Dr. Nadia Roan is a senior co-author of the study.

(Medford MA, January 11, 2023) – PolyBio is excited to announce that a study supported by its LongCovid Research Consortium was published today in the journal Nature Immunology. The paper is titled “Long COVID manifests with T cell dysregulation, inflammation and an uncoordinated adaptive immune response to SARS-CoV-2 systemic inflammation and immune dysregulation.” The work was led by a University of San Francisco California team with Drs. Nadia Roan and Timothy Henrich as co-senior authors and Drs. Kailin Lin and Michael Peluso as co-first authors.

To perform the research, the team used advanced technologies to deeply characterize the activity of T and B cells in the blood of Long COVID patients. They performed the same analyses in a group of individuals who had fully recovered from COVID-19 to serve as a source of comparison. Long COVID patients showed differences in the distributions of their T cells, implying ongoing immune responses. The team also documented a mis-coordination between the SARS-CoV-2-specific T and B cell responses of Long COVID patients.

What underlies the T and B cell dysfunction identified in the study? Data point to the possibility that persistent SARS-CoV-2 reservoirs in patient tissue are a contributing factor. Indeed, in a related study, members of the project team identified SARS-CoV-2 reservoirs in the gut wall of Long COVID patients for up to 2.5 years after initial infection. In the new study by Dr. Roan and team, Long COVID study participants displayed increased frequencies of CD4+ T cells poised to migrate to inflamed tissues. This migration could represent an attempt by the immune cells to recognize and target SARS-CoV-2 reservoirs in such sites. Long COVID patients also showed exhausted SARS-CoV-2-specific CD8+ T cells and higher levels of SARS-CoV-2 antibodies. The findings are consistent with potential ongoing stimulation by persistent viral reservoirs in patient tissue.

“The findings position Long COVID as a tissue-based disease with ongoing SARS-CoV-2 stimulation,” says study author Dr. Michael Peluso. “They support targeting SARS-CoV-2 viral reservoirs in clinical trials.” To pursue that exact goal, several Long COVID clinical trials designed to target SARS-CoV-2 reservoirs are already underway at Peluso and Roan’s UCSF site. These include a trial of an Aerium monoclonal antibody and Shinogi’s antiviral ensitrelvir. The trials are part of the Long-term Impact of Infection with Novel Coronavirus (LIINC) cohort study, which is supported by PolyBio. LIINC is serving as a clinical sample and data core for the PolyBio LongCovid Research Consortium (LCRC) and other Long COVID research teams committed to open science. PolyBio is also supporting an infrastructure for biopsies of Long COVID gut, lymph node, bone marrow and other tissues to be collected and analyzed at the site – a program that will be further announced in the coming month.