Increased incidence of abnormal TREC/ KREC levels is revealed in virtually healthy individuals over the post-pandemic period

The COVID-19 pandemic has posed an unprecedented challenge to global public health. Poor clinical outcomes in COVID-19 were associated with a pathogenic triad of interrelated mechanisms: immune dysregulation, coagulopathy, and secondary immunodeficiency, which collectively establish a selfperpetuating cycle of progressive multiorgan dysfunction. The failure of immune defense stems, in part, from T and B cell depletion due to immune resource exhaustion during acute infection. The extent of immune system impairment may be assessed by quantifying biomarkers of lymphocyte function: T cell receptor excision circles (TREC) and κ-deleting recombination excision circles (KREC) for T and B cells, respectively. The aim of our study was to evaluate the prevalence of abnormal TREC/KREC levels in peripheral blood among apparently healthy individuals during the post-pandemic period. We analyzed whole peripheral blood samples from 4,433 apparently healthy adults (≥ 18 years), residents of St. Petersburg and Leningrad Region. The samples were collected during two population studies: June 15-21, 2020 (n = 717) and September 4-29, 2023 (n = 3,716). TREC/KREC quantification was performed by means of real-time PCR with “TREC/KREC-AmpPS” commercial kit (St. Petersburg Pasteur Institute, St. Petersburg, Russia) following manufacturer’s protocol. The prevalence of reduced TREC/KREC levels increased significantly from pre-pandemic (14.2% and 5.7%, respectively) to post-pandemic periods (50.1% and 21.2%, respectively), thus representing a 3.6-fold increase. The mentioned differences in pathological biomarker levels were observed across all age groups. Characteristic immunological disturbances manifested as either isolated T cell deficiencies or combined T/B cell dysfunction, with no isolated B cell defects detected, thus suggesting the pivotal role of T cell impairment in observed immunopathological changes. Post-pandemic findings included decreased minimal population TREC values in older age groups and a paradoxical 50.5% increase in lower threshold KREC levels. Our findings demonstrate a substantially increased prevalence of abnormal TREC/KREC values, which seems to reflect long-term immune alterations following COVID-19. These changes underscore the critical need for the ongoing immunological surveillance in the post-pandemic era. Future research should focus on temporal dynamics of these disturbances and develop preventive strategies to mitigate long-term COVID-19 sequelae.