Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents

Kudryavtsev, I. V.; Arsentieva, Natalia A.; Batsunov, Oleg K.; Korobova, Zoia R.; Khamitova, Irina V.; Isakov, Dmitry V.; Кузнецова, Р. Н.; Rubinstein, Artem A.; Stanevich, Oksana V.; Lebedeva, Aleksandra A.; Vorobyov, Evgeny A.; Vorobyova, Snejana V.; Kulikov, Alexander N.; Sharapova, Maria A.; Pevtcov, Dmitrii E.; Тотолян, Арег А.

doi:10.3390/cimb44010014

Cited by 22 publications

(12 citation statements)

References 39 publications

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“…Thus, altered B cell activation in circulation and vitamin D deficiency could be associated with an increased risk of autoimmune disorders and poor outcomes of infectious diseases. Finally, an increased level of activated B cells and altered B cell subset composition was detected in the peripheral blood of patients recovered after COVID-19 [55,56]; thus, future studies will be needed to investigate whether supplementation with regular vitamin D can prevent or reduce the risk of developing severe pathologies associated with 'post-COVID' syndrome.…”

Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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Recent studies showed that a low 25-hydroxyvitamin D (25(OH)D) level was associated with a higher risk of morbidity and severe course of COVID-19. Our study aimed to evaluate the effects of cholecalciferol supplementation on the clinical features and inflammatory markers in patients with COVID-19. A serum 25(OH)D level was determined in 311 COVID-19 patients. Among them, 129 patients were then randomized into two groups with similar concomitant medication. Group I (n = 56) received a bolus of cholecalciferol at a dose of 50,000 IU on the first and the eighth days of hospitalization. Patients from Group II (n = 54) did not receive the supplementation. We found significant differences between groups with the preferential increase in serum 25(OH)D level and Δ 25(OH)D in Group I on the ninth day of hospitalization (p < 0.001). The serum 25(OH)D level on the ninth day was negatively associated with the number of bed days (r = −0.23, p = 0.006); we did not observe other clinical benefits in patients receiving an oral bolus of cholecalciferol. Moreover, in Group I, neutrophil and lymphocyte counts were significantly higher (p = 0.04; p = 0.02), while the C-reactive protein level was significantly lower on the ninth day of hospitalization (p = 0.02). Patients with supplementation of 100,000 IU of cholecalciferol, compared to those without supplementation, showed a decrease in the frequencies of CD38++CD27 transitional and CD27−CD38+ mature naive B cells (p = 0.006 and p = 0.02) and an increase in the level of CD27−CD38− DN B cells (p = 0.02). Thus, the rise in serum 25(OH)D level caused by vitamin D supplementation in vitamin D insufficient and deficient patients may positively affect immune status and hence the course of COVID-19.

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Section: Discussionmentioning

confidence: 99%

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

et al. 2022

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“…Therefore, it can be concluded that decreased B cell counts in the acute stage of COVID-19 are related to the impairment of their maturation at the level of antigen-independent differentiation. Furthermore, B cell subset alterations could persist for at least several months after the acute stage of the disease [ 35 ]. Such long-term impairment of adaptive humoral immunity may be closely associated with an increased risk of a wide range of autoimmune disorders [ 36 , 37 ], the incidence of which dramatically increases after COVID-19 [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Different Stages of the Disease

Савченко

Тихонова

Kudryavtsev

et al. 2022

Viruses

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Background: T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19. Methods: We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry. Results: Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3+CD4+CD45RO−CD62L− and CD3+CD8+CD45RO−CD62L− T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3+CD4+CD45RO−CD62L+ and CD3+CD8+CD45RO−CD62L+ T cell frequencies and increased CD3+CD8+CD45RO−CD62L− cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets. Conclusions: The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19.

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“…B cells are classified based on surface CD27 and CD38 expression into transitional (CD27 - CD38 ++ ), naïve (CD27 - CD38 + ), plasmablasts (CD27 ++ CD38 + ), memory unswitched (IgD + CD27 + CD38 - ), memory switched (IgD - CD27 + CD38 - ), and double-negative cells (CD27 - CD38 - ) ( 240 ). The prototypical B cell response to a viral infection features an initial extrafollicular (EF) B cell signature, which involves the differentiation of naive B cells into plasmablasts that generate low-affinity and temporary antibodies.…”

Section: Adaptive Immune Response Against Sars-cov-2mentioning

confidence: 99%

Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

Shafqat

Salameh

et al. 2022

Front. Immunol.

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Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which causes coronavirus-19 (COVID-19), has caused significant morbidity and mortality globally. In addition to the respiratory manifestations seen in severe cases, multi-organ pathologies also occur, making management a much-debated issue. In addition, the emergence of new variants can potentially render vaccines with a relatively limited utility. Many investigators have attempted to elucidate the precise pathophysiological mechanisms causing COVID-19 respiratory and systemic disease. Spillover of lung-derived cytokines causing a cytokine storm is considered the cause of systemic disease. However, recent studies have provided contradictory evidence, whereby the extent of cytokine storm is insufficient to cause severe illness. These issues are highly relevant, as management approaches considering COVID-19 a classic form of acute respiratory distress syndrome with a cytokine storm could translate to unfounded clinical decisions, detrimental to patient trajectory. Additionally, the precise immune cell signatures that characterize disease of varying severity remain contentious. We provide an up-to-date review on the immune dysregulation caused by COVID-19 and highlight pertinent discussions in the scientific community. The response from the scientific community has been unprecedented regarding the development of highly effective vaccines and cutting-edge research on novel therapies. We hope that this review furthers the conversations held by scientists and informs the aims of future research projects, which will potentially further our understanding of COVID-19 and its immune pathogenesis.

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Alterations in B Cell and Follicular T-Helper Cell Subsets in Patients with Acute COVID-19 and COVID-19 Convalescents

Cited by 22 publications

References 39 publications

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study

TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Different Stages of the Disease

Mechanistic Insights Into the Immune Pathophysiology of COVID-19; An In-Depth Review

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