Cellular Immunity-The Key to Long-Term Protection in Individuals Recovered from SARS-CoV-2 and after Vaccination

Abstract

Previous clinical and epidemiological studies have shown that over time antibody titers decrease, and they do not provide long-term mucosa protection against SARS-CoV-2 infection. Additionally, the increase in breakthrough infections that occur more frequently in the vaccinated than in the study participants with previous SARS-CoV-2 infection has recently become a priority public health concern. We measured the amount of interferon-gamma (Quan-T-Cell ELISA) and the level of antibodies (Anti-SARS-CoV-2 QuantiVac ELISA IgG) in the blood of the same patients simultaneously to compare cellular and humoral immunity. A total of 200 study participants (before Omicron variant appearance) were divided into four groups whose levels of cellular and humoral immunity we compared: study participants previously infected with SARS-CoV-2 (group 1); study participants vaccinated with EMA-approved vaccines (group 2); study participants previously infected with SARS-CoV-2, and vaccination history (group 3); and study participants without a history of SARS-CoV-2 infection or vaccination (group 4). Our results showed that study participants who received one of the EMA-approved vaccines and who recovered from COVID-19 (group 3) had significantly higher levels of cellular immunity and antibody titers in comparison with groups 1 and 2. Additionally, we have noticed that the study participants previously infected with SARS-CoV-2 and the study participants vaccinated with EMA-approved vaccines had a long-lasting cellular immunity. Furthermore, antibody levels showed a negative correlation with time since the last contact with a viral antigen, while cellular immunity within 20 months showed as long-term protection. Moreover, out of 200 study participants, only 1 study participant who recovered from COVID-19 (0.5%) was re-infected, while a total of 6 study participants (3%) were infected with SARS-CoV-2 after receiving the vaccine. This study suggests that cellular immunity-unlike humoral immunity, thanks to memory T cells-represents long-term protection in individuals recovered from SARS-CoV-2 and after vaccination.

Keywords: COVID-19; Delta variant; Omicron variant; SARS-CoV-2; breakthrough infection; cellular immunity; humoral immunity; infection; vaccination.

Figure 1

Level of cellular (A) and humoral (B) immunity in study participants with a previous SARS-CoV-2 infection (group 1), study participants vaccinated with one of the SARS-CoV-2 vaccines (group 2), study participants who had a past SARS-CoV-2 infection and a vaccination history (group 3), and study participants without a history of SARS-CoV-2 infection or a vaccination (group 4). *—p < 0.05 (Mann–Whitney); **—p < 0.001 (Mann–Whitney).

Figure 2

Level of humoral (A) and cellular (B) immunity in study participants exposed to the viral antigen less than six months prior than those exposed more than six months prior. Levels of humoral (C) and cellular (D) immunity in different age groups show age-dependent differences in distribution. In Figure 2A,B, study participants were divided into two groups, with an arbitrary limit of 6 months. *—p < 0.05 (Mann–Whitney); **—p < 0.001 (Mann–Whitney).