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 Measurements—Steve 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.
