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Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 74, Issue 6

SARS-CoV-2 and neurotropism: evidence, gaps and reflections Open Access

Abstract

Coronavirus disease 2019 (COVID-19) patients may present with a wide clinical spectrum, including extrapulmonary involvement, such as neurological damage. Although the pathogenesis of neurological COVID-19 still remains unclear, some studies have discussed the potential association between tissue injury and severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection in the central nervous system (CNS) and/or immune imbalance. These two mechanisms are non-mutually exclusive; however, exacerbated inflammatory-response-induced neurological damage appears to be more aligned with COVID-19 pathogenesis, whereas SARS-CoV-2 infection/replication in the CNS remains widely discussed. Herein, we dissect this last issue, highlighting some evidence on SARS-CoV-2 neuroinvasion, as well as discussing gaps that should be addressed for a better understanding of its potential neurotropism, specifically in the CNS. Finally, we propose some deeper reflections on the SARS-CoV-2 neurotropic potential.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): coronavirus , coronavirus disease 2019 (COVID-19) and tropism
© 2025 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. The Microbiology Society waived the open access fees for this article.
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2025-06-16
2025-07-14
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References

  1. Pang Z, Tang A, He Y, Fan J, Yang Q et al. Neurological complications caused by SARS-CoV-2. Clin Microbiol Rev 2024; 37:e0013124 [View Article] [PubMed]
     [Google Scholar]
  2. López Lloreda C. COVID’s toll on the brain: new clues emerge. Nature 2024; 628:20 [View Article] [PubMed]
     [Google Scholar]
  3. Beckman D, Bonillas A, Diniz GB, Ott S, Roh JW et al. SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19. Cell Rep 2022; 41:111573 [View Article] [PubMed]
     [Google Scholar]
  4. Jacob F, Pather SR, Huang W-K, Zhang F, Wong SZH et al. Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-CoV-2 neurotropism predominates in choroid plexus epithelium. Cell Stem Cell 2020; 27:937–950 [View Article] [PubMed]
     [Google Scholar]
  5. Jiao L, Yang Y, Yu W, Zhao Y, Long H et al. The olfactory route is a potential way for SARS-CoV-2 to invade the central nervous system of rhesus monkeys. Signal Transduct Target Ther 2021; 6:169 [View Article] [PubMed]
     [Google Scholar]
  6. Kumar N, Santhoshkumar R, Agrawal R, Singh A, Kalyan V et al. Neuropathogenesis of SARS-CoV-2 in human neuronal, microglial and glial cells. Arch Microbiol 2024; 206: [View Article]
     [Google Scholar]
  7. Mesci P, de Souza JS, Martin-Sancho L, Macia A, Saleh A et al. SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir. PLoS Biol 2022; 20:e3001845 [View Article] [PubMed]
     [Google Scholar]
  8. Mukerji SS, Solomon IH. What can we learn from brain autopsies in COVID-19?. Neurosci Lett 2021; 742:135528 [View Article] [PubMed]
     [Google Scholar]
  9. Pellegrini L, Albecka A, Mallery DL, Kellner MJ, Paul D et al. SARS-CoV-2 infects the brain choroid plexus and disrupts the blood-CSF barrier in human brain organoids. Cell Stem Cell 2020; 27:951–961 [View Article] [PubMed]
     [Google Scholar]
  10. Ramani A, Müller L, Ostermann PN, Gabriel E, Abida-Islam P et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J 2020; 39:e106230 [View Article] [PubMed]
     [Google Scholar]
  11. Oliveira AO, Malwade S, Rufino de Sousa N, Goparaju SK et al. SARS-CoV-2 promotes microglial synapse elimination in human brain organoids. Mol Psychiatry 2022; 27:3939–3950 [View Article] [PubMed]
     [Google Scholar]
  12. Zhang B-Z, Chu H, Han S, Shuai H, Deng J et al. SARS-CoV-2 infects human neural progenitor cells and brain organoids. Cell Res 2020; 30:928–931 [View Article] [PubMed]
     [Google Scholar]
