U.S. study finds that SARS-CoV-2 invades the peripheral sensory neurons first before spreading through the bloodstream
Nikhil Prasad Fact checked by:Thailand Medical News Team Jul 28, 2024 3 months, 3 weeks, 3 days, 23 hours, 1 minute ago
COVID-19 News: A groundbreaking study conducted by researchers at Virginia Polytechnic Institute & State University (Virginia Tech)-USA has provided new insights into how the SARS-CoV-2 virus, responsible for COVID-19, invades the human nervous system. The study, which included scientists from various departments such as Translational Biology, Medicine, and Health, and Biomedical and Veterinary Science, revealed that the virus targets peripheral sensory neurons before spreading through the bloodstream in a process known as viremia. This
COVID-19 News report delves deeper into the study's key findings and their implications.
SARS-CoV-2 invades the peripheral sensory neurons first before spreading through the bloodstream
Initial Entry into Peripheral Sensory Neurons
The team, led by Dr Jonathan D. Joyce, Dr Greyson A. Moore, Dr Poorna Goswami, and others, discovered that SARS-CoV-2 rapidly infects peripheral sensory and autonomic neurons. This occurs before the virus enters the bloodstream, suggesting the nervous system is one of the first targets upon viral entry into the body. "Our study shows that sensory and autonomic neurons in the peripheral nervous system (PNS) are highly susceptible to SARS-CoV-2 infection," the researchers noted.
Methodology and Key Findings
The researchers used transgenic mice that express the human angiotensin-converting enzyme 2 (hACE2), wild-type mice, and golden Syrian hamsters to trace the virus's progression. They observed the presence of viral RNA, proteins, and infectious virus in peripheral neurons, satellite glial cells, and connected central nervous system (CNS) tissues. This was evident even without detectable viremia.
"The presence of viral RNA and proteins in the trigeminal ganglia (TG) and superior cervical ganglia (SCG) indicates that these neurons serve as initial sites of infection," explained the team. The TG provides sensory innervation to the face, including the nasal septum, while the SCG supplies sympathetic innervation to the head and neck, making these pathways potential routes for CNS invasion.
Detailed Examination of Affected Neurons
Infected neurons showed significant pathology. In the TG, approximately 41% of neurons in hACE2 mice and 37% in wild-type mice were found to be positive for the SARS-CoV-2 nucleocapsid (N) protein. In the SCG, the infection rate was even higher, with nearly all neurons in hACE2 mice (97%) showing presence of the virus. Notably, the SCGs exhibited substantial pathology, including vacuolated neurons and loss of ganglionic architecture.
The research also highlighted that sensory neurons in the lumbosacral dorsal root ganglia (LS-DRG) and the lumbosacral spinal cord (LS-SC) were susceptible to infection. Viral RNA and proteins were detected in these regions, suggesting the virus spreads from peripheral sites to the CNS via connected neural pathways.
Role of Neuropilin-1 in Neuronal Entry
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One of the significant findings of the study was the role of neuropilin-1 (NRP-1) in facilitating the virus's entry into neurons. The research demonstrated that blocking NRP-1 significantly reduced viral RNA concentrations in primary cultured PNS neurons from both hACE2 and wild-type mice. This suggests that NRP-1 enhances the virus's ability to enter and infect neurons, even in the absence of the hACE2 receptor.
"NRP-1 acts as an entry factor for SARS-CoV-2 in PNS sensory neurons," noted the researchers. "This could explain why some individuals experience neurological symptoms without severe respiratory involvement."
Thailand Medical News had already covered a number of earlier studies that showed that the SARS-CoV-2 virus could also use NRP-1 as a receptor for viral entry in humans and with disastrous long-term effects!
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Implications for COVID-19 Symptoms
The study's findings offer a potential explanation for the neurological symptoms reported by many COVID-19 patients, both during acute infection and in long COVID. Symptoms such as anosmia (loss of smell), headaches, and neuropathic pain may result from the virus's initial invasion of the PNS and subsequent spread to the CNS.
The research also highlights the need for further studies to explore the neuroinvasive potential of different SARS-CoV-2 variants and the long-term impacts on the nervous system. "Understanding the mechanisms of SARS-CoV-2 neuroinvasion is crucial for developing targeted therapies to mitigate these symptoms," the researchers emphasized.
Case Studies and Patient Impacts
Up to 80% of people infected with SARS-CoV-2 report neurological symptoms, which can include fatigue, memory issues, "brain fog," hyperesthesia (increased sensitivity to stimuli), and autonomic dysfunction. These symptoms often persist as part of post-COVID-19 syndrome, also known as long COVID, long after the acute infection has resolved.
Detection of the virus, viral RNA, and antigens in the cerebrospinal fluid and brains of COVID-19 patients indicates that SARS-CoV-2 is neuroinvasive, a characteristic shared with other coronaviruses such as those causing the common cold and past epidemics like SARS and MERS.
Exploring Alternative Routes of CNS Invasion
The research also explored the possibility of SARS-CoV-2 invading the CNS through alternative routes besides the olfactory pathway. The oronasal mucosa and other target organs of the virus, like the lungs and gut, are heavily innervated by sensory and autonomic neurons of the PNS. This suggests that the virus might enter peripheral neurons directly from the mucosa, facilitating rapid CNS invasion through connected neural pathways.
Future Research Directions
While the study focused on the original strain of SARS-CoV-2, the team plans to investigate the neuroinvasive properties of newer variants, such as Omicron. Preliminary data suggest that these variants may exhibit different patterns of neuroinvasion, potentially leading to varied neurological outcomes.
"Infection with ancestral SARS-CoV-2 showed a significant neuroinvasive potential, which may differ with current variants," the researchers stated. "Future studies will help us understand these differences and adapt treatment strategies accordingly."
Broader Implications for Public Health
The study's insights into SARS-CoV-2's ability to invade the nervous system could have significant implications for public health strategies. Understanding the pathways of neuroinvasion and the role of NRP-1 could lead to the development of new therapeutic interventions aimed at preventing or mitigating neurological symptoms of COVID-19.
The study findings were published in the peer-reviewed International Journal of Molecular Sciences.
https://www.mdpi.com/1422-0067/25/15/8245
For the latest COVID-19 News, keep on logging to Thailand Medical News.
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