As experts think about the next phase of the COVID-19 pandemic, big questions loom: How many people have been exposed to the virus? How long does immunity last? When and under what circumstances will it be safe to return to work?

With questions this vast, one of the biggest challenges is knowing where to start. At a virtual meeting at the end of March, investigators involved in the recently formed Mass General Brigham COVID Center for Innovation (MGB CCI) began laying out a plan. To understand exposure, immunity and other critically important factors when thinking about how to bring people back to work, Mass General Brigham — and the world beyond — would need fast, reliable and scalable diagnostic tests. And these tests would need to be accessible from outside of a hospital setting. Ideally, individuals would take these tests at home (direct-to-consumer testing) or at the point of care (for instance, at a pharmacy or doctor’s office).

Hundreds of these tests have been in development and yet there was little verified data on which tests could yield reliable results. With so much work to do, the nascent center’s co-directors, David Walt, PhD, of the Brigham’s Department of Pathology and a core faculty member at the Wyss Institute at Harvard University, and Guillermo “Gary” Tearney, MD, PhD, of the Department of Pathology at Mass General, put out a call for volunteers to form working groups to divide up these big problems into manageable pieces. Researchers across the Brigham and Mass General are now working together on multiple fronts to: understand what clinicians need, scour the world for the most promising diagnostic solutions, put those tests through the paces and hit the accelerator on putting them into action.

“We Needed to Move Faster”

Aditi Hazra, PhD, MPH, who joined the Direct to Consumer working group of the Diagnostics pillar of the COVID Center for Innovation, could tell from the start that this was going to be an outcomes-focused initiative. Hazra is an epidemiologist with a background in genomics, and a former emergency medical technician. The weekend after the center’s meeting about diagnostics, Hazra had taken part in an MIT COVID-19 Challenge focused on the pandemic, learning everything she could about COVID-19 and immunity. Inspired, she began to think about how to rapidly understand the diagnostic needs of her clinical colleagues.

“MGB CCI working groups are made up of researchers — of diverse backgrounds since many clinicians with infectious disease expertise are on the frontlines treating patients,” said Hazra. To better understand what kinds of diagnostic tests would best serve clinical needs, Hazra began doing short, individual interviews with infectious disease leaders at the Brigham.

“I soon realized we needed to move faster,” she said.

So Hazra and colleagues in the Diagnostics Direct-to-Consumer working group, including Mehdi Jorfi, PhD, and Fanny Herisson, MD, PhD, both of Mass General, and Aishwarya Chander, who graduated from Sri Ramachandra Institute of Higher Education and Research, Tamil Nadu, India, just a few weeks ago, designed a four-minute survey for clinicians. The survey asked whether respondents thought there was a potential role for DTC testing in assessing patients and what criteria would help distinguish the most useful tests. DTC tests are designed for consumers to collect a specimen (for instance, blood from a swab, finger prick or saliva) and run the test at home, getting results within 20 minutes.

Hazra asked friends, colleagues at the Brigham and Mass General to circulate the survey. She went to sleep anxious but woke up the next day to 85 responses from clinicians and epidemiologists.

“Overwhelmingly, the answer was, ‘Yes, we think there’s a potential role,’” said Hazra. “With this feedback, we knew it was time to start scanning the horizon for tests that could fit our criteria.”

Horizon Scanning

Working groups, including Direct to Consumer, have been meeting virtually to drive efforts forward during COVID-19. From left: Trey Toombs, Rushdy Ahmad, Nell Meosky Luo, Aditi Hazra and Glenn Miller.

Based on the results from the survey, researchers in the DTC working group developed a set of standards and specifications by which they were able to do a very quick cut of hundreds of tests.

“There’s a common piece of advice in business: ‘Don’t boil the ocean.’ Take on too big a problem, and you’ll never make progress. The working groups wanted to take a targeted approach,” said Glenn Miller, PhD, of Partners Innovation. Miller has been sitting in on all the diagnostic working groups’ meetings for the last month, looking for ways to help connect ideas that transcend the groups.

