Americans infected with the coronavirus’s omicron variant are less likely to develop symptoms typical of long COVID than those who had COVID-19 earlier in the pandemic, according to the largest-ever study of who is most vulnerable to being sickened – or debilitated – by the virus’s lingering effects.

The analysis of nearly 5 million U.S. patients who had COVID, a study based on a collaboration between The Washington Post and research partners, shows that 1 in 16 people with omicron received medical care for symptoms associated with long COVID within several months of being infected. 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.

This pattern mirrors what leading doctors who treat long COVID – and some scientists who study it – have noticed as the coronavirus pandemic evolves. But the reasons they offer for the shifting rates are closer to conjecture than to proof.

“Long COVID is a complicated beast,” said Ziyad Al-Aly, director of the Clinical Epidemiology Center at Washington University School of Medicine in St. Louis and a major researcher into the disease.

The findings also show that patients with certain underlying medical conditions are twice as likely as previously healthy people to seek care for symptoms associated with long COVID: About 9 percent of patients with any of those preexisting conditions received treatment for long-COVID symptoms in the six months after they came down with COVID, compared with 4.6 percent who did not have those prior health problems, the analysis shows.

Obese patients were about three times as likely to report long-COVID symptoms as those without any previous medical conditions, while people with lung diseases or kidney disorders were close behind.

These and other findings from The Post’s partnership trace the contours of a troubling ripple effect from the country’s worst public health crisis in a century. Researchers made rapid headway in understanding COVID’s patterns of sickness and death and in developing vaccines and treatments. But as the pandemic enters its fourth year, the precise nature of long COVID and the remedies for it reside in a black box.

Its causes have not advanced beyond theories. Its symptoms differ among patients, and, as the study demonstrates, some are common even before people catch the virus, making it hard at times to fathom what is caused by a coronavirus infection and what is incidental. Doctors treat the symptoms by borrowing from what they know about other diseases. And although physicians are familiar with post-viral syndrome – lingering symptoms after the flu, pneumonia, Epstein-Barr and other viral ailments – long COVID tends to persist far longer.

“It’s scary not to be who I was before,” said Noemi Chiriac of Dallas, who has not regained her senses of taste and smell since a second bout of COVID days before Christmas 2021, when the virus’s delta variant overlapped with the early stage of the omicron variant. “It’s losing your identity.”

Chiriac, 45 and single, finally can go on the miles-long walks she treasures, but becomes short of breath if she tries talking with anyone at the same time and needs to nap for hours once she gets home.

In summer 2021, the aerospace and defense company where Chiriac worked chose her to compete for more-senior management jobs as part of a “talent pool.” She flubbed an interview. She was asked how she would handle situations with company leaders, but brain fog, lingering from her first round of COVID seven months before, got in the way of her recalling their names.

“I could see their faces. I know exactly who they are, but I could not remember,” Chiriac said. She was taken out of the running for talent pool jobs.

An emerging body of studies in the United States and elsewhere has been trying to figure out who is most vulnerable to the wide constellation of symptoms, such as those Chiriac experiences, that typify long COVID. But the findings vary substantially because of different research methods, the small cohort of patients on which many studies are based and researchers’ lack of consensus over how the syndrome should be defined.

The study with The Post’s partners, based on anonymous medical records of COVID patients across the country, adds to the coalescing portrait of long COVID. Altogether, the analysis shows that about 1 in 14 – slightly more than 7 percent – of U.S. patients who had COVID visited health-care practitioners within six months of their initial infections complaining of at least one symptom typical of long COVID they’d not had before. That proportion is within the range identified by some smaller studies but is lower than that found by other research using broader definitions of long COVID.

In a country where at least 200 million people have been infected with SARS-CoV-2, according to federal estimates, the rate detected by The Post translates into about 14 million U.S. residents who survived the virus and are struggling with long-lasting effects that often alter their lives.

“It’s a staggering amount of people,” said endocrinologist Zijian Chen, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York, among the first U.S. medical centers to create an interdisciplinary clinic to care for patients with the fledgling symptoms that would become known as long COVID.

“And the implication for long-term care for some of these people, and the implication for health-care dollars we need to use to care for these people, it’s pretty huge,” Chen said.

The Post’s analysis is based on data from a Wisconsin company called Epic Systems, which houses the nation’s largest collection of electronic medical records from hospitals, health systems and medical practices. The Kaiser Family Foundation, a nonprofit health-policy organization, is a partner in this research collaboration, helping to decide how the analysis would be carried out and to interpret the results.

