Coronaviruses can be ‘neuroinvasive’ and have impacts on the brain from inflammation to demyelination
With the psyche of the entire world consumed by Coronavirus, as fellow brain researchers you may have wondered if Coronaviruses can get into the brain, and if so, what they do there. The short answer is yes they can, and they do many unpleasant things.
First some basics on the Coronavirus. Coronaviruses are a large family of viruses of which Covid-19 is just one. They are spherical virions with spike-like projections on the surface that give the appearance of a solar corona – hence the name. The virion encapsulation or envelope is essentially made of lipids. Within the virion is the nucleocapsid that houses its positive-sense single stranded RNA. What this means is that the RNA can function as both a genome and mRNA which can be translated into proteins using the ribosomes of the host cell. The genome of coronaviruses are much heavier than most viruses and encode all the major proteins required for their assembly.
How do they get into the brain?
Coronaviruses are one of several virus families that are considered ‘neuropathological’. Others include the human respiratory syncytial virus (hRSV), the influenza virus (IV) and the human metapneumovirus (hMPV). Generally the blood brain barrier does a good job of keeping out these viruses. However, sometimes respiratory coronaviruses are able to jump the blood brain barrier and find their way in. While exactly how they do this is not known, the main path appears to be through the olfactory bulb. Other ways may be by entry through the vagus nerve which has been found in cases of influenza viruses. From a molecular perspective studies suggest that this requires some compromise of the tight junctions in the blood brain barrier which may arise from inflammation. That said, the specific mechanism by which this happens seems to be unknown. Once they get into the brain however, they can permeate the CNS in less than 7 days and begin to appear in cerebrospinal fluid.
Which coronaviruses have been found in the brain?
One hypothesis is that the more virulent the coronavirus, the more likely it is to be neuroinvasive. SARS for example, which is a coronavirus, has been found in the brain. An autopsy study of 18 SARS patients found SARS viral particles and genomic sequence in neurons from the brain in addition to a number of other organs. Other strains of coronavirus (e.g. 229E) have also been found in the brains of patients with Multiple Sclerosis (MS) which brings us to the effects of neuroinvasion of coronaviruses.
Effect of coronavirus on the brain
Coronaviruses in the brain can cause all kinds of havoc. They can cause inflammation of the brain (encephalitis) or the brain and spinal cord (encephalomyelitis) which can result in various acute symptoms such as the usual headaches and fevers but also febrile seizures, status epilecticus, convulsions and loss of consciousness. More insidious perhaps is the effect of demyelination leading to coronavirus as a suspect in the onset of MS. Some studies suggest that they are gliotropic since coronavirus infection causes glia to release all sorts of factors including interleukins which are inflammatory proteins and chemokines that are involved in the onset of MS.
Finally, besides all the neurological effects but there could well be long lasting cognitive and mental effects as well. They simply haven’t been studied. As this coronavirus pandemic progresses, we may be about to find out.
Bohmwald K. et al., Front Cell Neurosci. 2018; 12: 386. 2018 Oct 26. Neurologic Alterations Due to Respiratory Virus Infections
Bleau et al, J Virol, 89 (19), 9896-908, Oct 2015 Brain Invasion by Mouse Hepatitis Virus Depends on Impairment of Tight Junctions and Beta Interferon Production in Brain Microvascular Endothelial Cells