The DTC working group performed a “deep horizon scan” of available tests — systematically searching for new and emerging technologies. They generated a list of tests that could detect evidence of the virus itself, with no false negative results, and tests for antibodies — produced by the immune system in response to infection — with no false positives. Nell Meosky Luo, the CEO of Folia Health, and her team collaborated with the group to scan these tests to see if they met specifications, assessed manufacturing and distribution capabilities and identified any potential supply-chain issues.

In a matter of 10 days, they had sorted through more than 300 offerings, scoring each one based on their criteria.

Rushdy Ahmad, PhD, of the Wyss Institute, led the working group’s efforts. Trey Toombs, PhD, senior program manager for the Brigham Research Institute, and Karen Bruynell, administrative director of the Brigham Education Institute, have served as project managers.

“The last five weeks have been a revelation for me as I had the good fortune to help lead a group of colleagues, now friends, on a journey to do all that we can to help mitigate the impact of the pandemic,” said Ahmad. “I don’t think I’ll ever forget this experience where a bunch of strangers got together and delivered results in a truly selfless manner. Our results comprising of recommendations for rapid antibody and antigen tests for COVID-19 will be used to implement solutions like going back to work in a safe manner.”

So far, the team has arranged for 15 products to be further evaluated in house: five have already arrived in the lab and the other 10 are in transit. Members of the working group are currently in discussion with seven additional companies to bring in their tests as well. The goal is to have these rigorously tested by the end of May.

Searching for Point-of-Service (POS) Solutions

Members of the Point of Service/Urgent Care Working Group gathered for virtual video meetings. From left to right:
Leonora Balaj, Pawan Jolly, Lori Garg,
Catherine Fink, Catherine Cabrera, Tiffany Tran
Hiroyuki Yoshida, Pelham Keahey

The Point-of-Service (POS)/Urgent Care working group also used a horizon-scanning approach to identify promising commercial technologies, but point-of-service testing presents its own unique challenges.

“We’re looking at solutions for a very wide range of needs. With high testing demand, supply-chain seems to be one of the main limiting factors today,” said Pawan Jolly, PhD, a senior research scientist at the Wyss Institute who is leading the working group, which includes subgroups focused on commercially available device-based molecular, antigen and serology tests. Lori Freed Garg, MD, MPH, and Pelham Keahey, PhD, both from Mass General, have served as project managers. “Our goal has been to provide near-patient testing, which may not only increase accessibility to tests but also reduce the burden of testing faced by emergency care facilities.”

Team members quickly developed a comprehensive questionnaire that was sent to various companies, surveying them about potential future issues, including scalability, reagent shortages, and emergency use authorization (EUA) from the Food and Drug Administration. The team then cataloged the tests based on different categories, the team’s assessment, and its recommendations.

Jolly notes that no single diagnostic test is perfect in all ways. The POS/Urgent Care group discussed what “good enough” could mean for different metrics and which diagnostic metrics could be relaxed so that others could be optimized.

Broad horizon scanning criteria and resulting working spreadsheet

In less than two weeks, the team has assessed almost 400 different tests (developed and under development) and systematically narrowed the list down to those that could be administered near-patient, for example at doctor’s offices or urgent care sites with low-level laboratory requirements. The group also developed a formalized way to document the decision-making process, making this process transparent and comprehensible and useful for future, similar decision-making efforts.

Based on the working group’s assessment, which was published on the MGB CCI website, five POS molecular diagnostic platforms, two reader-based serology tests and one reader-based antigen test have been shortlisted. Just like the DTC working group’s top contenders, the next stop for these tests is the Diagnostic Accelerator.

Korneel Grauwet (left) provides an overview of the biosafety level sections in the Hale building lab.

