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Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host–Virus Interaction, and Proposed Neurotropic Mechanisms

  • Abdul Mannan Baig*
    Abdul Mannan Baig
    Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan
    *Tel: +92-(0)333-2644-246. E-mail: [email protected]
  • Areeba Khaleeq
    Areeba Khaleeq
    Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan
  • Usman Ali
    Usman Ali
    Medical College, Aga Khan University, Karachi 74800, Pakistan
    More by Usman Ali
  • , and 
  • Hira Syeda
    Hira Syeda
    Department of Biosciences, Mohammad Ali Jinnah University, Karachi 75400, Pakistan
    More by Hira Syeda
Cite this: ACS Chem. Neurosci. 2020, 11, 7, 995–998
Publication Date (Web):March 13, 2020
https://doi.org/10.1021/acschemneuro.0c00122
Copyright © 2020 American Chemical Society
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Abstract

The recent outbreak of coronavirus infectious disease 2019 (COVID-19) has gripped the world with apprehension and has evoked a scare of epic proportion regarding its potential to spread and infect humans worldwide. As we are in the midst of an ongoing pandemic of COVID-19, scientists are struggling to understand how it resembles and differs from the severe acute respiratory syndrome coronavirus (SARS-CoV) at the genomic and transcriptomic level. In a short time following the outbreak, it has been shown that, similar to SARS-CoV, COVID-19 virus exploits the angiotensin-converting enzyme 2 (ACE2) receptor to gain entry inside the cells. This finding raises the curiosity of investigating the expression of ACE2 in neurological tissue and determining the possible contribution of neurological tissue damage to the morbidity and mortality caused by COIVD-19. Here, we investigate the density of the expression levels of ACE2 in the CNS, the host–virus interaction and relate it to the pathogenesis and complications seen in the recent cases resulting from the COVID-19 outbreak. Also, we debate the need for a model for staging COVID-19 based on neurological tissue involvement.

  Note

This article is made available via the ACS COVID-19 subset for unrestricted RESEARCH re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

1. The Novel COVID-19 Virus

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The first reports of the viral infection attracted attention in late December 2019 in Wuhan, the capital of Hubei, China. Later, it was revealed that the virus responsible for causing the infections was contagious between humans. By early January, terms like “the new coronavirus” and “Wuhan coronavirus” were in common use. On February 11, 2020, a taxonomic designation “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2) became the official means to refer to the virus strain, that was previously termed as 2019-nCoV and Wuhan coronavirus. Within a few hours on the same day, the WHO officially renamed the disease as COVID-19.

2. The Genome of the COVID-19 Virus

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The complete genome of SARS-CoV-2 from Wuhan, China was submitted on January 17, 2020 in the National Center for Biotechnology (1) (NCBI) database, with ID NC_045512. The genome of SARS-CoV-2 is a 29,903 bp single-stranded RNA (ss-RNA) coronavirus. It has now been shown that the virus causing COVID-19 is a SARS-like coronavirus that had previously been reported in bats in China.

3. Tissue Distribution of ACE2 in Human Organs and Tissues

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In order to discover the neurovirulence of SARS-CoV-2 and relate it to neurological tissue expression of ACE2, data retrieval was done from human protein databases. Most of the evidence of ACE2 expression in the brain (Figure 1) comes from literature and mammalian tissue expression databases, (2) which prompted us to investigate neurotropic effects of SARS-CoV-2 and its contribution toward the morbidity and mortality of patients with COVID-19.

Figure 1

Figure 1. Tissue distribution of ACE2 receptors in humans. Viremia (A) disseminates the COVID-19 virus throughout the body via the bloodstream (B). Neurotropism may occur via circulation and/or an upper nasal trancribrial route that enables the COVID-19 to reach the brain (C) and bind and engage with the ACE2 receptors (D, blue). COVID-19 docks on the ACE2 via spike protein (D, golden spikes). Shown are lungs, heart, kidneys, intestines, brain, and testicles that are well-known to express ACE2 receptors and are possible targets of COVID-19.

