November 22nd, 2022
Media contact: firstname.lastname@example.org
The Patient-Led Research Collaborative’s Patient-Led Research Fund announced $4.8 million in biomedical research awards today, funding 9 research projects in Long COVID, ME/CFS, dysautonomia, and associated conditions.
This fund and awarded projects are distinctly meaningful for four major reasons:
First: a panel of 15 patient researchers with infection-onset illness, including Long COVID, ME/CFS, and dysautonomia, decided how the $4.8 million in research funding should be allocated and prioritized, including calling for specific areas of research. This is a change from the typical power dynamic of biomedical research, especially in chronic illness, where large organizations decide where funding should go, and patients have no input into what is studied. The panel consisted of patient researchers, most with science or medical backgrounds, with a broad range of expertise in addition to their lived experience with chronic illness.
Second: to date, Long COVID research has fallen short of its promise to improve patient health and largely disregarded insight from decades of research into infection-associated chronic illnesses. The awarded projects were chosen with an emphasis on impact and on research directions that are well informed by the existing body of research.
Third: the awarded projects themselves showcase some of the diverse topics that Long COVID and ME/CFS patients would like to see pursued. The projects span many investigative paths, including microclots, spinal-structural abnormalities, immunologic dysfunction, microbiome changes, mechanisms of sleep dysfunction, computational drug repurposing, and a clinical trial of a promising and widely available drug.
Fourth: Each project that doesn’t already have patient representatives on the project will receive 1-2 paid patient representatives from the Patient-Led Research Collaborative to inform study design. This will ensure that the lived experience of patients are incorporated in all steps of the research process.
The awarded projects are:
1. Microbial metabolites as disease-modifying factors in Long-COVID – Dr. David Esteban – Vassar College
Under healthy conditions, gut microbes produce an abundance of small molecules from tryptophan, which enter cells and activate the aryl hydrocarbon receptor (AhR). AhR induces expression of genes that limit inflammation and maintain the gut barrier. These ligands can also cross into the bloodstream and activate AhR distally to control inflammation and other processes. Under certain disease conditions, an altered microbial community is less able to produce AhR ligands from tryptophan. AhR therefore does not maintain the gut barrier and does not help control inflammation, while pro-inflammatory bacterial components are allowed to cross into the bloodstream. The purpose of this study is to investigate the production of, and response to, microbially derived AhR ligands in the microbiomes of people with Long COVID. Due to the established connection between the gut microbiome, brain, and immune system, such a foundation will be critical in understanding the basis of neuroinflammation, immune dysfunction, and gastrointestinal homeostasis, in post-infectious chronic diseases.
2. Unraveling the pathophysiology of post-exertional malaise in Long COVID and ME/CFS – Prof. Dr. Michele van Vugt – Amsterdam University Medical Centers; Dr. Rob Wüst – Vrije Universiteit Amsterdam; and Brent Appelman – Amsterdam University Medical Centers
This project is a deep dive into the pathophysiology of post-exertional malaise (PEM), which is a major symptom distinct from fatigue that appears in Long COVID and ME/CFS. The study will perform multi-omics on muscle biopsies and blood from patients during periods of post-exertional malaise to try to provide an in-depth understanding of one of the most debilitating pathophysiological occurrences in Long COVID and ME/CFS. This project will provide an in-depth biomedical understanding of the pathophysiology of post-exertional malaise, including newly discovered blood/muscle biomarkers, which benefit future clinical trials and biomedical research into treatment options for patients suffering from Long COVID and ME/CFS.
3. Characterizing non-restorative sleep in post-viral disease to advance intervention innovations – Drs. Janet Mullington, Robert Thomas, Larissa Engert, Samuel Frank, Monika Haack, Jason Maley, Recep Ozdemir, Haoqi Sun, Alicia Stokes, John Torous, and Brandon M. Westover – Harvard Medical School and the Open Medicine Foundation-Supported Ronald G. Tompkins Harvard ME/CFS Collaboration
The goal of this project is to characterize several features of sleep regulation in ME/CFS and Long COVID compared with age and sex matched healthy sleep controls. The study will look at four primary components: 1) sleep-circadian dysfunction; 2) how immune function, specifically specialized pro-resolving mediators (SPMs), are changed in relation to sleep dysfunction; 3) brain electrical activity; and 4) mechanisms of state-boundary control and neurodegenerative diseases.
4. A pre- and postoperative study of patients with ME/CFS operated for foraminal stenosis – Prof. Per Sjogren, Dr. Bo Bertilson, Dr. Helena Huhmar, Dr. Lauri Soinne, Dr. Olli Polo, Dr. Jonas Bergquist, and Dr. Bjorn Bragée – Bragee ME Clinic, Stockholm
In a 2020 study based on MRI findings, Dr Bragée et al. showed that many patients with ME displayed narrowing of the spinal and/or foraminal canals in the craniocervical region. Unexpectedly, over 50% of the 229 studied patients also had hypermobility syndromes, a known risk factor for ligament injuries in the spine. Of the 115 patients with prominent neck pain, 80% had craniocervical obstructions. This study will examine whether surgery that relieves pressure on nerves (cervical radiculopathy) and corrects cervical obstructions can turn around the often-poor prognosis of patients with ME and have an effect on not only the radiculopathy but also other aspects of their illness.
