Science is just beginning to uncover a startling fact about viruses: Some viruses can affect our brains over a long period of time. It came as a shock that Sars-CoV-2 can lead to long-lasting neurological problems, a post-viral syndrome we call long COVID. But this phenomenon may not be unique to this virus. Scientists have found links between common viruses such as influenza and brain diseases such as multiple sclerosis, Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis (ALS). It is hoped that identifying the viral link may help uncover the causes of these mysterious diseases and help 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 types of infections. The biggest viral-risk factor for dementia was encephalitis, an infection of the brain most often caused by a mosquito- or tick-borne disease. Other viruses associated with dementia include influenza, herpes zoster (shingles), and HPV.
Earlier studies looked for specific viral links to Alzheimer’s and found associations with herpes and some forms of HPV. And last year a study showed that the Epstein-Barr virus was necessary for multiple sclerosis (MS) to develop. But scientists still haven’t figured out what role the viruses play: whether they are a direct trigger or have some peripheral role. Nearly everyone on the planet carries the Epstein-Barr virus, which causes mononucleosis, but only a small fraction get MS.
To better understand how viruses can affect the brain, I stopped by the National Institutes of Health to meet with Avindra Nath, a neurologist specializing in viruses. In 2014, he was the first neurologist to travel to Liberia to treat Ebola patients, and he noted that some of those who have recovered have long suffered from neurological symptoms of Covid, particularly chronic fatigue. He told me that he was interested in viruses that are embedded in our genetic code, called endogenous retroviruses. They may have entered through a sexually transmitted virus that works itself in a fetus. These viruses are a source of genetic variation and can add novel DNA to our genomes. Like mutations, these sometimes take advantage and spread through the population. About 8% of our genome is made up of these embedded viruses.
Nath’s interest in these began when he was treating a patient with both HIV and ALS, and the ALS disappeared after taking antiretroviral drugs. A series of human and animal studies convinced Nath that sometimes ALS could 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 down. Sometimes, he told me, these ‘off switches’ fail, and one of the embedded viruses can reactivate. That failure may be part of the cause of ALS. After animal studies, he began a preliminary human trial of the antiviral drugs’ effects on ALS patients and plans a placebo-controlled clinical trial for drugs he has shown can suppress Herv-K.
Nath said that viruses are more likely to trigger brain diseases indirectly: not directly in neurons, but by fueling inflammation. It is the immune system’s response to what causes the problem.
Nath is currently studying neurological problems after Covid – which is estimated to have affected about 10% of people infected before vaccines were available and a much smaller fraction today. At first, he said he was very skeptical of the claim that the virus lurks in the brain, but recent studies have made him take it seriously, particularly the autopsy studies by Dan Cherto at the NIH. It may be that those residual traces of the virus are causing persistent inflammation. It is possible that this has always been the case with some fraction of people who get normal viruses. It’s just that it didn’t get much attention before Covid, because virology and neurology were seen as separate fields.
If viruses do indeed play a role in some of our most dreaded diseases, it could point the way to a new approach to treatment and prevention. In the future, everyone could be vaccinated against the Epstein-Barr virus as protection against MS. And it may turn out that you can lower your odds of getting Alzheimer’s disease by getting the shingles vaccine and the flu vaccine every year. If HPV adds to the risk, vaccination efforts for the virus may be doubled.
Scientists may also eventually develop a universal, variant-proof Covid vaccine that will eventually stop the risk of prolonged Covid.
Someday, people may look at all the expensive drugs we’ve tested for dementia and other brain diseases and wonder how we overlooked the benefits of cheaper vaccines for so long.
Faye Flamm is a Bloomberg Opinion columnist covering science.
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