3.1. Evidence of the Distribution of ACE2 in the Human Brain

The brain has been reported to express ACE2 receptors (Figure 1A, C) that have been detected over glial cells and neurons, which makes them a potential target of COVID-19. Previous studies have shown the ability of SARS-CoV to cause neuronal death in mice by invading the brain via the nose close to the olfactory epithelium. (3) The contribution of the neurotropic potential of SARS-CoV-2 in patients reported in the recent outbreak of COVID-19 remains to be established. In the SARS-CoV infections that were reported in the past, autopsy findings of the patients have shown strong evidence of the presence of SARS-CoV by electron microscopy, immunohistochemistry, and real-time reverse transcription-PCR (3). Patients with acute SARS-CoV illness have also demonstrated the presence of the virus in cerebrospinal fluid. The role of the blood-brain barrier in containing the virus and preventing it from gaining access to the neural tissues needs to be further explored in patients diagnosed with COVID-19. Recently, a study posted in medRxiv (4) has reported neurological manifestations in COVID-19 in the current outbreak that involved 214 patients, of which 78 (36.4%) patients had neurologic manifestations, which affirms our rationale of the neurotropic potential in the COVID-19 virus. Also, a finding published on a patient who had loss of involuntary control over breathing (5) during the recent outbreak with several other patients suffering acute respiratory failure implores healthcare professionals and clinicians to segregate COVID-19 patients into neurologically affected cases and those who are devoid of neurological deficits.

4. Host–Virus Interaction: How the ACE2 Receptor Is Exploited by the COVID-19 Virus to Gain Entry Inside the Host Cells

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With the mRNA encoding several other proteins, (1) the COVID-19 virus, like SARS-CoV, uses a spike protein S1 that enables the attachment of the virion to the cell membrane by interacting with host ACE2 receptor (3,6) (Figure 1C, D). In the later study, (6) it was shown that the ACE2 binding affinity of the 2019-nCoV spike protein ectodomain was 10–20-fold higher than that of the SARS-CoV spike protein. A BLASTp search of the COVID-19 virus (SARS-CoV-2) receptor binding domain (RBD) subdomain-1 (319th to 591st aa) fetched a spike glycoprotein [bat coronavirus RaTG13] and S1 protein partial [SARS coronavirus GD322] as homologs. Pairwise sequence alignments of the three sequences show that although the spike proteins of all three CoV are highly similar they are not identical (Figure 2A, horizontal arrows), which may be the reason for the higher binding affinity of the COVID-19 spike protein to the human ACE2 receptor. Homology modeling of SARS-CoV-2 RBD subdomain-1 (319th to 591st aa) in the SWISS-MODEL automated server developed a template-based model of the SARS-CoV-2 spike glycoprotein with a single receptor-binding domain in the up configuration (Figure 2A1) with 100% sequence identity. Of the other template-based models developed, it expectedly showed a model of the structure of the SARS-CoV spike glycoprotein, conformation 2 with about 74% sequence identity (Figure 2B, B1), which shows them to be structurally and evolutionarily related.

Figure 2

Figure 2. (A) Sequence alignment of COVID-19 RBD subdomain-1 (319th to 591st) amino acid (top row) with the bat and SARS-CoV spike protein (middle and bottom row) that were fetched from BLASTp results of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acids. Note horizontal arrows that show areas of contrast between the sequences. (A1) Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template (6vsb.1. A)-based model of the COVID-19 virus spike glycoprotein. (B). Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template-(5x5b.1.A) based model of the prefusion structure of SARS-CoV spike glycoprotein in conformation 2 (B1) with 73.96% sequence identity. [Uniprot and SWISS-MODEL automated server were used for sequence alignments and development of the templates and models, respectively.]

5. A Proposed Cascade of Cerebral Involvement in the COVID-19 Infections

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The dissemination of COVID-19 in the systemic circulation or across the cribriform plate of the ethmoid bone (Figure 1) during an early or later phase of the infection can lead to cerebral involvement as has been reported in the past for SARS-CoV affected patients. (3) The presence of the COVID-19 virus in the general circulation understandably enables it to pass into the cerebral circulation (Figure 1A–C) where the sluggish movement of the blood within the microcirculation could be one of the factors that may facilitate the interaction of the COVID-19 virus spike protein with ACE2 expressed in the capillary endothelium. Subsequent budding of the viral particles from the capillary endothelium and damage to the endothelial lining can favor viral access to the brain (Figure 1B). Once within the milieu of the neuronal tissues, its interaction with ACE2 receptors (Figure 1C, D) expressed in neurons (2) can initiate a cycle of viral budding accompanied by neuronal damage without substantial inflammation as has been seen with cases of SARS-CoV (3) in the past. It is important to mention here that, long before the proposed anticipated neuronal damages occur, the endothelial ruptures in cerebral capillaries accompanied by bleeding within the cerebral tissue can have fatal consequences in patients with COVID-19 infections. The movement of the COVID-19 virus to the brain via the cribriform plate close to the olfactory bulb can be an additional pathway that could enable the virus to reach and affect the brain. Additionally, the findings like an altered sense of smell or hyposmia in an uncomplicated early stage COVID-19 patient should be investigated thoroughly for CNS involvement.

