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Can the SARS-CoV-2 coronavirus affect our brain?

Text updated on 2020-06-11

The COVID-19 disease mainly affects the lungs and blood vessels. It could also affect the nervous system.

The neurological manifestations of COVID-19 may be:

- Mild (benign): temporary loss of smell (anosmia) and taste (agueusia), dizziness, headache. The loss of smell and taste is a symptom of COVID-19 which has been spotted since the beginning of the epidemic in Europe, whereas it is not part of the list of symptoms recorded in China.

- Moderate: muscle damage, seizures

- Severe: Viral encephalitis (rare); encephalopathy due to acute respiratory distress syndrome and abnormal immune response; stroke.

Since the disease COVID-19 is very recent (December 2019), we do not yet know what the long-term neurological consequences may be.

The loss of smell does not necessarily imply that the structures of the brain are affected: it is possible that this anosmia is due to an alteration of the mucous membrane of the nose (olfactory neurons, support cells, or stem cells that ensure the renewal of the mucous membrane) without further alteration.

Nevertheless, in some cases, transient brain damage has been identified by Magnetic Resonance Imaging (MRI) of the brain regions involved in olfaction.

Similarly, the rare severe neurological manifestations observed (cerebrovascular accidents, encephalopathy) may be indirect consequences. Respiratory deficiencies can indeed lead to brain damage due to the lack of oxygen, while an abnormal immune response by the patient can generate massive inflammation of the brain or its blood vessels and thus brain damage.

Several studies suggest that the SARS-CoV-2 coronavirus could nevertheless directly affect the brain. SARS-CoV-2 is similar to the SARS virus (SARS-CoV-1) which can enter the brain and reach specific areas such as the thalamus and brain stem. The two receptors (ACE2 and TMPRSS2) that these coronaviruses recognize to infect cells are distributed in many organs of the body, including the brain's nerve cells.

So, the presence of the receptors would explain:

  1. why these coronaviruses are able to invade and reproduce in neural tissue in a way that could aggravate respiratory symptoms,
  2. neurological symptoms, such as loss of smell and taste, headaches, fatigue, confusion, or dizziness.

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This article summarizes the neurological symptoms observed in patients with COVID-19 between January and April 2020:

Calcagno, N., Colombo, E., Maranzano, A., Pasquini, J., Keller Sarmiento, I. J., Trogu, F., & Silani, V. (2020). Rising evidence for neurological involvement in COVID-19 pandemic. Neurological Sciences.

Neurological symptoms are observed in one-third of patients with COVID-19 and in half of the patients with severe conditions:

Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Miao, X., Li, Y., & Hu, B. (2020). Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology.

Evidence of infection of the central nervous system with the SARS-CoV-2 coronavirus :

De Felice, F. G., Tovar-Moll, F., Moll, J., Munoz, D. P., & Ferreira, S. T. (2020). Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System. Trends in Neuroscience, S0166223620300916.

The SARS-CoV-2 coronavirus ACE2 receptor is found in the human brain and nerves:

Li, Y., Bai, W., & Hashikawa, T. (2020). The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology, 92(6), 552-555.

The SARS-CoV-2 coronavirus associated with COVID-19, as well as SARS-CoV-1, which led to SARS, infects the nervous system and its gateway could be sensory cells in the lungs as well as cells in the nose.

Conde Cardona, G., Quintana Pájaro, L. D., Quintero Marzola, I. D., Ramos Villegas, Y., & Moscote Salazar, L. R. (2020). Neurotropism of SARS-CoV 2: Mechanisms and manifestations. Journal of the Neurological Sciences, 412, 116824. https://doi.org/10.1016/j.jns.2020.116824

The coronavirus can enter through the nose by infecting support cells, which could explain the disruption of the sense of smell.

Brann, D. H., Tsukahara, T., Weinreb, C., Lipovsek, M., Van den Berge, K., Gong, B., Chance, R., Macaulay, I. C., Chou, H., Fletcher, R., Das, D., Street, K., de Bezieux, H. R., Choi, Y.-G., Risso, D., Dudoit, S., Purdom, E., Mill, J. S., Hashem, R. A., ... Datta, S. R. (2020). Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia [Preprint]. Neuroscience.

The coronavirus can enter through the nose by infecting support cells located near olfactory receptor neurons, which may explain the disruption of the sense of smell.

Fodoulian, L., Tuberosa, J., Rossier, D., Landis, B. N., Carleton, A., & Rodriguez, I. (2020). SARS-CoV-2 receptor and entry genes are expressed by sustentacular cells in the human olfactory neuroepithelium [Preprint]. Neuroscience.

SARS-CoV-2 coronavirus neurotropism may contribute to respiratory failure in patients with the COVID-19 disease.

Li, Y., Bai, W., & Hashikawa, T. (2020). The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology, 92(6), 552-555.

Magnetic resonance imaging (MRI) of the brain in a patient with COVID-19 and having lost the sense of smell.

Politi, L. S., Salsano, E., & Grimaldi, M. (2020). Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. JAMA Neurology.

Transient oedema of the olfactory bulbs in a patient with anosmia related to COVID-19.

Laurendon, T., Radulesco, T., Mugnier, J., Gérault, M., Chagnaud, C., El Ahmadi, A. A., & Varoquaux, A. (2020). Bilateral transient olfactory bulbs edema during COVID-19-related anosmia. Neurology.

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