A University of Hawaii Cancer Center researcher and a local genomics company are trying to decipher why COVID-19 hits some people much harder than others — by examining their DNA.
“In simple terms, we are trying to understand how your DNA impacts your ability to get infected with the coronavirus and the severity of your symptoms,” said Cyril Moukarzel, CEO of LifeDNA Inc. “Based on genetics, certain individuals and populations may be impacted more severely.”
The new study will draw on Hawaii’s multiethnic population and explore how variations in a certain gene might affect the susceptibility of different individuals and groups to the virus.
“Epidemiological studies indicate that populations carry different variants of the ACE2 gene,” said Maarit Tiirikainen, a molecular epidemiologist and associate professor at UH Manoa who is leading the scientific study.
“This variation in the gene coding for the ACE2 receptor may have an effect on the number of ACE2 receptors on the lung cells, as well as on how effectively the virus binds to the receptor,” she said. “There may also be genetic differences in immunity and other important genes explaining why some people get more sick than others.”
The virus has proved to be most lethal to seniors. As people age, they have more ACE2 receptors in their lungs, according to Tiirikainen. Older people also tend to have other underlying diseases that raise the risk of death.
“Age definitely is a factor in getting the infection,” Tiirikainen said. “There is a higher density of the receptors in older people. … Smoking is also known to increase the density of this receptor.”
“We will try to focus on younger individuals because age is such a strong factor,” she added.
Mortality rates vary widely among countries, with Italy and Spain particularly hard-hit, according to international data. A host of factors underlie those outcomes, but genetics could well play a part.
“It’s very complex — how much of it is genetics and how much of it is culture — for example, how close people live together,” Tiirikainen said. “And there is lifestyle, socioeconomic status, access to care, and also, of course, the major factor is the government actions.”
“It may be hard to parse out where the differences really stem from,” she added.
Moukarzel highlighted data on “closed cases” in each country, defined as people who tested positive for COVID-19 and have either recovered or died of it. Those “closed cases” do not include still-active cases or people with mild or nonexistent symptoms who have not even been tested.
“There are certain parts of the world where the death rate among closed cases is less than 4%, while others, like Italy, are over 40%,” he said. “In Italy there are 39,360 closed cases and over 16,523 are dead — that’s 42%.”
“Obviously, there are different factors, such as the age of the population and availability of beds and respirators, etc.” Moukarzel said. “And there could also be a genetic component.”
“That’s what we seek to understand with the study,” he said. “If there is a genetic component, what does it look like, and which subset of the population does that impact the most and what can we do about it?”
The study is just getting started, and the researchers are looking for laboratories and clinicians as collaborators. They are seeking DNA samples, in roughly equal numbers, from people who test positive and negative for the virus.
“We would preferably have people who represent different racial and ethnic groups,” Tiirikainen said. “We are also considering crowdsourcing.”
The goal of the research, ultimately, is to help identify people or groups that may be vulnerable to future severe coronavirus outbreaks.
“What we are thinking is to identify the individuals that are more at risk and then look into some preventive strategies and personalized therapies,” she said.
Moukarzel said his company, founded in May 2017, hopes to contribute to the body of knowledge about COVID-19 and SARS-CoV-2, the virus that causes the disease.
“We believe that every single person and every single business needs to do their part in trying to defeat this disease and this horrible virus,” he said.