Tag: long covid

Doctor’s Checklist for Treating Long COVID Patients

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April 4, 2023 – Lisa McCorkell had a mild bout of COVID-19 in March 2020. Young and healthy, she assumed that she would bounce back quickly. But when her fatigue, shortness of breath, and brain fog persisted, she realized that she most likely had long COVID. 

“Back then, we as patients basically coined the term,” she said. While her first primary care provider was sympathetic, they were unsure how to treat her. After her insurance changed, she ended up with a second primary care provider who didn’t take her symptoms seriously. “They dismissed my complaints and told me they were all in my head. I didn’t seek care for a while after that.”

McCorkell’s symptoms improved after her first COVID vaccine in the spring of 2021. She also finally found a new primary care doctor she could trust. But as one of the founders of the Patient-Led Research Collaborative, a group of researchers who study long COVID, she says many doctors still don’t know the hallmark symptoms of the condition or how to treat it. 

“There’s still a lack of education on what long COVID is, and the symptoms associated with it,” she said. “Many of the symptoms that occur in long COVID are symptoms of other chronic conditions, such as myalgic encephalomyelitis / chronic fatigue syndrome, that are often dismissed. And even if providers believe patients and send them for a workup, many of the routine blood and imaging tests come back normal.”

The term “long COVID” emerged in May 2020. And though the condition was recognized within a few months of the start of the pandemic, doctors weren’t sure how to screen or treat it. 

While knowledge has developed since then, primary care doctors are still in a tough spot. They’re often the first providers that patients turn to when they have symptoms of long COVID. But with no standard diagnostic tests, treatment guidelines, standard care recommendations, and a large range of symptoms the condition can produce, doctors may not know what to look for, nor how to help patients.

“There’s no clear algorithm to pick up long COVID – there are no definite blood tests or biomarkers, or specific things to look for on a physical exam,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center in New York City. “It’s a complicated disease that can impact every organ system of the body.”

Even so, emerging research has identified a checklist of sorts that doctors should consider when a patient seeks care for what appears to be long COVID. Among them:

  • The key systems and organs impacted by the disease
  • The most common symptoms
  • Useful therapeutic options for symptom management that have been found to help people with long COVID
  • The best heathy lifestyle choices that doctors can recommend to help their patients 

Here’s a closer look at each of these aspects, based on research and interviews with experts, patients, and doctors. 

Key Systems, Organs Impacted                                                                                                 

At least 10% of people who are infected with COVID-19 go on to have long COVID, according to a recent study that McCorkell helped co-author. But more than 3 years into the pandemic, much about the condition is still a mystery. 

COVID is a unique virus because it can spread far and wide in a patient’s body. A December 2022 study, published in the journal Nature, autopsied 44 people who died of COVID and found that the virus could spread throughout the body and persist, in one case as long as 230 days after symptoms started. 

“We know that there are dozens of symptoms across multiple organ systems,” said McCorkell. “That makes it harder for a primary care physician to connect the dots and associate it with COVID.”

A paper published last December in Nature Medicine proposed one way to help guide diagnosis. It divided symptoms into four groups: 

  • Cardiac and renal issues such as heart palpitations, chest pain, and kidney damage
  • Sleep and anxiety problems like insomnia, waking up in the middle of the night, and anxiety
  • In the musculoskeletal and nervous systems: musculoskeletal pain, osteoarthritis, and problems with mental skills
  • In the digestive and respiratory systems: trouble breathing, asthma, stomach pain, nausea, and vomiting

There were also specific patterns in these groups. People in the first group were more likely to be older, male, have other conditions and to have been infected during the first wave of the COVID pandemic. People in the second group were over 60% female, and were more likely to have had previous allergies or asthma. The third group was also about 60% female, and many of them already had autoimmune conditions such as rheumatoid arthritis. Members of the fourth group – also 60% female – were the least likely of all the groups to have another condition.

