Population Health Studies Examine Role of Genetics in COVID-19

As organizations across the healthcare landscape seek to maintain or improve population health during the COVID-19 pandemic, researchers are turning to genetics to better understand patient outcomes from the virus.

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Recently, researchers at the University of North Carolina (UNC) at Chapel Hill and Vanderbilt University Medical Center (VUMC) received a $500,000 grant from Google’s philanthropy, Google.org. The study will aim to discover how COVID-19 alters gene expression in some ways that may be linked to their risk of severe illness and death.

Researchers will analyze blood samples collected in the past 16 months from more than 4,000 participants in the Cameron County Hispanic Cohort, some of whom have been infected with COVID-19. Cameron County is located along the southern Texas-Mexico border, and it has one of the highest rates of COVID-19 in the US.

For the first time, researchers will compare RNA, a marker of gene expression, from the blood collected over years from the same individuals before and after COVID-19 infection. The team will also compare participants’ RNA expression profiles to those of other cohort participants who have not been infected.

“This study is absolutely unprecedented,” said Kari North, professor of epidemiology in the UNC Gillings School of Global Public Health and the project’s principal investigator. “The identification of changes in gene expression associated with COVID-19 infection and severity will contribute to global knowledge on the biology of SARS-CoV-2.”

The group will use artificial intelligence tools to scan the genome for changes in gene expression that may be due to COVID-19 infection and are associated with severe respiratory illness and other long-term or potentially life-threatening complications.

“We really don’t fully understand the mechanism by which COVID-19 is able to wreak so much havoc on so many different systems within the body,” said the project’s co-principal investigator, Jennifer Below, associate professor of medicine in the Vanderbilt University School of Medicine.

“If we could identify which molecular pathways are being perturbed by the infection, that would give us a window into developing targeted therapeutics and pharmaceuticals that could potentially prevent such negative consequences.”

The funding is part of Google.org’s $100 million commitment to support COVID-19 relief efforts by nongovernmental organizations and academic institutions on behalf of vulnerable populations.

The Cameron County Hispanic Cohort was initially established in 2004, with the goal of studying disproportionately high rates of diabetes, obesity, and cardiovascular disease in Mexican-Americans living in Cameron County.

With the rapid spread of COVID-19, researchers saw an opportunity to use the biological samples collected from cohort participants to reveal how COVID-19 impacts the body at a molecular level.

The team will conduct genome-wide association studies to identify changes in gene expression that may result from COVID-19 infection. The goals are to obtain RNA samples and health assessments from 250 cohort participants who have been infected with COVID-19 and from 250 uninfected controls. Researchers hope to complete the study within a year.

“This is an extremely important public health issue,” said North. “We need to work hard to make sure that the populations most burdened by disease are not overlooked by genomic studies. We cannot afford for disease disparities to get worse.”

Researchers from the University of Minnesota are also working to improve population health and COVID-19 outcomes by analyzing patients’ genetics. The team recently published a study about how individualization of pharmacogenomics – the study of how genes affect a person’s response to drugs – may improve the safety and efficiency of COVID-19 drugs.

“The application of pharmacogenomic tests can help eliminate fatal hypersensitivity for patients prescribed certain drugs,” said University of Minnesota College of Pharmacy faculty Pamala Jacobson. “We asked the question if selecting a COVID-19 medication or the dose using an individual's genetic information could improve effectiveness or safety.”

In the last few months, leaders have investigated a number of drugs to treat COVID-19 without well-established safety or data to support these claims. Some of these treatments may have underlying genetic reasons for not being effective, resulting in fatal adverse effects. The study aimed to uncover genetic factors influencing the efficacy of therapies.

“One of the biggest success stories of using pharmacogenomics is with the HIV treatment abacavir,” said University of Minnesota College of Pharmacy faculty Melanie Nicol. “Which is now a standard test for potential treatment for those living with HIV and has virtually eliminated fatal hypersensitivity associated with that drug.”

The study examined a variety of literature for drug therapies for COVID-19, including hydroxychloroquine, remedesivier, tocilizumab, and steroids. The results showed that there are several gene variants that alter how an individual’s body metabolizes and processes COVID-19 therapies and may increase the risk of adverse effects.

Additionally, the study revealed that the risk of taking these therapies is complex because patients with COVID-19 are usually taking a number of other medications and could have underlying conditions that affect the drug. Data for pharmacogenomics is also limited because of the early stages of the clinical trials investigating treatments.

“While we did not find direct evidence to support use of pharmacogenomic testing for COVID-19, we did identify many actionable genetic markers that may have promise to improve efficacy and safety,” said Jacobson. “Clinical studies in patients with COVID-19 are needed before routine testing can be recommended.”