6. Conclusions and Future Directions

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Autopsies of the COVID-19 patients, detailed neurological investigation, and attempts to isolate SARS-CoV-2 from the endothelium of cerebral microcirculation, cerebrospinal fluid, glial cells, and neuronal tissue can clarify the role played by this novel COVID-19 causing coronavirus in the ongoing mortalities as has been in the recent outbreak. It is important to mention here that although the cerebral damage may complicate a COVID-19 infection, it appears that it is the widespread dysregulation of homeostasis caused by pulmonary, renal, cardiac, and circulatory damage that proves fatal in COIVD-19 patients. With that being said, a dominant cerebral involvement alone with the potential of causing cerebral edema in COVID-19 can take a lead in causing death long before systemic homeostatic dysregulation sets in. Access of the COVID-19 virus to the brain via the transcribrial route, as described previously for other CNS targeting pathogens, (7) could have been the case in a recently reported patient with hyposmia and the cases of acute respiratory failure in COVID-19, (5) which needs to be further elucidated by isolating the SARS-CoV-2 virus from the zones that are in proximity to the olfactory bulb. It is expected that the differences in the sequence of spike proteins between COVID-19 virus and SARS-CoV (Figure 2A) will enable scientists to identify epitopes in COVID-19 virus for the development of monoclonal antibodies against this virus. With the recent COVID-19 outbreak, there is an urgent need to understand the neurotropic potential of the COVID-19 virus in order to prioritize and individualize the treatment protocols based on the severity of the disease and predominant organ involvement. Also, a staging system based on the severity and organ involvement is needed in COVID-19 in order to rank the patients for aggressive or conventional treatment modalities.

Author Information

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  • Corresponding Author
  • Authors
    • Areeba Khaleeq - Department of Biological and Biomedical Sciences, Aga Khan University, Karachi 74800, Pakistan
    • Usman Ali - Medical College, Aga Khan University, Karachi 74800, Pakistan
    • Hira Syeda - Department of Biosciences, Mohammad Ali Jinnah University, Karachi 75400, Pakistan
  • Funding

    This project was partly funded by Aga Khan University.

  • Notes
    The authors declare no competing financial interest.

    The terms COVID-19 virus and SARS-CoV-2 are used in this paper, that refer to the novel coronavirus involved in the ongoing outbreak.

Acknowledgments

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The authors would like to thank the staff and faculty members of the Department of Biological & Biomedical Sciences, Aga Khan University, who, despite their busy schedule, made it to the COVID-19 presentations made by the authors and provided them with their input on the rationale of this study. The authors would also like to acknowledge the efforts of Ms. Preet Katyara for her critical review of our paper.

References

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Jump To

This article references 7 other publications.

  1. 1
    Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome. Nucleotide, National Center for Biotechnology Information (NCBI), National Library of Medicine (US), National Center for Biotechnology Information, Bethesda, MD, https://www.ncbi.nlm.nih.gov/nuccore/1798174254 (accessed on 2020-02-28).
  2. 2
    Palasca, O., Santos, A., Stolte, C., Gorodkin, J., and Jensen, L. J. (2018) TISSUES 2.0: an integrative web resource on mammalian tissue expression. Database 2018, bay003  DOI: 10.1093/database/bay003
  3. 3
    Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., and Perlman, S. (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 82 (15), 726475,  DOI: 10.1128/JVI.00737-08
  4. 4
    Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Li, Y., Jin, H., and Hu, B. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.02.22.20026500 DOI: 10.1101/2020.02.22.20026500 (accessed on 2020-02-28).
  5. 5
    Li, Y. C., Bai, W. Z., and Hashikawa, T. (2020) The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J. Med. Virol.  DOI: 10.1002/jmv.25728
  6. 6
    Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., Graham, B. S., and McLellan, J. S. (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science eabb2507  DOI: 10.1126/science.abb2507
  7. 7
    Baig, A. M. (2016) Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri. ACS Chem. Neurosci. 7 (8), 10269,  DOI: 10.1021/acschemneuro.6b00197

