THE IMMUNOLOGICAL MEMORY TO SARS-CoV-2 S-PROTEIN PERSISTS 4 YEARS AFTER THE DISEASE

Abstract

The COVID-19 pandemic end did not exclude the continuation of breakthrough infections caused by SARS-CoV-2 mutant strains. The rate of SARS-CoV-2 mutations increased with the emergence of the omicron strain and exceeds that of the influenza virus. It remains unclear what IgG antibody levels are able to protect against new mutant SARS-CoV-2 and how long the immune protection will last. Objective: to monitor the maintenance of humoral and cellular immunity to SARS-CoV-2 virus antigens for 4 years after the disease. Thirty-two adult reconvalescents after COVID-19 were annually examined for humoral and cellular immunity to the SARS-CoV-2 S-protein. Humoral immunity was assessed by ELISA, cellular immunity - by the expression of CD107a on CD8^hi lymphocytes after recognition of S-protein antigens. A four-year observation of a group of patients who recovered from COVID-19 in 2020 (the Wuhan strain of SARS-CoV-2) and were in contact with freely circulating new mutant VoC showed that after 1 year, all subjects retained IgG antibodies to the S-protein, mainly the IgG1 subclass, but the antibody avidity index barely exceeded 50%. After a breakthrough disease caused by the omicron strain, the level of IgG antibodies to the S protein increased significantly, the antibody avidity also increased significantly, and antibodies to the S-protein of the IgG2, IgG3, and IgG4 subclasses appeared in the spectrum of subclasses. The level of specific IgA decreased 1 year after the disease relative to the level after the primary disease, but after breakthrough infections it significantly increased to 4-5 PR. Cellular immunity to the SARS-CoV-2 S-protein was detected in all subjects 1 year after the primary disease. After repeated infection with the omicron strain, it increased significantly and remained at this level for another year, and in a 4 years it decreased to the level that was a year after the disease. Thus, humoral and cellular immunity to the S-protein does not disappear, but continues to actively form, mature and be maintained at a level that allows, when meeting a new VoC, to endure such a meeting either asymptomatically or in the form of a mild cold. Against the background of frequent mutations in the S-protein, the role of T-cell responses in protecting against diseases increases significantly. When developing new vaccines, it is necessary to rely on the formation of cellular immunity.