News from LCRI
Introducing a Global Initiative to Address Long Covid
Today we are excited to announce the launch of the Long Covid Research Initiative (LCRI). LCRI is a collaboration among scientists, clinicians, and patients to rapidly and comprehensively study and treat Long Covid, a debilitating condition currently afflicting over 150 million people — and growing. LCRI launches with more than $15 million in funding commitments.
Long Covid is no longer a mystery. New research is revealing key drivers of the condition, including evidence strongly suggesting that patients with Long Covid 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 Long Covid Research Initiative is establishing a virtual research institute with a two-pronged approach, consisting of research and therapeutics, with a shared focus on the topic of viral reservoir:
- The LCRI Research Program, in which scientists from top global institutions unite their collective expertise to study the disease mechanisms of Long Covid
- The LCRI Clinical Trials Program, in which Research Program findings are translated into therapeutic targets to be used in clinical trials
These programs include scientists and clinicians from Harvard, Stanford, UCSF, the J. Craig Venter Institute, Johns Hopkins, University of Pennsylvania, Mount Sinai, Cardiff, and Yale.
Our growing coalition of philanthropic backers includes Balvi, a scientific investment fund led by Vitalik Buterin that has donated $15 million, and the Chan Soon-Shiong Family Foundation, led by Dr Patrick Soon-Shiong.
Dr Patrick Soon-Shiong commented “We are extremely concerned about the consequences of Long Covid. This virus has a remarkable capacity to evade the immune system and the consequences of latent virus particles in subjects infected with this virus need urgent understanding, and more importantly pro-active therapies to overcome and prevent the potentially life threatening sequelae. I am pleased to support and participate with LCRI. This initiative is one of the most important in our times.”
A Global Emergency
Long Covid is a condition in which a subset of patients infected with SARS-CoV-2 develop a wide range of debilitating chronic symptoms that do not resolve even years later. No FDA-approved treatments exist. These symptoms frequently impact the brain, the heart, the lungs, and the nervous system. A growing body of evidence now positions SARS-CoV-2 viral reservoir at the center of the Long Covid disease process. Spike protein has been found in Long Covid blood and SARS-CoV-2 has been shown capable of persisting for months after initial illness, in tissues including the brain, the lungs, and the lining of the gut.
The CDC estimates that 7.5% of the current adult US population is now suffering with Long Covid. 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 brings a financial cost of $386 billion just to the US economy alone.
Despite the enormity of the problem, global research efforts are underfunded and moving slowly. There is no research program specifically focused on viral reservoir in Long Covid – the central question in the disease – and no clinical trials program focused on therapeutics to clear the virus. LCRI is jump-starting both research and clinical trials by building a global coalition of diverse stakeholders: scientists, philanthropists, pharma, and the patient community, who will all contribute their support and shared expertise to tackle Long Covid. By engaging private funders and working as a lean organization, we are moving rapidly and openly, sharing ideas and research results across different institutions, laboratories, and clinics.
The Long Covid Research Initiative
The Long Covid Research Initiative has developed a comprehensive research program with the goal not only to understand if Long Covid patients still harbor the SARS-CoV-2 virus, but to determine what exactly the virus is doing to drive chronic disease. We will identify the virus’s effects on the immune system, and its impact on a wide range of processes such as blood clotting, nerve signaling, and cognitive function.
Our Research Program includes:
- 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.
- 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.
- 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.
- 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.
- 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.
These projects push the boundaries of how cutting-edge technologies can be used in the study of chronic disease. These include 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.
Our Clinical Trials Program will build on the findings of the Research Program to identify a pipeline of therapeutics that LCRI will position into clinical trials. Candidate therapeutics include SARS-CoV-2 antivirals, immunomodulators, targeted anticoagulants, and microbiome-based therapeutics. We will draw on the patient community to communicate the urgent need for rapid clinical trials to regulatory agencies and pharmaceutical companies.
What Makes our Approach Unique?
- A research team of leading experts working collaboratively and across institutions to execute a coordinated research program.
- Treating patients is our priority. Our goal is to find effective treatments for those suffering, and everything we do works towards this aim.
- A focus on the root cause. We will identify and treat the drivers of the disease, not just the symptoms, using the latest bleeding-edge technologies and artificial intelligence computation.
- Less bureaucracy. Researchers often spend half of their time on grant applications. We will break this model of medical research by engaging private funders and working as a lean organization to move fast.
- An operating model with the urgency and pragmatism of a startup. LCRI brings cross-institution collaboration, an innovative trials program, and high levels of patient engagement.
The initiative is led by a group who have personal connections to the condition. Our Chief Scientific Officer, Dr Amy Proal of the PolyBio Research Foundation, is a microbiologist with extensive experience researching infection-associated chronic disease, including Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS). Leading operations and development are dedicated patients and allies who are devoted to accelerating the race for treatments.
Our Research and Clinical Trials Program will be executed by our growing scientific team of leading experts in Long Covid, including:
- Amy Proal, PhD, PolyBio
- Steven Deeks, MD, UCSF
- Diane Griffin, MD, PhD, Johns Hopkins
- John Wherry, PhD, University of Pennsylvania
- David Putrino, PhD, Mount Sinai
- Patrick Soon-Shiong, MD
- Chris Dupont, PhD, JCVI
- Linda Geng, MD, PhD, Stanford
- Alessio Fasano, MD, Harvard
- Richard Scheuermann, PhD, JCVI
- Harlan Krumholz, MD, Yale
- Gene Tan, PhD, JCVI
- Vince Marconi, MD, Emory
- Akiko Iwasaki, PhD, Yale
- Mike VanElzakker, PhD, Harvard Medical School
- Tim Henrich, MD, UCSF
- David Price, PhD, Cardiff
- Helen Davies, MD, Cardiff
- Peter Novak, MD, PhD, Harvard Medical school
- Sara Cherry, PhD, University of Pennsylvania
- Henry VanBrocklin, PhD, UCSF
- Wes Ely, MD, Vanderbilt
- Marcelo Freire, PhD, JCVI
- Zian Tseng, MD, UCSF
- David Systrom, MD, Harvard Medical School
- Marco Schito, PhD, Critical Path Institute
The LCRI is a PolyBio Research Foundation Initiative. PolyBio is a registered 501(c)(3) nonprofit. We are raising funding for our ambitious research agenda, and would like to speak to philanthropists with an interest in the space.
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 LCRI 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.
– Amy Proal, Nick Harrold, Henry Scott-Green, Helga Gutmane, and the Long Covid Research Initiative team