2021
DOI: 10.4049/jimmunol.2100446
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The Quality of SARS-CoV-2–Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated

Abstract: of the experiments and analyzed the data. L.X. performed some of the experiments and analyzed the data. W.S. (a clinician scientist in critical care medicine and infectious disease) identified and recruited patients for the study. M.O., a clinician scientist (Rheumatologist), contributed in patients' recruitment. N.B. performed the ELISAs. D.R. contributed in clinical data collection. S.M. and E.P.R. assisted in blood processing and experimental setups. J.W. as a clinician scientist (Oncologist) provided advic… Show more

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Cited by 52 publications
(78 citation statements)
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“…Additionally, this study documented increased plasmablast (CD38 + CD27 + cells) but reduced effector B cell frequencies in those with severe disease [ 99 ]. Consistent with most reports, we have observed a significant reduction in percentages of CD3 + , CD4 + , CD8 + T, and B cells in the peripheral blood of COVID-19 patients compared to healthy controls [ 100 ]. Notably, we found that lymphopenia was more CD8 + T cell biased especially in those in the intensive care unit (ICU) and the deceased had significantly greater lymphopenia compared to those who survived COVID-19 disease [ 100 ].…”
Section: Sars-cov-2 Infection and Lymphopeniasupporting
confidence: 92%
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“…Additionally, this study documented increased plasmablast (CD38 + CD27 + cells) but reduced effector B cell frequencies in those with severe disease [ 99 ]. Consistent with most reports, we have observed a significant reduction in percentages of CD3 + , CD4 + , CD8 + T, and B cells in the peripheral blood of COVID-19 patients compared to healthy controls [ 100 ]. Notably, we found that lymphopenia was more CD8 + T cell biased especially in those in the intensive care unit (ICU) and the deceased had significantly greater lymphopenia compared to those who survived COVID-19 disease [ 100 ].…”
Section: Sars-cov-2 Infection and Lymphopeniasupporting
confidence: 92%
“…Recent studies suggest that enhanced T cell-associated cytotoxicity could contribute to severe disease symptoms [ 108 ]. As such, the increased capability of IL-17 secreting T cells in critically ill patients has been proposed to heighten inflammation [ 100 ] and the subsequent activation and induction of neutrophils [ 109 ]. In line with these results, cells present in the lungs exhibited more IL-17 production capacity than those in the peripheral blood [ 110 , 111 ].…”
Section: Sars-cov-2 Infection and Lymphopeniamentioning
confidence: 99%
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“…Correlation of PD-L1 expression in APCs with PD-1 expression in T cells observed in our patient cohort indicated that PD-1 –PD-L1 interactions may regulate T cell responses. Whether this interaction leads to T cell exhaustion in COVID-19 patients is controversial [ 38 ] as SARS-CoV-2-specific T cells expressing PD-1 were shown to be activated and fully capable of responding to antigenic restimulation [ 53 , 54 ].…”
Section: Discussionmentioning
confidence: 99%
“…A new study found that severe COVID-19 is not preferentially associated with the quantity of the CD4 + T cell response, but rather poor polyfunctionality and proliferative capacity, as well as enhanced immune activation [ 31 ]. An increased immune activation profile has been distinguished in numerous studies, and together with differential Th2, Th17 or Tfh responses to SARS-CoV-2 been associated with distinct disease outcomes [ 32 , 33 ]. Collectively, the current human data indicate that early induction of functional SARS-CoV-2-specific T cells correlate with viral control and mild disease, whereas delayed T cell activation leads to poor functional responses and clearance of the virus and, ultimately, severe and fatal COVID-19.…”
Section: T Cell Responses In the Acute Phasementioning
confidence: 99%