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, 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.

Detection of pre-existing SARS-CoV-2-reactive T cells in unexposed renal transplant patients

“…This can lead to a severe course of disease as shown for CMV [ 34 ] or BKV [ 23 ] infections. On the other hand, an acute SARS-CoV-2 infection with critical course is linked to immunopathogenesis [ 10 ], and overwhelming immune reactions can be moderated by immunosuppressive drugs, as has been discussed for the IL-6 neutralizing antibody, tocilizumab [ 35 ] or the corticoid, dexamethasone [ 36 ]. First case reports on heart [ 37 ] or renal [ 38 ] transplant patients show the possibility of controlling an acute COVID-19 infection, even when the patients remain on tacrolimus or mycophenolate mofetil (MMF).…”

“…It is striking that unexposed RTx patients and healthy individuals have a similar frequency of SARS-CoV-2-specific CD8 + T cells compared to COVID-19 patients. Although we analyzed CD8 + T cell response in mild and moderate COVID-19 patients, which are lower compared to patients with a critical course of infection [ 10 ], we would expect a clearly increased frequency in acutely infected patients compared to unexposed individuals. The identical frequencies of memory and naïve CD8 + T cells in COVID-19 patients compared to unexposed RTx patients and healthy individuals may be caused by the migration of SARS-CoV-2 CD8 + T cells into the infected tissues in COVID-19 patients with the subsequent depletion of these cells from the circulation.…”

“…An insufficient immune response, due to weak antigen presentation or insufficient functionality of SARS-CoV-2-reactive T cells, has been suggested to cause critical COVID-19 [ 6 , 8 , 9 ]. On the other hand, an excessive immune response has also been associated with a critical COVID-19 disease course [ 10 ].…”

The Magnitude and Functionality of SARS-CoV-2 Reactive Cellular and Humoral Immunity in Transplant Population Is Similar to the General Population Despite Immunosuppression

“…COVID-19 severity was evaluated according to a guideline of the German Robert Koch Institute, as previously described. 23 Of patients with multiple samples, the worst disease classification of this patient was reported. Samples of patients with moderate and severe COVID-19 were collected shortly after symptom-onset and positive SARS-CoV-2 PCR.…”

Detection of SARS-CoV-2 Specific Memory B cells to Delineate Long-Term COVID-19 Immunity

“…One potential approach that can help to improve the detection of longterm immunity is the analysis of SARS-CoV-2-specific memory T and B cell formation. We and others have reported on the detection of a strong SARS-CoV-2 specific memory T cell response in immune-competent and immunosuppressed patients [14][15][16][17][18] . Similar studies of B cell-related immunity have so far focused mainly on characterizing antibody specificities [19][20][21][22][23][24] .…”