The current coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the greatest medical crises faced by our current generation of health care providers. Although much remains to be learned about the pathophysiology of SARS-CoV-2, there is both historical precedent from other coronaviruses and a growing number of case reports and series that point to neurologic consequences of COVID-19.
Recent Findings
Olfactory/taste disturbances and increased risk of strokes and encephalopathies have emerged as potential consequences of COVID-19 infection. Evidence regarding whether these sequelae result indirectly from systemic infection or directly from neuroinvasion by SARS-CoV-2 is emerging.
Summary
This review summarizes the current understanding of SARS-CoV-2 placed in context with our knowledge of other human coronaviruses. Evidence and data regarding neurologic sequelae of COVID-19 and the neuroinvasive potential of human coronaviruses are provided along with a summary of patient registries of interest to the Neurology community.
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The authors report no disclosures relevant to the manuscript. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
Take-home Points
→ Human coronaviruses have been shown to be neuropathogenic.
→ Potential mechanisms of neuropathogenesis of SARS-CoV-2 include hematogenous and transsynaptic spread based on viral receptor expression.
→ Neurologic sequelae of COVID-19 involve indirect, direct, and postinfectious disease mechanisms with consequences that include stroke, encephalitis/encephalopathy, and Guillain-Barré syndrome.
→ Patient registries will be useful to identify and track neurologic sequelae of SARS-CoV-2 infection and will improve our understanding of the impact of COVID-19 on the nervous system.
Study Funding
B.H. is supported by funding from the NIH (NIDCD DC014728-04S1 to Dr. Finger). A.M.H. is supported by a fellowship from the NIAID (F30 AI136403-01A1). K.L.T. is supported by funding from the NIH (R01 NS101208) and is the recipient of a VA Merit Award.
Medical Scientist Training Program (BH, AMH), Rocky Mountain Taste and Smell Center (BH), Department of Neurology (KLT, ALP, VSP), and Department of Ophthalmology (VSP), University of Colorado School of Medicine, Aurora.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
Medical Scientist Training Program (BH, AMH), Rocky Mountain Taste and Smell Center (BH), Department of Neurology (KLT, ALP, VSP), and Department of Ophthalmology (VSP), University of Colorado School of Medicine, Aurora.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
(1) NIH NIAID, invited speaker with paid travel expenses
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
(1) NIH NIAID, F30 AI136403, PI, 2
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
Medical Scientist Training Program (BH, AMH), Rocky Mountain Taste and Smell Center (BH), Department of Neurology (KLT, ALP, VSP), and Department of Ophthalmology (VSP), University of Colorado School of Medicine, Aurora.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NOT Related to SARSCoV2 or the manuscript(1) DNAtrix Therapeutics, Houston TX (DSMB, active)
Editorial Boards:
1.
(1) Associate editor, Journal of NeurovirologyEditorial Boards: (2) Annals of Neurology (3) JAMA Neurology(4) Neurology(5) Experimental Neurology(6) Journal of Infectious Disease(7) Microbial Pathogenesis(8) Virology(9) Pathogens(10) Frontiers in NeurologyALL Current
Patents:
1.
NONE
Publishing Royalties:
1.
(1) Handbook of Clinical Neurology, Elsevier vol. 95, 2010(2) Harrison's Principles & Practices of InternalMedicine, McGraw-Hill (20th ed), 2018(Both are Royalties)
Employment, Commercial Entity:
1.
(1) University of Colorado School of Medicine(2) Department of Veterans Affairs (Rocky Mountain VAMedical Center)
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE related to SARSCoV2 or manuscript(1) Taiga Biotechnologies- Research Support- for studies of a peptide immunoadjuvant in viral infections that caninvolve the nervous system. (2) Anti-Plasmin Technology- studies related to treatment of EV-D68(3) Zab Bio- studies of MAbs in treatment of EV-D68(4) Collaborations Pharma- Drugs for treatment of EV-D68
Research Support, Government Entities:
1.
NONE related to SARSCoV2 or manuscript(1) NIH/NINDS, 1R01 NS101208, PI, 2018-2022(2) Dept. of Veterans Affairs Merit Grant BX000963, Role: PI, 2017-21(3) NIH/NINDS, 5R21NS103186, Role: PI, 2017-2019No grants relate to SARSCoV2
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
Medical Scientist Training Program (BH, AMH), Rocky Mountain Taste and Smell Center (BH), Department of Neurology (KLT, ALP, VSP), and Department of Ophthalmology (VSP), University of Colorado School of Medicine, Aurora.
Disclosure
Scientific Advisory Boards:
1.
(1) Genentech, consultant on scientific advisory board
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
(1) Honoraria from MedLink
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
(1) Donation from the Drank family through the Children's Hospital of Colorado Foundation
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
Medical Scientist Training Program (BH, AMH), Rocky Mountain Taste and Smell Center (BH), Department of Neurology (KLT, ALP, VSP), and Department of Ophthalmology (VSP), University of Colorado School of Medicine, Aurora.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
Royalties are recvd semi-annually for these publication sin UpToDate.1.Pelak VS, Quan D. Ocular Myasthenia Gravis. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA. 2006.2.Pelak VS. Visual Hallucinations I and II. In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2009.3.Pelak VS. Release Visual Hallucinations (Charles Bonnet Syndrome). In: UpToDate, Rose, BD (Ed), UpToDate, Wellesley, MA, 2009.
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
2002-presentConsultant for second level patient appeals (Anthem Blue Cross and Blue Shield, UNUMProvident)2003-presentConsultant for review of policies and treatment guidelines (Anthem Blue Cross and Blue Shield, UNUMProvident, Prescription Solutions, Micromedex/Thomson Publishing)
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NIH, 1R01AG058772-01A1, Co-Investigator, 5 years, NIA
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
1. North American Neuro-ophthalmology Society2. Alzheimer's Association3. Visual Snow Institute
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
UpToDate,Inc, Royalties; Articles (as noted in question)
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
1) expert witness testimony and deposition - private lawyers2) treating physician deposition - private lawyers3) expert for National Vaccine Injury Compensation Program, Health and Human Services, Health Resources & Services Administration
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/cp.
*
These authors contributed equally to the manuscript.
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