Long covid studies may teach us how to take on Alzheimer’s
PremiumResearch on how viruses can cause brain ailments has gained pace
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PremiumScience has just begun 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 spotted links between common viruses such as influenza and brain diseases like multiple sclerosis, Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS). The hope is that identifying a viral link might help work out what causes these mysterious ailments and develop new treatments.
A new study, published last week and summarized in Science, used a trove of 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 last year showed that Epstein-Barr virus was necessary for developing multiple sclerosis (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 affect the brain, I stopped by the National Institutes of Health to visit Avindra Nath, a neurologist specializing in viruses. 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 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 foetal 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. 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 animal studies, he started preliminary human trials of the effects of antiviral drugs on ALS patients and plans a placebo-controlled clinical trial for drugs that he’s shown can suppress Herv-K.
Nath said 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.
Nath is currently studying neurological problems following covid—which he estimates affected about 10% of people infected before vaccines were available and a much smaller fraction today. At first, he said he was very sceptical of claims that the virus hides 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 did not get much attention before covid, as virology and neurology were seen as different fields.
If viruses do indeed play a role in some of our most feared 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, vaccination efforts for the virus can be redoubled.
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.
Faye Flam is a Bloomberg Opinion columnist covering science.
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