COVID-19 & The Brain

What We Know Now

Coronavirus Disease 2019 (COVID-19), an illness caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has globally spread within the past months and there are over 6.8 million active cases (9/1/2020) and more than 25 million cases in total reported, as of today (1). This number is presumably much greater, as many individuals are suspected to have COVID-19 without any symptoms (2). Increasing evidence has been found supporting the neuro-invasive potential of SARS-CoV-2; patients are reporting a variety of neurological symptoms of varying severity, from confusion or loss of smell to strokes and seizures. This leads to an increasing awareness of the importance of monitoring patients’ brain health.

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A clinic in Wuhan found diverse neurological symptoms in over 36% of their patients, such as dizziness, confusion, headache as well as taste, smell and vision impairment (3). More studies have shown that COVID-19 can lead to severe neurological complications and neuropsychiatric illness including psychosis, delirium, encephalitis and serious brain damage (4, 5, 6). More recently, an imaging study investigated patients 3 months after they were initially diagnosed with COVID-19 disease. The researchers found persistent neurological symptoms in more than half of these patients (7). Importantly, the symptoms were not only found in patients with severe disease courses, but also affected patients with mild COVID-19 symptoms. The researchers concluded that COVID-19 possibly disrupts micro-structural and functional brain integrity, potentially leading to long-term neurological consequences. Long-term consequences such as chronic fatigue, depression and sleep disturbance have also been found in patients infected with the previous SARS-CoV-1 virus (8) and more and more reports of long-term consequences of COVID-19 are being released (9, 10, 11).

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How, or if the virus enters the brain directly is not completely clear yet. Neurological symptoms could be the result of general inflammation, an immune response or physiological changes induced in the body by COVID-19, i.e. fevers, low oxygen levels and organ failures.

SARS-CoV-1 virus was shown to invade the central nervous system and peripheral tissues (12) and COVID-19 might directly invade the brain through the olfactory pathway, as was previously shown in SARS-CoV-1 in mice (13). The loss of smell, an often-reported symptom in patients, could be a neurological effect (14). SARS-CoV-2 RNA has been detected in the cerebrospinal fluid (15, 16), and viral particles were found in human brain cells (17).

A new study just came out, providing the first clear evidence that COVID-19 invades brain cells. The research team was able to demonstrate in mice, that COVID-19 is neuroinvasive and that an infection in the brain, rather than a respiratory infection, is associated with mortality. Further, they found SARS-CoV-2 in cortical neurons of humans and observed pathologic features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of COVID-19 and a direct infection of neurons by SARS-CoV-2 (18).

COVID-19 is a silent infection with evasion mechanisms. Some people may be more susceptible, because of their genetic background or high viral load. According to Dr. Robert Stevens, a neurologist at Johns Hopkins University, 40-60% of hospitalized COVID patients experience neurological complications, including nerve damage and stroke (19,20), underlining the dangerous potential of COVID-19.

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Neurological symptoms of COVID-19 are found in patients with varying courses of disease and might only manifest over time. This raises the importance of continuous monitoring of patients’ brain health. To optimize helping patients in case of neurological deviation and promote brain healing, it is crucial to understand neurological deficits in COVID-19 patients early. Therefore, a brain MRI baseline has been advised for COVID-19 patients, to have a starting point to treat them successfully in the future (18).



Dr. Katharina Koch is a Clinical Psychologist and earned a PhD in Psychology and Neuroscience.

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References

[1] Coronavirus Cases. Available online: https://www.worldometers.info/coronavirus/ (accessed on 19 August 2020)

[2] Wells, P. M., Doores, K. M., Couvreur, S., Martinez, R. M., Seow, J., Graham, C., ... & Matos, P. (2020). Estimates of the rate of infection and asymptomatic COVID-19 disease in a population sample from SE England. medRxiv.

[3] Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., ... & Miao, X. (2020). Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA neurology, 77(6), 683-690.

[4] Paterson, R. W., Brown, R. L., Benjamin, L., Nortley, R., Wiethoff, S., Bharucha, T., ... & Vivekanandam, V. (2020). The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain.

[5] Baig, A. M. (2020). Updates on what ACS reported: emerging evidences of COVID-19 with nervous system involvement. ACS Chemical Neuroscience, 11(9), 1204-1205.

[6] Huang, Y. H., Jiang, D., & Huang, J. T. (2020). A Case of COVID-19 Encephalitis. Brain, Behavior, and Immunity.

[7] Lu, Y., Li, X., Geng, D., Mei, N., Wu, P. Y., Huang, C. C., ... & Yin, B. (2020). Cerebral Micro-Structural Changes in COVID-19 Patients–An MRI-based 3-month Follow-up Study. EClinicalMedicine, 100484.

[8] Moldofsky, H., & Patcai, J. (2011). Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC neurology, 11(1), 37.

[9] Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent symptoms in patients after acute COVID-19. Jama.

[10] - https://www.theguardian.com/australia-news/2020/jul/17/most-covid-19-patients-admitted-to-a-sydney-hospital-in-march-still-have-symptoms?fbclid=IwAR1SyWW1K7p_cz1jS_0NsSSCDPc_InK-x6K2eeVR21kKMcAlUjDmRiq1Uwo

[11] Kings College London/ZOE Covid Symptom Study

[12] Miller, K. D., Schnell, M. J., & Rall, G. F. (2016). Keeping it in check: chronic viral infection and antiviral immunity in the brain. Nature Reviews Neuroscience, 17(12), 766.

[13] Netland, J., Meyerholz, D. K., Moore, S., Cassell, M., & Perlman, S. (2008). Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. Journal of virology, 82(15), 7264-7275.

[14] Le Guennec, L., Devianne, J., Jalin, L., Cao, A., Galanaud, D., Navarro, V., ... & Demeret, S. (2020). Orbitofrontal involvement in a neuroCOVID‐19 patient. Epilepsia.

[15] Moriguchi, T., Harii, N., Goto, J., Harada, D., Sugawara, H., Takamino, J., ... & Nakao, A. (2020). A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International Journal of Infectious Diseases.

[16] Virhammar, J., Kumlien, E., Fällmar, D., Frithiof, R., Jackmann, S., Sköld, M. K., ... & Ryttlefors, M. (2020). Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid. Neurology.

[17] Paniz‐Mondolfi, A., Bryce, C., Grimes, Z., Gordon, R. E., Reidy, J., Lednicky, J., ... & Fowkes, M. (2020). Central nervous system involvement by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). Journal of medical virology, 92(7), 699-702.

[18] Song, E., Zhang, C., Israelow, B., Lu-Culligan, A., Sprado, A., Skriabine, S., ... & Szigeti-Buck, K. (2020). Neuroinvasion of SARS-CoV-2 in human and mouse brain. bioRxiv.

[19] How the Coronavirus Attacks the Brain, NYT, Sept. 9, 2020. https://www.nytimes.com/2020/09/09/health/coronavirus-brain.html?searchResultPosition=1

[20] Varatharaj, A., Thomas, N., Ellul, M. A., Davies, N. W., Pollak, T. A., Tenorio, E. L., ... & Coles, J. P. (2020). Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study. The Lancet Psychiatry.

[21] Fotuhi, M., Mianc, A., Meysamid S. & Rajic, C. A. (2020). Neurobiology of COVID-19. Journal of Alzheimer’s Disease 76, 3–19. https://www.j-alz.com/content/three-stages-covid-19-brain-damage-identified-top-neurologists-journal-alzheimer-disease?fbclid=IwAR3bTxI8Xeg_Bw-F5BJIfqjdFEzy6b4ixx-dRuF3bsbil1HnOKVdazsR__g

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