Your Genes May Determine Your Covid-19 Risk
By: Emily Mullin
Tags: Health, Covid 19, Coronavirus, Science, Genetics

In the early throes of the coronavirus pandemic, two brothers in the Netherlands fell sick with Covid-19. They were young — 29 and 32 — and previously healthy. But both brothers developed severe symptoms and, at the end of March, were admitted to the intensive care unit. Within days, the older brother couldn’t breathe on his own and needed ventilation. His younger brother came down with an unusually high fever and eventually died from complications of the disease.

A physician took note of the cases and contacted Alexander Hoischen, PhD, a geneticist at Radboud University Medical Center in Nijmegen, who set out to investigate why these brothers were so unusually affected. Sure, it could have been a coincidence, but Hoischen thought it was also possible that the brothers shared a genetic trait that compromised their immune systems.

“If you look at all the men hospitalized from Covid-19, it’s extremely unlikely that that happens to such young individuals, and then it happened twice in the same family,” Hoischen tells Elemental. “That was extremely remarkable to us.”

Days later, a second pair of brothers landed in separate Dutch hospitals. Both men, just 21 and 23 years old, also had difficulty breathing and were put on ventilators. CT scans revealed that the SARS-CoV-2 virus had ravaged the younger brother’s lungs. After more than a week in the hospital, both brothers were discharged. When Hoischen learned of the second pair of brothers, he was even more convinced that there was a genetic component to the young men’s severe disease.

Over the course of the pandemic, it has become clear that certain factors — being elderly, male, obese, or a racial or ethnic minority — raise a person’s risk of developing severe Covid-19 and dying from it. Having an underlying chronic condition like diabetes, heart disease, or high blood pressure also significantly increases the likelihood of death. These factors can explain many cases of severe Covid-19 — but not all.

What’s so puzzling about the coronavirus is the wide spectrum of symptoms associated with it. Why do some people get a mild cough or no symptoms at all, while others go into respiratory failure? Why do many feel better within days, while others struggle to recover for weeks or months after infection? And why does a healthy person in his 20s succumb to a disease that spares the vast majority of people his age?

A person’s genetics could play a role. To learn more, scientists all over the world have been scanning huge genetic datasets, collecting DNA samples from Covid-19 patients, and analyzing their genomes in hopes of finding genetic signatures that explain why some people develop very serious symptoms.

Academic researchers and biotech companies have come together to form the Covid Human Genetic Effort and the Covid-19 Host Genetics Initiative, international consortiums that are pooling together data from thousands of patients in dozens of countries. Meanwhile, consumer genetics companies 23andMe and Ancestry are scouring DNA data from millions of customers to look for genetic links.

The results of these studies could help researchers develop new treatments or repurpose existing drugs to treat Covid-19 alongside other therapies. They could also lead to genetic tests that could predict someone’s Covid-19 risk. Genetic traits that predispose a person to more serious symptoms could even guide vaccine distribution. People with these traits could be prioritized for a vaccine, when one becomes available.

“It’s not unprecedented for people to have genetic differences that make them more or less susceptible to infection,” Catherine Ball, PhD, chief scientific officer at Ancestry, tells Elemental.

“There will most definitely be a genetic component associated with disease severity… However, the degree to which the impact is seen is yet to be determined.”

Perhaps the most well-known genetic trait associated with immunity is the sickle cell trait, which is most common in people from Africa or those of African descent. Carriers of sickle cell disease — those who have one sickle cell gene and one normal gene — are protected from malaria infection. But people who inherit two copies of the sickled gene from each parent develop sickle cell disease, a chronic and painful blood condition.

Another genetic trait with an effect on immunity is a specific mutation in the CCR5 gene. This subtle genetic change provides protection against HIV by blocking the virus from entering immune cells. Only about 1% of northern Europeans carry two copies of the mutation; one copy does not prevent infection.

Researchers have also identified single-gene mutations, known as inborn errors of immunity, that weaken the immune system. While some undermine the body’s ability to fight all infections, others may affect a person’s risk to a specific pathogen, like influenza or Epstein-Barr virus. Now, early research is revealing that a subset of people with severe Covid-19 harbor similar single-gene mutations that seem to have a big impact on the course of their disease. These mutations are likely rare in the general population. For others, a combination of several genetic variants and other risk factors, like preexisting conditions, may explain some extreme cases.

“There will most definitely be a genetic component associated with disease severity,” Joseph Petrosino, PhD, chair of molecular virology and microbiology at Baylor College of Medicine, tells Elemental. “However, the degree to which the impact is seen is yet to be determined.”