Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model

Käufer, Christopher; Schreiber, Cara S.; Hartke, Anna-Sophia; Denden, Ivo; Stanelle-Bertram, Stephanie; Beck, Sebastian; Kouassi, Nancy Mounogou; Beythien, Georg; Becker, K.; Schreiner, Tom; Schaumburg, Berfin; Beineke, Andreas; Baumgärtner, Wolfgang; Gabriel, Gülşah; Richter, Franziska

doi:10.1016/j.ebiom.2022.103999

Cited by 57 publications

(61 citation statements)

References 81 publications

(104 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Indeed, a COVID-19 postmortem study detected major neurological damage, but only low levels of SARS-CoV-2 RNA in the brains of expired patients [ 325 ]. Furthermore, cortical accumulation of total α-syn was observed following viral eradication in a SARS-CoV-2 intranasally-infected hamster model without any indication of inflammation and neurodegeneration [ 326 ]. Extending the Braak hypothesis, one could argue that any neurological sequelae and neuropathological outcomes observed in COVID-19 survivors may emerge both directly, due to virus-exerted effects, and indirectly, through molecular and neuroinflammatory mediators, carried by SARS-CoV-2-related exosomes remaining in circulation even after elimination of the virus.…”

Section: Sars-cov-2-related εXosomal Cargo and Its Potential Roles In...mentioning

confidence: 99%

Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis

Mysiris

Vavougios

Karamichali

et al. 2022

IJMS

View full text Add to dashboard Cite

Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.

show abstract

Section: Sars-cov-2-related εXosomal Cargo and Its Potential Roles In...mentioning

confidence: 99%

Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis

Mysiris

Vavougios

Karamichali

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…The olfactory nerve connects the olfactory mucosa directly with the olfactory bulb in the brain providing an efficient anatomical entry point from the nasal cavity into the brain [24]. Once within the CNS, the neurotropism of SARS-CoV-2 appears to be restricted to a subset of permissive CNS cells based on in vivo (human, hamster, non-human primates, ferrets) [22,23,[25][26][27][28][29][30] and in vitro [30][31][32][33][34][35][36][37][38] studies. So far, efficient replication of SARS-CoV-2 has only been observed in choroid plexus epithelial cells in vitro [31,33].…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants

Bauer

Rissmann

Benavides

et al. 2022

acta neuropathol commun

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. Although the mechanism is not fully understood, several studies have shown that neuroinflammation occurs in the acute and post-acute phase. As these studies have predominantly been performed with isolates from 2020, it is unknown if there are differences among SARS-CoV-2 variants in their ability to cause neuroinflammation. Here, we compared the neuroinvasiveness, neurotropism and neurovirulence of the SARS-CoV-2 ancestral strain D614G, the Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529) variants using in vitro and in vivo models. The Omicron BA.1 variant showed reduced neurotropism and neurovirulence compared to Delta and D614G in human induced pluripotent stem cell (hiPSC)-derived cortical neurons co-cultured with astrocytes. Similar differences were obtained in Syrian hamsters inoculated with D614G, Delta and the Omicron BA.1 variant 5 days post infection. Replication in the olfactory mucosa was observed in all hamsters, but most prominently in D614G inoculated hamsters. Furthermore, neuroinvasion into the CNS via the olfactory nerve was observed in D614G, but not Delta or Omicron BA.1 inoculated hamsters. Furthermore, neuroinvasion was associated with neuroinflammation in the olfactory bulb of hamsters inoculated with D614G. Altogether, our findings suggest differences in the neuroinvasive, neurotropic and neurovirulent potential between SARS-CoV-2 variants using in vitro hiPSC-derived neural cultures and in vivo in hamsters during the acute phase of the infection.

show abstract

“…Given the typically slow progress of neurodegenerative disease, if such a phenomenon exists, it will most probably take some time to become evident epidemiologically. In an animal model study performed by Käufer et al (2022) , microglial activation and neuronal proteinopathy persisted even beyond viral clearance. Viral protein exposure in the nasal cavity led to pronounced microglia activation in the olfactory bulb beyond viral clearance.…”

Section: Olfactory Impairment In Covid-19 and Parkinsonismmentioning

confidence: 98%

Smell deficits in COVID-19 and possible links with Parkinson's disease

Emmi

Sandre

Porzionato

et al. 2022

International Review of Neurobiology

View full text Add to dashboard Cite

Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model

Cited by 57 publications

References 81 publications

Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis

Post-COVID-19 Parkinsonism and Parkinson’s Disease Pathogenesis: The Exosomal Cargo Hypothesis

In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants

Smell deficits in COVID-19 and possible links with Parkinson's disease

Contact Info

Product

Resources

About