The formation of syncytia and the induction of cellular senescence are important aspects of SARS-CoV-2 infection. Syncytia are multinucleated cells that arise from the fusion of infected cells with neighbouring cells, and these syncytia frequently contain senescent cells. Below you will find a summary of the relevant data and a rough estimate of the overall impact on cells:
Formation of syncytia
- Cell-type dependence: The ability to form syncytia upon SARS-CoV-2 infection varies depending on the cell type and the expression level of ACE2 and the spike protein. For example, 293T cells and A549-ACE2 cells readily form syncytia after infection, whereas Caco2 cells do not[1][2].
- Quantification: In experimental settings, syncytium formation can be very extensive. In Vero cells transfected with the spike protein, for instance, syncytium formation was significant, with large areas of fused cells observed within 24 hours[3][4].
Senescent cells
- Senescence induction: SARS-CoV-2 infection induces cellular senescence in various cell types, including lung epithelial cells, endothelial cells and dopaminergic neurons. In lung tissue samples from COVID-19 patients, 8-21 % of infected alveolar type 2 (AT2) cells showed features of cellular senescence[5].
- Syncytia and senescence: The syncytia formed upon SARS-CoV-2 infection predominantly contain senescent cells. This is due to the activation of signalling pathways such as the cGAS-STING pathway and the TNFα-TNFR2 axis, which drive these fused cells into a senescent state.
Rough estimate
Given the data:
- If we assume that in certain tissues up to 21 % of infected cells can become senescent and that syncytium formation can affect a considerable proportion of these cells, a rough estimate can be made.
- Assuming that syncytium formation and senescence are not mutually exclusive and that there is substantial overlap, the combined effect could mean that a considerable proportion of infected cells in certain tissues (possibly up to 30 % or more) could be either senescent or part of syncytia.
Conclusion
Although it is difficult, owing to the variability between different tissues and individual responses, to determine exact percentages for the entire human organism, it is clear that a SARS-CoV-2 infection can lead to a considerable proportion of cells becoming senescent or forming syncytia. In certain tissues this could affect up to 30 % or more of the cells and contribute to the severe inflammatory and pathological consequences observed in COVID-19.
