SARS-CoV-2 is the virus responsible for the COVID-19 disease pandemic. The elderly and individuals with comorbities are high risk groups for severe disease symptoms and mortality - but many of their cellular determinants for poor prognosis are yet to be identified. The high magnitude of inflammatory imbalances, inadequate immune response and long-covid aetiology in COVID-19 infections also remains 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 increase in metabolic and secretory activity.
Current literature suggests there are several similarities between the biological and signalling properties of senescence and COVID-19 manifestations. These include higher proportions of pro-inflammatory molecules, changes in tissue morphology, increase in cellular metabolism, decreased immune capacity and higher occurrence of ARDS. This research studied these similarities in order to determine whether or not cellular senescence plays a role in COVID-19 disease severity and long-covid aetiology.
A number of immortalised and primary human cell models were infected with live SARS-CoV-2 virus, before screening for senescence induction through the use of confocal immunofluorescent imaging, qRTPCR and senescence associated Beta-Galactosidase staining. It was evident that the infected models had a substantially higher count of senescence in contrast to the mock non-infected cell models.
The results showed that infection with SARS-CoV-2 can induce senescence in human cells. This may explain the reduction of immune capacity seen in severe COVID-19 infections, as well as the increased production of pro-inflammatory molecules that induce to the cytokine storm. It also provided an insight into long-covid aetiology; as senescence can cause extended disease morbidity, an increased persistence of pathogens and accumulation of proinflammatory molecules - leading to a higher prevalence of tissue and organ damage.
Fortunately, there are pharmaceuticals known as senolytics available that can remove senescent cell accumulation, and have been shown to reduce COVID-19 severity in human cell lines and animal models. This will hopefully advance the screening of senolytics into human trials and help us to reduce long-term symptoms in otherwise recovered COVID-19 patients.