Central Nervous System Involvement in COVID-19.

Novel coronavirus disease (COVID-19) was initially diagnosed with flu (influenza)-like symptoms and respiratory distress in December 2019 in Wuhan, China (1). However, further studies showed a few neurological symptoms in some patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such as headache, languidness, unstable walking, and malaise (2), cerebral hemorrhage (3), and cerebral infarction (4). According to the study on 241 definitive patients with COVID-19, more than one third of patients had neurological manifestations; its severity varied depending on the progression of the disease, e.g., patients with more severe infection had acute cerebrovascular diseases, impaired consciousness, and skeletal muscle injury (3). Another study showed acute necrotizing encephalopathy (ANE) in the brain magnetic resonance imaging (MRI) of the patient with COVID-19. Images from brain MRI demonstrated hemorrhagic rim, enhancing lesions within the bilateral thalami, medial temporal lobes, and subinsular region (5).

The exact reason for involvement of central nervous system (CNS) in COVID-19 is still unclear. It seems that the lung epithelial cells are infected with COVID-19 because of angiotensin-converting enzyme 2 (ACE2) receptor (6). The virus binds to the receptor through the protein S, which helps the virus genome to enter the human epithelial cell (6). Cerebral hemorrhage due to increased blood pressure could be a consequence of the ACE2 receptor expression, affected by COVID-19 (7). Indeed the serum samples of patients with COVID-19 show coagulopathy and prolonged prothrombin time (8). Increasing D-dimer due to COVID-19 could subsequently lead to intracranial clots and cerebral hemorrhage (9).

ANE is a fatal complication that rarely results from an indirect viral invasion such as influenza (10). According to the pathology of ANE, an overreaction of the immune cells to a viral infection leads to a cytokine storm (11), which could break the blood-brain barrier (11). Current evidences suggest cytokine storm in COVID-19 (12,13), which could be the cause of ANE in affected patients (5).

It should be mentioned that SARS-CoV was previously detected in the cerebrospinal fluid (CSF) of SARS patients with epilepsy (14). Therefore as of structural and genetic similarities between SARS and SARS-CoV2 (15), the potential risk of entering SARS-CoV-2 to the CSF of patients with COVID-19 should be considered.

Finally, it should be emphasized that almost all recent studies on COVID-19 indicated that the SARS-CoV2 infection is not limited to the respiratory system. So, as of the importance of neurological damage, any neurological sign and symptom of patients with COVID-19 should be closely monitored.