Quantitative and phenotypic transformation of CD16<sup>+</sup>IFNα/βR1<sup>-</sup>CD119<sup>+</sup>, CD16<sup>+</sup>IFNα/βR1+CD119<sup>-</sup> and CD16<sup>+</sup>IFNα/βR1<sup>+</sup>CD119<sup>+</sup> neutrophil granulocytes subsets in patients with post-COVID syndrome

Abstract

In patients who underwent COVID-19, various manifestations of post-COVID syndrome (PCS) are noted, causing the development of disorders accompanying severe viral infections, complicated by chronic fatigue syndrome (CFS) and severe cognitive disorders (CD). Studying the molecular mechanisms of these disorders in the system of neutrophilic granulocytes (NG) in patients with PCS associated with IFN production, receptor function of NG, in particular, their subsets expressing IFN/R, IFNR(CD119), is relevant for the search for therapeutic strategies, restoration and enhancement of the innate immune response after COVID-19.
 Our objective was to clarify the quantitative and phenotypic characteristics of certain subsets of neutrophil granulocytes, i.e., CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+, in peripheral blood of patients with post-COVID syndrome.
 We have examined 39 patients (24-60 years old) with PCS 3 months after COVID-19 (study group 1, SG1). The comparison group (CG) included 30 volunteers examined over the pre-COVID period. Detection of herpesvirus infections (HSV1, EBV, HHV6, CMV) was carried out in scrapings from the tonsils and the posterior wall of the pharynx. To determine the severity of the clinical PCS symptoms, a questionnaire was used to assess its severity using a point scale. The content and phenotype of NG subsets CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+ were assessed by means of FC 500 (Beckman Coulter, USA).
 In all patients of SG1, clinical manifestations of CFS and CD were revealed, at the average severity rates of 16.0 points (14.75-20.25). When detecting herpesvirus infections, 37.2% had only HSV1 infection; 62.8% of patients showed mixed infection (HSV1, EBV, HHV6), which exhibited more pronounced clinical symptoms. We have noted absence of CD16+IFN/R1+CD119+NG subset and phenotype transformation of CD16+IFN/R1-CD119+NG, CD16+IFN/R1+CD119-NG subsets. Increased density expression of CD16, IFN/R1, CD119 receptors was also found (p1-3 0.05) thus suggesting ability to accept the interferon signaling and response.
 Reduced infectious burden in the post-COVID period and adequate functioning of the immune system, including the neuroimmunoendocrine regulation mechanisms, should contribute to the functional recovery of various organs, systems, thus neutralizing the PCS manifestations. Therefore, usage of recIFN2b in combination with highly active antioxidants may contribute to development of protective immunity, prevention of acute respiratory viral infections, exacerbation of chronic infections, and restoration of the NG phenotypes followed by restoration of anti-infectious immune balance.