Omicron amplifies concerns about long COVID and its causes

More than a year after a battle with COVID-19, Rebekah Hogan still suffers from severe brain fog, pain and fatigue that renders her unable to do her day job as a nurse or do household chores.

Long COVID makes her question her worth as a wife and mother.

“Is this permanent? Is this the new norm?” said the 41-year-old woman from Latham, New York, whose three children and husband also have signs of the condition. “I want my life back.”

According to some estimates, more than a third of COVID-19 survivors will develop such ongoing problems. Now, with omicron sweeping across the world, scientists are trying to pinpoint the cause of the fatal condition and find treatments before it explodes in long-running COVID cases.

Could it be an autoimmune disease? That could explain why long-standing COVID-19 affects women disproportionately, who are more likely than men to develop autoimmune diseases. Could microclots be the cause of symptoms ranging from memory lapses to discolored toes? That might make sense, since abnormal blood clotting can occur with COVID-19.

As these and other theories are tested, there is new evidence that vaccination can reduce the chance of a long COVID.

Whether people infected with the highly contagious Omicron variant will develop the mysterious constellation of symptoms, which is usually diagnosed many weeks after the initial illness, is not yet foreseeable. But some experts think a long COVID wave is likely and say doctors need to be prepared.

With $1 billion from Congress, the National Institutes of Health is funding a variety of research into the condition. And clinics dedicated to research and treatment of this disease are popping up around the world, affiliated with places like Stanford University in California and University College London.


Momentum is built around a few key theories.

One is that the infection or remnants of the virus persist beyond the original disease and trigger inflammation that leads to a long COVID.

Another reason is that latent viruses in the body, such as the Epstein-Barr virus that causes mononucleosis, become reactivated. A recent study in the journal Cell pointed to Epstein-Barr in the blood as one of four possible risk factors, which also include pre-existing type 2 diabetes and levels of coronavirus RNA and certain antibodies in the blood. These results need to be confirmed by further investigations.

A third theory is that autoimmune responses develop after acute COVID-19.

With a normal immune response, viral infections activate antibodies that fight invading viral proteins. But sometimes, as a result, the antibodies remain high and mistakenly attack normal cells. This phenomenon is believed to play a role in autoimmune diseases such as lupus and multiple sclerosis.

Justyna Fert-Bober and Dr. Susan Cheng was among the researchers at Cedars-Sinai Medical Center in Los Angeles who found that some people who have had COVID-19, including cases without symptoms, have a variety of these elevated “autoantibodies” for up to six months after recovery. Some are the same ones found in people with autoimmune diseases.

Another possibility is that tiny blood clots play a role in long COVID. Many COVID-19 patients develop elevated levels of inflammatory molecules that promote abnormal clotting. This can lead to blood clots throughout the body, which can cause strokes, heart attacks, and dangerous blockages in the legs and arms.

In her laboratory at the University of Stellenbosch in South Africa, scientist Resia Pretorius has found microclots in blood samples from patients with COVID-19 and in patients who later developed COVID for a long time. She also found elevated protein levels in the blood plasma that prevented the normal breakdown of these clots.

She believes these clotting abnormalities persist in many patients after an initial coronavirus infection and that they reduce oxygen delivery to cells and tissues throughout the body, leading to most, if not all, of the symptoms associated with a long COVID became.


Although there is no set list of symptoms that define the condition, some of the most common include fatigue, impaired memory and thinking, loss of taste and smell, shortness of breath, insomnia, anxiety, and depression.

Some of these symptoms may first appear during an initial infection but persist or recur a month or more later. Or new ones develop that last for weeks, months, or over a year.

Because so many of the symptoms are common to other diseases, some scientists question whether the coronavirus is always the trigger. The researchers hope their work will provide definitive answers.

Long COVID affects adults of all ages as well as children. Research shows that it is more common in those who have been hospitalized, but also strikes a significant proportion who were not.

Retired flight attendant Jacki Graham’s battle with COVID-19 early in the pandemic wasn’t bad enough to hospitalize her. But months later, she experienced shortness of breath and a racing heart. She could neither taste nor smell. Her blood pressure shot up.

In the fall of 2020, she became so tired that her morning yoga routine sent her back to bed.

“I’m an early riser, so I would get up and push myself, but then I was done for the day,” said Graham, 64, of Studio City, California. “Six months ago I would have told you that COVID ruined my life.”

Hogan, the New York City nurse, was also not hospitalized with COVID-19 but has been debilitated since her diagnosis. Her husband, a disabled veteran, and their children, ages 9, 13, and 15, fell ill shortly thereafter and suffered from fever, abdominal pain, and weakness for about a month. Then everything seemed to get a little better until new symptoms appeared.

Hogan’s doctors believe autoimmune abnormalities and a pre-existing connective tissue disorder that causes joint pain may have predisposed her to developing the condition.


There are no treatments specifically approved for long COVID, although some patients experience relief from pain relievers, medications for other conditions, and physical therapy. But maybe more help is in sight.

Immunobiologist Akiko Iwasaki is studying the tantalizing possibility that the COVID-19 vaccine could long reduce COVID symptoms. Her team at Yale University is working with a patient group called Survivor Corps on a study that includes vaccination of previously unvaccinated long COVID patients as a possible treatment.

Iwasaki, who is also an investigator at the Howard Hughes Medical Institute, which supports The Associated Press’ health and science division, said she is doing this study because patient groups have reported improvement in some people’s long COVID symptoms after they get their shots had.

Study participant Nancy Rose, 67, of Port Jefferson, New York, said many of her symptoms subsided after the vaccination, although she still had bouts of fatigue and memory loss.

Two recently published studies, one from the US and one from Israel, provide preliminary evidence that vaccination prior to contracting COVID-19 could help prevent the ongoing disease, or at least lessen its severity. Both were done before omicron appeared.

Neither has been published in a peer-reviewed journal, but outside experts say the results are encouraging.

In the Israeli study, about two-thirds of the participants received one or two Pfizer shots; the others were unvaccinated. Those who received two vaccinations were at least half as likely to report fatigue, headaches, muscle weakness or pain, and other common long-term COVID symptoms as the unvaccinated group.


As there are still few clear answers, the future looks bleak for patients.

Many, like Graham, see improvement over time. She sought help through a long COVID program at Cedars-Sinai, enrolled in a study there in April 2021 and was vaccinated and boosted.

Today, she said, her blood pressure is normal, and her sense of smell and energy levels are approaching pre-COVID levels. Despite this, she took early retirement because of her ordeal.

Hogan still struggles with symptoms such as excruciating nerve pain and “spaghetti legs,” or limbs that suddenly go limp and unable to support weight, a condition that also affects her 13-year-old son.

Some scientists worry that long-COVID could turn into a form of chronic fatigue syndrome in certain patients, a poorly understood, long-lasting condition for which there is no cure or approved treatment.

One thing is certain, some experts say: Long COVID will have a huge impact on individuals, healthcare systems and economies around the world, costing many billions of dollars.

Even with insurance, patients can lose thousands of dollars at a time if they are too ill to work. For example, Graham said she paid about $6,000 out of pocket for things like scans, labs, doctor visits, and chiropractic care.

Pretorius, the scientist in South Africa, said there was a real concern things could get worse.

“So many people are losing their livelihoods, their homes. You can’t work anymore,” she said. “A long COVID is likely to have a more severe impact on our economy than an acute COVID.”


The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education. The AP is solely responsible for all content.

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