Nature communicationsAug 30, 2026

Myeloid immune cells linked to long-term brain symptoms after COVID-19 in mice over time

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Updated Sep 1, 2026

Abstract

SARS-CoV-2-infected mice show prolonged neuroinflammation lasting up to 120 days post-infection.

NeuroPASC symptoms include neurological and neuropsychiatric issues following COVID-19.
A coordinated involvement of both infiltrating and resident immune cells is observed in neuroinflammation.
Microglia exhibit sustained expansion of specific subclusters associated with inflammation and stress response.
Border-associated macrophages increase monocyte attractants during the acute phase of infection.
Transient inflammatory responses from peripherally derived monocytes and neutrophils could lead to lasting microglial reactivity.

Simplified

Neurological and neuropsychiatric symptoms, collectively termed neuroPASC, are among the most prevalent Post-Acute Sequelae of COVID-19 (PASC). Neuroinflammation - particularly microglia reactivity - has been implicated in neuroPASC. We previously established a PASC model in which SARS-CoV-2-infected mice developed persistent behavior alterations and prolonged neuroinflammation for up to 120 days post-infection (dpi). Here, we extend these results to a longitudinal single-cell RNA sequencing analysis of brain immune cells collected at 0, 6, 30, and 100 dpi. We identify a coordinated contribution of infiltrating and resident myeloid cells to the initiation and persistence of neuroinflammation. In specific, microglia display sustained expansion of subclusters characterized by inflammatory, stress response, and metabolic signatures. Border-associated macrophages upregulate monocyte attractants during acute infection. Concurrently, peripherally derived monocytes and neutrophils mount transient inflammatory responses, potentially triggering long-term microglial reactivity. Together, these findings provide a high-resolution atlas of brain myeloid immune dynamics during neuroPASC and highlight a central role for microglia in sustaining chronic neuroinflammation.

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Myeloid immune cells linked to long-term brain symptoms after COVID-19 in mice over time

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