Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Du, Juan; Wei, Lan; Li, Guoli; Hua, Mingxi; Sun, Yao; Wang, Di; Han, Kai; Song, Chuan; Song, Rui; Zhang, Henghui; Han, Junyan; Liu, Jingyuan; Kong, Yaxian

doi:10.3389/fimmu.2021.735125

Cited by 49 publications

(41 citation statements)

References 50 publications

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“…Our study clearly shows that activation of CD4 + and CD8 + T cells is a key finding in COVID-19 patients during active disease, and this is in agreement with others [39,55]. Concerning the activated CD8 + T cell population expressing CD38 and HLA-DR, the levels were elevated compared to healthy controls and were sustained for more than 6 weeks, whereas the CD4 + T cells decreased over time within the COVID-19 patients.…”

Section: Discussionsupporting

confidence: 92%

“…Classical markers of early and late activation of T cells are represented by CD69 and CD38/HLA-DR, respectively [37, 38]. Persistent expression of these markers is suggestive of a hyper-immune activation state and affirms an ongoing phase of systemic inflammation and tissue injury occurring in severe COVID-19 [55]. Hence, to examine the activation status of CD4 + and CD8 + T cells, we assessed the cells for CD38 + HLA-DR + and CD69 + expression ( Figure 4 ).…”

Section: Resultsmentioning

confidence: 99%

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Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Govender

Hopkins

Göransson

et al. 2022

Preprint

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COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Govender

Hopkins

Göransson

et al. 2022

Preprint

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“…In relation to COVID-19, it was shown, that two different subpopulations of CD8 + CD38 + HLA-DR + cells are present in COVID-19 patients. The subset of CD8 + CD38 hi HLA-DR + T cells was considered overactivated with diminished effector function, prone to apoptosis, related to immune dysregulation, systemic inflammation and tissue injury in severe COVID-19 patients ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

“…Comparisons between survivors and non-survivors on admission and after one week of hospitalization (Mann-Whitney test), longitudinal changes in survivors and non-survivors (Wilcoxon rank-sum test). S, survivors; NS, non-survivors; IQR, interquartile range; ns, not significant, *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 function, prone to apoptosis, related to immune dysregulation, systemic inflammation and tissue injury in severe COVID-19 patients(48).…”

mentioning

confidence: 99%

Activated CD8+CD38+ Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients

et al. 2022

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.

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“…HLA DR is a marker of activation and inflammation; a number of studies traced the connection of its elevated expression on T-lymphocytes with autoimmune and infectious diseases, in particular, as a marker of an early stage of non-surgical sepsis, etc. (Fernández-Grande et al, 2019;Du et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Immune factors and health of Antarctic explorers

Kozeretska

Deineko

Anoshko

et al. 2021

UAJ

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The immune system plays a major role in human homeostasis, yet a body’s unique individuality complicates the diagnostic forecasting of unfavourable physiological states and diseases. Studying the immunophenotypic features of winterers of the Ukrainian Antarctic Expeditions before, during, and after their assignments might shed some light on the possible place of immune accentuations in the development of certain physiological states. To determine the natural-killer (NK) cytotoxicity and the immunophenotype in 52 applicants who wanted to take part in an expedition and nine participants who had come back, we used flow cytofluorometry. Blood serum samples taken before, during, and after the expeditions were also tested for hormones, anti-infective, anti-parasitic, and autoimmune antibodies. The high absolute and relative numbers of NK lymphocytes, high NK cytotoxicity, and high expression of HLA-DR on the CD3+CD8+ lymphocytes were correlated with a person’s unfavorable health status during the expedition. In Antarctica, cortisol levels sharply increased, yet they normalized upon return. In most winterers, there were no significant health complications during the expeditions. Neither reactivated nor primary viral infections were registered, as well as clinical autoimmune ones. Upon return, the winterers had significantly lower leukocytes and lymphocytes and increased expression of activation markers (HLA-DR) on the T-cells. The found risk factors can characterize the polar researchers’ immunophenotypes yet require validation on larger samples. The expedition environment causes increased stress, entailing, however, neither clinical manifestations nor elements of immunosuppression. The polar researchers bear the consequences of the prolonged stress that inhibit leucopoiesis as late as six months after their return, which should be considered while reviewing applications for the next season.

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Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Cited by 49 publications

References 50 publications

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

Activated CD8+CD38+ Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients

Immune factors and health of Antarctic explorers

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