Project team members Dr. Michael VanElzakker, Dr. Lael Yonker, and Dr. Amy Proal at a meeting with Dr. Resia Pretorius to maximize microclot identification methods (Team member Dr. Daniel Irimia not pictured).

(Medford MA, December 28 2023) – PolyBio Research Foundation is excited to announce a grant from the Wallace Foundation – a non-profit dedicated to supporting medical research, education, and the environment. Funding will expand the scope and speed of the study “Delineation of coagulation, innate immune, and vascular blood-based biomarkers in Long COVID.” This includes extending the research to include housebound/bedbound Long COVID patients and to include children with Long COVID. The grant is coordinated by PolyBio Research Foundation via the Long Covid Research Consortium, with project sample analysis and technology development taking place at Harvard Medical School/Massachusetts General Hospital.

Expansion of the project is being directed by four scientists with complimentary expertise. Neuroscientist Dr. Michael VanElzakker is overseeing recruitment of housebound/bedbound Long COVID patients for the study. A nurse will visit the homes of these patients to obtain blood samples. Pediatric pulmonologist Dr. Lael Yonker is leading the study’s in-depth analysis of blood collected from Long COVID children. “It is very important to our team that housebound and pediatric Long COVID patients – who are often marginalized from research – are able to participate in our study” says Dr. Yonker.

Dr. Daniel Irimia, an internationally recognized expert in bioengineered microsystems and related tools, is spearheading the development of microfluidic devices that will allow project biomarkers to be more precisely quantified. Dr. Amy Proal is helping to oversee the work and ensuring that findings are communicated to other Long Covid Research Consortium teams. One expanded arm of the study will test the hypothesis that persistence of the SARS-CoV-2 virus in tissue “reservoirs” may contribute to changes in clotting, immune activation, and blood vessel issues in Long COVID. Specifically, the SARS-CoV-2 spike protein (which is being measured by the project team) may “leak” from reservoirs into blood, directly contributing to microclotting and neutrophil abnormalities. Neutrophils are immune cells that create molecular strings called NETs to trap and engulf pathogens or other foreign substances.

A figure created by the project team. In blood from childhood MIS-C patients, addition of SARS-CoV-2 protein led to formation of pathological antigen-antibody immune complexes.

In an important series of experiments, members of the project team added spike protein to blood from recovered COVID-19 patients containing SARS-CoV-2 antibodies. This led to the formation of protein–antibody immune complexes that induced NET formation. “Our study is expanding on these findings to determine if Long COVID blood also contains spike protein-antibody immune complexes, and if the complexes also stimulate NET formation,” says project member Dr. VanElzakker. This includes the use of culture models to probe the relationship between spike-related NET activity and blood vessel injury.

The project team is optimistic that findings will clarify key Long COVID blood biomarkers. Data from the project should also clarify how treatments targeting clotting, immune activation and viral persistence in Long COVID may best be used synergistically.