High levels of SARS-CoV-2–specific T cells with restricted functionality in severe courses of COVID-19

Abstract

BACKGROUND Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) differ in the severity of disease. We hypothesized that characteristics of SARS-CoV-2–specific immunity correlate with disease severity. METHODS In this study, SARS-CoV-2–specific T cells and antibodies were characterized in uninfected controls and patients with different coronavirus disease 2019 (COVID-19) disease severity. SARS-CoV-2–specific T cells were flow cytometrically quantified after stimulation with SARS-CoV-2 peptide pools and analyzed for expression of cytokines (IFN-γ, IL-2, and TNF-α) and markers for activation, proliferation, and functional anergy. SARS-CoV-2–specific IgG and IgA antibodies were quantified using ELISA. Moreover, global characteristics of lymphocyte subpopulations were compared between patient groups and uninfected controls. RESULTS Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2–specific T cells as compared with convalescent individuals. SARS-CoV-2–specific CD4 + T cells dominated over CD8 + T cells and closely correlated with the number of plasmablasts and SARS-CoV-2–specific IgA and IgG levels. Unlike in convalescent patients, SARS-CoV-2–specific T cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 + and CD8 + T cells in general. CONCLUSION Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered characteristics may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung. FUNDING The study was supported by institutional funds to MS and in part by grants of Saarland University, the State of Saarland, and the Rolf M. Schwiete Stiftung.

Transbronchial biopsies’ histopathological findings leading to successful late steroid therapy in Covid-19 acute respiratory failure

“…Our findings show a predominance of CD8 + lymphocytes in both the early and late phases, which is not consistent with what has generally been described in Europe [9]. The difference in this pattern due to geographical differences allows us to speculate whether the prevalence and previous infections with coronavirus bias the immune response to CD4 vs. CD8 T cells, and the effects thereof on the clinical outcome.…”

Impact of COVID-19 in solid organ transplant recipients

“…Risk factors for serious disease and mortality in the general population include older age, obesity, and comorbidities affecting the lung or the heart 1,2 . Disease severity may be influenced by the viral inoculum, dissemination, pre‐existing immunity toward other coronaviruses, individual immunocompetence, and other host factors 3‐9 …”

“…In the general population, infection is followed by the induction of innate inflammatory responses and of SARS‐CoV‐2‐specific humoral and cellular immunity including CD4 and CD8 T cells 3‐6,10 . The magnitude of specific immunity may be directly related to viral load, dissemination to the lower respiratory tract, and/or disease severity 6,10 .…”

“…In the general population, infection is followed by the induction of innate inflammatory responses and of SARS‐CoV‐2‐specific humoral and cellular immunity including CD4 and CD8 T cells 3‐6,10 . The magnitude of specific immunity may be directly related to viral load, dissemination to the lower respiratory tract, and/or disease severity 6,10 . In addition, SARS‐CoV‐2‐specific T cells in patients with severe disease have a restricted functionality and higher expression levels of co‐inhibitory receptors, which also extended to T cells in general 6,11 .…”

Recombinant interleukin-2 stimulates lymphocyte recovery in patients with severe COVID-19

“…In addition, rIL-2 may mimic the effect of native IL-2 and stimulate the survival, proliferation, differentiation and antibody production of B cells, which accelerates the clearance of the virus. Furthermore, rIL-2 may relieve the inflammatory storm by decreasing the levels of cytokines (20)(21)(22). However, the precise mechanisms have remained to be elucidated.…”