Four years on, long covid still confounds us. Here’s what we now know.

Many people now view covid-19 as an almost routine inconvenience, much like flu, RSV and other seasonal infections. But four years after reports surfaced of a new respiratory illness, prompting a massive response among researchers, the disease’s aftereffects — commonly called long covid — continue to confound doctors and patients alike.

“We know a lot about this particular coronavirus,” said Francesca Beaudoin, chair of the department of epidemiology at Brown University. “That does not translate into an understanding of the long-term consequences of infection.”

As many as 7 percent of Americans report having suffered from a slew of lingering symptoms after enduring covid-19, including fatigue, difficulty breathing, brain fog, joint pain and ongoing loss of taste and smell, according to the Centers for Disease Control and Prevention. But there is still no clearly defined cause of, or cure for the syndrome.

The costs of our lack of understanding are vast, Beaudoin and others say, creating a huge new burden on the health-care system, as people report limitations in their daily activities including being able to work.

How is long covid diagnosed?

This is where some of the most intriguing scientific advances lie.

Doctors typically diagnose long covid through a process of elimination, ruling out other causes for the lingering symptoms reported by patients who have had a bout of covid.

But in September, the journal Nature published a study showing that people with long covid have distinct blood biomarkers - a finding that could lead to the development of diagnostic blood tests.

“This is really exciting,” said Ziyad Al-Aly, chief of research at VA St. Louis Health Care System and clinical epidemiologist at Washington University in St. Louis, who studies long covid. “It provides objective evidence to legitimize the disease and show it is not made up in people’s heads. And it provides clues as to the mechanism.”

The study, conducted by researchers at the Icahn School of Medicine at Mount Sinai in New York and Yale School of Medicine, first appeared in preprint form more than a year ago. It showed patients’ personal stories typically matched the scientific evidence of long covid, reinforcing the notion that patients have a clear understanding of what’s happening to their bodies.

There’s an important message in that for doctors, said David Putrino, the study’s lead author and director of the Abilities Research Center at the Mount Sinai Health System: Believe your patient!

What is long covid, anyway?

Patients who shared their stories on social media brought long covid to public attention early in the pandemic. But not even the name - or definition - for the clusters of as many as 200 different symptoms is settled.

Long covid is also known as PASC, for post-acute sequelae of covid, and PCC, for post-covid conditions, the term favored by the CDC for the wide range of health effects that can be present four or more weeks after infection with SARS-CoV-2 and can last weeks, months or even years.

Several theories exist for what causes long covid, including inflammation, a form of autoimmunity triggered by the virus, lasting damage to tissue and the persistence of the virus. Many researchers find that last theory particularly intriguing.

“It’s not so unusual for viruses to persist,” said E. John Wherry, director of the Institute for Immunology at the University of Pennsylvania’s Perelman School of Medicine. In the case of SARS-CoV-2, researchers have looked hard for viral persistence. “There is a lot of information out there, but we still haven’t found a direct causal link between the virus persisting in the body and symptoms of long covid.”

The study published in Nature in September found that long covid also appears to reactivate some common viruses, including Epstein-Barr and mononucleosis.

Many researchers believe not all long covid cases fit under a single umbrella.

A large study conducted by the National Institutes of Health’s RECOVER Initiative and published in May in JAMA has helped to define long covid through a symptom-based scoring system. Study participants reported more than 30 symptoms affecting different organ systems and parts of the body, out of which analysts were able to identify the 12 most common among those with long covid. They included fatigue, dizziness, gastrointestinal symptoms, heart palpitations and issues with sexual desire.

Who gets it?

Anyone, regardless of their age or severity of their original symptoms, according to the World Health Organization.

Data published in September by the CDC’s National Center for Health Statistics found that in 2022, 6.9 percent — or about 18 million — U.S.adults reported having had long covid while 3.4 percent — or 8.8 million — said they currently had the condition.

Nearly twice as many women - 4.4 percent - said they currently had long covid compared with 2.3 percent of men.

