Impact of COVID-19 on the Nervous System
Post by Amanda McFarlan
What's the science?
The spread of the SARS-CoV-2 virus, better known as COVID-19, has become a global public health concern. Infection with COVID-19 is known to affect the respiratory system, causing fever, dry coughs, and in more serious cases, shortness of breath and chest pain. Although it is less common, some individuals infected with COVID-19 also display neurological symptoms such as headache, dizziness, and a loss of taste and smell. However, it remains unknown exactly what the COVID-19 virus is doing in the body to cause these neurological symptoms. This week in Cell, Iadecola and colleagues summarized the recent data describing the effects of COVID-19 on the nervous system.
What do we already know?
Neurological abnormalities, ranging from a headache to total delirium, have been observed in ~30% of hospitalized individuals infected with COVID-19. In some cases, COVID-19 has also been shown to have delayed neurological symptoms post-infection affecting both the central and peripheral nervous systems. Studies have shown that infection with COVID-19 increases an individual’s risk of having a stroke. Indeed, the incidence of stroke in hospitalized patients with COVID-19 is ~7 times higher compared to patients with influenza, which suggests that the COVID-19 virus is likely to be involved in causing vascular brain injuries. Additionally, the majority of studies testing the cerebrospinal fluid (CSF) and brain tissue samples of COVID-19 patients with neurological abnormalities did not show evidence of viral invasion, however, small quantities of the COVID-19 virus were detected in the CSF of at least two cases of hospitalized individuals with severe infectious encephalopathy (altered mental state due to damage to the brain). The peripheral effects of COVID-19 could potentially explain the occurrence of encephalopathy without evidence of brain invasion by the virus. For example, COVID-19 is known to act on the respiratory system and in severe cases, can cause lung damage which can lead to hypoxia (lack of oxygen). In line with this, post-mortem studies from COVID-19-related deaths revealed that there was brain damage in regions most susceptible to hypoxic brain injury: the neocortex, hippocampus, and cerebellum.
What’s new?
One major question to ask when investigating the effects of COVID-19 on the nervous system is: can the COVID-19 virus enter the brain, and if so, how? The main entry point for COVID-19 into human cells is through an enzyme that is located on the membrane of cells in the lungs, kidneys, arteries, heart, and intestines called the angiotensin converting enzyme-2 (ACE2). Recent data has shown that ACE2 was also expressed in the choroid plexus (brain cells that produce CSF) and in neocortical neurons. In support of these findings, it was shown in studies using organoids and transgenic mice expressing the human ACE2 gene that the COVID-19 virus can infect neurons and cause cell death in an ACE2-dependent manner. Since one of the common neurological symptoms associated with COVID-19 is a loss of smell and taste, the olfactory system may be a possible route for the virus to enter the brain. Indeed, studies have shown that olfactory epithelial cells had detectable levels of ACE2 protein and RNA, although it is unknown whether the virus could reach the olfactory neurons to enter the brain. Additionally, since COVID-19 has been described as being blood-borne, it could potentially enter the brain via the blood-brain-barrier or infected immune cells. Thus, there are many possible ways in which the COVID-19 virus could invade the brain, however, more conclusive data from CSF and post-mortem tissue is required to determine the exact route of entry.
What’s the bottom line?
The evidence to date suggests that the COVID-19 virus can result in acute and prolonged neurological abnormalities that range in level of severity. Most of this data, however, is derived from case studies, which means that the acute and long-term neurological effects of COVID-19 at the population level are still unclear. The development of adequate experimental models as well as the collaboration between clinical and basic scientists around the world will be critical for answering these questions quickly and efficiently.
Iadecola et al. Effects of COVID-19 on the nervous system. Cell (2020). Access the original scientific publication here.