Lu et al. (2026)
- Authors: Peiwen Lu, Saef Izzy, Patrick Da Silva, Harm Tjebbe Imkamp, Jonathan R. Christenson, Taha Yahya, Maryam Hazim Al Mansi, Amir Alawi, Thais G. Moreira, Michelle Monje, Howard L. Weiner, Akiko Iwasaki
- Institutes: Department of Immunobiology, Yale University, New Haven, CT, USA, Immunology of Brain Injury Program, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA, Ann Romney Center for Neurologic Diseases, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA, USA, Howard Hughes Medical Institute, Yale University, New Haven, CT, USA
- Publisher: bioRxiv
- Link: DOI
Summary
This research identifies a potential breakthrough for treating ‘brain fog’ and cognitive impairment in Long COVID patients. By using a non-invasive nasal spray to recruit regulatory immune cells to the brain, the study demonstrated that it is possible to reverse chronic neuroinflammation and restore the birth of new neurons. These findings offer a clear biological pathway for future human clinical trials using existing anti-CD3 therapies.
What was researched?
The study investigated the effectiveness of intranasal anti-CD3 monoclonal antibody 💊 treatment in reducing brain inflammation and restoring cognitive function in a mouse model of Long COVID.
Why was it researched?
Cognitive impairment is a major symptom of Long COVID, likely driven by persistent neuroinflammation and abnormal immune responses in the brain. Researchers sought a non-invasive way to ‘reset’ this harmful immune activity and promote brain repair.
How was it researched?
Scientists used a mouse model of mild respiratory SARS-CoV-2 infection and administered nasal anti-CD3 antibodies during either the early or chronic phase of the illness. They analyzed changes in regulatory T cells (Tregs), glial cell activity, hippocampal neurogenesis, and cognitive performance. Additionally, they compared these findings with blood samples from Long COVID patients with neurological symptoms.
What has been found?
The treatment increased the presence of protective regulatory T cells in the brain and shifted harmful microglia toward a restorative state. This shift successfully reduced brain inflammation, restored the production of new neurons in the hippocampus, and significantly improved the mice’s short-term memory. The researchers also confirmed that humans with neurological Long COVID have lower levels of the same protective immune cells found to be effective in mice.
Discussion
The results suggest that nasal anti-CD3 therapy acts as a ‘peacekeeper’ for the brain’s immune system, moving it from a destructive to a protective state. A key advantage is the treatment’s ability to be effective even when started weeks after the initial infection. This mechanism targets the underlying immune imbalance rather than just suppressing the entire immune system.
Conclusion & Future Work
Intranasal anti-CD3 antibody treatment is a promising, non-invasive strategy to treat cognitive deficits in Long COVID. Future research should focus on clinical trials to confirm these neuroprotective effects in human patients.