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  45. Difang Sun, Zongyi Zhan, Bin Wang, Ting Liu, Minbin Yu, Yuqing Lan, Jun Li. Expression of the SARS-CoV-2 Receptor ACE2 and Protease TMPRSS2 in Ocular Hypertension Eyes of Nonhuman Primate and Human. Current Eye Research 2024, 49 (3) , 270-279. https://doi.org/10.1080/02713683.2023.2291749
  46. Salma Ahsanuddin, Ryan Jin, Aatin K. Dhanda, Kirolos Georges, Soly Baredes, Jean Anderson Eloy, Christina H. Fang. Otolaryngologic Side Effects After COVID ‐19 Vaccination. The Laryngoscope 2024, 134 (3) , 1163-1168. https://doi.org/10.1002/lary.30923
  47. Hyunjin Ju, Jin Myoung Seok, Yeon Hak Chung, Mi Young Jeon, Hye Lim Lee, Soonwook Kwon, Sunyoung Kim, Ju-Hong Min, Byoung Joon Kim. Evaluation of SARS-CoV-2 Vaccine-Induced Antibody Responses in Patients with Neuroimmunological Disorders: A Real-World Experience. Diagnostics 2024, 14 (5) , 502. https://doi.org/10.3390/diagnostics14050502
  48. Gauthier Duloquin, Thibaut Pommier, Marjolaine Georges, Maurice Giroud, Charles Guenancia, Yannick Béjot, Gabriel Laurent, Claudio Rabec. Is COVID-19 Infection a Multiorganic Disease? Focus on Extrapulmonary Involvement of SARS-CoV-2. Journal of Clinical Medicine 2024, 13 (5) , 1397. https://doi.org/10.3390/jcm13051397
  49. Yangguang Lu, Jialing Lou, Bohuai Yu, Yiran Bu, Feitian Ni, Di Lu. The prevalence and risk of depression in aged COVID ‐19 survivors: a bibliometric and meta‐analysis. Psychogeriatrics 2024, 24 (2) , 458-472. https://doi.org/10.1111/psyg.13057
  50. Rosa María Romero Castro, Gabriela González Cannata, Ana Sánchez Tlapalcoyoatl. Posterior Segment Ocular Findings in Critically Ill Patients with COVID. 2024https://doi.org/10.5772/intechopen.1004050
  51. Alessanda S. Rieder, Angela T. S. Wyse. Regulation of Inflammation by IRAK-M Pathway Can Be Associated with nAchRalpha7 Activation and COVID-19. Molecular Neurobiology 2024, 61 (2) , 581-592. https://doi.org/10.1007/s12035-023-03567-6
  52. Lei Liu, Ya Li, Jia-Xin Li, Xue Xiao, Tian-Tian Wan, Hui-Hua Li, Shu-Bin Guo. ACE2 Expressed on Myeloid Cells Alleviates Sepsis-Induced Acute Liver Injury via the Ang-(1–7)–Mas Receptor Axis. Inflammation 2024, 6 https://doi.org/10.1007/s10753-023-01949-5
  53. Jane Shi, Helen V. Danesh-Meyer. A review of neuro-ophthalmic sequelae following COVID-19 infection and vaccination. Frontiers in Cellular and Infection Microbiology 2024, 14 https://doi.org/10.3389/fcimb.2024.1345683
  54. Jieun Shin, Sung Ryul Shim, Jaekwang Lee, Hyon Shik Ryu, Jong-Yeup Kim. Otorhinolaryngologic complications after COVID-19 vaccination, vaccine adverse event reporting system (VAERS). Frontiers in Public Health 2024, 11 https://doi.org/10.3389/fpubh.2023.1338862
  55. Sara Manti, Giulia Spoto, Antonio Gennaro Nicotera, Gabriella Di Rosa, Giovanni Piedimonte. Impact of respiratory viral infections during pregnancy on the neurological outcomes of the newborn: current knowledge. Frontiers in Neuroscience 2024, 17 https://doi.org/10.3389/fnins.2023.1320319
  56. Xiaolan Zhao, . Present situation about COVID-19 patients with myocarditis: how to protect the at-risk crowd. 2024, 79. https://doi.org/10.1117/12.3013055
  57. Kowsar Bavarsad, Davood Shalil Ahmadi, Mohammad Momeni, Mohammad Jafar Yadyad, Roya Salehi Kahyesh, Hamid Moradzadegan, Samireh Ghafouri. Evaluation of the relationship between serum BDNF concentration and indicators of oxidative stress and inflammation in COVID-19 patients with neurological disorders - a pilot study. Neurological Research 2024, 46 (1) , 33-41. https://doi.org/10.1080/01616412.2023.2257448
  58. Artur Fedorowski, Alessandra Fanciulli, Satish R. Raj, Robert Sheldon, Cyndya A. Shibao, Richard Sutton. Cardiovascular autonomic dysfunction in post-COVID-19 syndrome: a major health-care burden. Nature Reviews Cardiology 2024, 21 https://doi.org/10.1038/s41569-023-00962-3
  59. Aline Diniz Gehren, Daniel Vicentini de Oliveira, Rose Mari Bennemann, Luciana Lozza de Moraes Marchiori, Caio Sabino Ferreira, Caroline Pereira Buturi Arruda, Mariana Zamboni Gasparini. The use of photobiomodulation in swallowing difficulties in individuals who developed the severe form of COVID-19. Revista CEFAC 2024, 26 (1) https://doi.org/10.1590/1982-0216/20242612823
