Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection

Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown...

Full description

Saved in:
Bibliographic Details
Main Authors: Jonathan D. Joyce, Greyson A. Moore, Christopher K. Thompson, Andrea S. Bertke
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/17/5/706
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850126155420532736
author Jonathan D. Joyce
Greyson A. Moore
Christopher K. Thompson
Andrea S. Bertke
author_facet Jonathan D. Joyce
Greyson A. Moore
Christopher K. Thompson
Andrea S. Bertke
author_sort Jonathan D. Joyce
collection DOAJ
description Neurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to be useful models of disease during the SARS-CoV-1 epidemic. However, their suitability for studying SARS-CoV-2 has not been experimentally demonstrated. To assess the suitability of guinea pigs as models for SARS-CoV-2 infection and the impact of SARS-CoV-2 infection on the PNS, and to determine routes of CNS invasion through the PNS, we intranasally infected wild-type Dunkin-Hartley guinea pigs with ancestral SARS-CoV-2 USA-WA1/2020. We assessed PNS sensory neurons (trigeminal ganglia, dorsal root ganglia), autonomic neurons (superior cervical ganglia), brain regions (olfactory bulb, brainstem, cerebellum, cortex, hippocampus), lungs, and blood for viral RNA (RT-qPCR), protein (immunostaining), and infectious virus (plaque assay) at three- and six-days post infection. We show that guinea pigs, which have previously been used as a model of SARS-CoV-1 pulmonary disease, are not susceptible to intranasal infection with ancestral SARS-CoV-2, and are not useful models in assessing neurological impacts of infection with SARS-CoV-2 isolates from the early pandemic.
format Article
id doaj-art-b31f3b0947ad4ed8949e2bfaad1ed6c0
institution OA Journals
issn 1999-4915
language English
publishDate 2025-05-01
publisher MDPI AG
record_format Article
series Viruses
spelling doaj-art-b31f3b0947ad4ed8949e2bfaad1ed6c02025-08-20T02:33:59ZengMDPI AGViruses1999-49152025-05-0117570610.3390/v17050706Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal InfectionJonathan D. Joyce0Greyson A. Moore1Christopher K. Thompson2Andrea S. Bertke3Translational Biology, Medicine and Health, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USABiomedical and Veterinary Science, Virginia Maryland College of Veterinary Medicine, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USASchool of Neuroscience, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USACenter for Emerging Zoonotic and Arthropod-Borne Pathogens, Virginia Polytechnic Institute & State University, Blacksburg, VA 24061, USANeurological symptoms involving the central nervous system (CNS) and peripheral nervous system (PNS) are common complications of acute COVID-19 as well as post-COVID conditions. Most research into these neurological sequalae focuses on the CNS, disregarding the PNS. Guinea pigs were previously shown to be useful models of disease during the SARS-CoV-1 epidemic. However, their suitability for studying SARS-CoV-2 has not been experimentally demonstrated. To assess the suitability of guinea pigs as models for SARS-CoV-2 infection and the impact of SARS-CoV-2 infection on the PNS, and to determine routes of CNS invasion through the PNS, we intranasally infected wild-type Dunkin-Hartley guinea pigs with ancestral SARS-CoV-2 USA-WA1/2020. We assessed PNS sensory neurons (trigeminal ganglia, dorsal root ganglia), autonomic neurons (superior cervical ganglia), brain regions (olfactory bulb, brainstem, cerebellum, cortex, hippocampus), lungs, and blood for viral RNA (RT-qPCR), protein (immunostaining), and infectious virus (plaque assay) at three- and six-days post infection. We show that guinea pigs, which have previously been used as a model of SARS-CoV-1 pulmonary disease, are not susceptible to intranasal infection with ancestral SARS-CoV-2, and are not useful models in assessing neurological impacts of infection with SARS-CoV-2 isolates from the early pandemic.https://www.mdpi.com/1999-4915/17/5/706SARS-CoV-2USA-WA1/2020COVID-19neuroinvasiontrigeminal gangliasuperior cervical ganglia
spellingShingle Jonathan D. Joyce
Greyson A. Moore
Christopher K. Thompson
Andrea S. Bertke
Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
Viruses
SARS-CoV-2
USA-WA1/2020
COVID-19
neuroinvasion
trigeminal ganglia
superior cervical ganglia
title Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
title_full Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
title_fullStr Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
title_full_unstemmed Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
title_short Guinea Pigs Are Not a Suitable Model to Study Neurological Impacts of Ancestral SARS-CoV-2 Intranasal Infection
title_sort guinea pigs are not a suitable model to study neurological impacts of ancestral sars cov 2 intranasal infection
topic SARS-CoV-2
USA-WA1/2020
COVID-19
neuroinvasion
trigeminal ganglia
superior cervical ganglia
url https://www.mdpi.com/1999-4915/17/5/706
work_keys_str_mv AT jonathandjoyce guineapigsarenotasuitablemodeltostudyneurologicalimpactsofancestralsarscov2intranasalinfection
AT greysonamoore guineapigsarenotasuitablemodeltostudyneurologicalimpactsofancestralsarscov2intranasalinfection
AT christopherkthompson guineapigsarenotasuitablemodeltostudyneurologicalimpactsofancestralsarscov2intranasalinfection
AT andreasbertke guineapigsarenotasuitablemodeltostudyneurologicalimpactsofancestralsarscov2intranasalinfection