Fight Aging!

Today I'll point out a couple of papers on the topic of why SARS-CoV-2 is so much more severe in the old. There has been a great deal of discussion about the age-related nature of COVID-19 mortality these past few years, though near entirely within the scientific community. The more severe cases involve runaway inflammation, and old people already suffer a raised level of chronic inflammatory signaling, making them that much more vulnerable to cytokine storm events in which the immune system runs wild to cause severe pathology and death. Sepsis is a similar problem, similarly age-related for reasons relating to increased vulnerability.

It isn't just a higher base level of inflammatory signaling with age, however. Nor is it only inflammatory signaling coupled with immunosenescence, the growing inability of the adaptive immune system to engage effectively with pathogens. Infectious diseases that are shrugged off in youth would be serious threats to the old and frail even if immunosenescence was the only consequence of aging. Unfortunately many other aspects of aging also conspire to make an old person more vulnerable to inflammatory infectious disease. This has long been well illustrated by the mortality that attends every winter influenza season, COVID-19 was an unneeded lesson. And yet the broader public is still largely unaware that working towards rejuvenation therapies is perhaps the best, most cost-effective way to prevent these continued losses of life.

Inflammaging at the Time of COVID-19

Most people infected with SARS-CoV-2 have a self-limiting infection and do recover; others experience more severe disease, with 10% of patients requiring intensive care unit (ICU) admission. The case-fatality rate of COVID-19 is approximately 1.5%. Most COVID-19-related deaths have occurred in those 60 years and older, and an even higher mortality was registered among the oldest old (ie, ≥80 years). The presence of a least 1 underlying chronic condition (eg, cancer, diabetes, hypertension, obesity, cardiovascular disease, cerebrovascular disease) is a major risk factor for death. Older adults are more susceptible to SARS-CoV-2 infection, more prone to develop severe COVID-19, and more frequently admitted to ICUs, with consequent increased mortality.

An extraordinary proliferation of studies suggests that SARS-CoV-2 infection unleashes an abnormal inflammatory response, the so-called cytokine storm. Indeed, severe COVID-19 in hospitalized patients is characterized by high circulating levels of C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and lymphopenia. The abnormal inflammatory response, along with hypercoagulability and defective viral clearance, contributes to the development of severe pneumonia and acute respiratory distress syndrome (ARDS), with subsequent end-organ damage, multiorgan system failure, and eventually death. Although severe COVID-19 disproportionally affects older people, systemic inflammation during SARS-CoV-2 infection is detected in patients of all ages, including children, in whom a severe multisystem inflammatory syndrome has been described. This implies that COVID-19-induced inflammation is not per se sufficient at inducing negative health outcomes. This article provides a pathophysiologic view of COVID-19 in older adults within the frame of inflammaging, with a focus on antiinflammatory treatments for acute and postacute disease.

How can Biology of Aging Explain the Severity of COVID-19 in Older Adults

Aging has been identified as one of the most relevant risk factors for poor outcomes in COVID-19 disease, independently from the presence of preexisting diseases. The COVID-19 mortality risk sharply increases for elderly subjects, as showed by the reports of China, Italy, and the United States. In particular, in Italy, case fatality rate for patient aged 40 to 49 years or younger was reported of about 0.4% or lower, 1% among those aged 50 to 59 years, 3.5% in those aged 60 to 69 years, 12.8% in those aged 70 to 79 years, to 20.2% from 80 years and older.

Age is not only an important predictor for mortality, but it is also associated with higher disease severity, in terms of increased hospitalization rates, length of hospital stay, need for intensive care, and invasive mechanical ventilation. Since now, different mechanisms responsible for worse outcomes in the elderly have been suggested, which include the remodeling of immune system, the higher prevalence of malnutrition and sarcopenia, the increased burden of multimorbidity, and, to a lesser extent, the direct effects of age on the respiratory system and hormonal profile. The interplay between all these causes, rather than the individual pathophysiological mechanism, explains the increased severity of the disease with age.