Elderly are generally defined as having a chronological age of 65 years or older 18. In Japan, where many elderly people live, this definition was reviewed 19. Thanks to the advances in medical and health science the lifespan has recently increased in Japan as well as in Italy. The simple chronological age appears to be no longer appropriate to the actual situation, in both Countries, where life expectancy is of 80 years and where there is an increased number of bright and energetic elderly people. Therefore, in Japan, the term of “late elderly” was introduced to indicate a new class of people, older than 75 years of age 18. Other factors besides the chronological age appear to play a major role in affecting the health status and the expectance of life and a careful assessment of the “elderly frailty’’ is required to determine the biological, functional, cognitive and clinical aspects of the elderly subjects 20. Previous reports indicate that elderly people are particularly susceptible to Community-Acquired Pneumonia 21–23. When a community-acquired pneumonia is diagnosed in very elderly people, there is a significant increase in morbidity and mortality 24. It has been observed that these patients often develop hospital-acquired complications and mortality occurs more frequently compared to younger people and to elderly ones. Moreover, the occurrence of pneumonia in elderly people is often the terminal event that complicates a long-term illness, such as dementia, cardiovascular disease, cancer, or prolonged immobilization syndrome 25. However, it is not always easy to dissect the relative contribution of other factors, including disability, frailty, comorbidities and the health status of these patients, prior to the development of the disease. COVID-19 is a severe disease, caused by the SARS-CoV-2 virus, mostly affecting the lung where an interstitial viral pneumonia is frequently observed, with typical patchy bilateral ground glass opacities and peripheral consolidations. Elderly people appear to be more susceptible, especially to the more severe forms of the disease 26. However, little information is available so far regarding the course of COVID 19 in very elderly people. It is well established that COVID-19 occurs more frequently among elderly people, with higher susceptibility to mortality and ICU admission 27, but a limited number of studies and of patients has focused the attention on a population over eighty years of age 3.
Our very elderly patients, showed a more severe disease, with higher level of serum marker of inflammation (hs-CRP and NLR) and higher severity respiratory indexes (PSI and P/F). This could be due to the increased inflammatory activity, associated with aging, reflected by increased circulating levels of TNF-alpha, IL-6, cytokine antagonists and acute phase proteins in vivo 28.
Experimental observations in mice, indicate that the SARS-CoV viral replication in aged mice is associated with clinical illness and pneumonia, demonstrating an age-related susceptibility to SARS disease in animals that parallels the human experience 29. Moreover, they demonstrated that replication of SARS CoV is enhanced in aged mice compared to younger and enhanced viral replication is accompanied by evidence of clinical illness, alveolar damage, and interstitial pneumonitis 29.
Besides to be stroked by a more severe disease, median duration of viral shedding in our very elderly patients is higher compared to that recently reported in younger and symptomatic (14 days) or asymptomatic patients (19 days) 30 and there is a statistically significant difference between the two groups. This also affects the length of the stay (LOS) in the hospital which result higher in Very Elderly. We don’t have data regarding the immune response in terms of cytokine production and production of specific immunoglobulins in our very elderly patients. However, the increased duration of viral shedding suggests that they may have a weaker immune response to SARS-CoV-2 infection, compared to younger patients. Increasing age has been defined as a predictive factor for mortality in pneumonia patients in many studies, especially among patients aged 65 years or older 31,32. Several studies, suggested that age ≥ 85 years was an independent predictive factor for mortality in patients affected with community acquired pneumonia 33,34. Calle et al reported that age ≥ 90 years was markedly associated with mortality 35. Ageing is associated with a progressively weakened immune system and decreased lung performance. For patients of extreme age (≥ 85 years in our study), these changes alone are probably drastic, which independently increases the risk of death due to pneumonia 34. In the study by Zunyou Wu et al., the overall case-fatality rate of those aged 70 to 79 years was 8.0% compared to aged 80 years and older where it was 14.8% 36. However, in this study only 3% of the total number of cases were 80 years of age or older. In another study by Niu et al., the mortality rate in patients over 80 was equal to 18% 3. Also Yan et al. reported that older patients (> 65 years) with comorbidities and ARDS are at increased risk of death, although even in this study patients over 80 years of age were a small number 37.
In our study the number of patients with more than 80 years of age is similar to that with 65-79. The mortality rate in Very Elderly was 37.5 % and this percentage was significantly higher compared to that observed in Elderly. Our findings suggest that, similarly with other severe acute respiratory outbreaks, age is a fundamental risk factor for mortality. These results also emphasize the importance of the very advanced age (i.e. ≥ 85 years).
When we try to identify which factors other than age may influence the course and outcome of the disease in these patients, two conditions appear to play a major role. The first is represented by the pre-existing health conditions or comorbidities. Patients with pre-existing pathological diseases, and in particular those affected by multiple comorbidities die more frequently than those with no or few comorbidities. In other words, COVID-19, as other community-acquired pneumonias, acts as terminal event that complicates long-term illnesses. This is in agreement with previous studies demonstrating that the presence of any comorbidity is associated with increased risk of poorer clinical outcomes 38.
The second one consisted in the observation that patients admitted to the hospital coming from previous LSRCHs, were in worst clinical conditions and died more frequently compared to those admitted coming from their homes. There are many possible explanations to that. Patients in LSRCHs may suffer of more comorbidities and fragilities, and as previously observed they are more prone to accumulate complications, thus resulting in unfavorable outcome. Another explanation is that, staying in a close environment, makes these patients more susceptible to infections. In this regard, the results of the Italian National Survey indicated that one of the major difficulties was to obtain an adequate isolation of the positive patients. Finally, the disease could be more severe because of a delay in its recognition, that, according to this survey, was due to insufficient availability of the nasal/oropharyngeal tests. Considering all these factors and based on our observations, it is necessary to obtain a better evaluation of the frailties of elderly and very elderly people that represent a population more prone to the condition of risk and vulnerability, characterized by an unstable equilibrium, if facing negative events.
Because of the rapid evolving outbreak globally, ongoing studies with the inclusion of more patients would be needed to increase the statistical power of our results.