Project Team
Shannon Stott, PhD, Associate Professor, Massachusetts General Hospital, Harvard Medical School.
Michael Peluso, MD, Assistant Professor of Medicine, University of California San Francisco
Project Summary:
To analyze Long COVID blood samples with a novel microfluidic technology that isolates rare, intact SARS-CoV-2 viral particles from complex biofluids. If viral particles are identified, the microfluidic technology could be used in clinical trials or related studies to identify SARS-CoV-2 reservoirs in Long COVID blood.
Project Background:
SARS-CoV-2 persistence in tissue or host cells has been documented in a subset of patients with Long COVID. However the degree to which persistent RNA, protein, or particles can be identified in accessible fluids such as blood remains an open questions. The project team recently developed an ultrasensitive microfluidic platform capable of identifying SARS-CoV-2 viral particles in the blood. The approach uses an engineered ACE2 to capture intact virus from plasma and other complex biofluids. The device leverages a staggered herringbone pattern, nanoparticle surface coating, and processing conditions to achieve detection of as few as 3 viral copies/mL.

Image from the project team showing captured of inactivated SARS-CoV-2 (Delta variant) captured on the ONI EV-profiler chip using ACE2ENG, stained with anti-spike antibody.
In a recent paper published in the journal Science Advances, the project team demonstrated the ability to isolate as few as three viral particles in 1mL of COVID-19. plasma. The team was also able to track viral load over time for COVID-19 patients after acute infection. In the current project, the team is pivoting use of their microfluidic platform to identify potential viral particles in blood collected from patients with Long COVID. Blood samples undergoing this analysis have been sent from the UCSF LIINC Study, which serves as a clinical core for scientists working as part of PolyBio’s Long COVID Research Consortium.
As part of the study, quality control samples will be run using contrived ‘viral samples’ that are made from internal plasma samples, spiked with known concentrations of inactivated viral particles. For Long COVID samples processed, the team will also evaluate if there is any correlation between clinical symptoms and virus levels, while also evaluating against SARS-CoV-2 antigen levels obtained using other technologies (when available).