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.
A study by Mao and colleagues found diverse neurological symptoms in over 36% of their patients, such as dizziness, confusion, headache as well as taste, smell, and vision impairment (3). A study by Sanchez and colleagues found neurologic manifestations in more than 57% of hospitalized patients with COVID-19 (22). More evidence has been found showing that COVID-19 can lead to severe neurological complications and neuropsychiatric illness including psychosis, delirium, encephalitis, deterioration of myelin, altered cortical thickness, and serious brain damage (4, 5, 6, 7, 22, 24, 27). A recent study by Liotta and colleagues found neurologic manifestations in 42.2% of their patients at COVID-19 onset, 62.7% showed neurologic manifestations at hospitalization, and 82.3% at any time during the disease course (26). An imaging study investigating patients 3 months after they were initially diagnosed with COVID-19 disease found persistent neurological symptoms in more than half of these patients (8). 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, (9, 25) and more and more reports of long-term consequences of COVID-19 are being released (10, 11, 12, 22, 27).
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 (13) and COVID-19 might directly invade the brain through the olfactory pathway, as was previously shown in SARS-CoV-1 in mice (14). The loss of smell, an often-reported symptom in patients, could be a neurological effect (15). SARS-CoV-2 RNA has been detected in the cerebrospinal fluid (16,17), and viral particles were found in human brain cells (18).
A new study is 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 (19). Now a new study published by Crunfli and colleagues found histopathological signs of brain damage in 19% of individuals who died of COVID-19. Their results provide evidence for the model that SARS-CoV-2 reaches the brain, infects astrocytes, and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients (2020).
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 (20, 21), underlining the dangerous potential of COVID-19.
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 maintain close neurologic surveillance for prompt recognition of these complications (22). 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 (23).
A brain MRI scan is a quick, non-invasive procedure that provides you with a brain baseline, which can make a crucial difference in the course of your brain health. BrainKey makes it possible to get a brain baseline with the BrainKey Scan: a brain MRI scan for $390 only. A BrainKey Scan takes less than 20 minutes and includes a clinical radiology report. Incidental findings, such as tumors or aneurysms, can be detected on a brain MRI scan, and it provides a brain baseline which helps you track your brain health over time.
A BrainKey Scan also comes with BrainKey’s brain metrics that can help indicate brain deterioration, even before the appearance of symptoms. BrainKey partners with high-end professional imaging centers to offer a great experience at a low price. In the case of incidental findings, BrainKey is working with excellent neurosurgery centers to guarantee the best further care possible. Find out more about the BrainKey Scan and how to get it here.
 Coronavirus Cases. Available online: https://www.worldometers.info/coronavirus/ (accessed on 19 August 2020)
 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.
 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.
 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.
 Baig, A. M. (2020). Updates on what ACS reported: emerging evidence of COVID-19 with nervous system involvement. ACS Chemical Neuroscience, 11(9), 1204–1205.
 Zanin, L., Saraceno, G., Panciani, P. P., Renisi, G., Signorini, L., Migliorati, K., & Fontanella, M. M. (2020). SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochirurgica, 1–4.
 Huang, Y. H., Jiang, D., & Huang, J. T. (2020). A Case of COVID-19 Encephalitis. Brain, Behavior, and Immunity.
 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.
 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.
 Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent symptoms in patients after acute COVID-19. Jama.
 — 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
 Kings College London/ZOE Covid Symptom Study
 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.
 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.
 Le Guennec, L., Devianne, J., Jalin, L., Cao, A., Galanaud, D., Navarro, V., … & Demeret, S. (2020). Orbitofrontal involvement in a neuroCOVID‐19 patient. Epilepsia.
 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.
 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.
 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.
 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.
 How the Coronavirus Attacks the Brain, NYT, Sept. 9, 2020. https://www.nytimes.com/2020/09/09/health/coronavirus-brain.html?searchResultPosition=1
 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.
 Romero-Sánchez, C. M., Díaz-Maroto, I., Fernández-Díaz, E., Sánchez-Larsen, Á., Layos-Romero, A., García-García, J., … & Gracia-Gil, J. (2020). Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. Neurology.
 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
 Scullen, T., Keen, J., Mathkour, M., Dumont, A. S., & Kahn, L. (2020). COVID-19 associated encephalopathies and cerebrovascular disease: the New Orleans experience. World Neurosurgery.
 Garrigues, E., Janvier, P., Kherabi, Y., Le Bot, A., Hamon, A., Gouze, H., … & Corre, F. (2020). Post-discharge persistent symptoms and health-related quality of life after hospitalization for COVID-19. Journal of Infection.
 Liotta, E. M., Batra, A., Clark, J. R., Shlobin, N. A., Hoffman, S. C., Orban, Z. S., & Koralnik, I. J. (2020). Frequent neurologic manifestations and encephalopathy‐associated morbidity in Covid‐19 patients. Annals of Clinical and Translational Neurology.