In the weeks before the St. Louis region saw its first patients with COVID-19, physician-scientists at Washington University School of Medicine began planning and preparing how best to collect blood and other biological samples from such patients so specimens could be quickly disseminated to researchers seeking strategies to treat, prevent and contain the novel coronavirus.
With financial support from The Foundation for Barnes-Jewish Hospital, Siteman Cancer Center and Washington University’s Institute of Clinical and Translational Sciences (ICTS), as well as input from the Community Advisory Board of Washington University’s Institute for Public Health and ICTS, the School of Medicine created a repository to store and manage specimens collected from adult and pediatric patients who have tested positive for SARS-CoV-2 — the virus that causes COVID-19. The sample-collection efforts are led by Philip Mudd, MD, PhD, an assistant professor of emergency medicine, and Jane O’Halloran, MD, PhD, an assistant professor of medicine.
To date, more than 350 patients have donated samples for the research effort, and over 7,000 samples have been distributed to more than 20 labs on the School of Medicine and Danforth campuses to help understand the basic biology of the infection and seek ways to prevent or treat it.
“The biorepository is an important resource for scientists working in many different areas of COVID-19 research,” Mudd said. “We are hopeful that the analysis of these samples will speed the development of treatments and new diagnostics that will help patients in St. Louis and around the world. We’re grateful for the support of the foundation’s donors and for the generosity of our patients and are optimistic that this work will lead to new and useful breakthroughs in the treatment of COVID-19.”
According to the investigators, collecting such samples — including blood, urine, stool and nasal swabs — via one centralized process speeds research, prevents scientists from duplicating work already underway and relieves patients of the burden of being asked to participate in multiple studies.
The project includes research teams that span the entire university, including investigators who are internationally recognized for their research into other viruses, such as Ebola, SARS, West Nile, Zika and emerging strains of influenza.
Studies underway include research to:
- Develop new diagnostic tests for COVID-19 and tests to predict the severity of illness in those who test positive.
- Identify human antibodies that neutralize COVID-19 and that could be used to develop new treatments and preventive therapies for this disease.
- Use viral samples from patients to establish the most relevant models to test possible treatments and vaccines against COVID-19.
- Perform studies of biomarkers of disease severity in humans to help predict, early in infection, patient outcomes.
- Conduct genetic studies to establish risk factors for severe illness.
To receive samples for research, investigators must submit an application to a committee that is part of Washington University’s ICTS, led by William G. Powderly, MD, the J. William Campbell Professor of Medicine and co-director of the university’s Division of Infectious Diseases. The ICTS committee managing patient specimens — led by Christina A. Gurnett, MD, PhD, the A. Ernest and Jane G. Stein Professor of Developmental Neurology and director of the Division of Pediatric and Developmental Neurology — is fielding many requests and encouraging a team science approach to enhance collaboration and reduce duplication of efforts. The biorepository has already led to new collaborations for researchers with complementary skills.
“It’s important to streamline this work from a research perspective, but it’s equally important to ease the process of participation for our patients,” O’Halloran said. “Ordinarily, individual researchers design studies and approach patients separately. Knowing we would have many scientists studying COVID-19, it was critical for us to find a way to facilitate the process of obtaining patient samples. We’re grateful to our patients for providing such a valuable resource to help us understand and combat this new virus.”
Because some of the research may involve sequencing the DNA of patients with COVID-19 to understand each person’s susceptibility to the illness, the researchers consulted the Community Advisory Board for guidance on how to address treatable genetic conditions — independent of COVID-19 — that might be revealed during the course of the research. The board, made up of 12 people with diverse leadership experience in local health-care and community organizations, provides advice to investigators on the conduct of clinical research involving the local community.
Anytime an individual undergoes whole genome sequencing, even people who may appear perfectly healthy, there is the potential to reveal genetic mutations that indicate a very high risk of developing a disease. Because some genetic conditions have treatments or prevention strategies available, doctors conducting COVID-19 research would like to have the ability to return this important information to patients, with patient permission, in a way that will allow patients and family members to make informed decisions about their health.
“As part of studying the genetics of COVID-19, the researchers may learn information about a research participant’s risk of developing any one of 59 hereditary conditions that lead to very high risk of developing life-threatening — but preventable or treatable — diseases such as breast cancer, heart arrhythmias or blood-clotting disorders,” said advisory board member Doug Lindsay, a personal medical consultant who advises patients with rare diseases or complex conditions. “How do you best provide this kind of information — if at all — to patients or family members who are totally preoccupied with the immediate crisis of COVID-19 illness?
“The overall thrust of our advice is, ‘Give patients the choice to know or not know,’” Lindsay said. “We also feel it is best to deliver this information at a later time, to give the patients, or family members if the patient has passed away, a chance to make an appointment to go over follow-up questions about the COVID-19 research study that they or their family members were enrolled in. The genetic studies of COVID-19 can reveal hereditary conditions, so the information is relevant for family members, too. We feel it is important to give people the mental space to deal with major medical decisions independent of the immediate pandemic.”
The committee also has recommended that genetic counselors be made available to patients who are found to have any of these 59 conditions and choose to learn their genetic status. The committee also wants to ensure that patients and families know the kinds of medical specialists they should follow up with based on their genetic information.
“These questions are about what a healthy relationship between participants and investigators looks like,” Lindsay said. “Participants who donate their data to these studies are real people. The information that the doctors are identifying may shape lives over more than one generation. We hope this kind of advice can help researchers be good stewards of the information put in their care.”
Added Gurnett, “The guidance provided by the Community Advisory Board has been critical to helping our investigators and clinicians provide the best possible care and conduct clinical research in the most ethical and respectful ways possible. We thank the patients and their families for their central contributions to the work of understanding this virus, as their participation is key to reducing its impact on our communities.”