T helper cell subsets and related target cells in acute COVID-19
Authors: Kudryavtsev I. V. , Golovkin A. S. , Totolian Areg A. 
Published: May 2022

Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets as well as related target cells. Effects of dendritic cell dysfunction induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 as well as co-stimulatory molecules CD80 and CD86, suggesting reduced antigen presentation, migratory and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 24 post-symptom onset, whereas the prolonged lack of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported about upregulated inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cells, whereas the macrophage count was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards dominance of Th2 cell subset in peripheral blood samples from patients with acute COVID-19. Furthermore, the decrease of circulating main Th2 target cells basophiles and eosinophils were associated with severe COVID-19, whereas the lung tissue was enriched with mast cells and relevant mediators released during degranulation. Moreover, the frequency of peripheral blood Th17 cells was closely linked to COVID-19 severity, so that low level of Th17 cells was observed in patients with severe COVID-19, but in BAL the relative number of Th17 cells as well as the concentrations of relevant effector cytokines were dramatically increased. It was shown that severe COVID-19 patients vs. healthy control had higher relative numbers of neutrophils if compared, and the majority of patients with COVID-19 had increased frequency and absolute number of immature neutrophils with altered ROS production. Finally, the frequency of Tfh cells was decreased during acute COVID-19 infection. Elevated count of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by decreased regulatory Tfh1 cell and increased pro-inflammatory Tfh2 as well as Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection werev reported as relative B cell lymphopenia with decreased frequency of nave and memory B cell subsets, as well as increased level of CD27hiCD38hiCD24 plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidence suggests that functional alterations occur in all Th cell subsets being linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune dysregulation and other persistent symptoms lasting for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.