Virus World

A forthcoming study from 23andMe shows that a person’s genetic code could affect how severely they experience Covid-19.  It’s an important confirmation of earlier work on the subject. People whose blood group is O seemed to test positive for Covid-19 less often than expected when compared to people with any other blood group, according to 23andMe’s data; people who tested positive and had a specific variant of another gene also seemed to be more likely to have serious respiratory symptoms. The study, which was released on a preprint server and which has not yet been peer-reviewed, could extend and confirm earlier work on the subject; 23andMe’s study relied on a larger dataset than earlier work and included a more diverse set of participants, the company said. Experts who aren’t affiliated with 23andMe praised the study design and the work.

“They clarify further what our data could only vaguely hint at,” said Tom Hemming Karlsen, a physician at Oslo University Hospital who published an article in the New England Journal of Medicine on genetic links with Covid-19 severity in June, and who was not associated with 23andMe’s work. But the outside experts also cautioned that the research won’t change treatment decisions. “It doesn’t have practical implications. There’s no treatment decisions that will be made from it — it’s just an interesting finding,” said Jennifer Lighter, a pediatrician and epidemiologist at NYU Langone who was not involved in the research. Unlike the study Karlsen and his colleagues ran, which only included people with severe Covid-19 symptoms, 23andMe included people who had both mild and severe cases — which allowed them to draw stronger conclusions, Karlsen said. The company’s study participants are also more diverse than Karlsen’s, which only studied people in Spain and Italy. However, the 23andMe study’s demographics still don’t fully reflect the population of the United States. A little more than 11% of the people in 23andMe’s studies said they were Latino; less than 3% said they were Black. (Latinos represent about 16% of the U.S. population, while Black people account for about 13% of the population.)

Both Karlsen and 23andMe’s team found that the genes that code for a person’s blood type seemed to be linked to whether a person would test positive for Covid-19; another section of chromosome 3 — referred to in both papers as chr3p21.31 — seemed to be linked to how severe a person’s response would be to a Covid-19 infection. Janie Shelton, a senior scientist at 23andMe and a lead author of the paper, and her colleagues noted that genetic associations did not seem to explain all the differences between populations; public health experts have noticed that people of color seem to be particularly at risk for Covid-19 due to some of the direct and indirect health effects of inequality and discrimination. Both studies suggested one gene found in that area on chromosome three — SLC6A20 — might be particularly related to worse outcomes; however, it’s not yet clear how a particular gene could make a meaningful difference in a person’s response to an infection...

Preprint of the study available at medRxiv (Sept. 7, 2020):

https://www.medrxiv.org/content/10.1101/2020.09.04.20188318v1

Respiratory failure is a key feature of severe Covid-19 and a critical driver of mortality, but for reasons poorly defined affects less than 10% of SARS-CoV-2 infected patients. Methods. We included 1,980 patients with Covid-19 respiratory failure at seven centers in the Italian and Spanish epicenters of the SARS-CoV-2 pandemic in Europe (Milan, Monza, Madrid, San Sebastian and Barcelona) for a genome-wide association analysis. After quality control and exclusion of population outliers, 835 patients and 1,255 population-derived controls from Italy, and 775 patients and 950 controls from Spain were included in the final analysis. In total we analyzed 8,582,968 single-nucleotide polymorphisms (SNPs) and conducted a meta-analysis of both case-control panels. Results. We detected cross-replicating associations with rs11385942 at chromosome 3p21.31 and rs657152 at 9q34, which were genome-wide significant (P<5x10-8) in the meta-analysis of both study panels, odds ratio [OR], 1.77; 95% confidence interval [CI], 1.48 to 2.11; P=1.14x10-10 and OR 1.32 (95% CI, 1.20 to 1.47; P=4.95x10-8), respectively. Among six genes at 3p21.31, SLC6A20 encodes a known interaction partner with angiotensin converting enzyme 2 (ACE2). 

The association signal at 9q34 was located at the ABO blood group locus and a blood-group-specific analysis showed higher risk for A-positive individuals (OR=1.45, 95% CI, 1.20 to 1.75, P=1.48x10-4) and a protective effect for blood group O (OR=0.65, 95% CI, 0.53 to 0.79, P=1.06x10-5). Conclusions. We herein report the first robust genetic susceptibility loci for the development of respiratory failure in Covid-19. Identified variants may help guide targeted exploration of severe Covid-19 pathophysiology.

Preprint available at medRxiv (June 2, 2020):

https://doi.org/10.1101/2020.05.31.20114991

Geneticists have turned up intriguing links between DNA and the disease. Patients with Type A blood, for example, seem to be at greater risk. Why do some people infected with the coronavirus suffer only mild symptoms, while others become deathly ill? Geneticists have been scouring our DNA for clues. Now, a study by European scientists is the first to document 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 patients with Covid-19, the researchers found. One of these spots includes the gene that determines blood types.  Having Type A blood was linked to a 50 percent increase in the likelihood that a patient would need to get oxygen or to go on a ventilator, according to the new study.

The study was equally striking for the genes that failed to turn up. The coronavirus attaches to a protein called ACE2 on the surface of human cells in order to enter them, for example. But genetic variants in ACE2 did not appear to make a difference in the risk of severe Covid-19. The findings suggest that relatively unexplored factors may be playing a large role who develops life-threatening Covid-19. “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, which is currently going through peer review....