Researchers in Arizona are investigating possible links between a person's genetics and their likelihood of contracting a severe case of COVID-19, information that could lead to better treatments or reveal whether some people are more likely to get sick.

The Translational Genomics Research Institute is ready to start mapping the DNA of patients who have tested positive for COVID-19. The institute will analyze that DNA for cluesabout genetic links to the disease.

Emerging data suggests there could be genetic factors that predispose some people to more severe cases of COVID-19, according to Nicholas Schork, deputy director of quantitative sciences at TGen. Though evidence is accumulating, he said it's still too early to tell whether there is a definitive link between certain genetic mutations and susceptibility to COVID-19.

"We'll probably need to collect a lot of data to really explain strong associations between someone's genetics and their outcomes," Schork said.

TGen has already been mapping the genetics of the virus from each patient sample, but mapping the human DNA from the samples is trickier. The virus's genetic material is made up of 30,000 fundamental genetic building blocks, whereas human DNA has more than 3 billion of these building blocks that would need to be sequenced.

Instead of analyzing all three billion parts of a patient's DNA, which would be extremely time-consuming, TGen must first zero in on the parts of the human DNA that researchers think are most important to how the virus works.

Once they've isolated these sections, they can begin to map them for each sample and analyze them, according to Schork.

What genetic differences could mean

One area that could be important to study is the part of the DNA that is responsible for blood type.

A preliminary study from China analyzed the blood types of more than 2,000 confirmed COVID-19 patients and found that people with type A blood were overrepresented in the data, whereas people with type O blood were underrepresented.

That suggests the people with type A blood may be more susceptible; people with type O blood may be less susceptible.

But that trend does not prove adirect link and does not prove that people with type A blood are more at risk. The study has not been peer-reviewed and its findings have not yet been replicated in any other data sets.

"We need to take this with a grain of salt," Schork said. "Other groups are now trying to see if, in fact, (the study finding) upholds."

A possibly more important area of human DNA scientists are looking at creates the receptor on a cell that the spikes on the outside of the novel coronavirus bind to.

"Imagine like a Lego — you have one Lego that can connect with another one based on the shape," Schork said.

This receptor is called the ACE2 receptor and is the same receptor used by a related strain of coronavirus that causes Severe Acute Respiratory Syndrome, or SARS. The ACE2 receptor is found in a variety of organs such as the lung, kidney, heart and intestines, but due to genetic variations, it doesn't look the same and may not have the same shape in everyone.

"The mutations that some people have disrupt the structure of the ACE2 gene and that might make it easier or harder for the spike protein to bind and connect to it," Schork said. "You might be fortunate enough to have a deformation ... that messes up the part of the ACE2 gene that binds to the spike protein and that might protect you on some level."

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The opposite is also a possibility: Some people may have genetic mutations that allow the spike of the novel coronavirus to easily latch on to their cells and not let go.

Another way that mutations could change the ACE2 receptor is that some people could have higher levels of the ACE2 receptor in their body than others.

"If there's more ACE2 protein that is floating around the body, then it's more likely this spike protein is going to find one and connect to it," Schork said.

Virus could have a second receptor

Without the ACE2 receptor, it's thought that the virus cannot infect somebody's cells, according to University of Arizona virologist Kurt Gustin. But there could be a second receptor, he said.

"The exact role of the secondary receptors is less clear," Gustin said.

He said this secondary receptor, called TMPRSS2, could help or hurt the virus' ability to bind with the primary ACE2 receptor. The TMPRSS2 receptor was identified as one of the co-receptors for SARS, but more work still needs to be done to determine its potential role for the virus that causes COVID-19.

Research done with HIV shows how important co-receptors can be, according to Gustin. HIV primarily binds to one receptor, but genetic mutations in a secondary co-receptor for the virus gives some individuals immunity.

"The mutation prevented them from getting HIV so they could never develop it," he said. "Then that was used to create HIV treatment that we have today."

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Co-receptors are one of many areas of human DNA that could come into play down the road.

"This is just the tip of the iceberg," Gustin said.

Since the virus needs to hijack a cell and turn it into a virus-making factory to replicate inside the human body, genetic mutations in different "parts" of a cell's factory could stop the virus from being able to copy itself once it infects a cell, he said.

Genetic mutations in our immune system responses could also make a difference in fighting the virus.

Data could pinpoint treatments

TGen will likely focus on analyzing the area of human DNA involved in creating the ACE2 receptor and in determining blood type, according to Schork.

Once researchers start mapping out the genetics of COVID-19 positive patients, TGen may collaborate with other institutions to speed up COVID-19 research globally.

"There are efforts under way for groups to contribute to kind of a pooled data set that would probably be large enough to actually look for patterns in trends that might be meaningful clinically or just biologically to understand what's going on," Schork said.

One such effort is the COVID-19 host genetics initiative, an effort to pool data on the genetics of COVID-19 patients from at least 113 different studies around the world. The knowledge could give researchers and health care workers clues about who is more vulnerable to the virus.

Data could also help pinpoint parts of the virus to target with vaccines and therapeutics, much like what happened with HIV.

In addition to studying the DNA of COVID-19 patients, TGen will continue to study the genetics of the virus itself in each patient, Schork said. Some strains of the virus could be more problematic than others, or could interact differently with people who have different genetic mutations.

The idea is to study the virus's genetic material along with the host's and understand the connection between the two, he said.

So far, there is no evidence to suggest that certain racial groups are more genetically prone to the virus than others, although there have been racial discrepancies in COVID-19 hospitalization rates and death rates.

Data released by the state's health department this week also shows that Native Americans make up 16% of those who have died from COVID-19, even though they only make up about 4.6% of Arizonans.

Nationally, 33% of patients hospitalized in 14 states were black, according to data from the Centers for Disease Control. By contrast, African Americans make up 13% of the U.S. population.

"Is that due to some genetic background differences ... or is it due to social factors, environmental issues and access to health care?" Schork said.

It's too early to tell, he said, but some groups of people, such as those with diabetes, heart disease and lung disease have a tougher time battling the new coronavirus.

Virus continues to mutate

Because the virus is mutating, time is critical for research like TGen's that could be used to help develop a treatment against the disease. Future mutations may mean that one vaccine or therapy won't work against all strains.

"We have to figure out how we're going to cut it off with the path ... and not have another outbreak," Schork said.

If the virus mutates too significantly, it could turn into a disease that reemerges every year with different strains and that doesn't have a vaccine that can completely stamp it out, similar to the flu.

Schork didn't have an estimate for when researchers might have significant findings from this type of data.

Amanda Morris covers all things bioscience, which includes health care, technology, new research and the environment. Send her tips, story ideas, or dog memes at amorris@gannett.com and follow her on Twitter @amandamomorris for the latest bioscience updates.

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.

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