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, and SARS-CoV-2 S-protein reactive T cell 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 CD11a-based immune signature as a possible prognostic marker.