5. Altered T cell responses in Long COVID (PASC) and ME/CFS – Dr. Liisa Selin and Dr. Anna Gil – University of Massachusetts Chan Medical School
Based on earlier research, this project hypothesizes that the common theme in Long COVID and ME/CFS is an aberrant response to an immunological trigger like infection that results in a permanently dysregulated immune system as a result of CD8 T cell exhaustion. This project will do a deep dive into the T cells of Long COVID and ME/CFS patients, looking for exhausted and activated subsets, and will additionally look at reactivated herpesviruses in relation to these findings.
6. Systems Biology Approaches to Uncovering Disease Mechanism and Drug Repurposing for Long COVID – Dr. Wenzhong Xiao – Massachusetts General Hospital and the Open Medicine Foundation-Supported Computational Research Center for Complex Diseases
This project will use deep machine learning and network medicine to parse through clinical information, research findings, and multi-omics data of Long COVID, ME/CFS, and related diseases with the collective knowledgebase of drugs, diseases, genes, and symptoms to discover disease gene modules, and identify potential drugs as candidates for repurposing for these illnesses.
7. Understanding the relationship between fibrin amyloid microclots and Long COVID – Dr. Caroline Dalton, Dr. Andrew Higham, Prof. Doug Kell, Prof. Resia Pretorius, Prof. David Price – Consortium of UK and South African universities
This project will develop a microclot test for Long COVID and associated conditions, including ME/CFS, and assess its ability as a diagnostic test, using multiple techniques. The team will also analyze microclot burden in patients over time, looking at the impact of infection and vaccination on microclot levels, and microclot dynamics over time.
8. Multi-omic approAches to Solve post-Acute COVID-19/SARS-CoV-2 Syndrome – MOSAICS – Prof. Alain Moreau – Université de Montréal and the Open Medicine Foundation-Supported ME/CFS Collaborative Center at CHU Sainte-Justine/Université de Montréal; Prof. Jonas Bergquist – Uppsala University, Sweden and the Open Medicine Foundation-Supported ME/CFS Collaboration at Uppsala University; Dr. Christopher Armstrong – University of Melbourne and the Open Medicine Foundation-Supported Melbourne ME/CFS Collaboration; Dr. Wenzhong Xiao – Harvard University and the Open Medicine Foundation-Supported Computational Research Center for Complex Diseases; Dr. Dawei Li – Florida Atlantic University; and Dr. Tse Man Sze – Université de Montréal
This project hypothesizes that Long COVID, and ME/CFS after COVID, is the result of a broad molecular-level reorganization occurring primarily at the epigenetic level. The study aims to understand the molecular mechanisms underlying the development of long-term sequelae following a SARS-CoV-2 infection, by looking at 4 specific aims: 1) Global expression profiling of circulating microRNAs, 2) Global DNA methylation profiling, 3) Global proteomic plasma profiling, and 4) Global metabolomic plasma and urine profiling.
9. Clinical trial on Low-dose naltrexone for the treatment of Long-COVID and ME/CFS – Dr. Jarred Younger – University of Alabama at Birmingham’s Neuro-inflammation, Pain and Fatigue Laboratory
This project is a clinical trial to determine the efficacy and safety of low-dose naltrexone (LDN) in treating Long COVID and ME/CFS. The hypothesis is that these patients have microglial cells that are continuously producing cytokines and other inflammatory agents. There is evidence that LDN can return microglia to their resting state and reverse neuroinflammation. The study is designed to answer 7 specific questions: 1) Is LDN an effective treatment for Long-COVID? 2) Is LDN an effective treatment for ME/CFS? 3) Do Long-COVID and ME/CFS participants respond similarly or differently to LDN? 4) What is the optimal dosage of LDN? 5) How long does it take for LDN to help? 6) What are the side-effects of LDN? 7) Which symptoms are most impacted by LDN?
PLRC is grateful to Balvi for funding the Patient-Led Research Fund and to Open Medicine Foundation, PolyBio, and Dysautonomia International for offering to facilitate the transfer of cryptocurrency to grantees.
For more information on the Fund, please see https://patientresearchcovid19.com/projects/patient-led-research-fund/. The initial announcement of funding can be found here (note that the Fund was increased from $2m to $4.8m in summer 2022).
For questions, please contact email@example.com.
About Patient-Led Research Collaborative: Patient-Led Research Collaborative (PLRC) is a multi-disciplinary group of people with lived experience of Long COVID, formed together in April 2020 through the Body Politic COVID-19 Support Group, and were the first to conduct research on Long COVID. PLRC’s work thus far has resulted in the identification of key symptoms, timeline, comorbidities, and possible treatment options for Long COVID, as well as a $4.8 million fund for biomedical research with awards decided by patients, a publication of patient-generated hypotheses, and research into the impact of reinfections, identifying Long Covid phenotypes, Long Covid impact in LMIC countries, and others. They have presented their work to the World Health Organization, United States House of Representatives, National Institutes of Health, and Centers for Disease Control and Prevention, and have influenced Long COVID clinical guidelines and legislation. For more on PLRC, visit patientledresearch.com.