Remember when SARS-CoV-2 infection was thought by some to be no worse than seasonal flu, or just another version of the cold virus? We have climbed a steep and thorny path through ignorance to come to this reckoning in 2021: There now is an open question about whether some people — healthcare workers and the public alike — could experience recurrent COVID-19 symptoms for years.

This is the nightmarish world of the so-called “long-haulers,” who have developed a seemingly chronic condition the Centers for Disease and Control and Prevention (CDC) is calling “long COVID.”1

“Some people got sick in March, so it has been a year for them,” says Natalie Lambert, PhD, associate professor of medicine at Indiana University.

Lambert is studying the condition and expects to publish a paper soon based on case reports, patient interviews, surveys, and other methods to find some meaning to this madness. Long COVID presents as a panoply of symptoms that can linger for months after even mild acute cases. Typical symptoms like fatigue or loss of sense of smell can recede completely for months, only to reappear — sometimes as different manifestations of COVID-19.

“With the most common symptoms, the time of duration was over three months,” she says. “For some long-haulers, the symptoms never go away. For others, after three, four, six months, they completely recover. Some who feel completely recovered have a relapse. For a lot of long-haulers, symptoms come and go, and then new ones come up. It’s just constant uncertainty.”

For example, a healthcare worker (HCW) may feel well enough to return to work only to get hit by the illness again in the future. No one has to tell employee health professionals that sick policies are a longstanding issue, with the need for staffing balanced against the threat of presenteeism that could endanger patients and co-workers.

“It makes it hard to go back to work, and it is also very difficult to explain to an employer, who might say, ‘I thought you were better,’” Lambert says. “But this is not a typical disease trajectory.”

Certainly, HCWs are aware of the job security issues in such scenarios, but they also have a deep moral obligation not to care for patients when they are feeling sick or impaired. For example, a common symptom is “brain fog,” which can affect cognitive function and decision-making.

“As you can imagine, healthcare workers are really concerned about having those kinds of symptoms,” Lambert says. “They don’t want to make mistakes while they are treating patients.”

Known Unknowns

The unknowns are legion, including whether HCWs experience a higher rate of long COVID than the general public, disease progression and duration, and infectiousness and transmission factors. Like seemingly every other aspect of this pandemic virus, there is no national reporting system to capture long COVID cases, meaning large population studies are considerably more difficult.

“The really hard part is that the data [source] that medical researchers like me typically use to answer questions like those is the electronic health record,” Lambert says. “[With that], we can look at tons of people, and compare them to background variables to answer different questions. There isn’t a whole lot of data on people with long COVID in the electronic healthcare record. There aren’t many treatments for these long-term cases yet. I’m collecting data mostly on people who are not hospitalized — these are the typical long-haulers.”

Although vaccines are rolling out and many healthcare workers are receiving it, the final insult of long COVID may be too much for some. They may struggle with intermittent symptoms and find it difficult to balance life and work. Some are considering leaving the profession.

“Some healthcare workers are saying, ‘It just doesn’t seem worth it to continue on under the current conditions,’” Lambert says. “They may be sick and have to return to work, but not have the support that they need. For example, not being able to get time off when we’re in a pandemic and it’s all hands on deck.”

Yet healthcare workers stepped in and held the line early in the epidemic, when there were no vaccines or treatments, and precious little personal protective equipment (PPE).

“They were willing to go in and fight the fight, treating patients without enough PPE and all of that, but there is a point as things drag on if there is not enough support for them, there is just not enough industry support,” Lambert says. “We are analyzing all of these health narratives scientifically to identify the prevalence of these themes, but I can say anecdotally reading them myself that this is something the world should be concerned about. Also, the mental health impact of the horrors healthcare workers are facing and have had to endure.”

Physicians and nurses are infamous for pushing through anything until the job is finished, even at the risk of their own health. The problem with this admirable work ethic is that long COVID might worsen if workers ignore the symptoms and forge ahead. The result could be a severe rebound of disease, and heart problems like tachycardia.

“If you are not feeling well, you should rest,” Lambert explains. “Healthcare workers are used to pushing through long shifts and getting things done. But if long-haulers try to do this, it can make their symptoms debilitating. The nature of COVID is that symptoms can come and go, and rest is essential for recovery. That information needs to become part of health leave policies, but right now it is not, as medical staff are needed more than ever.”

The CDC View

The CDC recently held a clinical outreach call on the long COVID phenomenon, which included an overview by Alfonso Hernandez-Romieu, MD, a member of the agency’s COVID-19 Late Sequelae Unit.

“Based on information available so far, persons with long COVID often present reporting persistent severe fatigue, headaches, and brain fog, which is defined as mild subjective cognitive impairment, approximately four weeks after acute illness,” he said. “Reports from clinicians have highlighted that long COVID may be independent of acute illness severity.”1

Researchers in China found that 76% of 1,733 patients reported at least one symptom of long COVID six months after their acute illness. Overall, 63% reported fatigue or muscle weakness, and 26% experienced labored breathing. Sleep problems occurred in 26%, and 22% reported anxiety or depression.2

“One in five patients not requiring supplemental oxygen during hospitalization had decreased lung function after six months,” Hernandez-Romieu said.

Indeed, long COVID can follow mild infections not requiring hospitalization. A study of patients in a post-COVID-19 clinic in France revealed 35% to 54% of patients with initial mild cases experienced persistent symptoms after two to four months.3

“Half to three-fourths of patients attending the post-acute COVID clinic in France [reported] new symptoms not initially present or symptoms that reappeared after initial resolution,” he said. “In addition, 9% of patients in a Faroe Islands study reported persistent severe symptoms at four months.”4

In the post-acute COVID-19 clinic in France, more than 25% of patients developed new neurological signs and symptoms after their acute COVID-19 illness. These included cognitive dysfunction, balance disorders, and swallowing and speech disorders, Hernandez-Romieu said.

