Imbalanced Immune Response of T-Cell and B-Cell Subsets in Patients with Moderate and Severe COVID-19

Abstract

Background: The immunological changes associated with COVID-19 are largely unknown. Methods: Patients with COVID-19 showing moderate (n = 18; SpO2 > 93%, respiratory rate > 22 per minute, CRP > 10 mg/L) and severe (n = 23; SpO2 < 93%, respiratory rate >30 per minute, PaO2/FiO2 ≤ 300 mmHg, permanent oxygen therapy, qSOFA > 2) infection, and 37 healthy donors (HD) were enrolled. Circulating T- and B-cell subsets were analyzed by flow cytometry. Results: CD4+Th cells were skewed toward Th2-like phenotypes within CD45RA+CD62L− (CM) and CD45RA–CD62L− (EM) cells in patients with severe COVID-19, while CM CCR6+ Th17-like cells were decreased if compared with HD. Within CM Th17-like cells “classical” Th17-like cells were increased and Th17.1-like cells were decreased in severe COVID-19 cases. Circulating CM follicular Th-like (Tfh) cells were decreased in all COVID-19 patients, and Tfh17-like cells represented the most predominant subset in severe COVID-19 cases. Both groups of patients showed increased levels of IgD-CD38++ B cells, while the levels of IgD+CD38− and IgD–CD38− were decreased. The frequency of IgD+CD27+ and IgD–CD27+ B cells was significantly reduced in severe COVID-19 cases. Conclusions: We showed an imbalance within almost all circulating memory Th subsets during acute COVID-19 and showed that altered Tfh polarization led to a dysregulated humoral immune response.

A single dose of COVID-19 vaccine induces a strong T cell and B cell response in healthcare professionals recovered from SARS-CoV-2 infection

“…2 b and 2c; Supplementary Information Table 1, Online Resource 1). CM Tfh1 reduction has been previously described in the course of the infection or shortly after recovering, but, in opposition to our results, some studies reported and increased percentage of CM Tfh17 in during severe COVID-19, as well as 4–9 weeks after recovering, and no differences 20–26 weeks after recovering [ 13 , 28 , 29 ]. Our data point out important long-term effects of SARS-CoV-2 infection in Tfh cells, translated as a marked decrease in Tfh cell numbers and activation status, as well as an altered polarization pattern, especially affecting Tfh17 cells.…”

Vitamin D Status and Immune Response in Hospitalized Patients with Moderate and Severe COVID-19

“…It is known that the severity of COVID-19 is due to the manifestations of a cytokine storm, which is accompanied by the dysregulation of both innate and adaptive immunity [ 28 , 29 , 30 ]. However, the relationship between vitamin D status and immune markers in patients with COVID-19 is unclear.…”

Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections—Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection

“…It was also observed that, in patients with severe COVID-19, CD4+ Th cells were skewed toward CCR4-expressing Th2-like phenotypes within CD45RA+CD62L− and CD45RA-CD62L− cells, while central memory CCR6+ Th17-like cells were decreased when compared with healthy controls, while patients with moderate COVID-19 had no differences with controls [46]. Furthermore, a Th2 predominance and an increased blood level of Th2 may be closely associated with COVID-19 symptoms, such as intestinal hyperperistalsis, increased acidity of gastric juice and shortness of breath [47]. In addition, an over-reactive CXCR3-CCR6-Th2 cell response was an independent risk factor for death [48].…”