Investigating the role of cellular senescence in SARS-CoV-2 (COVID-19) infections.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly transmissible respiratory virus responsible for the Coronavirus Disease of 2019 (COVID-19) pandemic. Since its original emergence in Wuhan China towards the end of 2019, it?s intercontinental spread has led to the infection of over 250 million people, and has resulted in the death of over 5 million individuals worldwide. The elderly and individuals with comorbities were identified as being at high risk for severe disease symptoms and mortality - but many of the cellular determinants for poor prognosis between these groups are still unknown. One significant commonality between each high-risk group is an accumulation of senescent cells. These are cells that have been subjected to cellular stress and or/injury, resulting in a loss of proliferative capacity, resistance to apoptosis, and an increase in metabolic and secretory activity. This project investigated the role of cellular senescence in SARS-CoV-2 (COVID-19) infections. The aims were to establish an in vitro model of cellular senescence and determine whether or not senescence upregulates viral infection and replication. The secondary aim was to determine whether or not the infection with SARS-CoV-2 induces senescence in healthy cells. The study was performed with intention of potentially identifying the underlying cellular mechanisms that contribute to severe disease symptoms and/or ?long-COVID? aetiology. The results from this study showed that SARS-CoV-2 infection and replication isn?t upregulated in non-permissive senescent cultures, but the infection with SARS-CoV-2 does induce senescence in healthy cell cultures. This could explain the long term tissue and organ damage seen in recovered COVID-19 patients. It could also provide the underlying mechanisms that make the high risk groups vulnerable to severe disease symptoms, and trigger the promising investigation into the use of senolytics for the treatment and prevention of severe COVID-19 disease.