“It is important for providers evaluating patients to perform baseline and serial comprehensive reviews of systems and physical exams to detect new or recurrent manifestations in patients with possible long COVID and improve its medical management,” Hernandez-Romieu explained. “There is still a lot we do not understand, and empathy toward patients experiencing long COVID is fundamental.”

Another speaker raised this point, emphasizing that long COVID patients should be reassured during treatment, even in the absence of medical explanations for some of the aspects of their suffering.

“While we don’t know what’s causing these symptoms, they are very real for patients, and we are seeing patients get better. I think it’s important to reassure them of that, while still supporting them in their journey,” Allison Navis, MD, lead clinical neurologist at the Center for Post-COVID Care at Mount Sinai Hospital in New York City, explained on the CDC clinical outreach call.1

Navis described a 42-year-old female patient who was experiencing cognitive issues, although she continued to work fewer hours. “She also noted physical fatigue that worsened with exercise,” she explained. “She had a tingling sensation throughout her body, but it was worse in her hands, and she also had heart rate elevations, palpitations, and shortness of breath.”

One of the initial clinical suspicions was that long COVID was a widespread neurological process that could include the brain. “There’s been some evidence that COVID can affect the brain, but that seems to be very rare and less common than the inflammatory changes,” Navis said.

Distinct from brain impairment, brain fog is one of the most common neurological symptoms seen in these patients.

“Brain fog is a symptom. It is not a diagnosis, and it means many different things to different people,” Navis said. “Oftentimes, it’s a combination of short-term memory issues, concentration, or a sort of word-finding speech difficulty.”

It is important to highlight that brain fog does not equal dementia. “Dementia is a neurological diagnosis, but we are seeing a lot of reassuring cognitive test results,” Navis said. “That doesn’t mean that these changes are not present and affecting these patients, but we’re not seeing patients who were previously high-functioning coming in with dementia”

Thus, it is unlikely that long COVID involves widespread infection in the brain. “There could be some inflammation. There could be a role of the vasculature playing into this, but we really don’t know,” Navis said. “Could the peripheral nervous system be affected? It absolutely could. It’s much more vulnerable to systemic insult. It’s not protected by the blood/brain barrier.”

Younger Patients Begin the Long Haul

Navis finds no “clear correlation with the severity of COVID infection, age, or risk factors — meaning that we’re seeing a lot of patients who had mild COVID and were not hospitalized. We’re seeing a lot of younger patients and those who were previously healthy.”

The symptoms often fluctuate, as patients report feeling like their normal selves and then will have bad day with fatigue and other symptoms.

“The impact on life varies,” she says. “Some patients are able to continue working. It might be a little bit more challenging, but they haven’t had to stop working. Whereas, others are on disability.”

Sleep disorders of some variety are common, with some long COVID patients struggling to fall asleep, or waking up frequently.

“We’re also seeing a lot of mood symptoms — so many patients expressing depression, anxiety, or post-traumatic stress disorder [PTSD]-like symptoms,” Navis said. “In addition to the brain fog, we’re also seeing these other symptoms as well. Headaches are probably the second most common symptoms that we’re seeing.”

These can vary from tension headaches to something that would be closer to a migraine. “Many [of these] patients don’t have a history of headaches, and now they complain of frequent headaches,” she said. “A lot of patients are complaining of tingling or numbness — sometimes a burning sensation. It can be local. It can be throughout the entire body, and sometimes alternating in locations, and more often, patients will say that it’s a little bit worse distally in their extremities.”

Clinicians also are seeing fluctuating heart rates and blood pressure, with patients complaining of lightheadedness, palpitations, and gastrointestinal disturbances. “In terms of neuroimaging, we’re really not seeing large, inflammatory, or infectious lesions,” Navis said. “We’re not seeing signs of what looks like encephalitis. We’re not even really seeing many strokes.”

There could be damage to the central nervous system, but again there is no substantive evidence to support or refute it on a large scale.

“Any inflammatory or metabolic changes can cause neuropathies, and we are seeing the presence of a small fiber neuropathy on some of our patients,” Navis said. “That could explain some of the symptoms, as well as dysautonomia and tingling.”

Broaching a delicate subject, Navis raised the question of whether and to what degree the mental health of patients could be contributing to long COVID symptoms.

“I want to highlight the importance of mental health aspects,” she said. “I think it’s extremely important to address those, to not be dismissive of them, but also not to [link] everything to it. A lot of patients do have depression and anxiety that’s secondary to these ongoing symptoms, and I think that’s extremely understandable. However, we do know that depression, anxiety, and PTSD can affect cognition and other symptoms. That is something we can act on, and, hopefully, improve those symptoms.”

With few available cures for neurological damage, a lot of the treatment will be therapeutic and supportive, with a multidisciplinary approach, she said.


  1. Centers for Disease Control and Prevention. Treating long COVID: Clinician experience with post-acute COVID-19 care. Jan. 28, 2021.
  2. Huang C, Huang L, Wang Y, et al. 6-month consequences of COVID-19 in patients discharged from hospital: A cohort study. Lancet 2021;397:220-232.
  3. Salmon-Ceron D, Slama D, De Broucker T, et al. Clinical, virological and imaging profile in patients with prolonged forms of COVID-19: A cross-sectional study. J Infect 2020;82:e1-e4.
  4. Petersen MS, Kristiansen MF, Hanusson KD, et al. Long COVID in the Faroe Islands — a longitudinal study among non-hospitalized patients. Clin Infect Dis 2020;ciaa1792. doi: 10.1093/cid/ciaa1792. [Online ahead of print].