This research is helpful, because it gives doctors a better sense of what conditions might make a patient more likely to get long COVID, as well as specific symptoms to look out for, said Steven Flanagan, MD, a physical medicine and rehabilitation specialist at NYU Langone Medical Center who also specializes in treating patients with long COVID. 

But the “challenge there, though, for health care providers is that not everyone will fall neatly into one of these categories,” he stressed.

Checklist of Symptoms 

Although long COVID can be confusing, doctors say there are several symptoms that appear consistently that primary care providers should look out for, that could flag long COVID. They include:

Post-exertional malaise (PEM). This is different from simply feeling tired. “This term is often conflated with fatigue, but it’s very different,” said David Putrino, PhD, director of rehabilitation innovation at the Mount Sinai Health System in New York City, who says that he sees it in about 90% of patients who come to his long COVID clinic. 

PEM is the worsening of symptoms after physical or mental exertion. This usually occurs a day or two after the activity, but it can last for days, and sometimes weeks. 

“It’s very different from fatigue, which is just a generalized tiredness, and exercise intolerance, where someone complains of not being able to do their usual workout on the treadmill,” he noted. “People with PEM are able to push through and do what they need to do, and then are hit with symptoms anywhere from 12 to 72 hours later.”

Dysautonomia. This is an umbrella term used to describe a dysfunction of the autonomic nervous system, which regulates bodily functions that you can’t control, like your blood pressure, heart rate, and breathing. This can cause symptoms such as heart palpitations, along with orthostatic intolerance, which means you can’t stand up for long without feeling faint or dizzy. 

“In my practice, about 80% of patients meet criteria for dysautonomia,” said Putrino. Other research has found that it’s present in about two-thirds of long COVID patients.

One relatively easy way primary care providers can diagnose dysautonomia is to do the tilt table test. This helps check for postural orthostatic tachycardia syndrome (POTS), one of the most common forms of dysautonomia. During this exam, the patient lies flat on a table. As the head of the table is raised to an almost upright position, their heart rate and blood pressure are measured. Signs of POTS include an abnormal heart rate when you’re upright, as well as a worsening of symptoms.

Exercise intolerance. A 2022 review published in the journal JAMA Network Open analyzed 38 studies on long COVID and exercise and found that patients with the condition had a much harder time doing physical activity. Exercise capacity was reduced to levels that would be expected about a decade later in life, according to study authors. 

“This is especially important because it can’t be explained just by deconditioning,” said Purpura. “Sometimes these patients are encouraged to ramp up exercise as a way to help with symptoms, but in these cases, encouraging them to push through can cause post-exertional malaise, which sets patients back and delays recovery.”

While long COVID can cause dozens of symptoms, a paper McCorkell co-authored zeroed in on some of the most common ones:

  • Chest pain
  • Heart palpitations
  • Coughing
  • Shortness of breath
  • Belly pain
  • Nausea
  • Problems with mental skills
  • Fatigue
  • Disordered sleep
  • Memory loss
  • Ringing in the ears (tinnitus)
  • Erectile dysfunction
  • Irregular menstruation
  • Worsened premenstrual syndrome

While most primary care providers are familiar with some of these long COVID symptoms, they may not be aware of others. 

“COVID itself seems to cause hormonal changes that can lead to erection and menstrual cycle problems,” explained Putrino. “But these may not be picked up in a visit if the patient is complaining of other signs of long COVID.” 

It’s not just what symptoms are, but when they began to occur, he added. 

“Usually, these symptoms either start with the initial COVID infection, or begin sometime within 3 months after the acute COVID infection. That’s why it’s important for people with COVID to take notice of anything unusual that crops up within a month or two after getting sick.”

Can You Prevent Long COVID?

You can reduce your risk by taking preventive measures such as wearing a mask, keeping your distance from others in crowded indoor settings, and getting vaccinated. Getting at least one dose of a COVID vaccine before you test positive for COVID lowers your risk of long COVID by about 35% according to a 2022 study published in Antimicrobial Stewardship & Healthcare Epidemiology. Unvaccinated people who recovered from COVID, and then got a vaccine, lowered their own long COVID risk by 27%. 

