Effects on the nervous system
The entry point for SARS-CoV-2 into the body is usually via angiotensin converting enzyme 2 (ACE2) in alveolar cells of the lungs. However, ACE2 is also expressed in a number of other cells and tissues, including the mucous membranes of the eyes, nose and oral cavity, neurons and glial cells, and endothelial cells, including those of the brain. These are thus potential targets for the virus (6). Transneuronal transmission of the virus via the olfactory nerve to the brain is one of several potential mechanisms by which the virus could act directly on the nervous system (7). SARS-CoV-2 has been detected in the cerebrospinal fluid in cases of encephalitis and meningitis (8). Strong immune responses to the virus in the form of a so-called cytokine storm, in which cytokines cross the blood-brain barrier, are associated with acute necrotising encephalopathy in cases of COVID-19 (9).
During the pandemic, there should be a low threshold for testing for SARS-CoV-2 in cases of new-onset neurological symptoms, including confusional states in the elderly
Nervous tissue can also be damaged indirectly as a result of incidental effects of the immune response, as in cases of Guillain-Barré syndrome (10) or demyelination of the central nervous system (11). Most neurological impairments in cases of COVID-19 are likely to be the result of systemic disease, hypoxia and, in some cases, hypercoagulability, a prominent feature of severe COVID-19 infections (2). SARS-CoV-2 proteins have been shown to interact with human proteins in several ageing-related processes (12). Long-term studies of the disease course will reveal whether COVID-19 leads to neurodegenerative conditions, as was seen with the Spanish influenza.
Increased understanding of neurological manifestations of COVID-19 is required in both the acute and post-infectious phases of the disease course. During the pandemic, there should be a low threshold for testing for SARS-CoV-2 in cases of new-onset neurological symptoms, including confusional states in the elderly. We recommend that these patients are evaluated by a neurologist and receive rehabilitation and follow-up of residual symptoms.