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.

Epstein-Barr virus (EBV) reactivation can lead to serious complications in kidney transplant patients, including post-transplant lymphoproliferative disorder (PTLD). Here, we have assessed the impact of EBV on B cell homeostasis at cellular and humoral level. In a multicenter study monitoring 540 kidney transplant patients during the first post-transplant year, EBV reactivation was detected in 109 patients. Thirteen soluble factors and B cell counts were analyzed in an EBV+ sub-cohort (N = 54) before, at peak and after EBV clearance and compared to a control group (N = 50). The B cell activating factor (BAFF) was significantly elevated among EBV+ patients. No additional soluble factors were associated with EBV. Importantly, in vitro experiments confirmed the proliferative effect of BAFF on EBV-infected B cells, simultaneously promoting EBV production. In contrast, elevated levels of BAFF in EBV+ patients did not lead to B cell expansion in vivo. Moreover, diminished positive inter-correlations of soluble factors and alterations of the bi-directional interplay between B cell and soluble factors were observed in EBV+ patients at peak and after clearance. Our data suggest that such alterations may counteract the proliferative effect of BAFF, preventing B cell expansion. The role of these alterations in lymphoma development should be analyzed in future studies.

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