COVID-19 mortality in Lombardy: the vulnerability of the oldest old and the resilience of male centenarians

Abstract

Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences. We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females.

What’s Testosterone Got to Do with It? A Critical Assessment of the Contribution of Testosterone to Gender Disparities in COVID-19 Infections and Deaths

“…Centenarian men are fewer but more selected and healthier and likely more resilient than centenarian women in highly stressful conditions such as COVID-19 pandemic. [74][75][76] We believe that the gradual shift observed in women and men as a function of age reflects comorbidities, and imbalances in the endocrine system attributed to aging, which impacts the immune system function. More importantly the impact of existing comorbidities, including hypertension, cardiovascular disease, and some chronic lung diseases, including chronic obstructive pulmonary disease.…”

The Lombardy Emergency Medical System Faced with COVID-19: The Impact of Out-of-Hospital Outbreak

“…EMS was therefore faced with requests for patients' home evaluation, transport from home to hospitals, transfers between hospitals, transfers outside the region by land and by air, increasing the disproportion between the need and the available resources (4,9,10) In Lombardy, the COVID-19 outbreak created serious problems to the health system, due to the speed of propagation of the infection in an extremely short time and in a limited area. The greatest spread of the virus concentrated in very few provinces, resulting in one of the highest mortality rates from COVID-19 worldwide (from Johns Hopkins website); we cannot exclude that this case mortality rate may be due to the age of the people who were getting infected (11). In this scenario, understanding how to deal with the increasing request of first aid was the top priority.…”

The role of extracellular DNA in COVID-19: Clues from inflamm-aging

“…On the other hand, people endowed with long telomeres may experience an advantage when facing the SARS-CoV-2 infection ( Lapham et al, 2015 ). We refer to extremely aged people such as centenarians that have been reported to carry longer than expected telomeres ( Storci et al, 2019 ; Marcon et al, 2020 ) and show a more plastic and adaptive response against SARS-CoV-2 infection (Balk et a., 2013). The above picture may even more complex, by taking into account that the shortening of telomeres triggers the transcription of an mRNA named as Telomere repeat-containing RNA (TERRA) ( Balk et al, 2013 ).…”

“…Moreover, despite the still unknown mechanism, the rate of telomere shortening in men is steeper than in women, especially above the age of fifty, i.e. the age at which SARS-CoV-2 infection starts to impinge upon population mortality ( Marcon et al, 2020 ) ( https://www.epicentro.iss.it/coronavirus/sars-cov-2-decessi-italia ). Furthermore, extremely old women are endowed with longer than expected telomeres, in respect to male age-matched subjects ( Lapham et al, 2015 ).…”