T‐Cell‐Dependent Bispecific IgGs Protect Aged Mice From Lethal SARS‐CoV‐2 Infection

T-cell ageing may be a key factor in the disproportionate severity of coronavirus disease 2019 (COVID-19) in older populations. For hospitalized COVID-19 patients, treatment involving the use of monoclonal antibodies with the ability to neutralize SARS-CoV-2 usually involves the administration of high doses but has not been very effective at preventing complications or fatality, highlighting the need for additional research into anti-SARS-CoV-2 therapies, particularly for older populations. In this study, it is discovered that older persons with a severe SARS-CoV-2 infection has weaker T-cell responses. Therefore the development and characterization of spike-targeting T-cell-dependent bispecific (TDB) full-length human immunoglobulin Gs with enhanced efficacy in the treatment of COVID-19 is described. Using S-targeting TDBs, polyclonal T cells are guided to target and destroy S-expressing cells, preventing the cell-to-cell transmission of SARS-CoV-2 and thereby eliminating the need for SARS-CoV-2-specific immunity. Using animal models of COVID-19, it is shown that the selective activation of T cells improves the efficiency of treatment in preinfected mice by attenuating disease-induced weight loss and death. The significance of T-cell-based immunity during infection is highlighted by the findings. These results have implications for better clinical effectiveness of therapies for COVID-19 and the development of T-cell-dependent medicines for the elderly population.