  13. Haverty R, McCormack J, Evans C, Purves K, O’Reilly S et al. SARS-CoV-2 infects neurons, astrocytes, choroid plexus epithelial cells and pericytes of the human central nervous system in vitro. J Gen Virol 2024; 105:002009 [View Article] [PubMed]
     [Google Scholar]
  14. Andrews MG, Mukhtar T, Eze UC, Simoneau CR, Ross J et al. Tropism of SARS-CoV-2 for human cortical astrocytes. Proc Natl Acad Sci USA 2022; 119:e2122236119 [View Article] [PubMed]
     [Google Scholar]
  15. Kong W, Montano M, Corley MJ, Helmy E, Kobayashi H et al. Neuropilin-1 mediates SARS-CoV-2 infection of astrocytes in brain organoids, inducing inflammation leading to dysfunction and death of neurons. mBio 2022; 13:e0230822 [View Article] [PubMed]
     [Google Scholar]
  16. Luo EY, Chuen-Chung Chang R, Gilbert-Jaramillo J. SARS-CoV-2 infection in microglia and its sequelae: what do we know so far?. Brain Behav Immun Health 2024; 42:100888 [View Article] [PubMed]
     [Google Scholar]
  17. Meinhardt J, Streit S, Dittmayer C, Manitius R v., Radbruch H et al. The neurobiology of SARS-CoV-2 infection. Nat Rev Neurosci 2024; 25:30–42 [View Article]
     [Google Scholar]
  18. Fujimoto T, Erickson MA, Banks WA. Neurotropism and blood-brain barrier involvement in COVID-19. Front Drug Deliv 2022; 2: [View Article]
     [Google Scholar]
  19. Boroojerdi MH, Al Jabry T, Mirarefin SMJ, Albalushi H. Insights into organoid-based modeling of COVID-19 pathology. Virol J 2023; 20:37 [View Article] [PubMed]
     [Google Scholar]
  20. Ostermann PN, Schaal H. Human brain organoids to explore SARS-CoV-2-induced effects on the central nervous system. Rev Med Virol 2023; 33:e2430 [View Article] [PubMed]
     [Google Scholar]
  21. Long S. SARS-CoV-2 Subgenomic RNAs: characterization, Utility, and Perspectives. Viruses 2021; 13:1923 [View Article] [PubMed]
     [Google Scholar]
  22. Stein SR, Ramelli SC, Grazioli A, Chung J-Y, Singh M et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature 2022; 612:758–763 [View Article] [PubMed]
     [Google Scholar]
  23. Burrell CJ, Howard CR, Murphy FA. Virion structure and composition. In Fenner and White’s Medical Virology, 5th ed 2017 pp 27–37 [View Article]
     [Google Scholar]
  24. Shi F-S, Yu Y, Li Y-L, Cui L, Zhao Z et al. Expression profile and localization of SARS-CoV-2 nonstructural replicase proteins in infected cells. Microbiol Spectr 2022; 10:e0074422 [View Article] [PubMed]
     [Google Scholar]
  25. Thermo Fisher Scientifi SARS-CoV NSP13 Antibodies. https://www.thermofisher.com/antibody/primary/target/sars-cov%20nsp13 accessed 2 March 2025
  26. Fan C, Wu Y, Rui X, Yang Y, Ling C et al. Animal models for COVID-19: advances, gaps and perspectives. Signal Transduct Target Ther 2022; 7:220 [View Article] [PubMed]
     [Google Scholar]
  27. McCray PB Jr, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol 2007; 81:813–821 [View Article] [PubMed]
     [Google Scholar]
  28. Dunai C, Hetherington C, Boardman SA, Clark JJ, Sharma P et al. Pulmonary SARS-CoV-2 infection leads to para-infectious immune activation in the brain. Front Immunol 2024; 15:1440324 [View Article] [PubMed]
     [Google Scholar]
  29. Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med 2021; 218:e20202135 [View Article] [PubMed]
     [Google Scholar]
  30. Hanley B, Naresh KN, Roufosse C, Nicholson AG, Weir J et al. Histopathological findings and viral tropism in UK patients with severe fatal COVID-19: a post-mortem study. Lancet Microbe 2020; 1:e245–e253 [View Article]
     [Google Scholar]
  31. Essaidi-Laziosi M, Perez Rodriguez FJ, Hulo N, Jacquerioz F, Kaiser L et al. Estimating clinical SARS-CoV-2 infectiousness in Vero E6 and primary airway epithelial cells. Lancet Microbe 2021; 2:e571 [View Article] [PubMed]
     [Google Scholar]
  32. Mautner L, Hoyos M, Dangel A, Berger C, Ehrhardt A et al. Replication kinetics and infectivity of SARS-CoV-2 variants of concern in common cell culture models. Virol J 2022; 19:76 [View Article] [PubMed]
     [Google Scholar]
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