D2.423 - Changes in the expression of regulatory receptors on CD8+ T cytotoxic lymphocytes as a marker of the risk of developing a post COVID-19 condition in patients after a severe course of COVID-19

Post COVID-19 condition (PCC, ICD-10 code U09.9) occurs after the initial SARS-CoV-2 infection, which is characterized by persistent pathological symptoms from various organs and systems for 12 or more weeks. Cellular immunity is the leader in antiviral protection. The key mechanism of functional activity of CD8+ T lymphocytes function is by inducing apoptosis in cells infected with the virus [Mitsuyama Y et al., 2021]. 

We examined 64 patients, 43 females and 21 males, aged 18-62 years, who were diagnosed with COVID-19 in 2020-2022 and had symptoms consistent with PCC [Bygdell M et al., 2023]. Patients were divided into three groups: 21 patients after a mild course, 22 patients after a moderate course, and 21 patients after a severe course of acute COVID-19 in their medical history; a control group consisted of 20 healthy participants. The study material was peripheral blood. By multiparametric flow cytometry on the cell surface of CD8⁺, the following were determined: expression of inhibitory receptor/ligand PD-1L (CD274⁺)/PD-1 (CD279⁺), TIM-3 receptor (CD366⁺), and regulatory receptor CD38⁺.

PD-1L (CD274⁺) expression was significantly higher in patients with a history of moderate (p=0.011) and severe COVID-19 (p=0.003) than in the control group. PD-1 (CD279⁺) expression in patients after severe COVID-19 was lower than in patients after mild COVID-19 (p=0.009) and in the control group (p=0.041). TIM-3 (CD366⁺) expression in patients after severe COVID-19 was significantly lower than in patients after mild and moderate COVID-19 (p=0.043) and in the control group (p=0.046). CD38⁺ expression in patients after severe COVID-19 was considerably higher than in the control group (p=0.042) and tended to be higher than in patients after mild and moderate COVID-19. We compared our data on long-term changes in the cytotoxic function of CD8⁺ T cells in patients after COVID-19 with results from other authors, showing that the condition following severe COVID-19 is associated with autoimmunity. We suggest that persistent immune dysregulation in patients with РCC following severe COVID-19 leads to a shift toward Th1 lymphocytes, upregulation of activating and inhibitory receptors, and increased CD38 expression. Together, these changes cause pathological consequences, particularly autoimmunity or other post-COVID immunopathology.

Patients with a history of severe COVID-19 exhibit cellular immune disorders, characterized by decreased numbers of CD8⁺ cytotoxic T lymphocytes (p < 0.05), and are at higher risk of autoimmunity, as the activator/inhibitor receptors on CD8⁺ T lymphocytes lose their ability to immunoregulate. These changes may also serve as risk markers for the development of post-COVID condition.