Striking Biological Gold

At a glance: 

• MassCPR biospecimens program will supply scientists with biologic samples for research on COVID-19 and other emerging infectious diseases
• The new program will include a database that contains key demographic, clinical, and biological information for biospecimens housed at six Massachusetts-based hospitals
• The biospecimens program aims to speed up research on SARS-CoV-2, while enabling scientists to design bigger and more diverse studies that include more diverse patients
• “You can’t really do comprehensive science to understand the biology of a new disease without samples from human beings,” said Kathryn Stephenson

Giving a blood or saliva sample at the doctor may be fairly routine for many of us, but for scientists on the receiving end of these biological samples, or biospecimens, there is no greater contribution to their research. In fact, during the past two-plus years of the COVID-19 pandemic, these precious samples have played a vital role in helping scientists answer a seemingly endless stream of urgent questions about an ever-changing virus.

Since the very beginning of the pandemic, the Harvard Medical School-led Massachusetts Consortium on Pathogen Readiness, or MassCPR, has been connecting scientists at different institutions with biospecimens for SARS-CoV-2 research.

Now, MassCPR is formalizing its biospecimens program to make the process even more efficient. The new program will feature a database that contains key demographic, clinical, and biological information for biospecimens housed at six Massachusetts-based hospitals. MassCPR scientists can use this database to quickly and easily identify the samples they need for their research—and while they can study any aspect of SARS-CoV-2, researchers will focus on long COVID and viral variants.

“You can’t really do comprehensive science to understand the biology of a new disease without samples from human beings,” said Kathryn Stephenson, HMS assistant professor of medicine at Beth Israel Deaconess Medical Center and co-director of the MassCPR biospecimens program. “What we’re trying to do is to create a biobank of samples from all these different types of people that had COVID-19, to serve as a repository for this pandemic and, importantly, to create a baseline for future illnesses that we can’t predict.”

Other co-directors of the MassCPR biospecimens program include Richelle Charles, HMS associate professor of medicine at Massachusetts General Hospital, and Manish Sagar, professor of medicine and associate professor of microbiology at Boston University School of Medicine and a physician at Boston Medical Center.

An early iteration

In February 2020, as the severity of COVID-19 was quickly becoming apparent, scientists from institutions all over Boston came together to form MassCPR.

“There was nothing formal. There was no infrastructure. Just a group of really brilliant scientists who wanted to work on the virus together,” recalled Howard Heller, HMS assistant professor of medicine at Mass General and the MassCPR senior advisor for clinical partnerships.

Almost immediately, the scientists realized that access to biospecimens would be absolutely essential for studying the new virus.

“Patients were flooding the hospitals, and investigators wanted their blood, their saliva, their nasal swabs, so that they could figure out what was causing the disease—why some people get sick, and others don’t.” Heller said.

However, there was a snag: Typically, researchers only have access to biospecimens collected at their own institutions—and because the samples are so valuable, it can be difficult to convince different institutions to work together and pool their resources. Moreover, the logistics of moving samples from one place to another can be cumbersome and slow.

To overcome these challenges, MassCPR created a biospecimen sample sharing system based on the principle that institutions would keep some portion of the samples they collected, while making the others available to other researchers. The system also included a Sample Access Accelerator Committee that was charged with reviewing requests and determining how many samples to dole out—while linking scientists working on similar research to prevent duplicate efforts. MassCPR also developed a standardized material-transfers agreement to streamline the process of transferring samples. 

“The idea was to enable rapid sharing of biospecimens in a fair and transparent way, so that everybody at every institution could see where these samples were going and who was getting them. This sharing created a culture of collaboration that had never really existed to that degree before.” Heller explained. “The incredible accomplishments of MassCPR during that first year were in large part because of the availability of biospecimens.”

Building on success

Moving into year two, MassCPR is pouring more funding and resources into its initial biobanking efforts to create a formal biospecimens program. The program will use a decentralized model, in which six Massachusetts-based hospitals—Brigham and Women’s Hospital, Mass General, Beth Israel Deaconess, Boston Medical Center, UMass Memorial Medical Center, and Tufts Medical Center—each collect and store biospecimens that are part of the MassCPR biobank.

