SARS–CoV-2–specific T cell responses and correlations with COVID-19 patient predisposition

Sattler, Arne; Angermair, Stefan; Stockmann, Helena; Heim, Katrin Moira; Khadzhynov, Dmytro; Treskatsch, Sascha; Halleck, Fabian; Kreis, Martin E.; Kotsch, Katja

doi:10.1172/jci140965

Cited by 200 publications

(223 citation statements)

References 52 publications

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“…In line with previous observations of SARS-CoV-2 T cells and ageing 23 , T cell responses in HCW (n=75) with laboratory confirmed SARS-CoV-2 correlated with age. There was a correlation with increasing age and T cell responses against Spike MEP2, NP1 OLP and ORF3a/7a MEP (Extended Data Fig.…”

supporting

confidence: 92%

“…Much debate has focused on the possibility that the Ab response to SARS-CoV-2 may be short-lived, while T cell recognition may be strong, durable, and more common 14,16,17,23,27,29 Analysis of nAbs shows that the majority of laboratory confirmed SARS-CoV-2 infected HCW with no symptoms or only mild disease had relatively high nAb IC50 at 16-18 weeks after UK lockdown. These IC50s were in the same range as those defined as conferring functional protection in macaque challenge studies 28 .…”

Section: Discussionmentioning

confidence: 99%

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Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave

Reynolds

Swadling

Gibbons

et al. 2020

Preprint

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Studies of adaptive immunity to SARS-CoV-2 include characterisation of lethal, severe and mild cases. Understanding how long immunity lasts in people who have had mild or asymptomatic infection is crucial. Healthcare worker (HCW) cohorts exposed to and infected by SARS-CoV-2 during the early stages of the pandemic are an invaluable resource to study this question. The UK COVIDsortium is a longitudinal, London hospital HCW cohort, followed from the time of UK lockdown; weekly PCR, serology and symptom diaries allowed capture of asymptomatic infection around the time of onset, so duration of immunity could be tracked. Here, we conduct a cross-sectional, case-control, sub-study of 136 HCW at 16-18 weeks after UK lockdown, with 76 having had laboratory-confirmed SARS-CoV-2 mild or asymptomatic infection. Neutralising antibodies (nAb) were present in 90% of infected HCW sampled after the first wave; titres, likely to correlate with functional protection, were present in 66% at 16-18 weeks. T cell responses tended to be lower in asymptomatic infected HCW than those reporting case-definition symptoms of COVID-19, while nAb titres were maintained irrespective of symptoms. T cell and antibody responses were discordant. HCW lacking nAb also showed undetectable T cells to Spike protein but had T cells of other specificities. Our findings suggest that the majority of HCW with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multi-specific T cell responses for at least 4 months after mild or asymptomatic SARS-CoV-2 infection.

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supporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave

Reynolds

Swadling

Gibbons

et al. 2020

Preprint

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“…Furthermore, these studies, although interesting, do not distinguish between Th1 and Th1/Th17 cells and do not include a comprehensive analysis of additional functional Thsubtypes. Interestingly, a reduced Th1-type specific immune response (i.e., a lower proportion of IFN-g secreting cells) against different SARS-CoV-2 antigens was observed and was related with age/comorbidity (32). Finally, data by Roncati and colleagues, suggest that the "moonlighting protein" CD26/DPP4 could explain the Th1 immune lockdown observed in severe cases of COVID-19 (33).…”

Section: Discussionmentioning

confidence: 92%

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset

et al. 2020

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The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.

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“…Both, CD4 + and CD8 + T cells highly express B and T lymphocyte attenuator (BTLA), which is responsible for increased mortality during sepsis via dysregulating innate immune response and lymphocyte apoptotic death [207] , [236] , [237] . However, the CD4 + /CD8 + T cell ratio in COVID-19 patients is higher than HDs indicating that CD8 + T cell loss is higher than CD4 + T cells [207] , [230] , [234] . The CD8 + T cells from severe COVID-19 patients also show lower IL-2 expression than HDs.…”

Section: Immunology Of the Sars-cov2 Infection Or The Covid-19mentioning

confidence: 89%

“…6 ) [71] , [179] , [226] , [227] , [228] , [229] . The severity of COVID-19 increases with the older age and comorbidity as these patients have higher number of SARS-CoV2-specific CD4 + T cells, harbor higher IL-2 levels, and their IFN-γ producing cells (NK, NKT, γδT, CD4 + Th1, and CD8 + cytotoxic T, and CD11a hi FcγRIII hi B cells, also called IFN-γ producing B cells) decrease [230] , [231] , [232] . The diminished frequencies of membrane protein reactive IFNγ + T cells (CD4 + and CD8 + T cells) in severe COVID-19 patients admitted in the intensive care unit (ICU) well correlate with APACHE II score of the severity.…”

Section: Immunology Of the Sars-cov2 Infection Or The Covid-19mentioning

confidence: 99%

Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics

Kumar

2020

International Immunopharmacology

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SARS–CoV-2–specific T cell responses and correlations with COVID-19 patient predisposition

Cited by 200 publications

References 52 publications

Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave

Healthcare workers with mild / asymptomatic SARS-CoV-2 infection show T cell responses and neutralising antibodies after the first wave

Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset

Understanding the complexities of SARS-CoV2 infection and its immunology: A road to immune-based therapeutics

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