Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis

Lu Tan; Abhishek K. Verma; Shea Lowery; Andrew Thurman; Alan Sariol; Cori Fain; Zhaoyuan Liu; Florent Ginhoux; John Harty; David K. Meyerholz; Stanley Perlman

doi:10.1038/s41467-026-76156-5

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Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis

Journal article

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Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis

Lu Tan, Abhishek K. Verma, Shea Lowery, Andrew Thurman, Alan Sariol, Cori Fain, Zhaoyuan Liu, Florent Ginhoux, John Harty, David K. Meyerholz, …

Nature communications, Vol.17(1), 9259

07/30/2026

DOI: 10.1038/s41467-026-76156-5

PMID: 42669720

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Abstract

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.

Details

Title: Subtitle: Longitudinal analysis reveals myeloid cell contributions to murine neuroPASC pathogenesis
Creators: Lu Tan - University of Iowa, Microbiology and Immunology
Abhishek K. Verma - University of Iowa
Shea Lowery - University of Iowa
Andrew Thurman - University of Iowa, Internal Medicine
Alan Sariol - Washington University in St. Louis
Cori Fain - University of Iowa
Zhaoyuan Liu - Shanghai Jiao Tong University
Florent Ginhoux - Agency for Science, Technology and Research
John Harty - University of Iowa
David K. Meyerholz - University of Iowa
Stanley Perlman - University of Iowa
Resource Type: Journal article
Publication Details: Nature communications, Vol.17(1), 9259
DOI: 10.1038/s41467-026-76156-5
PMID: 42669720
ISSN: 2041-1723
eISSN: 2041-1723
Publisher: Springer Nature
Grant note: Division of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID): NS R01 NS36592, P0 AI060699, AI129269
This work is supported in part by grants from the NIH (R01 NS36592, P01 AI060699, R01 AI129269 awarded to S.P.).
Language: English
Electronic publication date: 07/30/2026
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
Record Identifier: 9985217831402771

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