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

Qin Luo#¹Qinqin Song#¹Yan Li²Kexin Zong³Ti Liu²Junming He⁴Guoyong Mei¹Haijun Du¹Zhiqiang Xia¹Mi Liu¹Juan Song¹Chen Gao¹Dong Xia¹Guangyu Xue¹Wenyan Tian¹Yinli Qu¹Zengqiang Kou^1*Zhongjun Dong^1*Jun Han^5*

• ¹National Institute for Viral Disease Control and Prevention (China CDC), Beijing, Beijing Municipality, China
• ²Shandong Center for Disease Control and Prevention, Shandong, China
• ³Xi'an Jiaotong University, Xi'an, China
• ⁴Beijing Tsinghua Changgung Hospital, Beijing, Beijing, China
• ⁵Chinese Center For Disease Control and Prevention, Beijing, China

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 CD38+T cells, as well as the increase of PD-1+, CTLA-4+ of CD4+/CD8+T cells and double negative B cells, indicate that sustained immune responses against BA.5 infection may wane more rapidly in elderly populations.