Long COVID: Could monoviruses or fat cells be playing a role?

A British historian, an Italian archaeologist and an American preschool teacher have never met in person, but they share a prominent pandemic link.

Plagued with eerily similar symptoms, the three women are credited with describing, naming, and helping bring prolonged COVID into the public consciousness in early 2020.

Rachel Pope, from Liverpool, took to Twitter in late March 2020 to describe her nagging, then unnamed, symptoms after a coronavirus infection. Elisa Perego in Italy used the term “prolonged COVID” for the first time, in a tweet from May of that year. Amy Watson in Portland, Oregon, was inspired to name her Facebook support group after the trucker hat she was wearing, and “long haul” soon became part of the pandemic lexicon.

Nearly three years into the pandemic, scientists are still trying to figure out why some people have long-term COVID and why a small portion, including the three women, have long-lasting symptoms.

Millions of people around the world have had COVID for a long time, reporting various symptoms including fatigue, lung problems, and brain fog and other neurological symptoms. Evidence suggests that most recover substantially within a year, but recent data shows that it has contributed to more than 3,500 deaths in the US.

Here are some of the most recent tests:

WOMEN AT HIGHER RISK?

Many studies and anecdotal evidence suggest that women are more likely than men to develop prolonged COVID.

There could be biological reasons.

Women’s immune systems generally have stronger reactions to viruses, bacteria, parasites and other germs, noted Sabra Klein, a Johns Hopkins professor who studies immunity.

Women are also much more likely than men to have autoimmune diseases, in which the body mistakenly attacks its own healthy cells. Some scientists believe that prolonged COVID could be the result of an autoimmune response triggered by the virus.

Women’s bodies also tend to have more fatty tissue, and emerging research suggests that the coronavirus may hide in fat after infection. Scientists are also studying whether women’s fluctuating hormone levels may increase risks.

Another possible factor: Women are more likely than men to seek medical care and are often more attuned to changes in their bodies, Klein noted.

“I don’t think we should ignore that,” he said. Biology and behavior are likely at play, Klein said.

So it may not be a coincidence that it was three women who helped shed the first light on long-term COVID.

Pope, 46, began recounting what he was experiencing in March 2020: flu-like symptoms, then his lungs, heart and joints were affected. After a month, she began to have a few “fine” days, but the symptoms persisted.

She and some equally ill colleagues connected with Perego on Twitter. “We started coming together because it was literally the only place we could do that,” Pope said. “In 2020, we were joking that we would get together for Christmas and have a party,” Pope said. “Then, obviously, it continued, and I think we stopped kidding around.”

Watson started her virtual long-distance group in April. The others soon learned of that nickname and adopted it.

MONKEY VIRUS

Several studies suggest that the ubiquitous Epstein-Barr virus could play a role in some cases of long-term COVID.

Inflammation caused by coronavirus infection can activate herpes viruses, which remain in the body after causing an acute infection, said Dr. Timothy Henrich, a virus expert at the University of California, San Francisco.

The Epstein-Barr virus is among the most common of these herpes viruses: an estimated 90% of the US population has been infected with it. The virus can cause mononucleosis or symptoms that can be ruled out as a cold.

Henrich is among the researchers who have found immunological markers signaling Epstein-Barr reactivation in the blood of long-term COVID patients, particularly those with fatigue.

Not all patients with prolonged COVID have these markers. But it’s possible that Epstein-Barr is causing symptoms in those who have them, though scientists say more study is needed.

Some scientists also believe that Epstein-Barr triggers chronic fatigue syndrome, a condition that has many similarities to long-term COVID, but is also unproven.

OBESITY

Obesity is a risk factor for serious COVID-19 infections, and scientists are trying to understand why.

Researchers at Stanford University are among those who have found evidence that the coronavirus can infect fat cells. In a recent study, they found the virus and signs of inflammation in fatty tissue taken from people who had died from COVID.

Laboratory tests showed that the virus can reproduce in fatty tissue. That raises the possibility that adipose tissue could serve as a “reservoir,” which could fuel prolonged COVID.

Could removing fat tissue treat or prevent some cases of long-term COVID? It’s a tempting question, but the research is preliminary, said Dr. Catherine Blish, a Stanford professor of infectious diseases and the study’s lead author.

Scientists at the University of Texas Southwestern Medical Center are studying leptin, a hormone produced by fat cells that can influence the body’s immune response and promote inflammation.

They plan to study whether injections of a manufactured antibody could reduce leptin levels and, in turn, inflammation from coronavirus infections or prolonged COVID.

“We have a good scientific basis together with some preliminary data to argue that we might be on the right track,” said Dr. Philipp Scherer.

DURATION

It has been estimated that around 30% of people infected with the coronavirus will develop prolonged COVID, based on data from early in the pandemic.

Most people who have persistent, recurring, or new symptoms after infection will recover after about three months. Among those with symptoms at three months, about 15% will continue to have symptoms for at least nine more months, according to a recent study in the Journal of the American Medical Association.

Finding out who is at risk of having symptoms for years to come “is a very tricky question,” said Dr. Lawrence Purpura, an infectious disease expert at Columbia University.

People with severe infections seem to be more at risk of prolonged COVID, although it can affect people with mild infections as well. Those whose infections cause severe lung damage, including scarring, may experience shortness of breath, coughing, or fatigue for more than a year. And a smaller group of patients with mild initial COVID-19 infections can develop neurological symptoms for more than a year, such as chronic fatigue and brain fog, Purpura said.

“Most of the patients will eventually recover,” he said. “It’s important that people know that.”

It’s small comfort to the three women who helped the world recognize long-term COVID.

Perego, 44, developed heart, lung and neurological problems and remains seriously ill.

She knows scientists have learned a lot in a short time, but says “there’s a gap” between protracted COVID research and medical care.

“We need to translate scientific knowledge into better treatment and policy,” he said.

Watson, who is nearing 50, says he has “never had any kind of recovery.” He has had severe migraines, as well as digestive, nervous and foot problems. He recently developed severe anemia.

She wishes the medical community had a more organized approach to treating long-term COVID. Doctors say that not knowing the cause or underlying causes makes it difficult.

“I just want to get my life back,” Watson said, “and it doesn’t seem like that’s all that’s possible.”

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