Cytokine profile and proteolytic enzyme levels in plasma of patients with chronic cerebral ischemia following COVID-19

Background. The purpose of this study was to determine the cytokine profile, levels of proteolytic enzymes, and the TIMP-1 in the plasma of patients with chronic cerebral ischemia (CCI) following symptomatic COVID-19, considering gender differences. Materials and methods. The research involved 108 patients with CCI aged 43 to 74 years, including 56 patients who had been diagnosed with COVID-19 in the past 9–12 months (CCI and COVID-19 group) and 52 patients with no history of SARS-CoV-2 infection (CCI group). The participants were also stratified by gender. Plasma levels of cytokines (IL-1, IL-4, IL-6, IL-8, IL-17, IL-18R, TNF-, and IFN-), matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, and MMP-10), and TIMP-1 were measured using enzyme-linked immunosorbent assay. Results. No significant differences were revealed in the levels of most cytokines in the plasma of CCI patients with and without a history of COVID-19, except for IL-1, which was elevated by 46.65 % in female CCI patients who had experienced symptomatic COVID-19. Higher levels of proteolytic enzymes MMP-1, MMP-2, and MMP-12 were found in the plasma of male CCI patients who recovered from COVID-19, with increases of 20.72, 27.33, and 20.37 %, respectively, compared to participants with no history of SARS-CoV-2 infection. No significant differences in TIMP-1 levels were observed between the CCI and CCI and COVID-19 groups. The obtained data may indicate gender-specific changes in the cytokine profile and proteolytic system in CCI patients following symptomatic COVID-19. Conclusions. SARS-CoV-2 infection, even after a long post-acute period, can activate alternative pathogenetic mechanisms, including dysregulation of cytokine, systemic inflammation, and proteolytic imbalance with gender-specific characteristics, which may exacerbate ischemic processes in patients with CCI and increase the risk of cerebrovascular complications.