Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China in December 2019. On February 11, the World Health Organization (WHO) announced the name for the new illness caused by SARS-CoV-2: COVID-19. By March 11, the outbreak of COVID-19 was declared a pandemic by the WHO. This virus has extensively altered daily life for many across the globe, while claiming hundreds of thousands of lives. While fundamentally a respiratory illness, many infected individuals experience symptoms that involve the central nervous system (CNS). It is likely that many of these symptoms are the result of the virus residing outside of the CNS. However, the current evidence does indicate that the SARS-CoV-2 virus can use olfactory neurons (or other nerve tracts) to travel from the periphery into the CNS, and that the virus may also enter the brain through the blood-brain barrier (BBB). We discuss how the virus may use established infection mechanisms (ACE2, NRP1, TMPRSS2, furin and Cathepsin L), as well mechanisms still under consideration (BASIGIN) to infect and spread throughout the CNS. Confirming the impact of the virus on the CNS will be crucial in dealing with the long-term consequences of the epidemic.
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Evidence from prior coronavirus studies, animal models, and post-mortem brain analyses of COVID-19 patients indicates that SARS-CoV-2 can cross the blood-brain barrier.
“Studies of previous coronaviruses (Netland et al., 2008), animal models (Burks et al., 2021), and brain analysis at post-mortem of COVID-19 patients (Paniz-Mondolfi et al., 2020) provide evidence that SARS-CoV-2 can penetrate the blood-brain barrier.”
From Long-term effects of COVID-19 on mental health: a systematic review (2022) · cites this paper as Burks et al., 2021
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- Authors
- Burks, S. M., Rosas-Hernandez, H., Alejandro Ramirez-Lee, M., Cuevas, E., & Talpos, J. C.
- Affiliations
- National Center for Toxicological Research (US)
- Corresponding author
- Talpos, John C.
- Venue
- Brain Behavior and Immunity
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 95
- Pages
- 7-14
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC7836942
- OpenAlex
- W3120169329
- Cited by
- 97
- References
- 111
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 25 · 2023: 24 · 2022: 22 · 2021: 13
- FWCI
- 2.69
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Long-Term Effects of COVID-19
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, COVID-19 pandemic, central nervous system infection, olfactory bulb, blood-brain barrier, olfactory sensory neurons, ACE2, neuropilin-1, TMPRSS2, furin, cathepsin L, CD147, neuroinvasion, neurological symptoms
- MeSH terms
- COVID-19, SARS-CoV-2, Blood-Brain Barrier, Central Nervous System, China, Humans, Olfactory Bulb
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