ACE2 polymorphisms as potential players in COVID-19 outcome

Khayat, André Salim; de Assumpção, Paulo Pimentel; Meireles Khayat, Bruna Claudia; Thomaz Araújo, Taíssa Maíra; Batista-Gomes, Jéssica Almeida; Imbiriba, Luciana Carvalho; Ishak, Geraldo; de Assumpção, Paula Baraúna; Moreira, Fabiano Cordeiro; Burbano, Rommel Rodriguez; Ribeiro-dos-Santos, André; Ribeiro-dos-Santos, Ândrea Kelly; dos Santos, Ney Pereira Carneiro; dos Santos, Sidney Emmanuel Batista

The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, there are ACE2 polymorphisms that could influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.