SARS-CoV-2 recombinant spike protein induces cell apoptosis in rat taste buds

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause loss or alteration of taste and smell as early symptoms or sequelae, but the detailed mechanism behind this phenomenon remains unclear. Here, we investigated whether the SARS-CoV-2 spike protein induces taste cell apoptosis and expression of the apoptosis-related cytokine TNF-α in male Sprague–Dawley rats. Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-fluorescein nick end labeling (TUNEL) assay results revealed a significantly higher apoptosis index for taste cells in the SARS-CoV-2 group than for those in the control group. An immunohistochemistry analysis indicated significantly more TNF-α-positive cells in the SARS-CoV-2 group compared with the control group. These data suggest that the SARS-CoV-2 spike protein promotes taste cell apoptosis and the release of apoptosis-related cytokine TNF-α, implicating its contribution to the taste malfunction caused by coronavirus disease 2019 (COVID-19).