Abstract Background Aging is a critical risk factor for unfavorable clinical outcomes among COVID-19 patients and may affect vaccine efficacy. However, whether the senescence of T cells impact the progression to severe COVID-19 in the elderly individuals remains unclear. Methods By using flow cytometry, we analyzed the frequency of senescent T cells (Tsens) in the peripheral blood from 100 elderly patients hospitalized for COVID-19 and compared the difference between mild/moderate and severe/critical illness. We also assessed correlations between the percentage of Tsens and the quantity and quality of spike-specific antibodies by ELISA, neutralizing antibody test kit and Elispot assay respectively, cytokine production profile of COVID-19 reactive T cells as well as plasma soluble factors by cytometric bead array (CBA). Results We found a significant elevated level of CD4 + Tsens in severe/critical disease compared to mild/moderate illness and patients with a higher level of CD4 + Tsens (&gt;19.78%) showed a decreased survival rate as compared to those with a lower level (&lt;19.78%), especially in the breakthrough infection. The percentage of CD4 + Tsens was negatively correlated with spike-specific antibody titers, neutralization ability and COVID-19 reactive IL-2 + CD4 + T cells. Additionally, IL-2 producing T cells and plasma levels of IL-2 were positively correlated with antibody levels. Conclusion Our data illustrated that the percentage of CD4 + Tsens in the peripheral blood could act as an efficient biomarker for the capacity of spike-specific antibody production and the prognosis of severe COVID-19, especially in the breakthrough infection. Therefore, restoration of the immune response of CD4 + Tsens is one of the key factors to prevent severe illness and improve vaccine efficacy in older adults.

CD4+T cell senescence is associated with reduced reactogenicity in severe/critical COVID-19