Heterogenous CD8+ T Cell Maturation and 'Polarization' in Acute and Convalescent COVID-19 Patients.

BACKGROUND: The adaptive antiviral immune response requires interaction between CD8+ T cells, dendritic cells, and Th1 cells for controlling SARS-CoV-2 infection, but the data regarding the role of CD8+ T cells in the acute phase of COVID-19 and post-COVID-19 syndrome are still limited. METHODS: . Peripheral blood samples collected from patients with acute COVID-19 (n = 71), convalescent subjects bearing serum SARS-CoV-2 N-protein-specific IgG antibodies (n = 51), and healthy volunteers with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 46) were analyzed using 10-color flow cytometry. RESULTS: Patients with acute COVID-19 vs. HC and COVID-19 convalescents showed decreased absolute numbers of CD8+ T cells, whereas the frequency of CM and TEMRA CD8+ T cells in acute COVID-19 vs. HC was elevated. COVID-19 convalescents vs. HC had increased naïve and CM cells, whereas TEMRA cells were decreased compared to HC. Cell-surface CD57 was highly expressed by the majority of CD8+ T cells subsets during acute COVID-19, but convalescents had increased CD57 on 'naïve', CM, EM4, and pE1 2-3 months post-symptom onset. CXCR5 expression was altered in acute and convalescent COVID-19 subjects, whereas the frequencies of CXCR3+ and CCR4+ cells were decreased in both patient groups vs. HC. COVID-19 convalescents had increased CCR6-expressing CD8+ T cells. Moreover, CXCR3+CCR6- Tc1 cells were decreased in patients with acute COVID-19 and COVID-19 convalescents, whereas Tc2 and Tc17 levels were increased compared to HC. Finally, IL-27 negatively correlated with the CCR6+ cells in acute COVID-19 patients. CONCLUSIONS: We described an abnormal CD8+ T cell profile in COVID-19 convalescents, which resulted in lower frequencies of effector subsets (TEMRA and Tc1), higher senescent state (upregulated CD57 on 'naïve' and memory cells), and higher frequencies of CD8+ T cell subsets expressing lung tissue and mucosal tissue homing molecules (Tc2, Tc17, and Tc17.1). Thus, our data indicate that COVID-19 can impact the long-term CD8+ T cell immune response.

SARS-CoV-2 herd immunity of the Kyrgyz population in 2021.

In the fight against coronavirus infection, control of the immune response is of decisive importance, an important component of which is the seroprevalence of antibodies to SARS-CoV-2. Immunity to SARS-CoV-2 is formed either naturally or artificially through vaccination. The purpose of this study was to assess the seroprevalence of antibodies to SARS-CoV-2 in the population of Kyrgyzstan. A cross-sectional randomized study of seroprevalence was carried out according to a program developed by Rospotrebnadzor and the St. Petersburg Pasteur Institute, taking into account WHO recommendations. The ethics committees of the Association of Preventive Medicine (Kyrgyzstan) and the St. Petersburg Pasteur Institute (Russia) approved the study. Volunteers (9471) were recruited, representing 0.15% (95% CI 0.14-0.15) of the total population, randomized by age and region. Plasma antibodies (Abs) to the nucleocapsid antigen (Nag) were determined. In vaccinated individuals, Abs to the SARS-CoV-2 receptor-binding domain antigen (RBDag) were determined. Differences were considered statistically significant at p < 0.05. The SARS-CoV-2 Nag Ab seroprevalence was 48.7% (95% CI 47.7-49.7), with a maximum in the 60-69 age group [59.2% (95% CI 56.6-61.7)] and a minimum in group 1-17 years old [32.7% (95 CI: 29.4-36.1)]. The highest proportion of seropositive individuals was in the Naryn region [53.3% (95% CI 49.8-56.8)]. The lowest share was in Osh City [38.1% (95% CI 32.6-43.9)]. The maximum SARS-CoV-2 Nag seropositivity was found in the health-care sector [57.1% (95% CI 55.4-58.8)]; the minimum was seen among artists [38.6% (95% CI 26.0-52.4)]. Asymptomatic SARS-CoV-2 Nag seropositivity was 77.1% (95% CI 75.6-78.5). Vaccination with Sputnik V or Sinopharm produced comparable Ab seroprevalence. SARS-CoV-2 Nag seropositivity in the Kyrgyz population was 48.75% (95% CI 47.7-49.7), with the mass vaccination campaign undoubtedly benefitting the overall situation.

