Reduced immune response to SARS-CoV-2 infection in the elderly after 6 months.

OBJECTIVES

To evaluate the immune persistence and cross-immune response of elderly individuals after Omicron BA.5 infections.

METHOD

The neutralizing antibodies against WT, BA.5, XBB.1 and EG.5 strains were analyzed. The T/B-cell subsets' responses were tested through intracellular cytokine staining and flow cytometry.

RESULTS

The neutralizing antibodies titers against WT and BA.5 strain, remaining high level for at least 6 months, were higher than that of both XBB.1 and EG.5 variants. The neutralizing antibodies of WT, BA.5, XBB.1, and EG.5 strains in the elderly were slightly lower than those in middle-age. The memory B cells decreased rapidly in the elderly, and Tfh, Th17 cells of the elderly continued to increase for only 3 months, while Tfh and Th17 cells increased in the middle-aged for over 6 months. For the elderly, after peptide stimulation, unswitched/switched memory B cells decreased, while double negative B cells displayed higher proliferation. The proportions of both naïve and Temra cells in CD4 and CD8 T cells declined, whereas those of Tcm and Tem cells elevated. In the meantime, both CD69 and CD38 T cells decreased, but the frequencies of PD-1 and CTLA-4 of CD4 and CD8 T cells showed an increasing trend. The proportions of PD-1 and CTLA-4 cells also increased in older people with long COVID symptoms at 3m post-infection.

CONCLUSIONS

Omicron BA.5 infection induced lower neutralizing antibodies against XBB.1 and EG.5 variant. The decrease of memory B cells, CD69 and CD38T cells, as well as the increase of PD-1, CTLA-4 of CD4/CD8T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.