Until 2002, coronaviruses (HCoV-NL63, HCoV-229E, HCoV-OC43 and HKU) were first known to cause common cold in humans. However, in 2002 the SARS-CoV emerged, and then in 2013 the MERS-CoV. The SARS-CoV and MERS-CoV caused severe respiratory syndrome and were highly pathogenic for humans, because of their ability to adapt to their host, notably to increase affinity for their receptor, leading to high infectivity in humans (1, 2). In December 2019, a new coronavirus, first called 2019-nCov and then SARS-CoV-2 for severe acute respiratory syndrome coronavirus 2, was identified in Wuhan, China (3). SARS-CoV-2 spreads very efficiently, causing the current COVID-19 (Coronavirus Disease 2019) pandemic, that by mid-May 2020 has already killed more than 300,000 people all over the world. The highest morbi-mortality of COVID-19 is observed among older patients (4). Patients in intensive care unit (ICU) are older than patients not requiring ICU (5). In a study using an observational database from 169 hospitals in Asia, Europe, and North America, an age of more than 65 years-old was associated with a higher risk of in-hospital death: 10.0% mortality rates for people ≥ 65 years-old vs. 4.9% for those < 65 years-old (6). In France, 3.6% of infected individuals needed to be hospitalized, with an average death rate of 0.7% ranging from 0.001% in individuals < 20 years-old, to 10.1% in those > 80 years-old (7). Not all older adults appear to be equally vulnerable to SARS-CoV-2 infection (8). Frailty is a clinical syndrome in older adults characterized by an increased vulnerability for adverse health outcomes and aging-associated functional declines (9). Frail older adults, especially those with comorbidities (eg, hypertension, obesity, diabetes) are at higher risk of death if they get infected than younger adults (10). Prevention interventions need to be developed to reduce the impact of COVID-19 in older people. Geroscience is an interdisciplinary field that seeks to understand the links of biological mechanisms of aging with biological mechanisms of disease and body functions (eg, mobility, cognition) to ultimately find potential interventions and promote health in older adults (11). In this perspective paper, we will describe SARS-CoV-2 properties; then we will focus in the relationship between SARS-CoV-2 and aging, discussing the potential roles of comorbidities, inflammaging, immunosenescence, and immune escape. Finally, we will introduce Geroscience as a global approach to treat and prevent the onset and decrease the severity of diseases during aging, notably COVID-19. SARS-CoV-2 properties Coronaviruses are members of the Coronaviridae family. They are divided into Alphacoronavirus and Betacoronavirus that can only infect mammals, and Gammacoronavirus and Deltacoronavirus which mostly infect birds (1). SARS-CoV-2 is a Betacoronavirus (subgroup B Sarbecovirus), enveloped, with a positive single-stranded large RNA that can infect animals and humans. As MERS-CoV and SARS-CoV, it may cause severe diseases and high fatality rate....

Objectives We aimed to evaluate the impact of neutralizing monoclonal antibodies (mAbs) treatment and to determine whether the mAbs selective pressure could facilitate the proliferation of virus variants with spike protein mutations that might attenuate mAb effectiveness. Patients and methods We therefore evaluated the impact of mAbs on the nasopharyngeal (NP) viral load and virus quasispecies of mAb-treated patients using single molecule real time sequencing (Pacific Biosciences). The mAbs used were: Bamlanivimab alone (4 patients), Bamlanivimab/Etesevimab (23 patients), and Casirivimab/Imdevimab (5 patients). Results The NP SARS-CoV-2 viral load of mAb-treated patients decreased from 8.2 log 10 copies/ml before administration to 4.3 log 10 copies/ml 7 days after administration. Five immunocompromised patients given Bamlanivimab/Etesevimab were found to have mAbs activity-reducing spike mutations. Two patients harbored SARS-CoV-2 variants with a Q493R spike mutation 7 days after administration, as did a third patient 14 days after administration. The fourth patient harbored a variant with a Q493K spike mutation 7 days post-treatment, and the fifth patient had a variant with a E484K spike mutation on day 21. The emergence of the spike mutation was accompanied by stabilization or rebound of the NP viral load in 3/5 patients. Conclusion Two-mAb therapy can drive the selection of resistant SARS-CoV-2 variants in immunocompromised patients. Patients given mAbs should be closely monitored and measures to limit virus spread reinforced.