1. High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4+ and CD8+ memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.
- Author
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Coulon, Pierre-Gregoire, Prakash, Swayam, Dhanushkodi, Nisha, Srivastava, Ruchi, Zayou, Latifa, Tifrea, Delia, Figueroa, Cesar, Schubl, Sebastian, Hsieh, Lanny, Nesburn, Anthony, Bahraoui, Elmostafa, Vahed, Hawa, Gil, Daniel, Jones, Trevor, Ulmer, Jeffrey, Kuppermann, Baruch, Edwards, Robert, and Benmohamed, Lbachir
- Subjects
SARS-CoV-2 ,CD4 + T cells ,CD8 + T cells ,COVID-19 ,asymptomatic ,common cold coronavirus ,exhaustion α-CCCs/SARS-CoV-2 cross-reactive T cells in asymptomatic COVID-19 infection ,symptomatic ,Humans ,COVID-19 ,SARS-CoV-2 ,CTLA-4 Antigen ,CD8-Positive T-Lymphocytes ,Common Cold ,Memory T Cells ,Hepatitis A Virus Cellular Receptor 2 ,Programmed Cell Death 1 Receptor ,CD4-Positive T-Lymphocytes ,Epitopes - Abstract
BACKGROUND: Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. METHODS: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. RESULTS: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. CONCLUSIONS: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.
- Published
- 2024