9Health Expert Dr. Payal Kohli answered our questions about a new study in The New England Journal of Medicine.
DENVER, Colorado — For months now, doctors have known age plays a role in how people respond to COVID-19.
Health conditions like heart disease and diabetes can also impact the severity of the infection.
But a new study in the New England Journal of Medicine suggests genetic markers might also help identify individuals who are most at risk for a severe response.
We took the study and our questions to 9Health expert Dr. Payal Kohli.
(Editor’s Note: Questions and answers may have been edited for context and clarity).
9NEWS: How reliable a source is the New England Journal of Medicine?
Dr. Kohli: “The New England Journal of Medicine is rated as the top medical journal. Actually, it has an impact factor that’s the highest of any other medical journal. So, studies published in the New England journal of medicine are really considered top-of-the-line studies.
Recently, in the last couple of weeks, there was a retraction that occurred from a study published in the New England Journal of Medicine. That certainly got a lot of people concerned but, in general, their reputation for several decades has been airtight.
What is the basis of the study?
Dr. Kohli: The reason this study really came about is we saw there was a dramatic variation in respiratory response. So, on this end of the spectrum, somebody who gets the infection but has no symptoms at all and on this end of the spectrum, somebody who gets the infection and has severe lung inflammation and ends up on a ventilator and in the Intensive Care Unit.
Interestingly, what we saw in many parts of Europe is there tended to be clustering in families. For example, in Europe, they have a blended family structure where everybody lives together. We often saw father-son pairs or mother-daughter pairs had similar responses in terms of their respiratory response. They tended to either all of very severe illness or all have very mild illness. That suggested perhaps there may be some genetic contribution to the body’s inflammatory response to this infection. That really led us down to do this Genome-Wide Association study.
What is a Genome-Wide Association study?
Dr. Kohli: Essentially, a genome-wide association study creates a genetic map of your DNA. So, the researchers took DNA from 2,000 patients with COVID and severe respiratory symptoms and 2,000 controls. They mapped out their DNA and looked for genetic differences that could potentially explain why these 2,000 people didn’t get that sick and these 2,000 people did. Then, they identified potentially which genes those differences mapped onto.
What did they find?
Dr. Kohli: Interestingly, a lot of those genes are involved in the response to COVID. The one that stood out the most was the blood type gene it mapped to. The blood type is called an ABO group blood type. Those cells are involved in part of our immune response as well. So, it’s not entirely surprising that it mapped to the blood type. What they found was blood group A had a 45% higher risk of having severe respiratory symptoms and blood group O had a 35% lower risk of having severe symptoms.
Some of the other genes they found that may be involved are genes involved in the lung, genes involved in the inflammatory response, and genes involved in the ACE2 receptor which is the doorway the virus uses to get into the lungs.
How does this improve our understanding of variations in reaction?
Dr. Kohli: It doesn’t necessarily mean the blood group is causing severe symptoms. It means that it’s potentially a genetic marker of risk. So, we’re getting a personalized risk score based on our genetics. If you’re blood group A, you should potentially think of yourself as a higher risk group. Especially if you have other high-risk markers like age, diabetes, high blood pressure, etc.
For me, it changes the conversation. All the risk factors start becoming cumulative. As you layer more and more risk factors on, you increase the risk. So, if someone is in their twenties and completely healthy and blood group A, I might tell them to be slightly more cautious because they are at higher risk of having severe complications. We’ve seen plenty of young people who’ve ended up in the intensive care unit as well.
I want to be sure to tell people who have blood group O, this doesn’t mean you should take it easy. This doesn’t mean you’re protected from having a bad outcome with COVID. It just means that in terms of your profile or your risk, you might be slightly lower risk.
How might this data help inform public health decisions?
Dr. Kohli: I think the study is very important because it suggests something different about the host’s response based on genetics that really determines who gets very sick and who doesn’t. This is the first study to look at genetics when it comes to COVID and how we respond to it. So, I think it’s a step in the right direction in terms of understanding that big scientific, clinical conundrum that we’ve been facing for the last several months. How do you predict who is going to get super sick and who isn’t?
In an ideal world, what I’d like to see is some kind of risk score being developed where you take a person’s age, they’re comorbidities, their genetics, their family history, put it all together in a calculator and really personalize the risk for who is going to get really sick and who isn’t. I think that will help inform our decisions about who is safe to travel, who is safe to go out to eat, who is safe to mingle with other people? Until we get a vaccine, we’re going to have to get better about refining our risk assessment with respect to COVID. It’s not okay to keep all the older people locked up forever and it’s not okay to tell the younger people that they’re completely risk-free. I think we really need to get more sophisticated in the risk assessment.
