Sex, Cardiovascular disease and Covid-19
Cardiovascular disease is more prevalent in males, and subjects with cardiovascular dysfunction infected with SARS-CoV-2 have a worse prognosis. Among the deceased Covid-19 patients in Italy, less than 4% had no comorbidity, while more than 60% had three or more comorbidities. Among these, cardiovascular comorbidities were the most represented. These include arterial hypertension (about 70% of deceased patients), followed by ischemic heart disease (about 30%), atrial fibrillation (about 20%), and heart failure (about 15%) (https://www.iss.it/coronavirus, accessed on May 13th2020). Most of the deceased patients were elderly (over 65 years) and obese (in the Italian report, obesity is present in 12% of the deceased patients). All these conditions are characterized by a deranged ACE/ACE2 ratio [Koni and Miyamori 2007; Colucci et al 2011; Wang et al. 2015, 2016; Santos et al 2013, Wakahara et al. 2016;]. It appears that a deranged ACE/ACE2 ratio is responsible for a high incidence of dramatic ARDS and cardiovascular complications and the high lethality of Covid-19. Downregulation of ACE2 has been observed in pulmonary arterial hypertension and cigarette smoker patients [Yuan et al 2015; Horn et al 2020]. Therefore, we wonder if it is worth trying to reestablish an adequate ACE/ACE2 ratio to have better outcomes in Covid19. Indeed, Covid-19 depletes and downregulates ACE2 [Moccia et al 2020]. Therefore, a potential therapy could be the administration of drugs that activate ACE2, which has anti-inflammatory effects (Fig 1). Of note exercise is a natural way to increase the ACE2/ACE ratio [Crisafulli and Pagliaro 2020].