Does Your Genetics Offer Protection, Create Vulnerability to COVID-19?

Two faculty members at the University of Minnesota Medical School lead a team contributing to an international study that hopes to answer a question about COVID-19 — what genetic factors, if any, lead to or protect against severe COVID-19 outcomes for patients under the age of 50 with no known pre-existing conditions?

“I became interested in this project because of the patients I have cared for,” said Meghan Rothenberger, MD, associate professor in the Department of Medicine’s Division of Infectious Diseases and International Medicine. “I’ve cared for a handful of very young patients who have had incredibly complicated courses of COVID-19, and in some of the situations, absolutely no underlying comorbidities.”

Dr. Rothenberger and Christen Ebens, MD, MPH, assistant professor in the Department of Pediatrics, lead the study site through the Medical School, serving as one institution, among dozens around the globe, that is collecting genetic samples from some of COVID-19’s most unexpected, yet sickest, patients. The international study called, COVID Human Genetic Effort, has recruited de-identified patient samples from Italy to Japan and now, Minnesota. Sites also ask for the genetic samples from first-degree relatives to accompany each COVID-19 patient sample.

“We’re enrolling first-degree relatives who haven’t gotten sick to help inform protective factors as well,” Dr. Ebens said. “If there are people who have a similar genetic makeup as you, but you got sick, and they didn’t, then we may be able to find certain genetic differences responsible for the different clinical outcomes.”

The collection process itself differs from many other COVID-19 studies. Dr. Rothenberger says that because this study focuses on genetics, samples can be collected now or many months later, which is unlike other studies that are limited to using samples only at the time of illness.

“Some studies also require getting patient consent when they are in the thick of their illness or require use of PPE, which is so limited right now,” Dr. Rothenberger said. “We don’t have any of those barriers, which is nice.”

Because of that, the duo will be able to retrospectively analyze M Health Fairview patient records dating back to March, reach out to those who fit the study criteria and ask for a blood sample. With the help of a CO:VID (Collaborative Outcomes: Visionary Innovation & Discovery) grant, they intend to collect 50 patient samples, as well as 50 to 100 samples from family members — an amount they feel can be collected quickly. The team de-identifies the samples before sending them to Washington University, one of the study’s hubs for genetic sequencing. From there, the international team will collate the information with the hope of finding genetic markers that inform future COVID-19 treatments and vaccines.

“If we understand better what pathways are affected, we can be more precise in targeting our therapies and increasing the likelihood of clinical trial success,” Dr. Ebens said. “If we have more data to support that this is what is likely to be the better target, we’ll be more successful in treating patients at the beginning.”

Dr. Rothenberger hopes the information, as well as this new infrastructure for scientific collaboration, will transform medicine for the future.

“It’s about not only understanding this disease and how it impacts patients that I take care of but also what lessons we can learn from this that will be applicable in the future,” Dr. Rothenberger said. “Despite the tragedy that COVID-19 is, the way that the science and medical community has come together across the world is actually amazing. This is a great example of that.”

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