Project Team

Christopher Dupont, PhD, Professor in Genomic Medicine, Environment & Sustainability, and Synthetic Biology, the J. Craig Venter Institute

Makoto Saito, PhD, Senior Scientist, Marine Chemistry and Geochemistry Department, Woods Hole 

Melanie Walker, MD, Clinical professor of Neurological Surgery at the University of Washington School Medicine  

Resia Pretorius, PhD, Head of Department and a Distinguished Research Professor in the Physiological Sciences Department, Stellenbosch University 

Michael VanElzakker PhD, Instructor, Division of Neurotherapeutics, Harvard Medical School

Amy Proal, PhD, President/Microbiologist, PolyBio Research Foundation

Project Summary:

Project co-lead Dr. Chris Dupont

A collaborative study to investigate the degree to which viral proteins or bacterial products contribute to the composition of Long COVID fibrinaloid microclots. Fibrinaloid microclots are being isolated from the blood of Long COVID study participants. Two complementary analyses are being performed on collected microclots: 1) metagenomic and metatranscriptomic sequencing to identify the genetic material of viral, bacterial or fungal organisms 2) advanced proteomics to identify proteins produced by viruses or bacteria (including the SARS-CoV-2 spike protein).  

Project background:

In 2021, project team member Dr. Resia Pretorius and team discovered and documented the presence of fibrinaloid microclots resistant to breakdown (fibrinolysis) in blood collected from study participants with Long COVID. Since that time other researchers are working to replicate the findings. However a central question remains: What biological factors that contribute to  microclot formation, and what exactly is inside the microclots?

Over the past decade, Dr. Pretorius and team have demonstrated that bacterial byproducts can cause the formation of microclots similar to those identified in Long COVID blood. For example, they showed that addition of lipopolysaccharide and lipoteichoic acid  – two products created by bacteria – into blood lead to amyloid- fibrin formation very similar to that identified in the microclots found in Long COVID. They have also demonstrated that gingapain proteins created by the bacterial species P. gingivalis lead to fibrin deposition and blood clotting. A similar effect was documented with the SARS-CoV-2 S1 protein. The team showed that addition of the SARS-CoV-2 S1 protein to healthy plasma resulted in structural changes to fibrinogen similar to that identified in Long COVID microclots. It follows that bacterial byproducts and viral proteins may contribute to Long COVID microclot formation, and that such products (and even the pathogens themselves) might be trapped inside the microclots. For more context on the topic, listen to this interview where Dr. Resia Pretorius describes mechanisms by which viral and bacterial pathogens can drive clotting processes in blood.

The current project will use state-of-the-art sequencing technologies to determine if Long COVID microclots contain bacterial, viral or fungal pathogens and/or the proteins they create. It will run in parallel with this study where Dr. Pretorius is using advanced fluorescence microscopy to identify potential biofilm in Long COVD and ME/CFS microclots. Overall, the analysis of Long COVID microclots for bacterial, viral, and biofilm components should help determine if antimicrobial or antiviral drugs could be combined with antibrinolytic or anticoagulant therapeutics in Long COVID clinical trials aimed at microclot disruption.

Image Credit: Kateryna Kon / Shutterstock.