Verma et al. (2026)
- Authors: Ajit K. Verma, Li Tan, Nathan Schuster, Stacey L. Moye, Li-Chun Lin, S. Lowery, E. Duraisami, J. E. A. Llorens, Q. Qiu, M. Hefti, D. K. Meyerholz, M. C. Coleman, C. R. Yu, M. W. Albers, S. Perlman
- Institutes: Department of Microbiology and Immunology, University of Iowa, Iowa City, IA, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, Stowers Institute for Medical Research, Kansas City, MO, Department of Neurology, Harvard Medical School, Boston, MA
- Publisher: Proceedings of the National Academy of Sciences (PNAS)
- Link: DOI
Summary
This research highlights a potential breakthrough in preventing Long COVID by shifting focus from solely clearing the virus to actively managing the early inflammatory storm. It provides a biological explanation for why some patients still develop neurological issues despite early antiviral use and suggests that a dual-treatment approach could significantly reduce the global burden of post-viral neurodegeneration.
What was researched?
This study examined how combined antiviral and anti-inflammatory treatments affect long-term neurological damage in mice following a respiratory SARS-CoV-2 infection.
Why was it researched?
Persistent neurological symptoms like “brain fog” and olfactory loss remain poorly understood, and existing antiviral treatments alone often fail to prevent these long-term complications in clinical settings.
How was it researched?
Researchers used a mouse-adapted SARS-CoV-2 model to observe brain changes over 120 days and compared the efficacy of antivirals, nirmatrelvir 💊 and molnupiravir 💊, against a combination of these antivirals plus corticosteroids 💊.
What has been found?
The study found that infection caused significant loss of dopaminergic neurons and sustained microglial activation similar to human neurodegenerative diseases, even without viral persistence in the brain. While antivirals alone were largely ineffective at preventing these changes, the combination therapy nearly restored full neurological and behavioral function even when started three days post-infection.
Discussion
The findings suggests that inflammation, rather than direct viral invasion of the brain, is the primary driver of persistent neurological deficits in this model. A limitation is the reliance on a mouse model, meaning clinical trials are necessary to confirm if these specific drug combinations and timings translate to human patients.
Conclusion & Future Work
Minimizing the early inflammatory response appears critical for preventing the neurological sequelae of COVID-19. Future research should focus on optimizing the therapeutic window for combined immunomodulation to mitigate post-acute sequelae.