The analysis relies on records, from Epic’s research database, of nearly 4.9 million patients diagnosed with COVID from the start of the pandemic in early 2020 through January 2022, forming the largest data set used in any long-COVID study in the world. The study marks the first time Epic has shared what the company calls its Cosmos data in a collaboration with a news organization. The analysis looks at which patients sought care for any of a list of diffuse symptoms that the Centers for Disease Control and Prevention identifies as common with long COVID, also known as long-haul or post-COVID syndrome. They include fatigue, breathing trouble, cough, rapid or uneven heart rhythms, difficulty thinking or concentrating, and many more.

In a twist on long-COVID research, The Post analysis also looked at who sought care for the same symptoms during a six-month window before they got COVID. By including this “before” time, the study shows that those symptoms circulate in the general population but are more common in the months after patients get the coronavirus than during the period before. That before-and-after comparison offers one way of understanding that long COVID – sometimes dismissed by doctors, especially early in the pandemic – is real.

And yet the appearance of the same symptoms before people develop COVID attests to the complexity of diagnosing long COVID and measuring its prevalence.

“We have work to do to understand what is long COVID and what is the [downstream effect] of being chronically unwell or having an acute condition,” CDC Director Rochelle Walensky said in an interview with The Post.

For that reason, The Post’s analysis and other studies might inadvertently overstate how common long COVID is, said Al-Aly, of Washington University, who has led major post-COVID studies using data from the Department of Veterans Affairs. At the same time, Al-Aly said, studies might underestimate how common long COVID truly is because, as the syndrome becomes better understood, researchers could discover symptoms not on the CDC list.

There is a need, Al-Aly said, to “shed light on the complexity of the matter.”

The Post analysis sought to identify who is most likely to seek medical care for symptoms typical of long COVID. Among the findings:

• The lower rate of symptoms from the omicron wave is consistent across age groups, gender, race and people of differing health status before they got COVID. The reduced rate of symptoms in that wave is driven in large part by young people representing a larger share of omicron cases than in earlier waves and the fact that they have been especially unlikely to seek care for symptoms of long COVID.

• Women are more likely than men to seek care for long-COVID symptoms – nearly 8 percent of women, compared with slightly more than 6 percent of men. Other long-COVID studies have identified a similar gap.

• Older survivors of a coronavirus infection are more prone to report a symptom of long COVID. Slightly more than 1 in 9 people 65 and older sought care for such symptoms in contrast with 1 in 24 people younger than 30.

• Patients with the most severe cases of COVID are more likely to develop long-haul symptoms. About 1 in 5 COVID patients who were in intensive care units reported post-COVID symptoms later on, compared with about 1 in 15 who were not hospitalized. But because of the simple math of the pandemic – the overwhelming majority of infected people are never hospitalized – patients with relatively mild COVID account for the bulk of those reporting post-COVID symptoms.

• Even though COVID cases and deaths have cut deepest in communities that are Black, Latino or poor, the same does not appear true for long-COVID symptoms. And patients on Medicaid, the public health insurance program for people with lower incomes and disabilities, have only marginally greater odds of reporting the symptoms than those with private insurance. Because the study is based on medical records, the lack of differences among racial, ethnic and income groups might say more about who has adequate access to health services than the actual incidence of long COVID in those communities, some physicians say.

“Health equity plays a huge role regarding the type of patients able to seek care for long COVID,” said Alba Azola, a co-director of the Johns Hopkins Post-Acute COVID-19 Team in Baltimore. “The people who make it to our … clinic are rich, White and able to access medical care.”

Among the three viral waves of the pandemic, long-COVID symptoms are consistently less frequent during the omicron period for each group of patients in the analysis. For instance, no matter whether patients had mild COVID cases or were in ICUs, they were less prone to report any post-COVID symptoms if they had omicron than if they had earlier versions of the virus.

‘A DIFFERENT INFECTION’

Pat Hill, a 76-year-old insurance agent in Shaker Heights, Ohio, outside Cleveland, was infected with the coronavirus during the time of delta, when the odds of developing long-COVID symptoms were less than during the early wave but greater than in the later omicron surge. She is part of the medical mystery that doctors and researchers are still trying to crack: Why do each of the pandemic’s major variants seem to produce different chances of lingering effects?

Hill has been in the habit for two decades, since being diagnosed with asthma, of buying N95 masks to protect herself and others any time a cold or flu circulates. Since the pandemic began, Hill said, “I have masks in my car, and a box by my door, and all my purses have masks. If I see somebody not wearing a mask that I think should wear [one], I’ll give away masks.”

