(Boston, MA, September 8, 2022) PolyBio Research Foundation is excited to announce a $15M gift from Balvi: a scientific and investment direct gifting fund established by Vitalik Buterin, co-founder of Ethereum. The funding will support the LongCovid Research Consortium (LCRC): a global scientific collaboration to rapidly and comprehensively study core biological drivers of LongCovid.

LongCovid is a condition in which a subset of patients infected with the SARS-CoV-2 virus driving the COVID-19 pandemic develop a wide range of debilitating chronic symptoms. No FDA-approved treatments for the condition currently exist. LongCovid symptoms frequently impact the brain, the heart, the lungs, and the nervous system.

SARS-CoV-2 viral particles (dark circles) inside neuronal cells from a brain organoid culture after infection. Image courtesy of Eric Song PhD, Iwasaki Lab, Yale University

The CDC estimates that 7.5% of the current adult US population is now suffering with LongCovid. In just the last 12 months, the number of patients has doubled to 150 million adults and 13 million children worldwide. In addition to the human cost, this has added a financial cost of $386 billion to the US economy alone.

To combat this growing medical emergency, PolyBio’s LCRC research program will move rapidly and openly – sharing ideas and research results across different institutions, laboratories and clinics. The LCRC collaboration includes scientists and clinicians from Harvard University, Stanford University, the J. Craig Venter Institute, Johns Hopkins University, University of Pennsylvania, the Icahn School of Medicine at Mount Sinai, University of California San Francisco, Cardiff University and the Karolinska Institute.

The LCRC Research Program

New research is revealing key biological drivers of LongCovid, including evidence strongly suggesting that patients with LongCovid do not fully clear the SARS-CoV-2 virus. Instead, the virus may persist in tissue where it continues to provoke the immune system. This could drive a wide range of downstream consequences such as blood clotting, neuroinflammation, and neuropathy. The persistence of SARS-CoV-2 in tissue is called a viral reservoir.

The LCRC has established a comprehensive research program on LongCovid disease mechanisms, with a focus on viral reservoir. The goal is to not only to understand if LongCovid patients still harbor the SARS-CoV-2 virus, but to determine what the virus is doing to drive chronic disease. We will identify the virus’ effects on the immune system, and its impact on a wide range of processes such as blood clotting, nerve signaling, neuroinflammation and cognitive function.

The research program is divided into 5 central areas of inquiry:

  1. Tissue biopsy studies: Designed to identify SARS-CoV-2, its proteins, and related changes to the immune and genetic landscape in intestinal, lung, lymph node, and other tissue samples collected from Long Covid patients.
  1. Autopsy and imaging studies: Designed to reveal the deep-tissue locations of SARS-CoV-2 reservoirs and ongoing antiviral T cell activity throughout the body and brain.
  1. Blood-based biomarker studies: Designed to capture key metrics in blood such as spike protein or immune cell patterns that can infer the presence of SARS-CoV-2 in tissue, making diagnosis easier outside of research labs
  1. Downstream consequences of persistence: Designed to characterize a wide range of downstream effects of SARS-CoV-2 persistence including impacts on clotting, cerebrospinal fluid flow, neuroinflammation, and vagus nerve signaling.
  1. Impact on other pathogens and microbiome: Designed to determine the extent to which SARS-CoV-2’s impact on the immune system facilitates the reactivation of other latent pathogens such as herpesviruses or the parasite Toxoplasma, and/or disrupts the delicate balance of the human microbiome.

The projects push the boundaries of how cutting-edge technologies can be used in the study of chronic disease. They include use of sequencing technologies like spatial transcriptomics that allow for a detailed understanding of immune activity near identified virus; whole-body PET imaging technologies that allow for visualization of SARS-CoV-2 in deep tissue reservoirs; and single nuclei RNA sequencing to characterize the landscape of tissue, blood vessel, and nervous system changes.

The Team

The LCRC is directed by Dr Amy Proal of PolyBio Research Foundation. Dr. Proal is a microbiologist with extensive experience researching infection-associated chronic disease including Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS).

Other team members include:

  • Diane Griffin, MD, PhD, Johns Hopkins
  • Sara Cherry, PhD, University of Pennsylvania
  • John Wherry, PhD, University of Pennslyvania
  • David Putrino, PT, PhD, Icahn School of Medicine at Mount Sinai
  • Akiko Iwasaki, PhD, Yale University
  • Harlan Krumholz, MD, Yale University
  • Linda Geng, MD, PhD, Stanford University
  • Alessio Fasano, MD, Harvard Medical School
  • Peter Novak, MD, PhD, Harvard Medical School
  • David Systrom, MD, Harvard Medical School
  • Mike VanElzakker, PhD, Harvard Medical School
  • Christopher Dupont, PhD, the J. Craig Venter Institute
  • Marcelo Freire, PhD, the J. Craig Venter Institute
  • Gene Tan, PhD, the J. Craig Venter Institute
  • Richard Scheuermann, PhD, the J. Craig Venter Institute
  • Vince Marconi, MD, Emory University
  • Tim Henrich, MD, University of California San Francisco
  • Henry VanBrocklin, PhD, University of California San Francisco
  • Zian Tseng, MD, University of California San Francisco
  • Steven Deeks, MD, University of California San Francisco
  • David Price, PhD, Cardiff University
  • Helen Davies, PhD, Cardiff University
  • Wes Ely, MD, Vanderbilt University
  • Marcus Biggest, PhD, Karolinska Institute
  • Soo Aleman MD, PhD, Karolinska Institute

The Big Picture

We stand at an important moment in time. Viruses beyond SARS-CoV-2 – such as Epstein-Barr Virus and the enteroviruses – are increasingly implicated in a growing number of chronic conditions including ME/CFS, multiple sclerosis, Parkinson’s, and Alzheimer’s disease. Bacterial pathogens such as Borrelia burgdorferi (Lyme disease) are also increasingly connected to the development of chronic disease symptoms. Persistent viral or bacterial activity may even play a role in the human aging process, positioning this work at the center of longevity research. We will iterate the LCRC collaborative infrastructure and cutting-edge technologies toward the study of pathogen activity in these related conditions. This could usher in an era in which antivirals, immunotherapies, and related therapeutics become treatment possibilities for millions of patients across the globe.

About Balvi

Balvi is a scientific investment and direct gifting fund established by Vitalik Buterin, co-founder of Ethereum. Balvi’s mission is to quickly deploy funding to high-value COVID-19 projects that traditional institutional or commercial funding sources tend to overlook for being too early or “outside the box”, or because there’s no financial incentive. Balvi supports many COVID-19 research programs, spanning innovative air filtration, testing, vaccine and medicine development, and Long Covid.

About PolyBio Research Foundation

PolyBio Research Foundation is a 501(c)3 transforming how infection-associated chronic conditions like LongCovid, ME/CFS & Post-Treatment Lyme disease are studied, diagnosed, and treated. PolyBio was founded by scientists with complementary expertise (neuroscience, microbiology & genetics). The core PolyBio team conceptualizes research projects that identify root cause drivers of these conditions, and build collaborative teams to make the projects a reality.