SCIENCE is starting to uncover an unnerving fact about viruses: Some might affect our brains over the long haul. It came as a shock that SARS-CoV-2 can lead to lingering neurological problems — a post-viral syndrome we call long COVID. But the phenomenon might not be unique to this virus.
Scientists are finding links between common viruses such as influenza and brain diseases like multiple sclerosis (MS), Parkinson’s, Alzheimer’s, and ALS. Researchers are hoping that identifying a viral link might finally allow scientists to figure out what causes these mysterious, deadly ailments and develop new treatments.
A new study, published last week and summarized in Science, used a vast trove of electronic medical records to find thousands of people with neurodegenerative diseases and tease out correlations with 22 different kinds of infections. The biggest viral risk factor for dementia was encephalitis, which is an infection of the brain often caused by a mosquito or tick-borne disease. Other viruses tied to dementia included influenza, herpes zoster (shingles), and HPV.
Earlier studies had looked for specific viral links to Alzheimer’s and found correlations with herpes and some forms of HPV. And a study published last year showed that Epstein-Barr virus was necessary for developing MS. But scientists still haven’t figured out exactly what role the viruses play — whether they’re a direct trigger or have some peripheral role. Almost everyone on the planet carries Epstein-Barr virus, which causes mononucleosis, but only a tiny fraction ends up getting MS.
To better understand how viruses might be affecting the brain, I stopped by the National Institutes of Health to visit Avindra Nath, who is one of the few neurologists specializing in viruses — an interest he picked up after treating AIDS patients in the early 1980s. In 2014, he was the first neurologist to travel to Liberia to treat Ebola patients, and he said a fraction of those who recover suffer neurological symptoms similar to long COVID — especially chronic fatigue.
He told me that what really interests him are viruses that are embedded in our genetic codes — called endogenous retroviruses. They may have snuck in through a sexually transmitted virus that works itself into an embryo. These viruses are a source of genetic variation — and can add novel DNA to our genomes. Like mutations, these occasionally incur an advantage and spread through the population. About 8% of our genome is made of these embedded viruses.
Nath’s interest in these started when he was treating a patient who had both HIV and ALS, and after taking antiretroviral drugs, the ALS disappeared. A series of human and animal studies convinced Nath that ALS might sometimes be triggered by an embedded virus called HERV-K.
Normally HERV-K is active during fetal development, so it may have spread through the human population because it does something useful in utero. But after we’re born, it normally shuts off (due to external chemical switches that bind to DNA).
Sometimes, he told me, these “off switches” fail, and one of these embedded viruses can become reactivated. That failure might be part of the cause of ALS. After years of animal studies, he started preliminary human trials assessing the effects of antiviral drugs on patients with ALS. He’s now planning a placebo-controlled clinical trial for drugs that he’s shown can suppress HERV-K.
He’s also studying the kinds of viruses we catch from the outside world. He thinks viruses are more likely to trigger brain diseases indirectly — not by getting directly into neurons, but by prompting inflammation. It’s the immune system’s response that causes the problem.
He’s now studying people with neurological problems following COVID infection — something that he estimates affected about 10% of people infected before vaccines were available and a much smaller fraction today. He said that at first he was very skeptical of claims that the virus hides out in the brain, but more recent studies have made him take it seriously, especially autopsy studies done by Dan Chertow at the NIH. It might be that those residual traces of the virus are causing persistent inflammation.
It’s possible that this has always been happening to some fraction of people who pick up common viruses. It’s just that it didn’t get all that much attention before the COVID pandemic. Nath said virology and neurology were two completely different worlds, and he was unique in trying to navigate both fields at the same time.
If viruses do indeed play a role in some of our most feared and costly diseases, that could point to a whole new approach to treatment and prevention. In the future, everyone might get vaccinated against Epstein-Barr virus as a protection against MS. And it may turn out that you can reduce your odds of getting Alzheimer’s disease by getting that shingles shot and a flu shot every year. If HPV adds to the risk, it could motivate the medical community to redouble its efforts to get that vaccine to more people.
Scientists could even eventually develop a universal, variant-proof COVID vaccine that would finally prevent the risk of long COVID.
Someday, people may look back at all the expensive drugs we tested for dementia and other brain diseases and wonder how we overlooked the benefits of cheap vaccines for so long.
BLOOMBERG OPINION