  60. Aline Diniz Gehren, Daniel Vicentini de Oliveira, Rose Mari Bennemann, Luciana Lozza de Moraes Marchiori, Caio Sabino Ferreira, Caroline Pereira Buturi Arruda, Mariana Zamboni Gasparini. O uso da fotobiomodulação na dificuldade de deglutição em indivíduos que desenvolveram a forma grave da COVID-19. Revista CEFAC 2024, 26 (1) https://doi.org/10.1590/1982-0216/20242612823s
  61. Negar Omidkhah, Farzin Hadizadeh, Razieh Ghodsi. HDAC Inhibitors against SARS-CoV-2. Letters in Drug Design & Discovery 2024, 21 (1) , 2-14. https://doi.org/10.2174/1570180819666220527160528
  62. Song Liu, Teli Liu, Wei Tian, Qian Zhang, Zilei Wang, Xingguo Hou, Yanan Ren, Wanpu Yan, Meng Xu, Hongbin Han, Hua Zhu. Unique role of molecular imaging probes for viral infection. TrAC Trends in Analytical Chemistry 2024, 170 , 117470. https://doi.org/10.1016/j.trac.2023.117470
  63. Ravindra Kumar Garg, Hardeep Singh Malhotra, Neeraj Kumar. Pathophysiology of Acute Disseminated Encephalomyelitis – Immune and Autoimmune Aspects. 2024, 963-1011. https://doi.org/10.1016/B978-0-323-99130-8.00004-0
  64. Omar Althomali, Junaid Amin, Daria Shaik, Wael Alghamdi, Ahmed Ibrahim, Hisham Hussein, Raheela Kanwal. Short-Term and Long-Term Impact of COVID-19 on Quality of Life and Psychological Outcomes in Saudi Arabia: A Comparative Cross-Sectional Study. Journal of Multidisciplinary Healthcare 2024, Volume 17 , 505-515. https://doi.org/10.2147/JMDH.S449152
  65. Majid Rezvani, Masih Sabouri, Bahram Aminmansour, Soheil Falahpour, Arman Sourani, Mohammad Sharafi, Sadegh Baradaran Mahdavi, Mina Foroughi, Roham Nik Khah, Armin Sourani, Shaahin Veisi. Spontaneous spinal epidural haematoma following COVID-19 vaccination: a case report. Annals of Medicine & Surgery 2024, 86 (1) , 612-619. https://doi.org/10.1097/MS9.0000000000001604
  66. Jin-Man Jung, András Gruber, Peter Heseltine, Kumar Rajamani, Sebastián F. Ameriso, Mark J. Fisher. New Directions in Infection-Associated Ischemic Stroke. Journal of Clinical Neurology 2024, 20 (2) , 140. https://doi.org/10.3988/jcn.2023.0056
  67. Eri Inoue, Irfan Kesumayadi, Shingo Fujio, Ryutaro Makino, Tomoko Hanada, Keisuke Masuda, Nayuta Higa, Shigeru Kawade, Yuichiro Niihara, Hirosuke Takagi, Ikumi Kitazono, Yutaka Takahashi, Ryosuke Hanaya. Secondary hypophysitis associated with Rathke’s cleft cyst resembling a pituitary abscess. Surgical Neurology International 2024, 15 , 69. https://doi.org/10.25259/SNI_947_2023
  68. Olena V. Lobova, Iryna V. Avramenko, Iryna I. Shpak. COVID-19 associated anosmia in pediatric patients: subject publications review. Wiadomości Lekarskie 2024, 77 (1) , 114-119. https://doi.org/10.36740/WLek202401114
  69. Charles W. Stratton, Yi-Wei Tang. COVID-19 therapy directed against pathogenic mechanisms of severe acute respiratory syndrome coronavirus 2. 2024, 2697-2726. https://doi.org/10.1016/B978-0-12-818619-0.00053-8
  70. Kaouther Chebbi, Aymen Ammari, Seyed Alireza Athari, Kashif Abbass. Do US States’ Responses to COVID-19 Restore Investor Sentiment? Evidence from S&P 500 Financial Institutions. SSRN Electronic Journal 2024, 74 https://doi.org/10.2139/ssrn.4748881
  71. Yan Zhao, Xin Gao, Guangping Wang, Jiali Ren, Weisan Chen, Ying Zhao, Xiankuan Li, Jian Zhang. Post-COVID-19 symptom burden: treatment with Forsythiae Fructus. Future Virology 2024, 19 (1) , 59-75. https://doi.org/10.2217/fvl-2023-0190
  72. 玉墀 温. Research Progress on the Relationship between Novel Coronavirus Infection and Sleep Disorder. International Journal of Psychiatry and Neurology 2024, 13 (01) , 1-7. https://doi.org/10.12677/ijpn.2024.131001
  73. Muhammad Hammad Sharif, Madeeha Khaleeque, Asad Ali Khan, Muhammad Hassan Jan, Atif Ahmed, Nida Latif, Abdul Qadir, Muhammad Hanif, Amjid Iqbal. Encephalitis as a Clinical Manifestation of COVID-19: A Case Series. Case Reports in Neurology 2023, 15 (1) , 131-139. https://doi.org/10.1159/000530926