But one morning in September 2021 – just days before she was scheduled to get her first booster of the Moderna vaccine – she went to a gathering with representatives of local insurance companies. The small room, meant for 10 people, was crammed with twice as many. “It set off an alarm” in her mind, she recalls. Still, she removed her mask long enough to munch a bagel and sip coffee.

Days later, when she had a runny nose, postnasal drip and a cough, Hill figured it was her usual late-summer ragweed allergy. But she saw a notice that Shaker Heights was offering coronavirus tests and got one, just to be sure. “I was shocked,” she said, when a nurse called. Positive.

Her bout of COVID was nothing like the fear she harbored of ending up hospitalized on a ventilator. “It was like a mild case of the flu,” Hill recalled. She was weary but never ran a fever, never saw her blood oxygen level tumble dangerously low. “I figured I’d do my quarantine, and I thought I’d get back to normal,” she said. The real trouble began a month later. Her fatigue deepened. She developed bronchitis. She became short of breath. Her legs and ankles swelled.

The reason the delta wave and the original form of COVID seem more likely to produce such symptoms than the more recent omicron and its subvariants is not fully understood. But physicians and biomedical researchers have some ideas.

One possibility is that the variants target cells in different parts of the respiratory tract, said Akiko Iwasaki, an immunologist at the Yale School of Medicine, with omicron affecting the upper part and earlier forms of the virus targeting lower down. “And the lower respiratory tract creates more damage.” As a result, Iwasaki said, omicron “could produce less severity and less long COVID.”

Omicron “appears to be somewhat of a different infection,” said Kathleen Bell, a rehabilitation medicine physician at the University of Texas Southwestern Medical Center in Dallas, which was among the first medical centers to create a clinic for treating patients with lingering symptoms.

Fewer patients infected with omicron arrive at the long-COVID clinic there with significant loss of smell or severe lung symptoms. The virus has “changed its attack,” said Bell, whose clinic still sees new patients turn up with symptoms that have persisted since they were diagnosed with COVID during the delta wave more than a year ago, rather than in the omicron wave.

For insurance agents such as Hill who specialize in Medicare health plans, the fall enrollment season is always the busiest. She had enough energy during her first autumn with long-COVID symptoms to send renewal reminders to only some clients. “When people have been with you for years, they are like family,” she said of the rest. “I felt like such a failure.”

In November 2021, two months after becoming infected, she heard of a long-COVID clinic at a branch of University Hospitals. The earliest appointment was three months later. She still sees an immunologist, a hematologist and a cardiologist. An acupuncture therapist treats her back pain, which can be a post-COVID symptom. She meets with a social worker. She has recently added a pulmonologist because her cough has worsened.

“I know it doesn’t feel like that to her, [but] it’s still early in the long-COVID journey,” said Juliane Torer, a nurse-practitioner at the suburban clinic who knows Hill.

In July, close to Hill’s birthday, a friend she considers a niece as part of her large “chosen family” surprised her with tickets to an Elton John concert. It was at Cleveland’s downtown baseball park, and they had to park two blocks away. Hill walked haltingly to their seats. While the audience stood rapturously clapping, she could not. On the way back to the car, she made it halfway with her cane to a bus stop, where she rested before walking the rest of the way. Still, Hill said, “I did it, and that was my bigger accomplishment than seeing Elton John.”

THE BATTLE JOINED

The Post review is one of several that have found an apparent link between long COVID and preexisting medical problems.

“The more severe COVID, the higher risk of long COVID. And people with comorbidities are at higher risk for severe COVID,” said Albert Ko, an epidemiologist at the Yale School of Public Health and specialist in infectious diseases.

Patty Reales is such a patient. Her parents didn’t want it known she had lupus as she was growing up in the Queens borough of New York, even though she was called names by other children because she was out sick from grammar school a lot and, when in school, was often too tired for gym class. The autoimmune disorder was the root cause of her kidney disease and, in turn, her high blood pressure. She has asthma, too.

By the time she was in her early 40s, sharing a three-apartment house with her parents and younger brother, and working as a grants administrator at Mount Sinai, Reales had been taking immune-suppressing drugs for decades and knew she was vulnerable to infections. The first time she got COVID symptoms, in March 2020, she was pretty certain she’d been exposed walking through the hospital lobby as New York was emerging as the nation’s hub of the young pandemic.

