SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals

Kared, Hassen; Redd, Andrew D.; Bloch, Evan M.; Bonny, Tania S.; Sumatoh, Hermi; Kairi, Faris; Carbajo, Daniel; Abel, Brian; Newell, Evan W.; Bettinotti, María P.; Benner, Sarah E.; Patel, Eshan U.; Littlefield, Kirsten; Laeyendecker, Oliver; Shoham, Shmuel; Sullivan, David J.; Casadevall, Arturo; Pekosz, Andrew; Nardin, Alessandra; Fehlings, Michael G.; Tobian, Aaron A.R.; Quinn, Thomas C.

doi:10.1172/jci145476

Cited by 241 publications

(252 citation statements)

References 38 publications

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“…Several studies using overlapping peptide pools spanning different region of SARS-CoV-2 viral proteins have shown a broad range of T cell activation in convalescent COVID-19 patients (8,9,11,14,15,(31)(32)(33)(34)(35). Our work now provides a detailed characterization of minimal epitopes derived from the complete SARS-CoV-2 genome for their CD8 + T cell immunogenicity, immunodominance, and functional and phenotypical characteristics in COVID-19 patients and healthy donors.…”

Section: Discussionmentioning

confidence: 77%

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

et al. 2021

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T cells are important for effective viral clearance, elimination of virus-infected cells and long-term disease protection. To examine the full-spectrum of CD8+ T cell immunity in COVID-19, we experimentally evaluated 3141 major histocompatibility (MHC) class I-binding peptides covering the complete SARS-CoV-2 genome. Using DNA-barcoded peptide-MHC complex (pMHC) multimers combined with a T cell phenotype panel, we report a comprehensive list of 122 immunogenic and a subset of immunodominant SARS-CoV-2 T cell epitopes. Substantial CD8+ T cell recognition was observed in COVID-19 patients, with up to 27% of all CD8+ lymphocytes interacting with SARS-CoV-2-derived epitopes. Most immunogenic regions were derived from open reading frame (ORF) 1 and ORF3, with ORF1 containing most of the immunodominant epitopes. CD8+ T cell recognition of lower affinity was also observed in healthy donors toward SARS-CoV-2-derived epitopes. This pre-existing T cell recognition signature was partially overlapping with the epitope landscape observed in COVID-19 patients and may drive the further expansion of T cell responses to SARS-CoV-2 infection. Importantly the phenotype of the SARS-CoV-2-specific CD8+ T cells, revealed a strong T cell activation in COVID-19 patients, while minimal T cell activation was seen in healthy individuals. We found that patients with severe disease displayed significantly larger SARS-CoV-2-specific T cell populations compared to patients with mild diseases and these T cells displayed a robust activation profile. These results further our understanding of T cell immunity to SARS-CoV-2 infection and hypothesize that strong antigen-specific T cell responses are associated with different disease outcomes.

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Section: Discussionmentioning

confidence: 77%

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

et al. 2021

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“…The T cell response to SARS-CoV-2 infection pivotally determines long-term protective immunity ( 33 ). Therefore, we also assessed the SARS-CoV-2 specific cell-mediated immunity in pregnant women and cord blood by applying an interferon gamma (IFN-ɣ) release assay.…”

Section: Resultsmentioning

confidence: 99%

Inefficient Placental Virus Replication and Absence of Neonatal Cell-Specific Immunity Upon Sars-CoV-2 Infection During Pregnancy

et al. 2021

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Pregnant women have been carefully observed during the COVID-19 pandemic, as the pregnancy-specific immune adaptation is known to increase the risk for infections. Recent evidence indicates that even though most pregnant have a mild or asymptomatic course, a severe course of COVID-19 and a higher risk of progression to diseases have also been described, along with a heightened risk for pregnancy complications. Yet, vertical transmission of the virus is rare and the possibility of placental SARS-CoV-2 infection as a prerequisite for vertical transmission requires further studies. We here assessed the severity of COVID-19 and onset of neonatal infections in an observational study of women infected with SARS-CoV-2 during pregnancy. Our placental analyses showed a paucity of SARS-CoV-2 viral expression ex vivo in term placentae under acute infection. No viral placental expression was detectable in convalescent pregnant women. Inoculation of placental explants generated from placentas of non-infected women at birth with SARS-CoV-2 in vitro revealed inefficient SARS-CoV-2 replication in different types of placental tissues, which provides a rationale for the low ex vivo viral expression. We further detected specific SARS-CoV-2 T cell responses in pregnant women within a few days upon infection, which was undetectable in cord blood. Our present findings confirm that vertical transmission of SARS-CoV-2 is rare, likely due to the inefficient virus replication in placental tissues. Despite the predominantly benign course of infection in most mothers and negligible risk of vertical transmission, continuous vigilance on the consequences of COVID-19 during pregnancy is required, since the maternal immune activation in response to the SARS-CoV2 infection may have long-term consequences for children’s health.

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“…Evidence suggests some of these immune perturbations persist into the convalescent phase of infection (1,8,9). Antigen-specific immune responses during the acute and early convalescent stages of infection have been found to play an important role in overall patient outcomes (10)(11)(12)(13)(14)(15). Reports have shown that SARS-CoV-2-specific T-cell memory is maintained for months after initial symptom onset in convalescent PBMC samples, but the magnitude of observed T-cell responses decreases over time (14,(16)(17)(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

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Sarkar²,

Fram.³

et al. 2021

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A subset of COVID-19 patients exhibit Post-Acute Sequalae of COVID-19 (PASC), but little is known about the immune signatures associated with these syndromes. We investigated longitudinal peripheral blood samples in 50 individuals with previously confirmed SARS-CoV-2 infection, including 20 who experienced prolonged duration of COVID-19 symptoms (lasting more than 30 days; median=74 days) compared to 30 who had symptom resolution in 20 days or less.Individuals with prolonged symptom duration maintained antigen-specific T-cell response magnitudes to SARS-CoV-2 spike protein in CD4+ and cTfh populations during late convalescence while those without persistent symptoms demonstrated an expected decline. The prolonged group also displayed increased IgG avidity to SARS-CoV-2 S-protein. Significant correlations between symptom duration and both SARS-CoV-2-specific T cells and antibodies were observed.Activation and exhaustion markers were evaluated in multiple immune cell types, revealing few phenotypic differences between prolonged and recovered groups suggesting that prolonged symptom duration is not due to persistent systemic inflammation. These findings demonstrate that SARS-CoV-2-specific immune responses are maintained in patients suffering from prolonged post-COVID-19 symptom duration in contrast to those with resolved symptoms and may suggest the persistence of viral antigens as an underlying etiology.

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SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals

Cited by 241 publications

References 38 publications

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

Inefficient Placental Virus Replication and Absence of Neonatal Cell-Specific Immunity Upon Sars-CoV-2 Infection During Pregnancy

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

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SARS-CoV-2–specific CD8+ T cell responses in convalescent COVID-19 individuals

Cited by 241 publications

References 38 publications

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 + T cell activation in COVID-19 patients

Inefficient Placental Virus Replication and Absence of Neonatal Cell-Specific Immunity Upon Sars-CoV-2 Infection During Pregnancy

Duration of post-COVID-19 symptoms are associated with sustained SARS-CoV-2 specific immune responses

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Product

Resources

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SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients

SARS-CoV-2 genome-wide T cell epitope mapping reveals immunodominance and substantial CD8 ⁺ T cell activation in COVID-19 patients