Immune Response Dynamics to SARS-CoV-2 in the Albanian Population: A Study on T-Cell and Antibody Interactions During the Transition From Pandemic to Endemic Phase
Authors: Sulcebe Genc , Shyti Erkena , Dashi-Pasholli Jonida , Kurti Margarita 
Published: December 2024

Abstract

Background:
The coronavirus disease 2019 (COVID-19) pandemic has resulted in a dynamic evolution of the immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), initially characterized by primary responses and later by secondary responses due to mass vaccination and viral variants. Understanding the interplay between humoral (antibody) and cellular (T-cell) immunity is crucial for effective public health strategies. This study aims to evaluate the correlation between T-cell responses and antibody levels in a sample of the adult Albanian population during the transition of COVID-19 from a pandemic to an endemic phase. The rationale for this investigation is to generate data that can inform the ongoing management of COVID-19, particularly in the context of vaccination and immunity monitoring, to ensure that public health strategies remain effective as the virus becomes more permanent in the population.

Methods:
This cross-sectional observational study involved individuals over 18 years of age who were randomly selected at intervals of every 20 records from the family doctor registries of five urban health centers in Tirana and Berat, Albania, between January 23 and April 3, 2023. Participants provided demographic and health data, including vaccination and infection history. Blood samples were analyzed for cellular immunity using an Interferon-gamma (IFN-γ) release assay and for humoral immunity using the enzyme-linked immunosorbent assay to measure anti-spike (S1) and anti-nucleoprotein (N) IgG antibodies. Statistical analyses were conducted to examine the relationships between levels of IFN-γ, anti-S1, and anti-N IgG antibodies and factors such as vaccination status, prior COVID-19 infections, and reinfection rates. These analyses employed bivariate and multivariate approaches, including Fisher’s exact test, the Mann–Whitney U test, the Kruskal–Wallis test, linear and multiple regression analyses, and Spearman’s correlation coefficient test.

Results:
The study involved 164 individuals (54.7% female, median age 43 years). Of these individuals, 62.8% (103/164) were vaccinated, primarily with the Pfizer-BioNTech vaccine. IFN-γ positivity was detected in 95.1% (156/164), and anti-S1 IgG positivity in 93.3% (153/164). Significant correlations were observed between IFN-γ and anti-S1 IgG levels (r = 0.502; P < 0.001). Vaccinated individuals exhibited significantly higher levels of IFN-γ and anti-S1 IgG than unvaccinated individuals (P < 0.05). Reinfections were more prevalent in unvaccinated individuals than vaccinated individuals (26.2% [16/61] vs. 12.6% [13/103], P = 0.034). According to multiple regression analysis, the levels of anti-S1 antibodies were significantly correlated with protection against reinfection (regression coefficient β = –0.003; P = 0.042), while IFN-γ levels did not exhibit such a correlation (regression coefficient β = –1.659; P = 0.146).

Conclusion:
Vaccination, especially when combined with previous infection, significantly boosts both cellular and humoral immunity against SARS-CoV-2. The close correlation between IFN-γ and anti-S1 IgG levels indicates that vaccinated individuals mount a robust immune response. The lower reinfection rates among vaccinated individuals highlight the importance of vaccination for sustained protection. Assessing anti-S1 IgG antibodies and IFN-γ levels could be particularly beneficial for immunocompromised individuals when making decisions about revaccination. This study highlights the critical role of comprehensive immune monitoring in the management of COVID-19 and offers insights for future vaccination strategies.