PolyBio Research Foundation Receives $1.3 Million Gift to Advance the study of SARS-CoV-2 Viral Persistence in patients with LongCovid 

Gift will support an innovative study to determine if LongCovid patients still harbor the SARS-CoV-2 virus in intestinal tissue

Study co-lead investigator Dr. Saurabh Mehandru

(Medford MA, July 18, 2022) – PolyBio Research Foundation has been gifted $1.3 million to spearhead a collaborative LongCovid research study with scientists from the Icahn School of Medicine at Mount Sinai in New York City and the J. Craig Venter Institute in San Diego. The funding from Balvi, a scientific investment and direct gifting fund for COVID projects, will allow the collaborative team to use innovative technologies to determine if SARS-CoV-2 or its proteins can persist for long periods of time in the gastrointestinal (GI) tract of patients with LongCovid. The study sets the stage for the possible use of antiviral treatments in LongCovid.

“Our collaborative study will test the straightforward possibility that at least some patients with LongCovid do not fully clear the SARS-CoV-2 virus after acute infection” says Amy Proal PhD, a microbiologist and President of PolyBio Research Foundation who helped conceptualize and organize the study. “Instead, the virus may persist in a ‘reservoir’ in patient tissue where it can no longer be identified via standard nasal swab or blood testing.”

Intestinal tissue is dense with the ACE2 receptors the SARS-CoV-2 virus uses for entry into cells, making it a very likely site of SARS-CoV-2 reservoir in LongCovid patients. Indeed, study principal co-investigator Saurabh Mehandru MD, Associate Professor of Gastroenterology at the Icahn School of Medicine at Mount Sinai, is a member of one of the first research teams in the world to demonstrate SARS-CoV-2 persistence in intestinal tissue. More specifically, the team identified SARS-CoV-2 antigens & immunoreactivity in intestinal tissue samples obtained from 7 asymptomatic individuals at ~4 months after the onset of COVID-19.

Immunofluorescence images showing SARS-CoV-2 N protein in intestinal tissue biopsies taken 92 days after onset of COVID-19 symptoms. Arrows indicate enterocytes with detectable SARS-CoV-2 antigen. Taken from Gaebler, Mehandru et al, PMID: 33461210

The current study is an extension of those important early findings. The research team will enroll 40 study volunteers of three types: LongCovid participants with gastrointestinal (GI) symptoms 6-12 months after COVID-19; participants with LongCovid who do not have GI symptoms 6-12 months after COVID-19, and participants who had COVID-19 and fully recovered with no persistent symptoms. All participants will complete a colonoscopy and endoscopy to collect intestinal tissue. Stool samples and blood will also be collected.

Study investigators will then use three forms of advanced microscopy to identify SARS-CoV-2 and its proteins in intestinal tissue samples. They will a use a range of technologies to document immune system activity in response to identified virus. The study will also employ a groundbreaking molecular profiling method called spatial transcriptomics to measure gene activity in each tissue sample and map exactly where viral activity is occurring. This will mark the first time spatial transcriptomics is used in LongCovid research. The team will further examine the relationship between SARS-CoV-2 persistence in tissue and activity of the gut microbiome & related immune perturbations in blood. They will even characterize divergence of the virus from nasopharyngeal strains to determine if viral persistence in intestinal tissue can lead to the emergence of viral variants.

“The study is exciting because we will utilize cutting-edge methods to not only identify SARS-CoV-2 in LongCovid tissue samples, but to also understand how the virus may be provoking the immune response or the activity of human genes to potentially drive debilitating symptoms” says co-principal investigator David Putrino, PhD, Director of Rehabilitation Innovation for Mount Sinai Health System. “The work will help us to better understand the potential utility of different antiviral therapies in treating LongCovid.”

The study is the first in a new partnership PolyBio Research Foundation is launching to rapidly execute a comprehensive research program on viral persistence in LongCovid. The partnership, called the “LongCovid Research Consortium” (LCRC) is a collaboration between scientists with leading global expertise on RNA virus persistence and the technologies needed to best study the topic. Other LCRC projects include dynamic studies of other LongCovid tissue types (lung, skeletal muscle, lymph node etc), correlation of viral reservoir with microbiome activity, development of imaging techniques to identify SARS-CoV-2 reservoir, and infectious contributions to coagulation-based sequelae.

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.

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 LongCovid.