Reales worked from home for a few days, through a fever, cough, headache and profound fatigue, and she lost taste and smell. When she started having trouble breathing, she went to Mount Sinai’s emergency room. Even though a coronavirus test – still in its infancy – did not turn up positive, she was admitted to an isolation unit as a “person under investigation.” When she returned home after three days, her cough and breathing were better. Other symptoms didn’t go away.

“I was easily tired,” she recalled. Her hobbies – running, exploring Manhattan’s neighborhoods, traveling every few months – were impossible. One summer day, a friend suggested they try an easy jog. “After like one block I couldn’t keep up,” Reales said. “I had to … call on her cellphone, and she realized I wasn’t behind her.”

The wheezing and fatigue lingered until the next winter. She’d finally begun feeling better and was up to date on her coronavirus vaccine when, in April 2021, another episode of COVID descended. That time, Reales said, “I really felt like I was struggling just to breathe. The fatigue was horrendous. I developed insomnia.” It was fall before her symptoms lifted. Then, four days before Christmas 2021, as omicron was starting to sweep the country, she tested positive again.

As with some – but not all – long-COVID patients, doctors say, her health has been improving slowly. In April, a year after her second bout of COVID, she entered a 5K race and sent her mother a photo of herself, beaming, in Flushing Meadows-Corona Park as she crossed the finish line. She ran another in May. In late June, she did a 10K.

“I was ready to give up after the fourth mile. I said, ‘This is too much.’ I just wanted to stop,” Reales recalled. But the cheering along the route kept her going. She finished.

Reales has a new job as a grants portfolio manager for Weill Cornell Medical College. It allows her to work full time from home. She is a student online for a bachelor’s degree in administrative studies. Still, when walking up a flight of stairs, she sometimes needs to stop and catch her breath. Brain fog has continued. “I’m usually on point, but I’ll forget things. It could be something I already told my mom before,” Reales said. “When I’m doing my schoolwork, I’ll have to read and read and read again.” It is such a struggle that she withdrew from three of four courses one recent semester.

“I already have one animal. That is the lupus,” Reales said. “Once you disturb that animal (with COVID and what follows), it’s like unshielding Pandora’s box.”

METHODOLOGY

The Washington Post worked with the electronic health records company Epic Systems and with input from Kaiser Family Foundation to design a study on who is most likely to report long-COVID symptoms.

The study looked at 4.88 million de-identified people of all ages in the national Epic Research Cosmos patient-record database who were diagnosed with COVID-19 for the first time between March 2020 and January 2022. The patients studied were separated into categories corresponding to the major coronavirus variant circulating at the time they became ill. The original variant was from March 2020 through June 2021. The delta variant was from August 2021 through November 2021. The omicron variant was in January 2022. July and December 2021 were omitted because of transitions between major variants during those periods.

Epic used a multistep process to identify patients reporting new symptoms. Epic analyzed each patient’s electronic health record going back to 2017. Using that history, Epic identified whether each patient had sought care for the first time for at least one symptom that the Centers for Disease Control and Prevention has listed as a potential indication of long-term COVID, including fatigue, difficulty breathing, cough, chest pain, brain fog, headache, sleep problems, dizziness, depression, muscle pain, rash and stomach pain. Only symptoms for which a person had not sought care since 2017 were classified as new symptoms.

The review established whether each patient sought care for any new symptoms from one month to six months after the coronavirus infection. A second step established whether each patient had reported any new symptoms in the six months before receiving a COVID diagnosis.

The share of patients with new symptoms before experiencing coronavirus infections established a baseline rate of how often these symptoms appear even without COVID. The share of patients with new symptoms in the period after infection constituted the rate after COVID.

Baseline rates and post-infection rates were calculated separately for the overall group and for each wave, as well as for demographic groupings by sex, age and race, and for groups of patients with various preexisting conditions (comorbidities), and with different severities of COVID infection. The baseline rate was subtracted from the post-infection rate to establish the change, expressed in percentage points.

Data shared with The Post was aggregated at the national level in accordance with the Epic Research standards to protect patient privacy.

Patients who had been hospitalized in intensive care units were excluded from most of the long-COVID analyses because the severity of their illness as well as post-ICU syndrome could cause symptoms that are indistinguishable from those of long COVID.

Patients may have been constrained from seeking care for new symptoms during the pandemic, especially in its early phases. That may have affected patients’ reported rates of new symptoms before they had coronavirus infections. The duration of symptoms or how many symptoms each patient had – or their severity – were not measured in this study.

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