroid treatment, inflammation-related parameters, neutrophilia, and lymphopenia.

Conclusion: Indeterminate QFT-TB results in COVID-19 patients occur in almost one-quarter of tests performed. Further studies are needed to assess associated factors.

Keywords: QuantiFERON; SARS‐CoV‐2; T cell response; latent tuberculosis.