Blood samples, which can be separated into serum, plasma, and other cell types to study different aspects of the immune response to the virus, will likely be the most commonly collected—but additional useful samples include nasal swabs, which can be used to sequence the virus, as well as saliva, other mucosal secretions, and perhaps even lymph node biopsies.

“As we formalize the program, we are setting targets for how many samples these different institutions are going to collect, and what types. We want it to be a mix of samples,” Stephenson said. She estimates that MassCPR has collected around 1,000 biospecimens so far, and it aims to collect 500 more this year.

Scientists will also run a set of standard tests, or assays, to gain basic biological information about each sample. “Investigators all want to know the same core pieces of information about samples, and this way they won’t have to duplicate efforts,” Charles said.

The assays must strike a balance between providing specific information and not getting so specific that the information becomes obsolete every time a new variant emerges, Stephenson added. Thus, the tests will focus on important yet generalizable features of the host immune response such as inflammatory markers, SARS-CoV-2 antibodies, autoantibodies, and antibodies to other pathogens. Ultimately, each sample, along with demographic, clinical, and biological information, will be added to a database that is integrated across the hospital systems, and readily accessible to MassCPR researchers. Anytime researchers want to conduct a study, they can go into the database, see what biospecimens are available, and request the samples they need.   

“We want the research to be driven by the investigators and what comes out of people’s creativity, so we’re really just trying to link people together to do cutting-edge science,” Stephenson said. One broader focus for MassCPR is long COVID, also known as post-acute sequelae of SARS-CoV-2 infection. In particular, researchers are interested in basic questions about who gets long COVID and how their immune systems respond to the virus. Another major research area is SARS-CoV-2 variants, including the transmission dynamics of new variants and the immune response they induce in the host, compared with previous variants. Ultimately, the information gained through research on biospecimens can be used to inform the development of new treatments and better vaccines for COVID-19.

A better way

Setting up a cross-institution biospecimens program is undoubtedly a major undertaking, but the advantages are many. Perhaps most significant is how quickly such a program allows research to move forward by providing scientists with enough samples for their work.

“We’ve all learned with this pandemic that speed is a huge factor,” Stephenson said.

When omicron emerged, for example, scientists instantly faced questions about the genetics of the variant, the rate of breakthrough infections, and how people’s immune systems were responding. “Those questions had to be answered immediately, so you couldn’t spend a couple of months setting up a new protocol to collect samples. You had to have ongoing systems,” Stephenson said.

By having a centralized database of information about the biospecimens, researchers can easily identify the specific samples they need, while ensuring that they aren’t duplicating the efforts of another research group. Pooling samples across institutions also means that scientists can design larger, stronger studies. “If you are working with a much bigger cohort of patients, it adds more confirmation and validation to the results that come out,” Charles said.

Moreover, she added, by drawing on samples from multiple hospitals with different patient populations, scientists can more easily capture demographic diversity in their studies—including age, racial, and ethnic diversity. “This program allows us to fund research that is more representative of the people that we serve and of the populations of Massachusetts,” Charles said.

The biospecimens program is currently focused on SARS-CoV-2 and COVID-19, but the researchers think it will remain an important tool for future diseases. “We are really committed to preparedness—keeping ourselves ready for the next pandemic or the next pathogen that arrives,” Stephenson said. For example, having such biospecimens on hand could help scientists more quickly unravel the recent mysterious outbreak of hepatitis in children or better understand the ongoing spread of monkeypox.

“Our goal is that this program continues in perpetuity, because there’s always going to be some pathogen that’s causing an issue,” Charles added.

Stephenson also hopes that the biospecimens program will continue to encourage partnerships between researchers and across institutions. “These new collaborations and friendships that didn’t exist before COVID-19 are incredibly helpful and amazing,” Stephenson said.

“With COVID-19 I think a lot of people saw how quickly the science moves forward when we all work together as opposed to working apart,” Charles agreed. “Hopefully everyone continues to do that as we move into other areas of research.”

Yet even as the biospecimens program evolves, the overarching objective remains the same: to make sure that each and every sample collected from a patient is used in a way that maximizes its impact on the research.

“We’re the stewards of these biospecimens, which are often given to us in times of sickness when people aren’t doing well,” Stephenson said. “They are very precious, and we need to treat them like gold.”