  74. V. T. Ivashkin, R. A. Abdulkhakov, I. G. Bakulin, S. V. Zaitsev, V. I. Luchina, S. N. Mekhtiyev, S. G. Peshekhonov, E. A. Poluektova, T. I. Semenova, S. N. Serikova, G. N. Tarasova, E. A. Trush, Y. P. Uspenskiy, I. B. Khlynov, V. V. Tsukanov, N. P. Chernus. COVID-19 Pandemic and IBS. Results of the All-Russian Observational Non-interventional Program to Study the Effectiveness of the Drug Kolofort® in Real Clinical Practice in Patients with Irritable Bowel Syndrome After a New Coronavirus Infection (VESNA). Russian Journal of Gastroenterology, Hepatology, Coloproctology 2023, 33 (5) , 41-53. https://doi.org/10.22416/1382-4376-2023-33-5-41-53
  75. Ahsan Riaz, Nimra Riaz, Hamad Raza, Farhan Mirza. Green Banking Practices: A Bibliometric Analysis and Systematic Literature Review. 2023, 299-317. https://doi.org/10.1108/978-1-80455-678-820231016
  76. Amir Aboofazeli, Sheida Sarrafzadeh, Ali Qaraee Najafabadi, Behnaz Hammami, Roben Soheili, Ahmadreza Sadeghi, Arash Letafati. A Survey on Respiratory and Neurological Symptoms in Alzheimer’s, Schizophrenia, Bipolar, and Migraine Patients Following COVID-19 Infection. Archives of Neuroscience 2023, 10 (4) https://doi.org/10.5812/ans-140959
  77. Chien-Chiang Lee, Chuan Zhang, Dan Ma. Can the Social Network Hinder the Impact of COVID-19 on Economic Uncertainty? New Evidence from China. Emerging Markets Finance and Trade 2023, 59 (15) , 4088-4106. https://doi.org/10.1080/1540496X.2023.2178844
  78. Shengnan Wang, Lijuan Wang, Jianglong Wang, Mingqin Zhu. Causal relationships between susceptibility and severity of COVID-19 and neuromyelitis optica spectrum disorder (NMOSD) in European population: a bidirectional Mendelian randomized study. Frontiers in Immunology 2023, 14 https://doi.org/10.3389/fimmu.2023.1305650
  79. Ted L. Rothstein. Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”. BMC Neurology 2023, 23 (1) https://doi.org/10.1186/s12883-023-03049-1
  80. Cun Li, Hong-bin Cai, Qing Zhou, Hua-qiu Zhang, Man Wang, Hui-cong Kang. Sleep disorders in the acute phase of coronavirus disease 2019: an overview and risk factor study. Annals of General Psychiatry 2023, 22 (1) https://doi.org/10.1186/s12991-023-00431-8
  81. Payman Asadi, Saba Maleki, Seyyed Mahdi Zia Ziabari, Nazanin Noori Roodsari. A 14-year-old boy with multiple trauma and bilateral basal ganglia hemorrhage due to coronavirus disease 2019: a case report. Journal of Medical Case Reports 2023, 17 (1) https://doi.org/10.1186/s13256-023-03824-1
  82. Darja Beyer, Christian Vaccarin, Xavier Deupi, Ana Katrina Mapanao, Susan Cohrs, Fan Sozzi-Guo, Pascal V. Grundler, Nicholas P. van der Meulen, Jinling Wang, Matthias Tanriver, Jeffrey W. Bode, Roger Schibli, Cristina Müller. A tool for nuclear imaging of the SARS-CoV-2 entry receptor: molecular model and preclinical development of ACE2-selective radiopeptides. EJNMMI Research 2023, 13 (1) https://doi.org/10.1186/s13550-023-00979-2
  83. Lamiaa I. Daker, Reham R. Elshafei, Mohammad Bahi, Asmaa Mohammed, Randa Erfan, Mohammed Gomaa. Could vertigo be a post-COVID-19 sequela or presenting symptom?. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery 2023, 59 (1) https://doi.org/10.1186/s41983-023-00659-x
  84. Srinagesh Mannekote Thippaiah, Shabbir Amanullah, Zi Huai Huang, Edward Goldschmidt, Basant Pradhan. Biological correlates of the neuropsychiatric symptoms in SARS-CoV-2 infection: an updated review. The Egyptian Journal of Neurology, Psychiatry and Neurosurgery 2023, 59 (1) https://doi.org/10.1186/s41983-023-00705-8
  85. Stefano Rigo, Vasile Urechie, Andrè Diedrich, Luis E. Okamoto, Italo Biaggioni, Cyndya A. Shibao. Impaired parasympathetic function in long-COVID postural orthostatic tachycardia syndrome – a case-control study. Bioelectronic Medicine 2023, 9 (1) https://doi.org/10.1186/s42234-023-00121-6
  86. Perez A. M. C., Silva M. B. C, Macêdo L. P. G., Chaves Filho A. C., Dutra R. A. F, Rodrigues M. A. B.. Physical therapy rehabilitation after hospital discharge in patients affected by COVID-19: a systematic review. BMC Infectious Diseases 2023, 23 (1) https://doi.org/10.1186/s12879-023-08313-w