In addition, a February study published in JAMA Internal Medicine found that women who were infected with COVID were less likely to go on to get long COVID and/or have less debilitating symptoms if they had a healthy lifestyle, which included the following: 

  • Healthy weight (a BMI between 18.5 and 24.7)
  • Never smoker
  • Moderate alcohol consumption
  • A high-quality diet
  • Seven to 9 hours of sleep a night
  • At least 150 minutes per week of physical activity

But McCorkell noted that she herself had a healthy pre-infection lifestyle but got long COVID anyway, suggesting these approaches don’t work for everyone.

“I think one reason my symptoms weren’t addressed by primary care physicians for so long is because they looked at me and saw that I was young and healthy, so they dismissed my reports as being all in my head,” she explained. “But we know now anyone can get long COVID, regardless of age, health status, or disease severity. That’s why it’s so important that primary care physicians be able to recognize symptoms.”

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Bias, Lack of Access Make Long COVID Worse for Patients of Color

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March 28, 2023 – Over and over, Mesha Liely was told that it was all in her head. That she was just a woman prone to exaggeration. That she had anxiety. That she simply needed to get more rest and take better care of herself. 

The first time an ambulance rushed her to the emergency room in October 2021, she was certain something was seriously wrong. Her heart raced, her chest ached, she felt flushed, and she had numbness and tingling in her arms and legs. And she had recently had COVID-19. But after a 4-day hospital stay and a battery of tests, she was sent home with no diagnosis and told to see a cardiologist. 

More than a dozen trips to the emergency room followed over the next several months. Liely saw a cardiologist and several other specialists: a gastroenterologist; an ear, nose, and throat doctor; a vascular doctor; and a neurologist. She got every test imaginable. But she still didn’t get a diagnosis. 

“I believe more times than not, I was dismissed,” said Liely, 32, who is Black. “I am female. I am young. I am a minority. The odds are up against me.”

By the time she finally got a diagnosis in May 2022, she felt like a bobble-head with weakness in her arms and legs, rashes and white patches of skin along the right side of her body, distorted vision, swelling and discomfort in her chest, and such a hard time with balance and coordination that she often struggled to walk or even stand up.

“I was in a wheelchair when the doctor at Hopkins told me I had long COVID,” Liely said. “I just broke down and cried. The validation was the biggest thing for me.”

Stark racial and ethnic disparities in who gets sick and who receives treatment have been clear since the early days of the pandemic. Black and Hispanic patients were more likely to get COVID than white people, and, when they did get sick, they were more likely to be hospitalized and more apt to die.

Now, an emerging body of evidence also suggests that Black and Hispanic patients are also more likely to have long COVID – and more likely to get a broader range of symptoms and serious complications when they do. 

One study recently published this year in the Journal of General Internal Medicine followed more than 62,000 adults in New York City who had COVID between March 2020 and October 2021. Researchers tracked their health for up to 6 months, comparing them to almost 250,000 people who never had COVID. 

Among the roughly 13,000 people hospitalized with severe COVID, 1 in 4 were Black and 1 in 4 were Hispanic, while only 1 in 7 were white, this study found. After these patients left the hospital, Black adults were much more likely than white people to have headaches, chest pain, and joint pain. And Hispanic patients were more apt to have headaches, shortness of breath, joint pain, and chest pain.

There were also racial and ethnic disparities among patients with milder COVID cases. Among people who weren’t hospitalized, Black adults were more likely to have blood clots in their lungs, chest pain, joint pain, anemia, or be malnourished. Hispanic adults were more likely than white adults to have dementia, headaches, anemia, chest pain, and diabetes. 

