Yale School of Medicine secures $575,000 grant for Long COVID research

Yale School of Medicine and its Center for Infection & Immunity (CII) are receiving a $575,000 grant from PolyBio Research Foundation to fund Long COVID research. The grant—issued via PolyBio's LongCovid Research Consortium (LCRC)— will support a collaboration to define mechanisms by which the SARS-CoV-2 virus can persist for long periods of time in tissue and blood.

There is growing evidence that SARS-CoV-2 may not fully clear from Long COVID patients after initial infection. Instead, reservoirs of the virus can persist in patient tissue for months or even years, with recent research finding the SARS-CoV-2 virus in gut tissue more than 600 days after infection. Persistent viral RNA or proteins have also been identified in blood samples collected from Long COVID patients, but the exact nature of the viral RNA that gives rise to this prolonged infection remains unclear.

Hoping to find answers, Yale School of Medicine scientists will analyze Long COVID tissue samples to uncover mechanisms by which the virus or its proteins persist. The team will also use mouse models to test therapeutics including antivirals, antisense oligonucleotides, and innate immune stimuli such as stem-loop RNA for their potential to eliminate persistent virus, which could ultimately inform Long COVID clinical trials. The research team includes:

• Akiko Iwasaki, PhD: Sterling Professor of Immunobiology and professor of dermatology; of molecular, cellular & developmental biology; and of epidemiology (microbial diseases); and Howard Hughes Medical Institute Investigator.
• Richard A. Flavell, PhD, FRS: Sterling Professor of Immunobiology and Howard Hughes Medical Institute Investigator.
• Anna Pyle, PhD: Sterling Professor of Molecular, Cellular & Developmental Biology and professor of chemistry
• Craig Wilen, MD, PhD: associate professor of laboratory medicine and of immunobiology, and medical director of Yale School of Medicine's Immune Monitoring Core Facility.

This new grant builds on an existing collaboration between PolyBio and Yale through CII, which Iwasaki heads. With support from PolyBio's LCRC, Iwasaki and CII have been working to characterize the activity of human endogenous retroviruses in patients with Long COVID. "Our hope is that by studying viral RNA persistence in Long COVID, we can better understand the pathogenesis and treatment of other related debilitating chronic conditions," says Iwasaki. Persistent RNA virus infection, including with enteroviruses, has been implicated in chronic conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which also is a subject of ongoing research by Iwasaki as well as other scientists.

Pyle leads a research group that specializes in the structure and function of large RNA molecules, RNA remodeling enzymes, and cellular RNA sensors.

Dr. Pyle boasts decades of experience in the study of RNA molecules. We are thrilled that her laboratory has pivoted its expertise to SARS-CoV-2 and Long COVID."

Amy Proal, PhD, President of PolyBio Research Foundation