Investigators from Mass General Brigham have found that a method originally designed for cancer detection can also identify and monitor even tiny amounts of SARS-CoV-2 intact viral particles in blood and other fluids from patients with acute COVID-19 infections, creating the potential for guiding future treatment of patients. The research is published in Science Advances.
"During the early days of the pandemic, we wanted to see if our approach for isolating small cancer vesicles could be adapted to isolate SARS-CoV-2 virus from biofluids like blood, stool, and saliva," said co–senior author Shannon L. Stott, PhD, a member of the faculty at the Center for Engineering in Medicine & Surgery at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. "We quickly built an interdisciplinary team of experts to adapt our technology to push the boundaries of intact virus detection."
Stott and colleagues in her lab, and the lab of Genevieve M. Boland, MD, PhD, surgical director of the Termeer Center for Targeted Therapies at MGH, found that their technique could detect as few as three viral particles in 1 milliliter of blood. When tested in more than 150 samples (103 plasma, 36 saliva, and 29 stool samples) from patients with COVID-19, the method accurately measured virus levels across time, with intact viral particles detected as far out as 50 days after an initial infection.
"With clinical needs changing, the ability to serially monitor viral load in this manner has great potential for guiding the treatment of patients with long Covid," said Stott. "This versatile technology could also have widespread applications in viral monitoring for current and future infectious diseases."
Authorship: In addition to Stott and Boland, Mass General Brigham authors include Daniel C. Rabe, Adarsh Choudhury, Dasol Lee, Evelyn G. Luciani, Uyen K. Ho, Sara Veiga, William A. Michaud, Diane Capen, Elizabeth A. Flynn, Nicola Hartmann, Alona Muzikansky, Marcia B. Goldberg, Douglas S. Kwon, Xu Yu, Aaron F. Carlin, Jochen K. Lennerz,Peggy S. Lai and Sayed Ali Rabi. Additional authors include Alex E. Clark, Jeffrey E. Glasgow, Aaron F. Garretson, Yves Theriault, James A. Wells, and Anh N. Hoang,
Disclosures: Mass General Brigham has filed a US Patent application (US 2023,334,830) on behalf of Stott, Boland, Rabi and Rabe for the isolation of SARS-CoV-2 using microfluidics. This application is still pending as of time of publication. Stott serves as an advisory board member for Streck, LLC, unrelated to this work.
Funding: This work was supported by National Center for Advancing Translational Sciences grant U18-TR003793, National Center for Advancing Translational Sciences grant UL1-TR002541 (Harvard Catalyst, Mass General Brigham Biobank), NIH RADx-rad DCC grant 1U24LM013755-01 "RADx-rad Discoveries & Data: Consortium Coordination Center Program Organization", National Institute of Allergy and Infectious Diseases grant P30-AI036214 (San Diego Center for AIDS Research, UCSD), National Cancer Institute grant R01-CA226871, National Cancer Institute (grant F32-CA236417), d'Arbeloff MGH Research Scholar Award, and American Cancer Society (grant 132030-RSG-18-108-01-TBG). Access to patient samples was facilitated by the MassCPR through the Massachusetts General Brigham Biobank (UL1-TR002541). Samples were collected at Massachusetts General Hospital, Boston through the Global TravEpiNet (GTEN) Program as part of the Centers for Disease Control and Prevention (CDC)–supported COVID response (U01CK000490 and U01CK000633). Transmission electron microscopy (TEM) imaging was performed in the Microscopy Core facility of the Massachusetts General Hospital (MGH) Program in Membrane Biology, which receives support from the Boston Area Diabetes and Endocrinology Research Center (DK135043) and the Center for the Study of Inflammatory Bowel Disease (DK043351).
Paper cited: Rabe, D C et al. "Ultrasensitive detection of intact SARS-CoV-2 particles in complex biofluids using microfluidic affinity capture" Science Advances DOI: 10.1126/sciadv.adh1167