Yet research also suggests that white people are more likely to get diagnosed and treated for long COVID. A separate study published this year in the journal BMC Medicine offers a profile of a typical long COVID patient receiving care at 34 medical centers across the country. And these patients are predominantly white, affluent, well-educated, female, and living in communities with great access to health care. 

While more Black and Hispanic patients may get long COVID, “having symptoms of long COVID may not be the same as being able to get treatment.,” said Dhruv Khullar, MD, lead author of the New York City study and a doctor and assistant professor of health policy and economics at Weill Cornell Medical College in New York City.

Many of the same issues that made many Black and Hispanic patients more vulnerable to infection during the pandemic may now be adding to their limited access to care for long COVID, Khullar said. 

Nonwhite patients were more apt to have hourly jobs or be essential workers without any ability to telecommute to avoid COVID during the height of the pandemic, Khullar said. They’re also more likely to live in close quarters with family members or roommates and face long commutes on public transit, limiting their options for social distancing. 

“If people that are going out of the home that are working in the subways or grocery stores or pharmacies or jobs deemed essential were disproportionately Black or Hispanic, they would have a much higher level of exposure to COVID than people who could work from home and have everything they needed delivered,” Khullar said. 

Many of these hourly and low-wages workers are also uninsured or underinsured, lack paid sick time, struggle with issues like child care and transportation when they need checkups, and have less disposable income to cover copays and other out-of-pocket fees, Khullar said. “They can get access to acute urgent medical care, but it’s very hard for a lot of people to access routine care like you would need for long COVID,” Khullar says.

These longstanding barriers to care are now contributing to more long COVID cases – and worse symptoms – among Black and Hispanic patients, said Alba Miranda Azola, MD, co-director of the Post-Acute COVID-19 Team at Johns Hopkins University School of Medicine in Baltimore. 

“They basically push through their symptoms for too long without getting care either because they don’t see a doctor at all or because the doctor they do see doesn’t do anything to help” said Azola, who diagnosed Mesha Liely with long COVID. “By the time they get to me, their symptoms are much worse than they needed to be.”

In many ways, Liely’s case is typical of the Black and Hispanic patients Azola sees with long COVID. “It’s not unusual for patients have 10 or even 15 visits to the emergency room without getting any help before they get to me,” Azola said. “Long COVID is poorly understood and underdiagnosed and they just feel gaslit.”

What sets Liely apart is that her job as 911 operator comes with good health benefits and easy access to care. 

“I started to notice a pattern where when I go to the ER and my co-workers are there or I am in my law enforcement uniform, and everyone is so concerned and takes me right back,” she recalled. “But when I would go dressed in my regular clothing, I would be waiting 8 to 10 hours and nobody would acknowledge me, or they would ask if I was just here to get pain medicines.”

Liely can easily see how other long COVID patients who look like her might never get diagnosed at all. “It makes me mad but doesn’t surprise me,” she says. 

After months of long COVID treatment, including medications for heart issues and muscle weakness as well as home health care, occupational therapy, and physical therapy, Liely went back to work in December. Now, she has good days and bad days. 

“On the days I wake up and feel like I’m dying because I feel so bad, that’s when I really think it didn’t need to be like this if only I had been able to get somebody to listen to me sooner,” she said.

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‘We’re Struggling’: Long COVID Mystery Has Doctors in the Dark

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March 23, 2023 — This month, I took care of a patient who recently contracted COVID-19 and was complaining of chest pain. After ruling out the possibility of a heart attack, pulmonary embolism, or pneumonia, I concluded that this was a residual symptom of COVID. 

Chest pain is a common lingering symptom of COVID. However, because of the scarcity of knowledge regarding these post-acute symptoms, I was unable to counsel my patient on how long this symptom would last, why he was experiencing it, or what its actual cause was. 

Such is the state of knowledge on long COVID. That informational vacuum is why we’re struggling and doctors are in a tough spot when it comes to diagnosing and treating patients with the condition.