Adults between 35 and 49 were the most likely age group to report having had long covid.

If you have had covid-19 once without developing long covid, that doesn’t mean you won’t get it the future. One 2022 study suggested that repeat infections with the virus increases the chances of developing long covid.

An analysis of nearly 5 million U.S. patients who had covid, based on a collaboration between The Washington Post and research partners, showed that people infected with the coronavirus’s omicron variant are less likely to develop symptoms typical of long covid than those who had covid earlier in the pandemic. Patients exposed to the coronavirus during the first wave of pandemic illness — from early 2020 to late spring 2021 — were most prone to develop long covid, with 1 in 12 suffering persistent symptoms, the study showed.

Can I stop myself from getting long covid?

Yes! By not getting covid in the first place. That means getting vaccinated, wearing a well-fitting mask, washing your hands and avoiding crowded, poorly ventilated indoor spaces.

And if that sounds like a tall order these days, you are right. Many people have given up on prevention, and covid cases are increasing according to the CDC, with a rising test positivity rate of 11.7 percent and a 6.6 percent increase in emergency department visits for covid in the past week.

The Food and Drug Administration has not approved any drug for preventing long covid, but reducing the severity of the initial infection through vaccination probably also reduces the risk of long covid, experts said.

For the increasing number of us who get infected, there is evidence that taking an antiviral such as Paxlovid may lower your risk of later developing long-covid symptoms.

The evidence comes from observational studies, in which researchers collect and study data from a sample group of patients rather than setting up clinical trials with controls. The RECOVER program, which was awarded $1.15 billion by Congress in 2021 to study long covid, has embarked on clinical trials of Paxlovid and other potential interventions.

The diabetes drug metformin may also be preventive. In one study, it was associated with a risk reduction of more than 40 percent.

What treatment is available?

There also are no approved drugs for treatment. Instead, doctors largely rely on managing their patients’ symptoms, which often resemble other familiar conditions, using standard pulmonary rehabilitation, for example, to treat respiratory problems. They also adapt strategies used with concussion patients to treat brain fog and other common cognitive complaints. Some doctors are prescribing low-dose naltrexone, a generic drug typically used to treat alcohol and opioid addiction.

“It’s a whack-a-mole approach,” Beaudoin said. “There is not a clear algorithm to follow.”

Patient advocacy groups continue to trade information about treatments on social media. But there are worrisome trends in the medical world, according to Harlan Krumholz, a cardiologist and long-covid researcher at Yale University: Long-covid clinics are shuttering their doors, and ambitious young physicians aren’t drawn to an intractable problem like long covid but are instead choosing specialties such as neurology and oncology with greater opportunities for breakthroughs.

What’s my chance of recovery?

Beaudoin and others counsel patience.

Most people do recover, they say, but the length of time varies. In general, more severe cases of acute illness are associated with more severe cases of long covid.

In addition to getting professional help from a primary care physician or at a long-covid clinic, some patients say they benefit from relaxation techniques and counseling to help with depression and anxiety that can come with suffering a long-term and poorly understood condition.

What more do you need to know?

Research is moving ahead across the country at institutions such as Mount Sinai, Stanford and Yale, and through the government-funded RECOVER program, which offers opportunities for people to enroll in clinical trials. The clinicaltrials.gov website offers sign-up possibilities for research underway around the world.

Long covid can be a disability under the Americans With Disabilities Act. People may qualify for benefits and exemptions if the condition limits their ability to perform major life activities such as working, sleeping or preparing food.

There are numerous resources for patients, some, such as the Patient Led Research Collaborative, run by fellow sufferers, while other programs operate out of medical institutions, including Johns Hopkins and the Mayo Clinic.

To end on a note of optimism, if you get covid today, you are less likely to develop long covid than in the past. That’s what Beaudoin and other researchers say, though they cannot yet explain why. “We suspect the virus is provoking less of an immune response,” Beaudoin said.