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

Marco Spanò,Giulia Fontanel,Gabriella Marcon,Alessandro Nobili,Claudio Franceschi,Giorgia Capacci,Gianluigi Forloni,Mauro Tettamanti

doi:10.18632/aging.103872

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.

Highlights

Was the first European country to suffer from the COVID-19 pandemic
The reasons of such a high vulnerability to COVID-19 is poorly understood but it has been suggested that a major role is played by inflammaging [5,6,7], i.e. the low-grade chronic inflammation that is a major driver of aging [8] and whose basic underlying mechanisms are shared with those responsible for frailty and age-related diseases (ARDs), including cardiovascular disease, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease and dementia, among others [9,10,11]
Important within the scenario of COVID-19 pandemic is that centenarians have a peculiar state/degree of inflammaging, which is much lower than that predicted by their chronological age and is biased toward anti-inflammaging, i.e. the production of antiinflammatory molecules and cells that the body produces lifelong as an adaptive, compensatory mechanisms to continuously down-regulate the inflammatory process and avoid its chronic detrimental effects [18,19,20]

Summary

Introduction

Was the first European country to suffer from the COVID-19 pandemic. A main characteristic of this pandemic, besides high infectivity of its causative agent, is a cytokine storm characterized by an IL-6 centered response [1, 2] and the uneven distribution of severity and mortality among different age classes. Old people, and those with one or more comorbidity, appear to be the most vulnerable [3, 4] The reasons of such a high vulnerability to COVID-19 is poorly understood but it has been suggested that a major role is played by inflammaging [5,6,7], i.e. the low-grade chronic inflammation that is a major driver of aging [8] and whose basic underlying mechanisms are shared with those responsible for frailty and age-related diseases (ARDs), including cardiovascular disease, type 2 diabetes, chronic obstructive pulmonary disease, chronic kidney disease and dementia, among others [9,10,11]. The oldest old, including centenarians, are high-selected, exceptionally robust subjects that can be taken as a model of successful/healthy aging [21]

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