Almost daily, new studies are published about long COVID (technically known as post-acute sequelae of COVID-19 [PASC]) and its societal impacts. These studies often calculate various statistics regarding the prevalence of this condition, its duration, and its scope. 

However, many of these studies do not provide the complete picture — and they certainly do not when they are interpreted by t

he lay press and turned into clickbait. 

Long COVID is real, but there is a lot of context that is omitted in many of the discussions that surround it. Unpacking this condition and situating it in the larger context is an important means of gaining traction on this condition. 

And that’s critical for doctors who are seeing patients with symptoms.

Long COVID: What Is It?   

The CDC considers long COVID to be an umbrella term for “health consequences” that are present at least 4 weeks after an acute infection. This condition can be considered “a lack of return to the usual state of health following COVID,” according to the CDC.

Common symptoms include fatigue, shortness of breath, exercise intolerance, “brain fog,” chest pain, cough, and loss of taste/smell. Note that it’s not a requirement that that symptoms be severe enough that they interfere with activities of daily living, just that they are present.

There is no diagnostic test or criteria that confirms this diagnosis. Therefore, the symptoms and definitions above are vague and make it difficult to gauge prevalence of the disease. Hence, the varying estimates that range from 5% to 30%, depending on the study. 

Indeed, when one does routine blood work or imaging on these patients, it is unlikely that any abnormality is found. Some individuals, however, have met diagnostic criteria and have been diagnosed with postural orthostatic tachycardia syndrome (POTS). POTS is a disorder commonly found in long COVID patients that causes problems in how the autonomic nervous system regulates heart rate when moving from sitting to standing, during which blood pressure changes occur. 

How to Distinguish Long COVID From Other Conditions

There are important conditions that should be ruled out in the evaluation of someone with long COVID. First, any undiagnosed condition or change in an underlying condition that could explain the symptoms should be considered and ruled out. 

Secondly, it is critical to recognize that those who were in the intensive care unit or even hospitalized with COVID should not really be grouped together with those who had uncomplicated COVID that did not require medical attention. 

One reason for this is a condition known as post-ICU syndrome or PICS. PICS can occur in anyone who is admitted to the ICU for any reason and is likely the result of many factors common to ICU patients. They include immobility, severe disruption of sleep/wake cycles, exposure to sedatives and paralytics, and critical illness. 

Those individuals are not expected to recover quickly and may have residual health problems that persist for years, depending on the nature of their illness. They even have heightened mortality. 

The same is true, to a lesser extent, to those hospitalized whose “post-hospital” syndrome places them at higher risk for experiencing ongoing symptoms. 

To be clear, this is not to say that long COVID does not occur in the more severely ill patients, just that it must be distinguished from these conditions. In the early stages of trying to define the condition, it is more difficult if these categories are all grouped together. The CDC definition and many studies do not draw this important distinction and may confuse long COVID with PICS and post-hospital syndrome.

Control Groups in Studies Are Key

Another important means to understand this condition is to conduct studies with control groups, directly comparing those who had COVID with those that did not. 

Such a study design allows researchers to isolate the impact of COVID and separate it from other factors that could be playing a role in the symptoms. When researchers conduct studies with control arms, the prevalence of the condition is always lower than without. 

In fact, one notable study demonstrated comparable prevalence of long COVID symptoms in those who had COVID versus those that believe they had COVID. 

Identifying Risk Factors

Several studies have suggested certain individuals may be overrepresented among long COVID patients. These risk factors for long COVID include women, those who are older, those with preexisting psychiatric illness (depression/anxiety), and those who are obese. 

Additionally, other factors associated with long COVID include reactivation of Epstein-Barr virus (EBV), abnormal cortisol levels, and high viral loads of the coronavirus during acute infection. 

None of these factors has been shown to play a causal role, but they are clues for an underlying cause. However, it is not clear that long COVID is monolithic — there may be subtypes or more than one condition underlying the symptoms. 

Lastly, long COVID also appears to be only associated with infection by the non-Omicron variants of COVID.

