T cell anergy in COVID-19 reflects virus persistence and poor outcomes

Renner, Karl; Mueller, Cynthia; Tiefenboeck, C; Salewski, Jan-Niklas; Winter, Frederike; Buchtler, Simone; Malfertheiner, Maximilian; Lubnow, Matthias; Lunz, Dirk; B, Graf; Hitzenbichler, Florian; Hanses, Frank; Poeck, Hendrik; Kreutz, Marina; Orsó, Evelyn; Burkhardt, Ralph; Niedermair, Tanja; Brochhausen, Christoph; Gessner, André; Salzberger, Bernd; Mack, Matthias

doi:10.1101/2020.09.21.20198671

Cited by 3 publications

(2 citation statements)

References 35 publications

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“…Early induction of a functional SARS-CoV-2-specific T cell response is associated with rapid viral clearance and milder disease (Tan et al, 2021b). On the contrary, T cell anergy is connected with a poor prognosis (Renner et al, 2020). Reduced diversity of T cell response is characteristic of patients with COVID-19 pneumonia (Chang et al, 2021), while decreased numbers of CD8 + T cells indicate a high probability of developing severe disease and even death (Wang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response

Zornikova

Khmelevskaya

Sheetikov

et al. 2022

Preprint

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T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. To identify epitopes that give rise to long-lived T cell memory, we performed ex vivo T cell expansion, MHC-tetramer cell-sorting, and high-throughput sequencing. We identified 756 clonotypes specific to nine known CD8+ T cell receptor (TCR) epitopes. Some epitopes were recognized by highly similar public clonotypes with restricted variable and joining segment usage. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We also tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence. Our study demonstrates the durability of SARS-CoV-2-specific CD8+ memory, and offers important implications for vaccine design.

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Section: Introductionmentioning

confidence: 99%

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response

Zornikova

Khmelevskaya

Sheetikov

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Early induction of a functional SARS-CoV-2-specific T-cell response is associated with rapid viral clearance and milder disease 23 . On the contrary, T-cell anergy is connected with a poor prognosis 24 . Reduced diversity of T-cell response is characteristic of patients with COVID-19 pneumonia 25 , while decreased numbers of CD8+ T cells indicate a high probability of developing severe disease and even death 26 .…”

mentioning

confidence: 99%

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response.

Zornikova¹,

Khmelevskaya²,

Sheetikov³

et al. 2022

Preprint

View full text Add to dashboard Cite

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. We identified 756 clonotypes specific to nine CD8+ T cell epitopes. Some epitopes were recognized by highly similar public clonotypes. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.

show abstract

Clonal diversity predicts persistence of SARS-CoV-2 epitope-specific T-cell response

et al. 2022

View full text Add to dashboard Cite

T cells play a pivotal role in reducing disease severity during SARS-CoV-2 infection and formation of long-term immune memory. We studied 50 COVID-19 convalescent patients and found that T cell response was induced more frequently and persisted longer than circulating antibodies. We identified 756 clonotypes specific to nine CD8+ T cell epitopes. Some epitopes were recognized by highly similar public clonotypes. Receptors for other epitopes were extremely diverse, suggesting alternative modes of recognition. We tracked persistence of epitope-specific response and individual clonotypes for a median of eight months after infection. The number of recognized epitopes per patient and quantity of epitope-specific clonotypes decreased over time, but the studied epitopes were characterized by uneven decline in the number of specific T cells. Epitopes with more clonally diverse TCR repertoires induced more pronounced and durable responses. In contrast, the abundance of specific clonotypes in peripheral circulation had no influence on their persistence.

show abstract

T cell anergy in COVID-19 reflects virus persistence and poor outcomes

Cited by 3 publications

References 35 publications

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response

Clonal diversity determines persistence of SARS-CoV-2 epitope-specific T cell response.

Clonal diversity predicts persistence of SARS-CoV-2 epitope-specific T-cell response

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