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

Background. Humoral immunity requires interaction between B cell and T follicular helper cells (Tfh) to produce effective immune response, but the data regarding a role of B cells and Tfh in SARS-CoV-2 defense are still sparse. Methods. Blood samples from patients with acute COVID-19 (n = 64), convalescents patients who had specific IgG to SARS-CoV-2 N-protein (n = 55), and healthy donors with no detectable antibodies to any SARS-CoV-2 proteins (HC, n = 44) were analyses by multicolor flow cytometry. Results. Patients with acute COVID-19 showed decreased levels of memory B cells subsets and increased proportion plasma cell precursors compared to HC and COVID-19 convalescent patients, whereas for the latter the elevated numbers of virgin naïve, Bm2′ and “Bm3+Bm4” was found if compared with HC. During acute COVID-19 CXCR3+CCR6− Tfh1-like cells were decreased and the levels of CXCR3−CCR6+ Tfh17-like were increased then in HC and convalescent patients. Finally, COVID-19 convalescent patients had increased levels of Tfh2-, Tfh17- and DP Tfh-like cells while comparing their amount with HC. Conclusions. Our data indicate that COVID-19 can impact the humoral immunity in the long-term.

Changes in Anti-SARS-CoV-2 IgG Subclasses over Time and in Association with Disease Severity.

IgG is the most prominent marker of post-COVID-19 immunity. Not only does this subtype mark the late stages of infection, but it also stays in the body for a timespan of at least 6 months. However, different IgG subclasses have different properties, and their roles in specific anti-COVID-19 responses have yet to be determined. We assessed the concentrations of IgG1, IgG2, IgG3, and IgG4 against different SARS-CoV-2 antigens (N protein, S protein RBD) using a specifically designed method and samples from 348 COVID-19 patients. We noted a statistically significant association between severity of COVID-19 infection and IgG concentrations (both total and subclasses). When assessing anti-N protein and anti-RBD IgG subclasses, we noted the importance of IgG3 as a subclass. Since it is often associated with early antiviral response, we presumed that the IgG3 subclass is the first high-affinity IgG antibody to be produced during COVID-19 infection.

Longitudinal Randomized Cohort Study of SARS-CoV-2 Antibody Seroprevalence in the St. Petersburg Population.

Introduction. Since the detection of the first COVID-19 patient, 2 years have passed, during which more than 287,862,000 people have fallen ill globally, of which about 1.9% died. The implementation of SARS-CoV-2 control programs required efforts from almost all countries. An important direction in the fight against COVID-19 has been the formation of herd immunity, the main tool for managing the pandemic. Study goal. The aim of the study was to assess the seroprevalence of antibodies (Abs) to SARS-CoV-2 nucleocapsid (Nc) and receptor binding domain (RBD) in the St. Petersburg population during the COVID-19 pandemic. Materials and methods. A longitudinal cohort randomized monitoring study of Ab seroprevalence (SARS-CoV-2 Nc, RBD) was organized and conducted according to a unified methodology developed by Rospotrebnadzor with the participation of the St. Petersburg Pasteur Institute. For this purpose, a cohort was formed of 1000 volunteers who participated in all five stages of seromonitoring. The cohort was divided into seven age groups: 1-17; 18-29; 30-39; 40-49; 50-59; 60-69; 70; and older (70+) years. Seropositivity levels (Nc, RBD) were assessed by quantitative and qualitative enzyme immunoassays. During the second year of monitoring, some volunteers were vaccinated with the GamCOVIDVac (84%) or EpiVacCorona (11.6%) vaccines approved in Russia. Statistical processing was carried out using Excel 2010. Confidence intervals for shares and percentages (95% CI) were calculated using the method of A. Wald and J. Wolfowitz with adjustment (A. Agresti, B.A. Coull). The statistical significance of differences was calculated by z-test, using the appropriate online calculator (p < 0.05) unless indicated. Results. There was a trend toward an increase in Nc seropositivity in stages 1-3 of seromonitoring, with a decrease in stages 4-5 among children and adults. The share of RBD seropositive steadily increased during all five stages of seromonitoring. The most frequent finding was low anti-RBD Abs levels (22.6-220 BAU/mL). High Ab levels were recorded statistically significantly less frequently. Asymptomatic forms were observed in 84-88% of SARS-CoV-2 seropositive volunteers. By the fifth stage of monitoring, this indicator significantly decreased to 69.8% (95% CI: 66.1-73.4). The monitoring revealed a statistically significant increase in anti-RBD Abs alongside a statistically significant decrease in the proportion of Nc seropositives. This dynamic was especially characteristic of persons vaccinated with GamCOVIDVac. Conclusion. Prior to the use of specific vaccines, a seroprevalence of anti-Nc Abs was noted. After the introduction of the GamCOVIDVac vaccine in adults, a decrease in the level of anti-Nc Abs was noted due to an increase in the proportion of RBD seropositive persons.