Impaired homeostasis of T follicular helper cells in elderly patients with COVID-19

Abstract

Abstract Background In December 2022, the discontinuation of China’s dynamic zero policy resulted in a nationwide surge of Corona Virus Disease 2019 (COVID-19)-related cases and hospitalizations. We sought to probe the immune profile of the elderly with COVID-19 and explore the feasibility of a certain cell population as biomarker for risk stratification, which may provide foundation for the diagnosis and treatment of upcoming COVID-19 wave this winter. Our study recruited 57 elderly patients with acute COVID-19 and 27 convalescent donors. SARS-CoV-2-specific adaptive immunity including binding antibodies, neutralizing antibodies and T-cell responses were assessed across the COVID-19 severity spectrum. Results Patients with acute illness underwent impaired CD4+ T homeostasis, preferential loss of follicular helper T cell (Tfh) subsets including Tfh-em, Tfh-cm, Tfh1, Tfh2, Tfh17 and T follicular regulatory cells (TFR), which correlated with antibody production through different pathways, were observed. Severity of acute respiratory distress syndrome correlated with the degree of Tfh deficiency, which may act as biomarkers for risk stratification of elderly patients with COVID-19. Moreover, vaccination ameliorated Tfh and TFR deficiency and helped to promote NAb production. Conclusion The elderly had gone through severity-dependent CD4+-biased lymphopenia post SARS-CoV-2 infection, and vaccination contributed to ameliorate prognosis of them via alleviating the impairment degree of Tfh subsets.