Comment: Research into long covid could advance other work

By Faye Flam / Bloomberg Opinion

Last week, the U.S. Congress failed to approve $15 billion needed to continue covid-19 precautions, even though today’s low case counts are likely to rise, as they are now in Europe, with the sub-variant called BA.2.

We’ve learned that some expensive mitigation measures, such as deep cleaning, are a waste of money, and could be scrapped, but funding for studying covid should increase; not just for prevention measures and vaccines, but for research into the long-term consequences of infection.

Some people who got covid-19 early in the pandemic still haven’t recovered, and what looked like “long covid” might, for some people, be a permanent condition if no treatment is found. The lingering symptoms are often different from those associated with acute infection. Patients report changes in memory, trouble thinking clearly or concentrating, mood disorders, sleep disturbances, changes in balance and gastrointestinal problems. Some have a form of fatigue that can get much worse with physical or mental exertion.

The good news is that some of the country’s top medical researchers have jumped on this problem and are gaining momentum. What they learn is likely to apply to other medical problems. Take the work of Mark Albers, a neurologist at Massachusetts General Hospital who had been uncovering the weird relationship between loss of sense of smell and Alzheimer’s disease. Now he’s expanded his research to learn about similar changes in covid-19 patients.

A few years back Albers developed a test of what he calls smell memory, which was connected to the earliest stages of Alzheimer’s disease. Smell, he told me, is the one sense that’s physiologically connected directly to our brain’s memory center, so smell changes are often the first clue something is wrong.

Now he’s also studying patients who have persistent loss of their olfactory sense after a covid infection; something that can drag on for months or, worse, return in a distorted way so that food smells like rotting fish or garbage.

A recent brain scanning study showed that people who had tested positive showed tiny but statistically significant changes in the brain regions that govern smell, which Albers says suggests that covid could lead to inflammation of this part of the brain; the same part that’s associated with early Alzheimer’s disease.

In studies in animals, he’s found that viral infection in the nose doesn’t directly infiltrate the brain, but the inflammation caused by a respiratory infection can. Scientists have already found connections between other infectious agents and Alzheimer’s disease; including herpes simplex virus and the bacteria implicated in gum disease. These might not be the root causes of dementia, but they could exacerbate the disease’s progression.

The brain imaging study shouldn’t be interpreted to mean that covid-19 causes dementia. The changes measured were minuscule and not linked to any lingering symptoms, and there’s a certain expected natural fluctuation in people’s brain images. Still, Albers said he’d like to see more research into the possibility that an infection could accelerate the progression of early-stage Alzheimer’s.

Bruce Levy, head of pulmonary care at Brigham and Women’s Hospital, has also shifted gears and is now leading a clinic and research group studying long covid. He told me that because Boston had one of the earliest surges of covid-19 back in the spring of 2020, he’s seeing patients who haven’t recovered for nearly two years. “We definitely need answers for those patients,” he says.

Some patients have protracted symptoms because they had severe cases that led them to the ICU, and organ damage. But other cases are more mysterious, occurring in people who had only a mild infection. Understanding why this happens is a key step to treating or preventing long covid. Most researchers favor the explanation that it’s chronic inflammation, perhaps triggered by an immune response that attacks the body’s own cells and doesn’t shut off properly. Others suspect it could be triggered by virus that hides out somewhere in the body.

Other scientists are trying to figure out how to predict who will completely recover and who won’t. A big collaboration of scientists just published a paper in the journal Cell using a “multi-omics” approach to finding hidden risk factors; that is, examining genes, immune system differences, chronic conditions, other viral infections and other factors that distinguish one patient from another. Levy says this kind of knowledge will be extremely valuable.

Levy says funding research into long covid could help people who suffer from other maladies. “There’s definitely an urgent need to learn more about long covid for the hundreds of thousands or millions of people that are experiencing it. I would also say that there is much to learn from long covid that may translate to other conditions.”

Why not fund a moonshot program for curing long covid? Ziyad Al-Aly, chief of research and development at the VA Saint Louis Health Care System, would like to see one. He has reason to think that long covid is intimately connected to other major health problems. He led a study showing that people who’ve had covid-19 are more likely to develop heart disease, and another showing that they are more likely to suffer mental health problems including anxiety and depression.

He said there’s been a longstanding neglect of post-viral syndromes: chronic fatigue syndrome, protracted symptoms from Lyme Disease and post-influenza symptoms. Sometimes these were written off as psychosomatic, he said.

Doctors have been slow to accept other instances where infectious agents were involved in chronic diseases; including the link between human papilloma virus and cervical cancer, and between h. pylori bacteria and ulcers. Studying long covid could help scientists unlock the mysteries of other illnesses, Al-Aly said.

The majority of people who get covid are fine, but even if only 5 percent or 6 percent have long-term symptoms, that still adds up to a lot of people. With tens of millions of people having been infected, that’s many, many people “who are still bearing the wounds and scars from it.”

In principle, with each new wave of covid we should be getting smarter; about mitigation, vaccines, tests, anti-viral treatments and long covid. Funding more research is essential for making sure we’re channeling resources toward measures that work.

Faye Flam is a Bloomberg Opinion columnist and host of the podcast “Follow the Science.” She has written for the Economist, the New York Times, the Washington Post, Psychology Today, Science and other publications.