Scientists find link between COVID-19 severity and genetics

The study, which has not been peer-reviewed yet, is the first to find a strong statistical link between genetic variations and COVID-19, the illness caused by the coronavirus.

Variations at two spots in the human genome are associated with an increased risk of respiratory failure in COVID-19 patients, according to the study. Patients with Type A blood were linked to a 50% increase in the likelihood in needing to get oxygen or go on a ventilator, reported the Times.

Oddly enough, variations in ACE2, the protein to which the virus attaches itself on the surface of human cells, did not seem to make a difference in the severity of the virus.

“There are new kids on the block now,” said Andre Franke, a molecular geneticist at the University of Kiel in Germany and a co-author of the new study, according to the Times.

While age and preexisting conditions have already been found to increase the risk of severe cases of COVID-19, geneticists are hoping that DNA tests could help identify at-risk patients as well.

The study was conducted by taking blood samples from 1,610 patients who needed an oxygen supply or were put on a ventilator and 2,205 blood donors with no evidence of COVID-19. DNA was extracted from the samples and scanned with genotyping.

The scientists found two spots in the genome, known as loci, shared by an unusually high number of severely ill patients compared with those who were not ill, including one locus which determines our blood type.

Chinese scientists also found that patients with blood type A were more likely to develop a severe case of COVID-19, according to the Times.

While the Chinese study does support the new study, questions remain on why blood type affects the severity of the illness. “That is haunting me, quite honestly,” said Franke.

The locus where the blood-type gene is located also contains DNA that acts an on-off switch for a gene producing a protein that triggers strong immune responses.

The novel coronavirus triggers an overreaction of the immune system in some people, leading to inflammation and lung damage. It could be that genetic variations influence that response.

The second locus found in the study, on Chromosome 3, has an even stronger statistical link to COVID-19, but the spot houses six genes so it’s still unclear which one influences the severity of the illness, according to the Times.

One of the six genes encodes a protein known to interact with ACE2, but another nearby gene encodes a potent immune-signaling molecule. It could be that this gene triggers an overreaction as well.

A thousand researchers in 46 countries, including the European scientists involved in the new study, are collecting DNA samples from people with COVID-19 and sharing the data on the website of the COVID-19 Host Genetics Initiative.

Andrea Ganna, a genetic epidemiologist at the University of Helsinki, said that the collected data of the initiative were beginning to point to a single spot on Chromosome 3 as a potentially important factor, according to the Times.

Jonathan Sebat, a geneticist at the University of California, San Diego, told the Times that it’s uncommon for genetic variants to emerge out of studies of so few people.

“We were all hoping optimistically this was one of those situations,” said Sebat, who is running a study in California to see if the two loci are as important as they seem.

Sebat stressed that the study focused on patients with respiratory issues.

Scientists conducting further studies may be able to zero in on exactly which gene in each locus affects the disease and may likely find many other genes with subtler influences on the course of the illness.

The variation in severity between patients has been attributed to other factors, including different strains of the virus, as well.

Over 30 different strains of the coronavirus were found in a study carried out in April by Professor Li Lanjuan and colleagues from Zhejiang University in Hangzhou, China and published in a non-peer reviewed paper released on website medRxiv.org.

Li ‘s team infected cells with COVID-19 strains carrying different mutations, of which the most aggressive strains were found to generate as much as 270 times as much viral load as the weakest strains. The aggressive strains also killed the human cells the fastest.

The results indicated “that the true diversity of the viral strains is still largely underappreciated,” Li wrote.

“Drug and vaccine development, while urgent, need to take the impact of these accumulating mutations into account to avoid potential pitfalls,” the scientists said.