Millions of people around the world have been infected with the novel coronavirus that causes COVID-19, but there is considerable disparity in how serious their symptoms can be. A European team has now analyzed the genetic profiles of COVID-19 patients from Spain and Italy who showed severe symptoms and found gene mutations that may be responsible for the severity of the disease.

Since its appearance in Wuhan, China in late 2019, COVID-19 has quickly spread to become a global pandemic. Although most infected people display mild symptoms or none, some patients develop serious lung diseases that could trigger life-threatening respiratory failure. These patients need early and prolonged oxygen support, or to be put on a mechanical ventilator.

Although pre-existing conditions, such as hypertension and diabetes, can worsen the risks from COVID-19, the underlying mechanism leading to these severe symptoms remains unclear. 

There are several genetic risk factors that link patient susceptibility to viral disease symptoms. This prompted Tom Karlsen from the University of Oslo in Norway and Andre Franke from Christian-Albrechts-University in Germany to investigate those connected to severe COVID-19. Karlsen explains that the COVID-19-related respiratory infection appears atypical and is associated with aggravated inflammation, which often could also point to a genetic predisposition.

“We felt obliged to do something in the serious situation of the pandemic,” Karlsen says.

The team enrolled 1980 confirmed patients with severe COVID-19 symptoms from seven hospitals in four cities of the Spanish and Italian pandemic epicentres. For comparison, they also recruited 2205 control participants—mostly healthy volunteers and a few COVID-19 infected individuals presenting mild or no symptoms.

The researchers evaluated the DNA sequences genomes of all patients and control participants to determine variations between their genetic profiles and identified certain mutations that appear related to COVID-19-induced respiratory failure on two distinct chromosomes in the patients. These mutations involved a gene cluster on chromosome 3, and the ABO blood type gene on chromosome 9. “The chromosome 3 mutation is the most interesting finding,” Karlsen says. It provides the strongest signal, becomes stronger when corrected for age and gender, and seems to be more pronounced in the most severe patients, he adds.

The team is planning to expand their assessment to more patients to find other genetic risk factors to specific COVID-19 symptoms. “We will try to contribute to the bigger effort of the scientific community to understand and deal with COVID-19,” Karlsen says.

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