{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:59:27Z","timestamp":1792807167468,"version":"4.5.0"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ontario Ministry of Colleges and Universities","award":["COVID-19 Rapid Research Fund"],"award-info":[{"award-number":["COVID-19 Rapid Research Fund"]}],"id":[{"id":"https:\/\/ror.org\/03tee2f33","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Research Council of Canada","award":["Pandemic Response Challenge Program Grant"],"award-info":[{"award-number":["Pandemic Response Challenge Program Grant"]}],"id":[{"id":"https:\/\/ror.org\/04mte1k06","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>This mini-review focuses on the mechanisms of how severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) affects the brain, with an emphasis on the role of the spike protein in patients with neurological symptoms. Following infection, patients with a history of neurological complications may be at a higher risk of developing long-term neurological conditions associated with the \u03b1-synuclein prion, such as Parkinson\u2019s disease and Lewy body dementia. Compelling evidence has been published to indicate that the spike protein, which is derived from SARS-CoV-2 and generated from the vaccines currently being employed, is not only able to cross the blood\u2013brain barrier but may cause inflammation and\/or blood clots in the brain. Consequently, should vaccine-induced expression of spike proteins not be limited to the site of injection and draining lymph nodes there is the potential of long-term implications following inoculation that may be identical to that of patients exhibiting neurological complications after being infected with SARS-CoV-2. However, further studies are needed before definitive conclusions can be made.<\/jats:p>","DOI":"10.3390\/vaccines10010001","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T09:50:43Z","timestamp":1640080243000},"page":"1","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["How Does Severe Acute Respiratory Syndrome-Coronavirus-2 Affect the Brain and Its Implications for the Vaccines Currently in Use"],"prefix":"10.3390","volume":"10","author":[{"given":"Philip R.","family":"Oldfield","sequence":"first","affiliation":[{"name":"Scientific and Regulatory Consultant, Rigaud, QC J0P 1P0, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hibberd","sequence":"additional","affiliation":[{"name":"Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1X3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8335-1118","authenticated-orcid":false,"given":"Byram W.","family":"Bridle","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Guelph, Guelph, ON N1G 2W1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1212\/WNL.0000000000009455","article-title":"Neurologic complications of coronavirus infections","volume":"94","author":"Nath","year":"2020","journal-title":"Neurology"},{"key":"ref_2","first-page":"520","article-title":"Neurological Complications Associated with the Blood-Brain Barrier Damage Induced by the Inflammatory Response during SARS-CoV-2 Infection","volume":"58","author":"Aguilera","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cmi.2020.03.026","article-title":"COVID-19, SARS and MERS: Are they closely related?","volume":"26","author":"Petrosillo","year":"2020","journal-title":"Clin. Microbiol. Inf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.idc.2019.07.001","article-title":"Severe Acute Respiratory Syndrome, Historical, Epidemiologic, and Clinical Features","volume":"33","author":"Hui","year":"2019","journal-title":"Infect. Dis Clin. N. Am."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.ijid.2014.09.003","article-title":"Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: A single-center experience in Saudi Arabia","volume":"29","author":"Saad","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_6","unstructured":"Government of Canada (2021, June 17). COVID-19 Sgns, Symptoms and Severity of Disease: A Clinician Guide, Available online: https:\/\/www.canada.ca\/en\/public-health\/services\/diseases\/2019-novel-coronavirus-infection\/guidance-documents\/signs-symptoms-severity.html."},{"key":"ref_7","first-page":"e8136","article-title":"Pathological Findings and Management of COVID-19 Patients: A Brief Overview of Modern-day Pandemic","volume":"12","author":"Mian","year":"2020","journal-title":"Cureus"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1093\/infdis\/jit504","article-title":"Active Replication of Middle East Respiratory Syndrome Coronavirus and Aberrant Induction of Inflammatory Cytokines and Chemokines in Human Macrophages: Implications for Pathogenesis","volume":"209","author":"Zhou","year":"2014","journal-title":"J. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.3389\/fimmu.2020.01022","article-title":"Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-CoV-2 Infection","volume":"11","author":"Liang","year":"2020","journal-title":"Front. Immu."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/nm1267","article-title":"A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus\u2013induced lung injury","volume":"11","author":"Kuba","year":"2005","journal-title":"Nat. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"349","DOI":"10.21037\/atm.2018.04.29","article-title":"Heart-lung interactions during mechanical ventilation: The basics","volume":"6","author":"Mahmood","year":"2018","journal-title":"Ann. Transl. Med."},{"key":"ref_12","first-page":"1","article-title":"Long-term Clinical Outcomes in Survivors of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) Coronavirus Outbreaks After Hospitalisation or ICU Admission: A Systematic Review and Meta-Analysis","volume":"52","author":"Ahmed","year":"2020","journal-title":"J. Rehabil. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/j.1440-1843.2010.01720.x","article-title":"The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status","volume":"15","author":"Ngai","year":"2010","journal-title":"Respirology"},{"key":"ref_14","first-page":"682","article-title":"How COVID-19 Affects the Brain","volume":"78","author":"Boldrini","year":"2021","journal-title":"JAMA Psych. Clin. Rev. Educ."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Brann, D.H., Tsukahara, T., Weinreb, C., Lipovsek, M., Van den Berge, K., Gong, B., Chance, R., Macaulay, I.C., Chou, H.-J., and Fletcher, R. (2020). Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19 associated anosmia. bioRxiv, preprint.","DOI":"10.1101\/2020.03.25.009084"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fodoulian, L., Tuberosa, J., Rossier, D., Boillat, M., Kan, C., Pauli, V., Egervari, K., Lobrinus, J.A., Landis, B.N., and Carleton, A. (2020). SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium. bioRxiv, preprint.","DOI":"10.1101\/2020.03.31.013268"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13045-020-00954-7","article-title":"SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19","volume":"13","author":"Zhang","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1084\/jem.20202135","article-title":"Neuroinvasion of SARS-CoV-2 in human and mouse brain","volume":"218","author":"Song","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1002\/mds.28084","article-title":"SARS-CoV-2: At the Crossroad between Aging and Neurodegeneration","volume":"35","author":"Lippi","year":"2020","journal-title":"Mov. Disord."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Philippens, I.H.C.H.M., B\u00f6sz\u00f6rm\u00e9nyi, K.P., Wubben, J.A., Fagrouch, Z.C., van Driel, N., Mayenburg, A.Q., Lozovagia, D., Roos, E., Schurink, B., and Bugiani, M. (2021). SARS-CoV-2 causes brain inflammation and induces Lewy body formation in macaques. bioRxiv, preprint.","DOI":"10.1101\/2021.02.23.432474"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.tins.2020.10.009","article-title":"Is COVID-19 a perfect storm for Parkinson\u2019s disease","volume":"43","author":"Brundin","year":"2020","journal-title":"Trends Neurosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"105131","DOI":"10.1016\/j.nbd.2020.105131","article-title":"The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood\u2013brain barrier","volume":"146","author":"Buzhdygan","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/s41593-020-00771-8","article-title":"The S1 protein of SARS-CoV-2 crosses the blood\u2013brain barrier in mice","volume":"24","author":"Rhea","year":"2021","journal-title":"Nat. Neurosci."},{"key":"ref_24","unstructured":"Ogata, A.F., Cheng, C., Desjardins, M., Senussi, Y., Sherman, A.C., Powell, M., Novack, L., Von, S., Li, X., and Baden, L.R. (2021). Circulating SARS-CoV-2 Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients. Clin. Infect. Dis., ciab465."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.heliyon.2021.e06187","article-title":"SARS-CoV-2 spike protein S1 subunit induces pro-inflammatory responses via toll-like receptor 4 signaling in murine and human macrophages","volume":"7","author":"Shirato","year":"2021","journal-title":"Heliyon"},{"key":"ref_26","unstructured":"FDA (2021, April 27). FDA Briefing Document Pfizer-BioNTech COVID-19 Vaccine, Available online: https:\/\/www.fda.gov\/media\/144245\/download."},{"key":"ref_27","unstructured":"European Medicines Agency (2021, January 06). Assessment Report-COVID-19 Vaccine Moderna (EMA\/15689\/2021). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/covid-19-vaccine-moderna-epar-public-assessment-report_en.pdf."},{"key":"ref_28","unstructured":"European Medicines Agency (2021, March 11). Assessment Report-COVID-19 Vaccine Janssen (EMA\/158424\/2021). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/covid-19-vaccine-janssen-epar-public-assessment-report_en.pdf."},{"key":"ref_29","unstructured":"FDA (2021, August 23). BLA (STN: BL 125742\/0) Approval Letter, Available online: https:\/\/www.fda.gov\/media\/151710\/download."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/ane.13417","article-title":"The potential neurological effect of the COVID-19 vaccines: A review","volume":"144","author":"Lu","year":"2021","journal-title":"Acta Neurol. Scand."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/ana.26065","article-title":"ANA Investigates: Neurological Complications of COVID-19 Vaccines","volume":"89","author":"Goss","year":"2021","journal-title":"Ann. Neurol."},{"key":"ref_32","first-page":"328","article-title":"Functional Neurological Disorders and COVID-19 Vaccination","volume":"90","author":"Chaudhuri","year":"2020","journal-title":"Ann. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/ane.13444","article-title":"Neurological side effects of COVID-19 vaccines are rare","volume":"144","author":"Lu","year":"2021","journal-title":"Acta Neurol. Scand."},{"key":"ref_34","unstructured":"(2021, August 25). The Label. COMIRNATY\u00ae (COVID-19 Vaccine, mRNA) Suspension for Injection, for Intramuscular Use. Initial U.S. Approval: 2021, Available online: https:\/\/www.fda.gov\/media\/151707\/download."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4049\/jimmunol.2100637","article-title":"Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines","volume":"207","author":"Bansal","year":"2021","journal-title":"J. Immunol."},{"key":"ref_36","unstructured":"Centers for Disease Control and Prevention (CDC) (2021, December 10). Clinical Considerations: Myocarditis and Pericarditis after Receipt of mRNA COVID-19 Vaccines among Adolescents and Young Adults, Available online: https:\/\/www.cdc.gov\/vaccines\/covid-19\/clinical-considerations\/myocarditis.html."},{"key":"ref_37","unstructured":"(2021, August 23). FDA-Summary Basis for Regulatory Action Date: 23 August 2021. Submitted a Biologics License Application (BLA) STN BL 125742 for Licensure of COVID-19 Vaccine, mRNA, Available online: https:\/\/www.fda.gov\/media\/151733\/download."},{"key":"ref_38","unstructured":"(2021, November 07). FDA-Guidance for Industry Preclinical Assessment of Investigational Cellular and Gene Therapy Products\u2014(Issued November 2013), Available online: https:\/\/www.fda.gov\/media\/87564\/download."},{"key":"ref_39","unstructured":"(2021, November 07). FDA-Development and Licensure of Vaccines to Prevent COVID-19 Guidance for Industry\u2014(Issued June 2020), Available online: https:\/\/www.fda.gov\/media\/139638\/download."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/1\/1\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:50:15Z","timestamp":1760169015000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/10\/1\/1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,21]]},"references-count":39,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["vaccines10010001"],"URL":"https:\/\/doi.org\/10.3390\/vaccines10010001","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,21]]}}}