Team famous for HIV breakthroughs demonstrates both persistent COVID virus and widespread immune activation in long COVID; provides clear targets for treatment

 Key points:

  • SARS-CoV-2 double-stranded RNA indicative of viral replication was found in long COVID gut tissue up to 676 days post-infection
  • T cell immune activation was documented across long COVID body sites including the spinal cord and gut wall
  • Clinical trials of drugs to target persistent virus or immune activation in long COVID must be urgently accelerated

Image from the study showing T cell activation levels across body regions.

PolyBio Research Foundation, July 3, 2024 – Research published today in Science Translational Medicine and supported by the PolyBio Research Foundation shows that the SARS-CoV-2 virus can chronically persist in the gut of patients with long COVID for over 2 years. The findings, published by a UC San Francisco team known for previous innovation in HIV research, also documented T cell immune activation across the bodies and brains of people after COVID. This T cell activation was particularly elevated in the spinal cord and gut wall of participants with long COVID.

“Long COVID is not a mystery” says Michael Peluso MD, an infectious disease researcher in the UCSF School of Medicine who co-led the study. “Our findings provide clear evidence of virus persistence and sustained immune activation after COVID-19. We must use this information to test treatments that might get people better.”

Two potential drivers of long COVID identified

Tens of millions of people across the globe are sick with long COVID: debilitating chronic symptoms that can last for years after initial infection. The new study findings provide compelling evidence for two potential causes of long COVID: persistent SARS-CoV-2 infection and aberrant T cell activation.

Image from the study showing SARS-CoV-2 single stranded spike RNA in long COVID gut tissue.

More specifically, the team used an advanced imaging method called whole-body positron emission tomography with a special tracer injected by vein to map activated T cells throughout the bodies of study participants from 27 to 910 days following COVID infection. Post-COVID study participants showed increased T cell activation in sites across the brain and body, including the brain stem, bone marrow, cardiac tissues, and the gut wall compared to people who were never infected with the virus.

Because the gut was a prime site of T cell activation in participants with long COVID, the scientists analyzed gut tissue obtained from a subset of patients. In these samples, they identified the presence of SARS-CoV-2 RNA up to 676 days following initial COVID onset. Viral RNA was detected in samples from all five long COVID patients tested. The chronic viral RNA was discovered in connective tissue of the gut wall, a site rich in immune cells. This suggests the persistent virus may be prompting an immune response, potentially driving long COVID symptoms.

Indeed some gut samples showed strong evidence of active viral presence. “We found SARS-CoV-2 double-stranded RNA in 3 long COVID gut samples” says Tim Henrich MD, a Professor of Medicine in Residence at UCSF who co-led the study. “This double-stranded RNA is usually produced during viral replication or active viral life cycling.”

The next step is to rapidly scale up clinical trials capable of treating persistent virus and immune activation in long COVID. Drs. Peluso, Henrich and team are already running clinical trials of monoclonals and antivirals to target persistent COVID, but many more trials with a wider range of therapeutics are urgently needed.

About PolyBio

PolyBio Research Foundation is a 501(c)3 transforming how complex chronic conditions like LongCOVID are studied, diagnosed, and treated. PolyBio conceptualizes research projects that identify root cause drivers of chronic conditions and builds collaborative teams to make the projects a reality. PolyBio is supported by numerous donors including Kanro – a philanthropic fund to support open source scientific research established by Vitalik Buterin, creator of Ethereum.