The impact of concomitant COVID-19 in patients with acute myocardial infarction on endothelial function, markers of systemic inflammation, and blood cell subpopulations in the long-term follow-up period

Abstract

The aim – to assess the course of the coronary artery disease (CAD), the state of endothelial function, intracardiac hemodynamics, and immune system response in the long term follow-up period after ST-elevation myocardial infarction (STEMI) in patients with concomitant COVID-19 for the development of personalized treatment approaches. 
Materials and methods. A cohort of patients with CAD (n=60; 85.0 % men; mean age 61.0±1.3 years) was examined 40-48 months after STEMI. Group 1 included patients treated in 2019 before the COVID-19 pandemic (n=30), and group 2 included patients treated during the pandemic in 2020–2022 (n=30) who had documented SARS-CoV-2 infection. The study excluded patients with diabetes mellitus, chronic kidney disease, cancer, chronic inflammatory diseases, high-grade chronic heart failure, and anemia. The examined sample was obtained through screening of 807 patients. All patients underwent a set of clinical, laboratory, and instrumental examinations, which included medical history collection (documented COVID-19 episodes, vaccination history, CAD exacerbations, treatment), cardiac ultrasound, endothelium-dependent vasodilation (EDVD) testing, general laboratory tests, and immunophenotyping of blood cell subpopulations by flow cytometry using the markers CD3, CD4, CD8, CD31, CD34, CD38, and CD309.
Results. Patients in the examined groups did not differ in age or baseline clinical and anamnestic characteristics (including the frequency of documented COVID-19 and vaccination history), and all demonstrated high adherence to treatment. According to EDVD test, endothelial dysfunction was detected in 70 % of patients in both groups, and the mean test values were comparable. Biochemical blood parameters also showed no differences between the groups, nor did inflammatory markers such as C-reactive protein, erythrocyte sedimentation rate, the neutrophil-to-lymphocyte ratio, and the platelet-to-lymphocyte ratio. Correlation analysis of EDVD with inflammatory markers did not reveal any significant associations.
However, immunophenotyping of blood cell subpopulations demonstrated significant differences between the groups. In group 2 patients, who had STEMI with concomitant COVID-19, lower levels of T lymphocytes and higher numbers of immature T-cell were observed, while the levels of T-helpers, T-suppressors, and their ratio did not differ from those in group 1. At the same time, the number of hematopoietic progenitor cells, activated T- and B-lymphocytes, as well as cells expressing vascular endothelial growth factor (VEGF) receptors, were increased. In this group, no significant correlations were found between EDVD results and any clinical, laboratory, or instrumental parameters, nor with the results of blood cell subpopulation phenotyping. 
When comparing subgroups of patients with markedly reduced endothelial function (values below the group mean), group 2 showed higher monocyte counts, lower lymphocyte counts, increased populations of activated T- and B-lymphocytes and immature T-lymphocytes, together with elevated levels of repair markers (CD309+ endothelial progenitors), while markers of endothelial activation and damage remained unchanged.
Conclusions. A study conducted in a carefully selected cohort of patients with CAD who had previously experienced STEMI revealed the negative consequences of its combination with COVID-19. Despite similar clinical, instrumental, and laboratory characteristics between the groups, patients with concomitant COVID-19 demonstrated impaired mechanisms of endothelial function regulation and immune system dysfunction, characterized by the development of a pro-inflammatory cellular phenotype. These changes occurred against the background of vascular injury and were accompanied by secondary activation of proangiogenic reparative potential.