Cited by 97Long-Term Effects of COVID-19SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

Can SARS-CoV-2 infect the central nervous system via the olfactory bulb or the blood-brain barrier?

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Burks, Susan M., Rosas-Hernandez, Hector, Alejandro Ramirez-Lee, Manuel, Cuevas, Elvis, Talpos, John C.·2021·Brain Behavior and Immunity

Abstract

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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Research works printed but not linked: 2

  1. Arslan O. Olfactory System. Neuroanatomical Basis of Clinical Neurology second ed. 2014 CRC Press 377 386
  2. Song E. Zhang C. Israelow B. Lu P. Weizman O.-E. Liu F. Dai Y. Szigeti-Buck K. Yasumoto Y. Wang G. Castaldi C. Heltke J. Ng E. Wheeler J. Alfajaro M.M. Fontes B. Ravindra N.G. Van Dijk D. Mane S. Gunel M. Ring A. Wilen C.B. Horvath T.L. Louvi A. Farhadian S.F. Bilguvar K. Iwasaki A. Neuroinvasive potential of SARS-CoV-2 revealed in a human brain organoid model bioRxiv 2020 2020.2006.2025.169946

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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)
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
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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