It is very clear from the data, as is the case for influenza, the mortality of the COVID-19 pandemic is suffered near entirely by the old. This is because the aged immune system is less capable of fighting off pathogens, but also because the state of chronic inflammation and other dysfunctions resulting from immune system aging makes the cytokine storm of a severe SARS-Cov-2 viral infection that much more likely and that much more severe. Patients with inflammatory age-related conditions, or conditions associated with obesity, a prominent cause of chronic inflammation, are much more likely to die from SARS-Cov-2 infection.
Since the first reported cases with severe acute respiratory syndrome caused by a novel coronavirus (SARS-CoV2), this disease called coronavirus disease (COVID-19) has expanded worldwide being considered by World Health Organization as a pandemic. Although this virus may infect people regardless of age, race or sex, older subjects have been identified as a high-risk group regarding the clinical outcome of the disease, both for developing severe pneumonia with respiratory distress and death. Although global mortality rate directly related to SARS-CoV2 infection is unknown (a real infectious rate is not well known), mortality rate among severely elderly patients (between 60-90 years old) is around 50%, even in countries with significant lower deaths. Hence, apart from other risk factors linked to a poor clinical outcome, such as hypertension, diabetes, cardiovascular disease, cancer, or chronic lung disease, old age itself can be also considered as an independent risk factor associated with SARS-CoV2-related severe pneumonia and death.
From an immunopathogenic viewpoint, COVID-19 disease has probably a multifactorial nature and the final severe lung damage observed in COVID-19 could be caused by an uncontrolled proinflammatory cytokine cascade (called "cytokine storm"), driven mainly by interleukin-6 (IL-6) and other proinflammatory cytokines such as IL1β, IL8, CXCL10, and CCL2. Based on this hypothesis, apart from non-specific antiviral agents, anti-inflamatory drugs have been proposed to be used in patients with advanced COVID-19 disease. However, which immunopathogenic status precedes this "cytokine storm" and why the elderly population is more severely affected, are currently unanswered questions. Thus, we propose that immunosenescence and age-related thymic dysfunction could play a relevant role in current COVID-19 disease scenario.
According to our dual physiopathological hypothesis, in addition to impaired thymic function, we believe that elderly subjects at baseline show a systemic low-level chronic inflammation. Their population of monocytes generate a great amount and variety of cytokines (multiple circulating cytokines). These cells of elderly subjects, when stimulated by pathogen-associated molecular patterns receptors like TLR by a novel agonist (SARS-CoV2 antigen), could generate the massive and polyfunctional proinflammatory cytokine release that characterized COVID-19, and that would trigger the respiratory distress and multiorgan failure as clinical outcome.