Working Group Leads

Pardis Sabeti Pardis Sabeti, Ph.D.
Professor, Department of Organismic and Evolutionary Biology, Harvard University
Professor of Immunology and Infectious Disease, Harvard T.H. Chan School of Public Health
Institute Member, Broad Institute of MIT and Harvard
Investigator, Howard Hughes Medical Institute
David Walt

David Walt, Ph.D.
Hansjörg Wyss Professor of Biologically Inspired Engineering, HMS
Professor of Pathology, BWH
Core Faculty-Wyss Institute for Bioinspired Engineering at Harvard University
Professor, Howard Hughes Medical Institute


Diagnostics Working Group

The Diagnostics Working Group began as a coalition of experts who came together in the earliest days of the pandemic as a rapid-response team to quickly develop diagnostic testing for Boston-area hospitals, including Mass General, Brigham and Women’s, Boston Children’s, and Boston Medical Center, among others. The group members subsequently turned their attention to identify and develop new technologies and approaches to provide accurate, rapid, and inexpensive testing that did not rely on access to extensive medical resources and infrastructure. This remains a critical focus of the group to this day. The group, which meets every two weeks, also collects and shares information on the FDA diagnostic test Emergency Use Authorization and approval process, large-scale test manufacturing, and other broad, systemic issues common in diagnostics research and development.

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Learn more about the Diagnostics Working Group

The Diagnostics Working Group was essential to the Boston medical community’s early response to the pandemic. Since then, it has helped create the Sample Access Accelerator, a consortium-wide COVID-19 clinical biospecimen repository supporting research, and contributed to the development of diagnostic tools like SHERLOCK one-pot testing. The technologies and advancements made over the last year have laid the foundation of strong pandemic preparedness and have potential to be used to improve diagnostics for many current global infectious diseases, which remain a leading cause of death worldwide.

Key findings funded by MassCPR

MassCPR helped to galvanize diagnostic and surveillance technologies, approaches, and platforms for (a) patient/individual testing, (b) community surveillance, (c) wastewater surveillance, and (d) immune response measurements. We summarize the major contributions of MassCPR-funded projects below. 

Patient/Individual Testing—MassCPR awardees created novel technologies, assays, and platforms for diagnosing and detecting SARS-CoV-2 infection in individual samples. Feng Zhang (MIT/Broad) developed StopCOVID, a simplified test protocol for CRISPR-based diagnostics (SHERLOCK) and a prototype device, establishing a new company, Proof Diagnostics, to commercialize this technology. Lee Gehrke (MIT) isolated B cells from convalescent patients to obtain antibodies that recognize and detect the viral nucleocapsid protein (NC), showed robustness to viral variants, and established a lateral flow-based assay. Wesley Wong (Children’s HMS, Wyss) developed DNA nanoswitches that undergo a conformational change in response to binding, to detect proteins within unpurified biological fluids with greater speed, ease, sensitivity, and specificity, and less expense than equivalent ELISA assays, pairing the assay with a portable reader. David Walt (BWH, HMS) developed ultrasensitive assays for detecting SARS-CoV-2 antibodies, neutralization, and antigens using the single molecule array (Simoa) platform. They quantified antigen and antibody levels in COVID-19 patients with longitudinal samples, correlating the results with patient admission status to the ICU and time to intubation. Wayne Marasco (DFCI) identified anti-SARS-CoV-2 antibodies that bind to different epitopes and decorate the surface of the spike, primarily for therapeutic purposes; some of these anti-SARS CoV-2 antibodies were used for diagnostic purposes by the Walt Lab.  

Community Surveillance—Awardees created impactful platforms to facilitate larger studies in the community. George J. Murphy (BU School of Medicine) developed an Emergency Use Authorization FDA approved lab-developed test to perform in-house, quantitative real time PCR for COVID-19 detection in the Boston Medical Center patient population. By further incorporating a data-driven, sample pooling strategy, they significantly increased the number of individuals who could be screened. Ann Moorman (UMASS Medical) enrolled healthcare workers (HCW) from the Emergency Department (ED) at UMass Memorial Hospital in Worcester, MA, and HCW household members to understand seroprevalence and household transmission. They also enrolled patients presenting in the ED with suspected or confirmed COVID symptoms to determine the duration of antibody responses. Jeremy Luban (UMASS Medical) developed experimental tools for faster assessment of SARS-CoV-2 nucleic acid sequence variants arising during the pandemic. They used them to characterize the effect of mutations in circulating not only Spike variants, but also in the M, E, and N genes, and their effects on virus infectivity and susceptibility to neutralizing antibodies.

Wastewater Surveillance—MassCPR awardees and larger community members spearheaded the innovative approach of testing wastewater to look at community prevalence of SARS-CoV-2.  Tim Erickson (BWH, HMS) measured SARS-CoV-2 in wastewater to monitor the virus for the City of Boston and adjoining neighborhoods. The project provided user-friendly maps of SARS-CoV-2 and helped assess the impact of policies surrounding the pandemic (e.g., shelter-in-place, reopening phases). Their wastewater-based epidemiology model has been adopted nationally and internationally, and they created an interactive dashboard to monitor the trend of SARS-CoV-2 virus titers nationwide.

Immune Response MeasurementsSteve Elledge (BWH, HHMI, HMS) performed a detailed analysis of the antibody response using VirScan, a programmable phage-display immunoprecipitation, and PhIP-Seq, sequencing-based technology. They examined COVID-19 patients over the course of infection and pre-COVID-19 era negative controls to characterize SARS-CoV-2-specific antibodies as well as cross-reacting antibodies. They developed a machine learning model trained on VirScan data that detects SARS-CoV-2 exposure history with high sensitivity and specificity. Christophe Benoist (HMS) analyzed both sides of the T cell balance and discovered antigenic epitopes in SARS-CoV-2 proteins recognized by CD8+ T cells and the T cell receptors, potentially forming the basis of a T-cell vaccine. They uncovered severe perturbations in the numbers and phenotypes of Treg populations, which may become super-suppressive, potentially leading to repression of an effective response.

Future areas of investigation in diagnostics

The COVID-19 pandemic has turned what began as a problem in obtaining enough diagnostic testing into a problem of best allocating and managing an ever-increasing array of technologies and resources for testing. Early in the outbreak the Diagnostics Working Group meeting was exceptionally active, engaging faculty across the MassCPR network, including microbiology lab leads looking to implement diagnostics to researchers from numerous fields creating new technologies. Over the course of the two years, thanks to exceptional progress and an associated decrease in prioritization of new technologies, activity has since slowed down. We have aimed to move to meet the new priorities, lowering the frequency of the meetings to once a month, and incorporating broader discussions on the post-COVID-19 era. In the coming years, we anticipate the Diagnostics Working Group will continue to be critical, but may maintain a slow and regular touch point, perhaps bi-monthly, with a potential for reactivation as new threats emerge. As funding becomes available, there is also value in continuing to invest in new potentially disruptive and impactful technologies, approaches, and platforms, or broader community projects. Here are some areas on which we may aim to continue to focus and prioritize:

  • Novel technologies for point-of-need testing, multi-analyte testing, and detection of variants
  • Bringing wastewater and other pooled/environmental testing to common practice everywhere, and incorporating the ability to detect many potential circulating microbes
  • Novel technologies to assess the full extent of immune responses, looking at past infection, neutralization, and T cell response
  • Decision support for testing laboratories such as our hospital microbiology labs and our large clinical labs (e.g., Broad, Harvard) to be most effective in a post-COVID-19 era
  • Novel technologies for managing, analyzing, visualizing, and disseminating data, with considerations on how testing can best help inform public health policies