Immune-mediated disorders in post-COVID patients and their relationship with impaired complement system activity

The COVID-19 pandemic caused by the SARS-CoV-2 virus has led to far-reaching consequences. The changes caused in COVID-19 patients may persist for more than 6-12 months after acute phase of the disease promoting post-COVID disorders of immune system. Patients who have had acute COVID-19 in both mild and severe forms suffer from various manifestations of post-COVID syndrome. However, the severity of these manifestations is quite variable. The aim of the study was to assess the effect of lung damage extent in acute period of COVID-19 on the severity of clinical manifestations in post-COVID syndrome as exemplified by immune-mediated syndromes, i.e., autoimmune disorders, proliferative conditions, and allergopathology. 131 patients who had who had a history of SARS-CoV-2 infection were examined. Anamnestic data from outpatient cards of patients were used for the study. Using the ELISA diagnostics method, IgA, IgM, IgG specific to SARS-CoV-2, complement components C1q, C3a, C5a were determined. The studies revealed a connection between the severity of post-COVID syndrome and the severity of the acute COVID-19 course. The SARS-CoV-2 virus is able of activating complement, and this activation persists for a long time (more than six months). This finding explains presence of clinical manifestations of post-COVID syndrome in individuals who have had a mild acute form of COVID-19 without CT-detected lung damage without phenotypes of immune system damage that we have previously identified (congenital – decreased expression of CD46 on T lymphocytes and decreased expression of CD46 on NK cells, and acquired – decreased level of T-cytotoxic lymphocytes and impaired level of B-cells CD45⁺CD3^-CD19⁺CD5⁺CD27⁺). The data obtained indicate that the examination of post-COVID patients should be carried out not only by their clinical characteristics, but also by assessing markers of their immune system in order to make a correct diagnosis and prescribe etiological and pathogenetic therapy, including immune therapy. Conclusions: 1. Autoimmune, proliferative and allergic diseases are directly related to disorders of the immune system. The severity of autoimmune disorders in the post-COVID period is more associated with basic corticosteroid therapy (GCS) both for the treatment of autoimmune processes and for the treatment of COVID-19 (except of treating autoimmune thyroiditis). GCS treatment used in acute period of infection reduced the number of recurrenct disorders. The situation is the opposite in rheumatoid arthritis: the use of GCS in the acute period of infection in patients already on basic corticosteroid therapy subsequently leads to an increase in the number of relapses in post-COVID patients. 2. In post-COVID patients, we revealed a trend towards an increase in the most clinically severe allergopathology: firstly, in all groups (52%) in the post-COVID period, exacerbations of such pathologies as Quincke’s edema, urticaria, anaphylaxis, vasculitis, alveolitis, and bronchiolitis became more frequent. These findings suggest that the worse condition of these patients in the post-COVID period was influenced by the past SARS-CoV-2 infection Allergic skin lesions were in second place in terms of the frequency of exacerbations (about 28%). 3. There is a tendency towards an increased frequency of proliferative diseases exacerbations in patients with more severe forms of acute COVID-19 infection. It should also be noted that the percentage of such patients is quite high, from 31.6% to 48%. 4. The SARS-CoV-2 virus may affect the complement activation system, thus explaining clinical manifestations of post-COVID syndrome in the persons who had a mild form of COVID-19 without evidence of lung damage immune system affection. Our data indicate that the examination of post-COVID patients should be carried out not only by assessing their clinical characteristics, but also by examining the state of the immune system in such patients in order to make a correct diagnosis and administer etiological and pathogenetic therapy, including immune therapy.