Interferon Gamma Release Assay Mitogen Responses in COVID-19

Background Elevated cytokine release and T cell exhaustion have been associated with COVID-19 disease severity. T cell activity may be indirectly measured through interferon gamma release assays (IGRAs), which use mitogen stimulation of T lymphocytes as a positive control. In our institution, an unexpectedly high rate of indeterminate IGRAs was noted in COVID-19–positive patients. We aimed to evaluate the clinical characteristics associated with indeterminate IGRA results and the difference in mitogen responses between COVID-19–positive and COVID-19–negative patients. Methods We reviewed all patients, regardless of COVID status, who were admitted between March 1, 2020, and May 31, 2020, and for whom an IGRA was collected. For COVID-19–positive individuals, we evaluated the statistical association of their IGRA results and clinical characteristics, including demographics, laboratory values, comorbidities, and hospitalization-related outcomes. For both COVID-19–positive and COVID-19–negative individuals, we evaluated IGRA mitogen control values relative to COVID-19 status as stratified by absolute lymphocyte count. Results In COVID-19–positive patients, indeterminate IGRA results were statistically associated with white blood cell count and other markers of inflammation. When comparing COVID-19–positive and COVID-19–negative patients, we noted a statistically significant difference in IGRA mitogen control values when stratified by absolute lymphocyte count. Conclusions Indeterminate IGRA results were associated with higher levels of inflammatory markers. Furthermore, when comparing mitogen responses between COVID-19–positive and COVID-19–negative patients, there was an observed difference in T cell reactivity between the groups. The mitogen response in IGRAs may serve as a surrogate for T cell function and a marker of disease severity in COVID-19.