Early on in its emergence, it became clear that the novel coronavirus is particularly dangerous to older people and those with pre-existing health conditions. But just as there are patterns, there are outliers. As the infection spread around the globe, reports started to pile up of young, previously healthy people whose disease suddenly turned fatal. Finding out what has made this group of people so vulnerable to the infection may be an important step in developing new ways to treat the disease or identify those at high risk. And scientists suspect the answer may be in their genes. “Infectious diseases are always an interplay between a pathogen and the host’s immunity,” says Jean-Laurent Casanova, MD, PhD, Head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University. “At least some of these patients may suffer from a genetic variation that make their host defense particularly vulnerable to SARS-CoV2.” Dr. Casanova, along with Dr. Helen Su at the National Institute of Allergy and Infectious Diseases (NIAID) are leading an international project, the COVID Human Genetic Effort (https://www.covidhge.com/), to comb through the genomes of many COVID-19 outliers in search of any rare gene variant that they may share, and that may explain their body’s insufficient response to the infection. All infections appear to come with what scientists call inter-individual clinical variability, meaning that a fraction of infected people are hit especially hard. With cytomegalovirus, for example, most cases are so mild that the infection goes unnoticed, yet it is often detrimental to fetuses and it kills one in a million infected individuals (https://www.rockefeller.edu/news/27419-unusual-patient-case-cmv-rare-immune-deficiency/). Tuberculosis, on the other hand, can kill as many as five percent of infected individuals.
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