Researchers Warn That Studies That Use Guinea Pigs to Observe How SARS-2-CoV-2 Affects the Nervous System Are Not Reliable!
Nikhil Prasad Fact checked by:Thailand Medical News Team May 16, 2025 7 hours, 29 minutes ago
Medical News: Guinea Pigs Fail as a Model for COVID-19 Nerve Damage According to New Study
A newly published study has delivered a surprising revelation—guinea pigs, long trusted in infectious disease research, are not a reliable model for studying how SARS-CoV-2 affects the nervous system. Despite their past utility during the SARS-CoV-1 epidemic and in respiratory virus studies, these popular lab animals failed to show any sign of infection or neurological response when exposed to the virus responsible for COVID-19.
Researchers Warn That Studies That Use Guinea Pigs to Observe How SARS-2-CoV-2 Affects the Nervous System Are Not Reliable!
Researchers from multiple departments at the Virginia Polytechnic Institute and State University—specifically the Center for Emerging Zoonotic and Arthropod-Borne Pathogens, Virginia Maryland College of Veterinary Medicine, the School of Neuroscience, and the Translational Biology, Medicine and Health program—set out to test whether guinea pigs could help uncover how COVID-19 enters and affects the nervous system. This
Medical News report explores their findings in detail and what it means for the future of COVID-19 research.
Why Guinea Pigs Were Considered in the First Place
Guinea pigs have been used as animal models for centuries. They’ve been valuable in research involving tuberculosis, influenza, and even neurological viruses like Zika and herpes. They also played a useful role during the earlier SARS-CoV-1 outbreak, showing signs of lung damage and producing antibodies when infected.
Given their respiratory system’s similarity to that of humans and their use in studying neurotropic viruses, it made sense to evaluate their usefulness in modeling SARS-CoV-2’s potential to infect and damage the central and peripheral nervous systems (CNS and PNS). But this latest study says otherwise.
How the Study Was Conducted
In a controlled biosafety lab, researchers intranasally infected healthy young female Dunkin-Hartley guinea pigs with the ancestral strain of SARS-CoV-2 (USA-WA1/2020) in two dosage groups: 103 and 105 plaque-forming units (PFU). The goal was to see if the virus would replicate, affect weight or temperature, or show up in any part of the nervous system or lungs.
Over six days, the guinea pigs were monitored for weight changes, fever, distress, or any neurological symptoms. Tissue samples were collected from different brain regions, sensory ganglia, the lungs, and the blood. Tests were conducted using RT-qPCR to detect viral RNA, immunostaining to identify viral proteins, and plaque assays to look for live infectious virus.
What the Researchers Found
Shockingly, the guinea pigs showed no symptoms of disease. While there were minor fluctuations in body temperature and a slight delay in weight gain compared to uninfected animals, none of the animals displayed fever, neurological problems, or distress.
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More importantly, viral RNA was found in only one blood sample out of all 24 infected guinea pigs—and even then, at a very low level (113 RNA copies). No viral RNA was detected in any nervous tissue, lung, or brain. No infectious virus was recovered through plaque assays. Immunostaining showed no sign of the viral nucleocapsid protein in any of the guinea pig tissues tested.
Why the Guinea Pigs Didn’t Get Infected
The study points to biological incompatibility as the reason. SARS-CoV-2 uses the ACE2 receptor to enter cells. Previous in vitro studies had suggested that guinea pig ACE2 receptors don’t bind well with the virus’s spike protein. This study confirms that poor binding is likely the reason the virus cannot establish infection in guinea pigs, even when introduced through the nose.
Additionally, the researchers highlighted that the guinea pig model used in SARS-CoV-1 research was infected via an intraperitoneal route (injection into the body cavity), which is not representative of how humans contract respiratory viruses. The intranasal route used in this study more closely mimics real-world exposure, reinforcing the study’s relevance.
Comparisons With Other Animal Models
The study contrasts guinea pigs with other animal models. For instance, golden Syrian hamsters and genetically modified mice expressing human ACE2 receptors (such as the K18-hACE2 mice) have shown significant lung and brain infection after SARS-CoV-2 exposure. In contrast, guinea pigs remained completely unaffected, highlighting their unsuitability for studying either respiratory or neurological aspects of COVID-19.
Other recent studies have shown similar results, further backing this study’s conclusion. One such study used a different SARS-CoV-2 strain that had a spike protein mutation (D614G), which increased infectivity in humans, yet guinea pigs still did not get infected.
Implications for COVID-19 and Long COVID Research
With neurological symptoms being among the most persistent and troubling features of both acute and long COVID—including headaches, brain fog, nerve pain, and autonomic dysfunction—reliable animal models are crucial for research. This study clearly shows that guinea pigs cannot help in this regard. As a result, researchers will need to rely on other models, such as transgenic mice and hamsters, to investigate how the virus affects the nervous system.
Still, guinea pigs may continue to be useful in some aspects of COVID-19 research, particularly in vaccine development and antibody testing. But when it comes to studying how the virus invades and harms nerve tissues, they’re off the table.
Conclusion
The new study provides clear and detailed evidence that guinea pigs are not susceptible to SARS-CoV-2 infection when exposed intranasally. This confirms earlier predictions based on genetic and lab-based research. Despite their long-standing role in infectious disease studies, guinea pigs lack the necessary biological compatibility for SARS-CoV-2 to infect them via natural respiratory routes. The virus does not replicate in their systems, does not reach the lungs or nervous tissue, and fails to produce measurable symptoms or immune responses. These findings significantly limit the animal's usefulness in neurological COVID-19 studies and underscore the need for more suitable models such as hamsters or transgenic mice that better mimic human disease.
The study findings were published in the peer-reviewed journal: Viruses
https://www.mdpi.com/1999-4915/17/5/706
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