Gathering Critical Clues

Gathering Critical Clues

Jun 04

To understand how any given disease affects the body, scientists need a wide array of tools. One of the most valuable and indispensable instruments in their toolkit are clinical samples—small amounts of blood, urine, mucus, spit, and tissue that can be used to study a disease in a patient.  For COVID-19, a disease that has an often unpredictable course, an incredible ability to infect, and a unusual immune response, the need for clinical samples grew as rapidly as the pandemic spread. 

Ragon Institute Group Leader Xu Yu and Brigham and Women’s Hospital (BWH) Infectious Disease Faculty Member Jonathan Li are answering the call, leading a team to collect clinical samples for the Massachusetts Consortium on Pathogen Readiness (MassCPR), a massive collaboration of researchers and clinicians from across the Greater Boston area. These samples may hold the key to understanding, and containing, the COVID-19 pandemic. 

Dr. Yu, who is also an Associate Professor of Medicine at Harvard Medical School, and Dr. Li, the Director of the Harvard/BWH Virology Specialty Laboratory and Assistant Professor of Medicine at Harvard Medical School, worked closely with Drs. Bruce Walker, Arlene Sharpe,  Katrina Armstrong, and Lindsey Baden, along with MassCPR leadership to create this biorepository of samples. Their work is supported by donations from Mark and Lisa Schwartz and Enid Schwartz, given at the very beginning of the pandemic in recognition of the incredible effort this would require. 

Collecting clinical samples is a demanding process at the best of times. Researchers must identify what types of specimens will be most useful (here, blood, respiratory secretions, urine, and stool), determine the best ways to process and store samples, and find people willing and eligible to participate in research. This requires careful planning and forethought, a deep understanding of the scientific process and pressing research questions, and a trained and dedicated team.  

But the pandemic has made this process even more daunting than usual. 

“This has been the most challenging environment for clinical and translational research that I have ever encountered, but it’s also brought out the best in people,” Dr. Li said. “I’ve been amazed at what the team has accomplished in such a short period of time, overcoming hurdle after hurdle. I couldn’t be prouder of our work.”

Why such efforts? Within these samples, donated by COVID-19 patients, healthcare workers, and community members, is a wealth of information about the SARS-CoV-2 virus and the disease it causes. Hidden in everything from immune cells circulating in the blood to proteins shed in urine, the information found in these clinical samples may lead the way to understanding the disease course, identifying effective vaccines and therapies, and revealing how we can lessen its grip on the world. 

Drs. Yu and Li knew that working within a pandemic, on COVID-19 itself, would require innovations and changes throughout the entire process. Their first step was to work with MassCPR, MGH, and Ragon leadership to establish one collection process, one consent form, and one central repository for all COVID-19 samples. This centralization reduced pressure on the entire system, making it easier to collect and share information, samples, observations, and results. 

Second, they relied on technology to enroll people in the study, using phones and iPads to virtually connect researchers with eligible participants, which kept the clinical staff safe from potential infection. The researchers also deepened collaboration with the medical staff, who were able to incorporate sample collection into standard care, including setting up research collection stations at outpatient respiratory infection clinics. These steps ensured no extra personal protective equipment (PPE) was required to obtain consent from patients or to collect the samples, preserving healthcare workers’ masks, gloves, and other PPE during shortage crisis.

Finally, the team had to redesign the sample processing and storage process to protect the researchers working on the project. Researchers were given masks and worked in clearly defined shifts, allowing them to maintain the recommended social distance. They were provided bicycles to allow them to commute without using public transit. Overall staffing increased, though the number of staff in the lab at any given time decreased, and researchers were divided into compartmentalized teams. This allowed any staff who tested positive or developed symptoms suggestive of COVID-19 to take quarantine while preserving the ability of the team to continue processing samples. 

The team’s quick innovation and hard work paid off. The team has collected samples from more than 400 COVID-19 patients in 7 weeks, which are being shared with members across the Boston-area hospitals and research institutes for COVID-19 research spanning from therapeutics to vaccine development to immune response. 

This is only possible because of the amazing group of people who make up this team, say Yu and Li. Yu adds. “I would really like to emphasize that this truly is teamwork – it would have not been possible without an incredible group of people, from our clinical teams to our lab members to our donors. I would especially like to sincerely thank all the study participants and their families for their selfless support of the scientific research and for their belief in us.”  

Drs. Yu and Li would like to acknowledge and thank their incredible team of clinical and research staff, for their hard work and dedication: Daniel Worrall, Kathy Hall, Sarah Luthern, Michael Dougan, Andrea Edlow, Alicja Piechocka-Trocha, Corrie Martin, Musie Ghebremichael, Raja Nakka, Francoise Giguel, Edward DeMers, Kelly Judge, Kristina Lefteri, Susan Slaugenhaupt, Keith Flaherty, Andrew Chan, Daniel Kuritzkes, Athe Tsibris, Francisco Marty, Martha Jones, Elizabeth Hohmann, Jesse Ripton, all the members and volunteers at the MGH Translational and Clinical Research Center, the Ragon Institute Clinical Platform, BWH Center for Clinical Investigation, the Ragon Institute Processing Laboratory, the Harvard/BWH Virology Specialty Laboratory, the ACTG processing laboratory, and Partners Institutional Review Board. This was an effort only made possible by an incredible feat of teamwork, and we are incredibly grateful to each and every one of you.