COVID-19 induces neuroinflammation and suppresses peroxisomes in the brain
- Citation:
- Roczkowsky, A., D. Limonta, J. P. Fernandes, W. G. Branton, M. Clarke, B. Hlavay, R. S. Noyce, J. T. Joseph, N. S. Ogando, S. K. Das, et al., "COVID-19 induces neuroinflammation and suppresses peroxisomes in the brain", Ann Neurol, 2023.
Abstract:
Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during SARS-CoV-2 infection using a multiplatform strategy.|Brain tissues from COVID-19 (n=12) and other disease control (ODC) (n=12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by ddPCR, RT-qPCR and immunodetection methods.|SARS-CoV-2 RNA was detected in the CNS of four patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p<0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11β and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 patients compared to ODCs (p<0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p<0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p<0.05).|COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. This article is protected by copyright. All rights reserved.
Notes:
Roczkowsky, A Limonta, D Fernandes, J P Branton, W G Clarke, M Hlavay, B Noyce, R S Joseph, J T Ogando, N S Das, S K Elaish, M Arbour, N Evans, D H Langdon, K Hobman, T C Power, C 2023/5/16