  87. Gisela Roxana Edith Lisi, Francisco Appiani, María Eugenia Basile, Marcelo Garro, Juan Manuel Duarte. Pathophysiological Hypothesis of COVID-19 Psychosis. Journal of Nervous & Mental Disease 2023, 211 (12) , 890-895. https://doi.org/10.1097/NMD.0000000000001624
  88. Ksenija Marinkovic, David R. White, Austin Alderson Myers, Katie S. Parker, Donatello Arienzo, Graeme F. Mason. Cortical GABA Levels Are Reduced in Post-Acute COVID-19 Syndrome. Brain Sciences 2023, 13 (12) , 1666. https://doi.org/10.3390/brainsci13121666
  89. Ya-Chun Chu, Shin-Tsu Chang, Hung-Yen Chan, Daniel Hueng-Yuan Shen, Hung-Pin Chan. Abnormalities in Regional Cerebral Blood Flow Due to Headache in a COVID-19 Infected Patient Observed on 99mTC-ECD Brain SPECT/CT. Reports 2023, 6 (4) , 58. https://doi.org/10.3390/reports6040058
  90. Sheng Zhong, Wenzhuo Yang, Zhiyun Zhang, Yangyiran Xie, Lin Pan, Jiaxin Ren, Fei Ren, Yifan Li, Haoqun Xie, Hongyu Chen, Davy Deng, Jie Lu, Hui Li, Bo Wu, Youqi Chen, Fei Peng, Vinay K. Puduvalli, Ke Sai, Yunqian Li, Ye Cheng, Yonggao Mou. Association between viral infections and glioma risk: a two-sample bidirectional Mendelian randomization analysis. BMC Medicine 2023, 21 (1) https://doi.org/10.1186/s12916-023-03142-9
  91. Rashmin Hira, Kavithra Karalasingham, Jacquie R. Baker, Satish R. Raj. Autonomic Manifestations of Long-COVID Syndrome. Current Neurology and Neuroscience Reports 2023, 23 (12) , 881-892. https://doi.org/10.1007/s11910-023-01320-z
  92. Jeyasakthy Saniasiaya, Jeyanthi Kulasegarah. Acute labyrinthitis: a manifestation of COVID-19 in a teenager. BMJ Case Reports 2023, 16 (12) , e258290. https://doi.org/10.1136/bcr-2023-258290
  93. Mumin Alper Erdogan, Miray Turk, Gizem Dinler Doganay, Ibrahim Halil Sever, Bahattin Ozkul, Ibrahim Sogut, Ebru Eroglu, Yigit Uyanikgil, Oytun Erbas. Prenatal SARS-CoV-2 Spike Protein Exposure Induces Autism-Like Neurobehavioral Changes in Male Neonatal Rats. Journal of Neuroimmune Pharmacology 2023, 18 (4) , 573-591. https://doi.org/10.1007/s11481-023-10089-4
  94. Martha-Lilia Tena-Suck, Steven-Andrés Piña-Ballantyne, Jesús Cienfuegos-Meza, Marco-Antonio Jiménez-López, Andrea Ávalos-Arias. Schwannoma and Post-vaccine Changes: A Case Report. Cureus 2023, 23 https://doi.org/10.7759/cureus.48223
  95. Nathan W. Churchill, Eugenie Roudaia, J. Jean Chen, Asaf Gilboa, Allison Sekuler, Xiang Ji, Fuqiang Gao, Zhongmin Lin, Mario Masellis, Maged Goubran, Jennifer S. Rabin, Benjamin Lam, Ivy Cheng, Robert Fowler, Chris Heyn, Sandra E. Black, Bradley J. MacIntosh, Simon J. Graham, Tom A. Schweizer. Persistent post‐COVID headache is associated with suppression of scale‐free functional brain dynamics in non‐hospitalized individuals. Brain and Behavior 2023, 13 (11) https://doi.org/10.1002/brb3.3212
  96. Giuseppina Amadoro, Valentina Latina, Egidio Stigliano, Alessandra Micera. COVID-19 and Alzheimer’s Disease Share Common Neurological and Ophthalmological Manifestations: A Bidirectional Risk in the Post-Pandemic Future. Cells 2023, 12 (22) , 2601. https://doi.org/10.3390/cells12222601
  97. Diogo Costa Garção, Alisson Guilherme da Silva Correia, Francisco José Silva Ferreira, Pedro Costa Pereira, Luiz Ricardo Góis Fontes, Lis Campos Ferreira. Prevalence and risk factors for seizures in adult COVID-19 patients: A meta-analysis. Epilepsy & Behavior 2023, 148 , 109501. https://doi.org/10.1016/j.yebeh.2023.109501
  98. Ceyda Hayretdağ. Mortality Attributed to Central and Peripheral Nervous System Disorders: A Five-years Comprehensive Review from Turkey. Medical Science and Discovery 2023, 10 (10) , 901-906. https://doi.org/10.36472/msd.v10i10.1086
  99. , S. A. Babanov, L. А. Strizhakov, , T. A. Azovskova, , N. E. Lavrentieva, . Multisystem pathological changes associated with COVID-19 in a medical worker (case study). Terapevt (General Physician) 2023, 52 (10) , 45-54. https://doi.org/10.33920/MED-12-2310-05
  100. Serdar Aykaç, Dilek Eker Büyükşireci, Hilal Boyaci. An analysis of neuropathic pain, vasomotor manifestations, and sympathetic skin reactions in post-COVID-19 patients relative to healthy individuals. Medicine 2023, 102 (43) , e35819. https://doi.org/10.1097/MD.0000000000035819
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  • Abstract

