Covid and the brain: what we know so far

I am going to talk about COVID and the brain. I am not going to give you a talk full of cytokines, proteins, and mechanisms, one because I don't think I'm the right person to talk about that, and two because I want to talk about something broader—how the story of COVID and the brain is really part of a bigger story. A couple of housekeeping notes: this isn't a finished story. I don't know the answer, and I don't believe anyone knows the finished story of what's going on here. Also, the brain and mind live in the same place, and I don't think it's possible to talk about one without the other. I am a neurologist, not a psychiatrist, but there isn't a clear-cut distinction between the two. I am speaking in broad terms about patients I've seen and research I've done; there will be individuals with different experiences, and that is okay.

When you think about COVID and the brain, it's helpful to consider acute problems that happen during or shortly after infection, and chronic problems that take months or years to develop. Acute problems include stroke, inflammation of the nervous system, and mental health issues. Chronic problems include dementia and long COVID. Are these all different ends of a multifocal pathology? I think they might be.

Stroke is a brain injury due to a loss of blood supply. We know the risk of stroke is increased during and after COVID infection, independent of other vascular risk factors like age, diabetes, and blood pressure, though it is also additive to those factors. Research has found that strokes associated with COVID tend to be severe, disabling, and involve multiple occlusions of large vessels. They often occur alongside extra-cranial clots in organs like the liver, kidney, or lungs, suggesting a global problem of blood clotting. The risk is highest in the first week but can persist for up to a year. Interestingly, while COVID treatments like dexamethasone and remdesivir reduce stroke risk, thrombectomy is more difficult in COVID-associated strokes, potentially because blood vessels themselves are inflamed.

It is important to look at the intersection of biology, psychology, and sociology. For example, during the pandemic, there was a massive decrease in stroke admissions to the NHS compared to the year before. This shows that behavioral and societal factors—such as lockdown and fear of presenting to the hospital—are part of the narrative alongside the biological effects of the virus.

Regarding brain inflammation, we have recognized various syndromes where the brain becomes inflamed shortly after COVID, such as leukoencephalopathy or conditions involving antibodies like MOG (myelin oligodendrocyte glycoprotein). We knew these conditions existed before COVID, but the virus may have a particular propensity to affect cerebral blood vessels, which widely express the ACE receptor that the virus binds to.

Does COVID actually infect the brain? While it is possible, it is certainly not common, and it is likely not relevant to the vast number of people suffering from neurological symptoms post-COVID. We have to be careful with definitions of infection versus tropism and actual damage.

There is robust evidence of a significant risk of mental health problems like depression, anxiety, and psychosis during and after COVID. This risk persists for at least a year and is comparable across Omicron and Delta variants. While vaccination reduces this risk, the absolute increase in risk is quite small, though the sheer number of people infected globally makes it a significant issue. This is not new; even in 1892, before viruses were discovered, physicians noted that mental health disorders were common following influenza.

In terms of long-term complications, we know there is an increased risk of cognitive decline and brain atrophy, particularly in the limbic system, which is linked to smell. Since loss of smell is common, it is possible this part of the brain is shrinking due to being disconnected from sensory input, a phenomenon seen in other conditions like deafness.

Finally, long COVID is perhaps the most important issue, as it likely incorporates mechanisms from all these areas—vascular, inflammatory, and psychological. We cannot look at the brain in isolation; we are one whole organism. All diseases are multi-system, and we must improve our understanding of how the brain is involved in systemic infection for the sake of those with post-COVID symptoms and the population at large.