Neurologic manifestations of COVID-19

Clinical Question

What are the neurologic manifestations of COVID-19?

Key Findings

  • Knowledge regarding the neurologic manifestations of COVID-19 and subsequent management is not well established and continues to evolve.
  • Multiple studies have demonstrated the presence of central nervous system (CNS), peripheral nervous system (PNS), and muscular symptoms in patients with COVID-19 infection[1][2][3]
  • CNS symptoms include (in descending order of frequency) dizziness, headache, impaired consciousness, acute cerebrovascular accident, ataxia, and seizure. PNS symptoms include hypogeusia (decreased taste), hyposmia (decreased smell), hypopnia (slow or shallow breathing), and neuralgia[1]
  • Multiple cases of meningitis/encephalitis attributed to COVID-19 have also been described[4][5]
  • At this time, information regarding the treatment and outcomes of these specific symptoms/syndromes is not available.

Summary of Information

Neurologic Manifestations

  • CNS: dizziness, headache, impaired consciousness, acute cerebrovascular accident, ataxia, seizure
  • PNS: hypogeusia, hyposmia, hypopnia, neuralgia
  • Muscle injury

A retrospective study of 213 COVID-19 positive patients in the Wuhan region assessed the symptoms listed above in patients with both severe and non-severe COVID-19 infection, finding that 36.4% (78/214) patients with COVID-19 developed at least 1 of these neurologic symptoms. They additionally found that patients with severe systemic and respiratory symptoms were more likely to develop CNS neurological symptoms than patients with moderate or mild disease. A small portion of these patients initially presented with their neurological symptoms.[1] The presence of hypogeusia and hyposmia has been further evaluated as a potential early sign of disease in otherwise asymptomatic patients.[2]

There have been multiple reports of meningitis/encephalitis related to COVID-19. One case report detailed a patient with neck stiffness and transient generalized seizures, CNS serologic testing positive for SARS-CoV-2 RNA (and negative for other CNS pathogens including HSV and VZV), and brain MRI showing temporal lobe hyperintensities in the absence of brain edema.[4] Another case report demonstrated altered mental status in a patient with severe COVID-19 and brain MRI consistent with acute necrotizing hemorrhagic encephalopathy, although CSF testing for SARS-CoV-2 RNA was unable to be performed.[5] Media sources also report a case of COVID-19 related viral encephalitis in the Beijing Ditan Hospital,[3][6] although this is unconfirmed by peer-reviewed literature. Viral encephalopathy is thought to be due to intracranial cytokine storms resulting in blood-brain-barrier breakdown but without direct viral invasion. Evidence suggests that some patients with severe COVID-19 may have cytokine storm syndrome,[7] which could serve as a trigger for the development of encephalitis in these patients. Although this suggests that immunosuppressive therapies may be helpful for the treatment of this specific presentation, no data on this subject is currently available.

Mechanism of Neurologic Damage Related to COVID-19

It may be difficult to distinguish whether the neurologic symptoms associated with COVID-19 are due to the direct effects of virus invasion on neurons and surrounding tissue, or factors related to the process of acute infection such as metabolic disorders, hypoxia, and systemic toxemia. Continued study of patients with COVID-19-related neurologic disease, including CSF analysis and pathologic evaluation of brain tissues, will be required to better understand these mechanisms.

Neurologic Manifestations of Coronaviruses Related to COVID-19

Many other coronaviruses related to COVID-19 have shared a similar ability to affect the nervous system, including SARS-CoV and MERS-CoV. SARS-CoV specifically shares highly homological sequences with COVID-19 (SARS-CoV-2),[8] suggesting they may have similar neurologic manifestations. SARS-CoV has been shown to induce neurological diseases such as encephalitis, aortic ischemic stroke, and polyneuropathy, among others, with associated findings of cerebral edema and meningeal vasodilation on autopsy.[9] Additionally, SARS-CoV has been demonstrated able to spread via a synapse-connected route from the respiratory airways to the medullary cardiorespiratory center, where virus-mediated damage may lead to decreased respiratory drive and be partially responsible for SARS-CoV-related respiratory failure. With the high similarity between SARS-CoV and SARS-CoV-2, it may be important to consider the role of this neuroinvasion in the respiratory failure of COVID-19 patients,[10] although the clinical implications of this knowledge remain to be seen.

Author Information

Authors: Garrett Timmons MS3; UC San Diego School of Medicine
Completed on: April 10, 2020
Last updated on: Not yet updated

Reviewed by: Gary Smithson MD
Reviewed on: April 19, 2020

This summary was written as part of the CoRESPOND Earth 2.0 COVID-19 Rapid Response at UC San Diego. For more information about the project, please visit http://earth2-covid.ucsd.edu

References

  1. Mao L, Wang M, Chen S, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: A Retrospective Case Series Study. Infectious Diseases (except HIV/AIDS); 2020. doi:10.1101/2020.02.22.20026500
  2. Giacomelli A, Pezzati L, Conti F, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020.  [PMID:32215618]
  3. Wu Y, Xu X, Chen Z, et al. Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain Behav Immun. 2020.  [PMID:32240762]
  4. Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International Journal of Infectious Diseases. 2020;94:55-58. doi:10.1016/j.ijid.2020.03.062
  5. Poyiadji N, Shahin G, Noujaim D, et al. COVID-19-associated Acute Hemorrhagic Necrotizing Encephalopathy: CT and MRI Features. Radiology. 2020.  [PMID:32228363]
  6. Huaxia. Beijing hospital confirms nervous system infections by novel coronavirus - Xinhua | English.news.cn. Xinhuanet. http://www.xinhuanet.com/english/2020-03/05/c_138846529.htm. Published March 5, 2020. Accessed April 29, 2020.
  7. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033-1034.  [PMID:32192578]
  8. Yu F, Du L, Ojcius DM, et al. Measures for diagnosing and treating infections by a novel coronavirus responsible for a pneumonia outbreak originating in Wuhan, China. Microbes Infect. 2020;22(2):74-79.  [PMID:32017984]
  9. Tsai LK, Hsieh ST, Chang YC. Neurological manifestations in severe acute respiratory syndrome. Acta Neurol Taiwan. 2005;14(3):113-9.  [PMID:16252612]
  10. Li Y, Bai W, Hashikawa T. The neuroinvasive potential of SARS‐CoV2 may play a role in the respiratory failure of COVID‐19 patients. J Med Virol. 2020;92(6):552-555. doi:10.1002/jmv.25728