More than two years have passed since COVID-19 became a global pandemic, and it is still very much a public health issue for everyone. While many countries have loosened control over the disease considering the reduced virulence of the more infectious SARS-CoV2 Omicron variants, scientists are still trying to understand the long-term effects of viral infections caused by SARS-CoV2 that are not as evident as acute respiratory symptoms. One of the potential harms caused by this virus could be its role in increased ageing in people. This has become even more relevant now as more people are getting infected with Omicron.
First and foremost, COVID-19 could contribute to immunological ageing, or immunosenescence. Normally, as we age, we accumulate small amounts of inflammatory markers over our lifetimes as a response to internal stressors such as telomeric erosion and external stressors such as pollution. However, with SARS-CoV2 infections, people may experience a ‘cytokine storm’ characterised by the release of certain cytokines and chemokines in elevated levels, sometimes causing systemic inflammation. Even after the virus is cleared by the immune system, it may have left lasting pro-inflammatory physical damage such as lung immune cell infiltration. Furthermore, infection with the virus may downregulate the expression of Angiotensin Converting Enzyme 2 (ACE2), which has an immunomodulatory role. With reduced ACE2 expression, affected cells assume a pro-inflammatory state and produce more angiotensin II. Under these chronic inflammation conditions, senescent cells may persist and take on abnormal secretion phenotypes that produce even more inflammatory factors, including matrix metalloproteinases, fibronectin, and reactive oxygen species. All these pro-inflammatory factors together contribute to inflammaging, which affects immune cell function and increases immunosenescence. Ageing in our immune system may be characterised by impaired antigen presentation and phagocytic capacities, altered responses to signals such as interferons, reduced cytotoxic activity of CD8+ T cells, reduced levels of antibody production, depletion of naïve T cell and B cell repertoires, and so on. Such a weakened immune system then becomes more prone to viral infections such as SARS-CoV2.
Additionally, COVID-19 may have a surprising role in metabolic ageing. One of the signs of metabolic ageing could be type 2 diabetes, and SARS-CoV2 is found to have caused healthy people to develop diabetes after infections. While scientists have not found a definitive cause for this rather abnormal development following a respiratory virus, there is increasing evidence that the SARS-CoV2 virus is capable of infiltrating and infecting cells outside of the respiratory system. One theory put forward is that SARS-CoV2 can infect pancreatic cells that express the same ACE2 surface proteins as lung cells. This would result in impaired pancreatic function, particularly its ability to produce insulin, which could result in a similar metabolically senescent phenotype as in type 2 diabetes. Alternatively, SARS-CoV2 may even make tissues all over the body less responsive to insulin by causing unwanted inflammation. For those already suffering from type 1 diabetes, SARS-CoV2 was found to induce insulin resistance, which would otherwise be associated with type 2 diabetes. Regardless of which mechanism is correct, SARS-CoV2 surely has the capacity to influence our metabolic processes and contribute to metabolic ageing.
Lastly, the psychological burdens caused by COVID-19 can reinforce its emerging role in ageing. During this pandemic, more and more people are experiencing stress and anxiety. Parents become stressed when schools are closed, consumers become stressed when stocks are empty, workers become stressed when jobs are lost, students become stressed when classes move online……and all of us become stressed with lockdowns, travel restrictions, positive LFD tests, isolations, and so much more. Not to mention the feeling of depression and anxiety when people experience persistent symptoms that do not seem to go away, such as chest pain, dry coughs, insomnia, and chronic fatigue. These diverse symptoms are termed ‘long COVID’, but the exact causes remain uncertain. But even more devastating is the emotional toll on those suffering from long COVID. Stress itself has been studied for a long time as a risk factor of ageing. It is associated with heart problems, cancer, and other chronic diseases. At the cellular level, stress may contribute to shortened telomere length. Elevated cortisol levels due to stress can promote pathways that damage telomeres, resulting in cellular ageing and reduced replication and DNA repair capacity.
Therefore, we must not think of SARS-CoV2 as merely a respiratory virus. It has much greater implications on human health, especially in the long run. As of now, we do not have any long-term observational data on people who had SARS-CoV2 infections because the virus has only been around for two years, but we expect to see more studies in this area in the coming years. Now that many restrictions are lifted, the important take-home message is: do not underestimate this virus and let your guard down. We should always try our best to protect ourselves and others around us from getting infected.
References
Bartleson, J.M., Radenkovic, D., Covarrubias, A.J. et al. SARS-CoV-2, COVID-19 and the aging immune system. Nat Aging 1, 769–782 (2021). https://doi.org/10.1038/s43587-021-00114-7
Geddes, Linda. “Covid Can Infect Cells in Pancreas That Make Insulin, Research Shows.” The Guardian, Guardian News and Media (2021).
https://www.theguardian.com/society/2021/sep/29/covid-can-infect-cells-in-pancreas-that-make-insulin-research-shows
Sohn, E. How the COVID-19 pandemic might age us. Nature 601, S5-S7 (2022)
https://doi.org/10.1038/d41586-022-00071-0