It’s hard to avoid COVID news, and it’s easy to become tired of it. The pandemic is definitely stressing our endurance, individually and collectively. But as the most recent wave of COVID indicates, this pandemic is not over yet. We also still have a lot to learn about COVID-19, especially its long-term effects, which we can only study once enough time has passed for there to be a long term.

A lot of focus in terms of the impact of COVID has been on the death toll, now over 614,000 in the US and 4.2 million world-wide. But medical specialists know that when evaluating the impact of an illness you don’t look just at mortality, you have to look at morbidity as well – negative health effects other than death. Now, at least, the media is talking about so-called “long COVID”, symptoms which persist long after the acute illness is over. Further, even though COVID was initially conceived of as a respiratory illness, it is now more accurately understood as a systemic and vascular illness.

Here I am going to focus on the neurological manifestations of COVID. I have been seeing patients in my neurology clinic with symptoms following COVID starting last Summer, and increasingly so this year. The most common symptom I see is “brain fog”, but headaches and fatigue are also common. There is now an emerging literature on the neurological effects of COVID, which are significant.

Even early in the pandemic it was clear that COVID had effects outside the respiratory system, including neurological. Most of this early data, however, was about acute illness. A French study published in June 2020 showed that 84% of hospitalized patients with COVID had neurological manifestations. A majority of patients admitted to ICU with COVID are found to have delirium (a type of confusion and disorientation). Loss of taste and smell was observed early to be a sign of COVID. Cases of COVID-induced Guillain-Barré syndrome (which mostly affects the nerves) were also observed.

But still it was not known early on if these effects were cause directly by infection with SARS-CoV-2, or an indirect effect of being critically ill. With further study it became clear that COVID affects the brain in a number of ways. We now know COVID is predominantly a vascular disease, affecting the blood vessels and causing blood clots throughout the body, including the brain. This can cause ischemia, or lack of oxygen, in the brain which causes damage. Patients with COVID may also have small bleeds in the brain, which also causes damage. Finally the virus can directly cause inflammation in the brain through infection, called encephalitis.

These are all conditions neurologists are very familiar with. They can make patients acutely very neurologically ill, and recovery can be slow. Full recovery is possible, and depends on the pre-morbid health and age of the patient. But it is also common for patients after a severe illness with encephalitis to never recover to their prior baseline. We are now starting to see data that shows the same is true following severe COVID as well. A study from October 2020 found that 82% of patients hospitalized with COVID had some neurological manifestation.

The most frequent neurologic manifestations were myalgias (44.8%), headaches (37.7%), encephalopathy (31.8%), dizziness (29.7%), dysgeusia (15.9%), and anosmia (11.4%).

A study in The Lancet published in July 2021 found:

People who had recovered from COVID-19, including those no longer reporting symptoms, exhibited significant cognitive deficits versus controls when controlling for age, gender, education level, income, racial-ethnic group, pre-existing medical disorders, tiredness, depression and anxiety. The deficits were of substantial effect size for people who had been hospitalised (N = 192), but also for non-hospitalised cases who had biological confirmation of COVID-19 infection (N = 326). Analysing markers of premorbid intelligence did not support these differences being present prior to infection. Finer grained analysis of performance across sub-tests supported the hypothesis that COVID-19 has a multi-domain impact on human cognition.

This is essentially one of the symptoms people are calling long-COVID. What is concerning in this data is that sustained neurological deficits were found even among those who were not sick enough to be hospitalized. Essentially, those with moderate to severe COVID infection statistically dropped a few IQ points, which is a marker of brain injury. It is possible that after 2-3 years of recovery this effect will significantly diminish and even go away, so there is more to learn from longer term data when enough time has passed. But this is a concerning sign of brain injury from COVID infection.

It is also possible, as some researchers are warning, that the damage caused to the brain from severe COVID might have long term effects that are not recognized for years. Ischemic and inflammatory damage to brain cells may accelerate degenerative processes, increasing the risk of developing degenerative brain disease (like Alzheimer’s disease) years down the road.

Yet another study found that 55% of hospitalized COVID patient had a co-infection with the Epstein-Barr virus (EBV), the virus that causes chronic fatigue syndrome in some patients. This may be due to an opportunistic reactivation of the dormant virus. It may also be partially responsible for the chronic fatigue many patients with long COVID experience. But further it reflects how much about COVID we still don’t understand – this is a complex and serious infection, and the more rocks we turn over, the more we are finding about its effects.

As was noted in an earlier SBM article, children may be relatively less affected by COVID than adults, but they are not immune. Recent data shows that:

9.8% of children aged 2–11 years and 13% aged 12–16 years reported at least one lingering symptom five weeks after a positive diagnosis.

A study published in JAMA in March 2021 found:

In this study of 1695 patients 21 years or younger hospitalized for acute COVID-19 or multisystem inflammatory syndrome, 365 (22%) had neurologic involvement. Forty-three patients (12%) developed COVID-19–related life-threatening neurologic disorders, 11 (26%) died, and 17 (40%) survived with new neurologic sequelae.

These numbers are alarming. They should not be considered less so simply because they are even worse in adults.

As we are facing a new wave of COVID, with the prospect of new variants in the future possibly extending the pandemic even further, it is important that the public have a clear picture of how serious this illness is. The death toll should be enough to indicate how severe COVID can be, but even that is not the whole picture. This is a systemic infection that can cause chronic illness, and neurological manifestations are common, more so in adults but children are affected too. This will have a significant effect on our healthcare system for decades to come.

I also have to point out that we have a powerful solution right in front of us – safe and effective vaccines.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.