bioRxiv : the preprint server for biologyApr 17, 2026

Nasal Anti-CD3 Antibody Treatment May Reduce Brain Inflammation and Improve Memory and New Brain Cell Growth After COVID in Mice

Updated Jun 27, 2026

Abstract

Essence

Intranasal anti-CD3 antibody reduced neuroinflammation and improved neurogenesis and short-term memory in a mouse model of post-COVID cognitive impairment.

Evidence

This was a preclinical respiratory-restricted mild SARS-CoV-2 mouse study, with supporting observation that Long COVID patients with neurological symptoms had lower circulating Treg populations.

Caveat

The therapeutic evidence comes from mice, while the human data were limited to circulating Treg differences rather than anti-CD3 treatment outcomes.

Simplified

Cognitive impairment is a disabling feature of Long COVID, with data supporting neuroinflammation and maladaptive glial responses as primary drivers. Nasal administration of an anti-CD3 monoclonal antibody (aCD3 mAb) has shown therapeutic benefits in autoimmune and CNS disease models. Using a respiratory-restricted mild SARS-CoV-2 mouse model of Long COVID, we show that nasal anti-CD3 mAb, administered shortly after infection or during chronic neuroinflammation, increased brain FoxP3+ IL-10+ Tregs, reduced microglial and astrocytic gliosis in the white matter and hippocampus, restored neurogenesis, and improved short-term memory. Nasal aCD3 mAb reprogrammed microglia from an antigen-presenting, NF-κB-driven inflammatory state toward chemokine signaling, phagosome, and TGF β-related regulatory phenotype. Patients with Long COVID with neurological symptoms had lower circulating Treg populations. These findings identify nasal administration of aCD3 mAb as a noninvasive strategy to control neuroinflammation, restore the neurogenic niche, and offer a novel approach to treating cognitive impairment in Long COVID.

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Nasal Anti-CD3 Antibody Treatment May Reduce Brain Inflammation and Improve Memory and New Brain Cell Growth After COVID in Mice

Abstract

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