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

Abstract

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.

New sights of low dose IL‐2: Restoration of immune homeostasis for viral infection

“…Now in the post‐COVID‐19 period, more attention is focused on prognosis rehabilitation of the post‐COVID condition [88]. Post‐COVID syndrome is accompanied by a series of immune disorders [89]. The latest research suggests that recombinant human IL‐2 contributes to the immune recovery of post‐COVID syndrome patients with low levels of NK cells, which is undoubtedly essential for the prevention of secondary infections [90].…”

Sarcoidosis-related autoimmune inflammation in COVID-19 convalescent patients

“…Profoundly altered thymic function and lowered thymic development of various “naive” T cell subsets in acute COVID-19 are evidenced by lowered TREC (T cell receptor excision circles) levels in the peripheral blood in severe and critical COVID-19 ( 187 , 188 ). Moreover, this may be related to SARS-CoV-2 infection of the thymic epithelial cells, resulting in altered T cell maturation and differentiation ( 189 ).…”

Dysregulated Immune Responses in SARS-CoV-2-Infected Patients: A Comprehensive Overview

“…The significantly decreased number of CD3+ T cells, as well as CD3+CD4+ and CD3+CD8+ T cells, dynamically correlated with the severity of COVID-19 cases [ 38 , 57 , 79 ]. Impaired thymus function and decreased ‘naïve’ T cell thymic output in patients with acute COVID-19 were confirmed by the low levels of peripheral blood circular excision products, so-called TRECs (T cell receptor excision circles), in patients with severe and critical COVID-19 [ 80 , 81 ]. In addition, a correlation was observed between the level of T cells in the peripheral blood and the severity of COVID-19 in APACHE III scores [ 27 ].…”