High and Sustained Ex Vivo Frequency but Altered Phenotype of SARS-CoV-2-Specific CD4+ T-Cells in an Anti-CD20-Treated Patient with Prolonged COVID-19

Here, we longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2 membrane protein (aa145-164) epitope-specific CD4(+) T-cells of an anti-CD20-treated patient with prolonged viral positivity in direct comparison to an immunocompetent patient through an MHC class II DRB1*11:01 Tetramer analysis. We detected a high and stable SARS-CoV-2 membrane-specific CD4(+) T-cell response in both patients, with higher frequencies of virus-specific CD4(+) T-cells in the B-cell-depleted patient. However, we found an altered virus-specific CD4(+) T-cell memory phenotype in the B-cell-depleted patient that was skewed towards late differentiated memory T-cells, as well as reduced frequencies of SARS-CoV-2-specific CD4(+) T-cells with CD45RA(-) CXCR5(+) PD-1(+) circulating T follicular helper cell (cT(FH)) phenotype. Furthermore, we observed a delayed contraction of CD127(-) virus-specific effector cells. The expression of the co-inhibitory receptors TIGIT and LAG-3 fluctuated on the virus-specific CD4(+) T-cells of the patient, but were associated with the inflammation markers IL-6 and CRP. Our findings indicate that, despite B-cell depletion and a lack of B-cell-T-cell interaction, a robust virus-specific CD4(+) T-cell response can be primed that helps to control the viral replication, but which is not sufficient to fully abrogate the infection.

Automated summary

This study longitudinally assessed the ex vivo frequency and phenotype of SARS-CoV-2-specific CD4(+) T-cells in an anti-CD20-treated patient and an immunocompetent patient. The results showed a high and stable CD4(+) T-cell response in both patients, with higher frequencies in the B-cell-depleted patient. However, the B-cell-depleted patient had an altered CD4(+) T-cell phenotype and weaker antiviral effect.