    Figure 1

    Figure 1. Tissue distribution of ACE2 receptors in humans. Viremia (A) disseminates the COVID-19 virus throughout the body via the bloodstream (B). Neurotropism may occur via circulation and/or an upper nasal trancribrial route that enables the COVID-19 to reach the brain (C) and bind and engage with the ACE2 receptors (D, blue). COVID-19 docks on the ACE2 via spike protein (D, golden spikes). Shown are lungs, heart, kidneys, intestines, brain, and testicles that are well-known to express ACE2 receptors and are possible targets of COVID-19.

    Figure 2

    Figure 2. (A) Sequence alignment of COVID-19 RBD subdomain-1 (319th to 591st) amino acid (top row) with the bat and SARS-CoV spike protein (middle and bottom row) that were fetched from BLASTp results of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acids. Note horizontal arrows that show areas of contrast between the sequences. (A1) Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template (6vsb.1. A)-based model of the COVID-19 virus spike glycoprotein. (B). Homology modeling of the COVID-19 virus RBD subdomain-1 (319th to 591st) amino acid developed a template-(5x5b.1.A) based model of the prefusion structure of SARS-CoV spike glycoprotein in conformation 2 (B1) with 73.96% sequence identity. [Uniprot and SWISS-MODEL automated server were used for sequence alignments and development of the templates and models, respectively.]

  • References

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    Jump To

    This article references 7 other publications.

    1. 1
      Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome. Nucleotide, National Center for Biotechnology Information (NCBI), National Library of Medicine (US), National Center for Biotechnology Information, Bethesda, MD, https://www.ncbi.nlm.nih.gov/nuccore/1798174254 (accessed on 2020-02-28).
    2. 2
      Palasca, O., Santos, A., Stolte, C., Gorodkin, J., and Jensen, L. J. (2018) TISSUES 2.0: an integrative web resource on mammalian tissue expression. Database 2018, bay003  DOI: 10.1093/database/bay003
    3. 3
      Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., and Perlman, S. (2008) Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J. Virol. 82 (15), 726475,  DOI: 10.1128/JVI.00737-08
    4. 4
      Mao, L., Wang, M., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Li, Y., Jin, H., and Hu, B. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv, 2020.02.22.20026500 DOI: 10.1101/2020.02.22.20026500 (accessed on 2020-02-28).
    5. 5
      Li, Y. C., Bai, W. Z., and Hashikawa, T. (2020) The neuroinvasive potential of SARS-CoV2 may be at least partially responsible for the respiratory failure of COVID-19 patients. J. Med. Virol.  DOI: 10.1002/jmv.25728
    6. 6
      Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C. L., Abiona, O., Graham, B. S., and McLellan, J. S. (2020) Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science eabb2507  DOI: 10.1126/science.abb2507
    7. 7
      Baig, A. M. (2016) Primary Amoebic Meningoencephalitis: Neurochemotaxis and Neurotropic Preferences of Naegleria fowleri. ACS Chem. Neurosci. 7 (8), 10269,  DOI: 10.1021/acschemneuro.6b00197

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