Vanderbilt University Medical Center (VUMC) and the University of North Carolina (UNC) at Chapel Hill have been awarded $500,000 by Google's philanthropy, Google.org, to study how COVID-19 alters gene expression in some people in ways that may be linked to their risk of severe illness and death.

The study will analyze blood samples collected during the past 16 years from more than 4,000 participants in theCameron County Hispanic Cohort. Some of them have been infected by SARS-CoV-2, the virus that causes COVID-19.

Cameron County, on the southern Texas-Mexico border, has one of the highest rates of COVID-19 in the United States.

Using artificial intelligence tools, the researchers will scan the genome for changes in gene expression that may be due to SARS-CoV-2 infection and which 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 "Piper" Below, PhD, associate professor of Medicine at VUMC.

"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," Below said.

"This study is absolutely unprecedented," said Kari North, PhD, professor of Epidemiology in the UNC Chapel Hill Gillings School of Global Public Health, and the project's principal investigator.

For the first time researchers are able to compare RNA, a marker of gene expression, from the blood collected over years from the same individuals before and after SARS-CoV-2 infection. Their RNA expression profiles also will be compared to those of other cohort participants who have not been infected.

"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," North said.

The funding announced today is part of Google.org's $100M commitment to support COVID-19 relief efforts by non-governmental organizations and academic institutions on behalf of vulnerable populations.

Established in 2004, the Cameron County Hispanic Cohort is led by Susan Fisher-Hoch, MD, PhD, and Joseph McCormick, MD, founder of the UTHealth School of Public Health in Brownsville, Texas.

The couple gained fame as "virus hunters" for the U.S. Centers for Disease Control and Prevention for their investigations of Ebola and other viral causes of hemorrhagic fever in Africa in the 1980s.

The cohort initially was established to study disproportionately high rates of diabetes, obesity and cardiovascular disease in Mexican-Americans living in Cameron County. The collaboration between Drs. North, Below, McCormick and Fisher-Hoch began about seven years ago.

With the arrival of COVID-19 and its disproportionate impact on Hispanic Americans, the researchers realized that biological samples collected from cohort participants over time also might reveal, at the molecular level, how SARS-CoV-2 impacts the body.

VUMC researchers will sequence RNA samples in VANTAGE, the Medical Center's advanced genomics core, and both UNC and VUMC will conduct genome-wide association studies to identify changes in gene expression that may result from SARS-CoV-2 infection.

The goals are to obtain RNA samples and health assessments from 250 cohort participants who have been infected by SARS-CoV-2 and from 250 uninfected controls, and to complete the study within a year.

The cohort "is an unbelievable resource that exists in very few places, let alone in an under-represented, medically underserved and socioeconomically depressed population," Below said. "This is a population that's being devastated. We're right at the beginning of being able to understand how (they) are being impacted by COVID-19 at the molecular level."

"This is an extremely important public health issue," added North, who has spent much of her career promoting research in diverse study populations. "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."