Start Your Engines

When Charles Jennings, PhD, executive director of the Brigham’s Program for Interdisciplinary Neuroscience, first saw the seventh floor of the Hale Building for Transformative Medicine, he could not have possibly imagined that it would one day be used for its current purpose. But when Jennings, a member of all of the Diagnostics working groups, heard that there was a need for laboratory space where the most promising COVID-19 diagnostics could be put to the test, he knew that the seventh floor could be a great fit. Working with Korneel Grauwet, PhD, Jennings helped put the pieces in place to temporarily repurpose the space — designed for the Brigham Neurotechnology Studio and for neurology faculty members — into a short-term home for the initiative known as the Diagnostic Accelerator (DA). The goal of the DA is to rigorously evaluate the most promising tests put forward by the other working groups.

“We’re in the process of gearing up and getting the lab ready,” said Grauwet, who previously studied oncolytic viruses in the Chiocca lab at the Brigham and most recently has been working on research related to CAR-T cells in the Maus lab at Mass General. “We’ve come together from a variety of different areas of expertise and across institutions to make this happen.”

The work of the Diagnostic Accelerator has been spearheaded by Lauren Ritterhouse, MD, PhD, associate director of the Center for Integrated Diagnostics at MGH. The Validation Working Group, led by Petr Jarolim, MD, PhD, medical director of clinical chemistry at the Brigham, established the testing criteria for the DA.

“There’s a flood of diagnostic tests coming onto the market,” said Lauren Ritterhouse. “We’re at the bottom of the funnel — our goal is to boil down dozens of tests selected by our colleagues and determine what’s most likely to succeed. To do so, we’ll pressure test them, benchmark them against each other and get a better sense of what the performance of these tests is in our hands.”

The team’s goal is to find the optimal tests to suit not only the needs of the Mass General Brigham community but also the world beyond. They are publishing results as soon as they become available in order to share what they are learning.

In addition, at the beginning of May, two new working groups were announced. A new Implementation working group will focus on community engagement. The group will be led by Cheryl Clark, MD, ScD, a hospitalist and researcher at the Brigham and by Deb Hung, MD, PhD, of the Broad Institute, Mass General and the Brigham. And a new Horizon Technologies Working Group, which will identify emerging diagnostic technologies that have the potential to impact the current COVID pandemic and accelerate their deployment, is being led by Wesley P. Wong, PhD, of Boston Children’s Hospital and the Wyss Institute.

“Our original mission was to start locally and then expand, with an initial focus on community testing in partnership with state and local government,” said Ritterhouse. “We’re starting to think about what will be most helpful for testing in other areas of the country too.”

Stronger Together

The Diagnostics Pillar’s working groups, including the Diagnostics Accelerator, have conducted their efforts virtually with support and coordination through the Brigham Research Institute (BRI), which has hosted town hall meetings, created Slack channels and more to connect research communities.

The center’s mission and operations continue to evolve as it nears its two-month birthday. David Walt noted that the diagnostics work would not have been possible without an incredible amount of administrative and operational support from the Brigham Research Institute (BRI), which served as central command for this particular pillar of the MGB CCI arranging for volunteer project managers, research administration liaisons and administrative support for each working group.

Jacqueline Slavik, PhD, executive director of the BRI, said that the BRI pivoted sharply at the end of March to focus the team’s efforts on supporting the MGB CCI. “Anu Swaminathan, PhD, took on the role of administrative director for the diagnostics pillar, working closely with David to pull together a staffing model with no initial resources and strictly volunteer staff, managing day to day operations,” said Slavik. “The BRI team collectively agreed that supporting the MGB CCI was the most important work we could be doing during this pandemic.”

“It’s been impressive to pull together an entire research operation in an accelerated timeline, especially when you consider everyone is volunteering their time,” said Ritterhouse. “I now have all of these new colleagues and collaborators I would never have met otherwise. I can’t wait to get to meet them in person someday.”

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