Genetic susceptibility to severe respiratory disease induced by SARS-CoV2

National Institute Of Environmental Health Sciences

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Abstract

Respiratory infectious diseases resulting from bacterial or viral pathogens such as Mycobacterium tuberculosis, Streptococcus pneumoniae, respiratory syncytial virus (RSV), and influenza, are major global public health concerns. Lower respiratory tract infections are leading causes of morbidity and mortality, behind only ischemic heart disease and stroke. The morbidity and mortality associated with the current COVID-19 pandemic caused by SARS-CoV-2 threaten to supersede those of all other respiratory diseases. As of the beginning of September 2020, the virus has infected over 27 million people globally and, while a majority of infected people recover, over 857,000 have died (World Health Organization). As with other viral infections, some human subpopulations are particularly vulnerable. Many factors may contribute to the inter-individual variation in response to respiratory infections, including gender, age, socioeconomic status, nutrition, pre-existing conditions or diseases (e.g. respiratory disorders, diabetes, obesity, cardiovascular disorders), and genetic background. Little is known about the genetic determinants of susceptibility to COVID-19, though gene candidates have been proposed. In collaboration with colleagues in Brazil and Argentina, we have considerable experience in identification of genetic variants that confer susceptibility to severe RSV disease in infected infants. We have also developed a genetic diagnostic single nucleotide polymorphism (SNP) panel to identify individuals that are highly susceptible to severe RSV disease. In our Intramural Targeted Anti-COVID-19 (ITAC) program award, we have proposed to 1) identify SNP variants in SARS-CoV-2 infected individuals that predispose to severe disease caused by the virus and 2) develop a diagnostic SNP panel that may be used to screen otherwise healthy individuals who may be highly susceptible to SARS-CoV-2-induced disease.