COVID-19-Induced ARDS Is Associated with Decreased Frequency of Activated Memory/Effector T Cells Expressing CD11a+

Abstract

Preventing the progression to acute respiratory distress syndrome (ARDS) in COVID-19 is an unsolved challenge. The involvement of T cell immunity in this exacerbation remains unclear. To identify predictive markers of COVID-19 progress and outcome, we analyzed peripheral blood of 10 COVID-19-associated ARDS patients and 35 mild/moderate COVID-19 patients, not requiring intensive care. Using multi-parametric flow cytometry, we compared quantitative, phenotypic, and functional characteristics of circulating bulk immune cells, as well as SARS-CoV-2 S-protein-reactive T cells between the two groups. ARDS patients demonstrated significantly higher S-protein-reactive CD4⁺ and CD8⁺ T cells compared to non-ARDS patients. Of interest, comparison of circulating bulk T cells in ARDS patients to non-ARDS patients demonstrated decreased frequencies of CD4⁺ and CD8⁺ T cell subsets, with activated memory/effector T cells expressing tissue migration molecule CD11a⁺⁺. Importantly, survival from ARDS (4/10) was accompanied by a recovery of the CD11a⁺⁺ T cell subsets in peripheral blood. Conclusively, data on S-protein-reactive polyfunctional T cells indicate the ability of ARDS patients to generate antiviral protection. Furthermore, decreased frequencies of activated memory/effector T cells expressing tissue migratory molecule CD11a⁺⁺ observed in circulation of ARDS patients might suggest their involvement in ARDS development and propose the CD11a-based immune signature as a possible prognostic marker.

Keywords: ARDS; COVID-19; S-protein-reactive T cells; SARS-CoV-2; immunity.