Role of Antivirals and Vaccines 

The use of vaccines has been shown to lower, but not entirely eliminate, the risk of long COVID. This is a reason why low-risk individuals benefit from COVID vaccination. Some have also reported a therapeutic benefit of vaccination on long COVID patients. 

Similarly, there are indications that antivirals may also diminish the risk for long COVID, presumably by influencing viral load kinetics. It will be important, as newer antivirals are developed, to think about the role of antivirals not just in the prevention of severe disease but also as a mechanism to lower the risk of developing persistent symptoms. 

There may also be a role for other anti-inflammatory medications and other drugs such as metformin.

 Long COVID and Other Infectious Diseases 

The recognition of long COVID has prompted many to wonder if it occurs with other infectious diseases. Those in my field of infectious disease have routinely been referred patients with persistent symptoms after treatment for Lyme disease or after recovery from the infectious mononucleosis. 

Individuals with influenza may cough for weeks post-recovery, and even patients with Ebola may have persistent symptoms (though the severity of most Ebola causes makes it difficult to include). 

Some experts suspect an individual human’s immune response may influence the development of post-acute symptoms. The fact that so many people were sickened with COVID at once allowed a rare phenomenon that always existed with many types of infections to become more visible.

Where to Go From Here: A Research Agenda

Before anything can be definitely said about long COVID, fundamental scientific questions must be answered. 

Without an understanding of the biological basis of this condition, it becomes impossible to diagnose patients, development treatment regimens, or to prognosticate (though symptoms seem to dissipate over time). 

It was recently said that unraveling the intricacies of this condition will lead to many new insights about how the immune system works — an exciting prospect in and of itself that will advance science and human health.

Armed with that information, the next time clinicians see a patient such as the one I did, we will be in a much better position to explain to a patient why they are experiencing such symptoms, provide treatment recommendations, and offer prognosis. 

Amesh A. Adalja, MD, is an infectious disease, critical care, and emergency medicine specialist in Pittsburgh, and senior scholar with the Johns Hopkins Center for Health Security.

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Q&A: The Future of COVID-19

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Senior writer Kara Grant co-authored this report.

March 15, 2023 – As we approach the third anniversary of the COVID-19 pandemic, experts and everyday Americans wonder if we are finally at the end of what has been a painful and exhausting ordeal that’s lasted 3 years. With vaccine and booster fatigue, COVID-19 cases leveling out, and a growing body of research that has helped us understand the virus more clearly, many are still asking: How concerned should I be?

 In February, the Biden administration announced that it was the end of the road for the COVID-19 emergency orders, which had been in place since January 2020. That came after a year still fraught with ups and downs, with the U.S. surpassing 1 million COVID-19 deaths and variants continuing to evolve.

 We asked experts their thoughts on the future of COVID-19 and how their perspectives have shifted over the years.

Where Are We Now With COVID-19?

While the Omicron variant is still lingering, we’re in a period of lower rates of COVID-19 transmission.

Vaccinations and boosters have helped. That, along with antiviral treatments and high rates of collective immunity, have kept COVID-19 at bay, but it’s important to remember that this virus isn’t going anywhere, says Ashwin Vasan, MD, the commissioner of the New York City Department of Health and Mental Hygiene.  

“The federal emergency will expire in May, and compared to where we’ve been, we’re not in an emergency today,” he says. “But we will have to use the tools and strategies to really manage whatever COVID-19 throws at us going forward – if it were to change or if it ends up being more of a seasonal virus, like other coronaviruses.”

One thing is for certain: Health care will never be the same, says Jennifer Gil, a registered nurse and a member of the American Nurses Association Board of Directors.

“While cases in our area are steadily declining, patients and health care workers continue to experience the long-lasting effects of the pandemic,” she says. “I witness it every day when I see the long-term impact it has had on patients, access to care, and health care workers’ mental and emotional well-being.”

Is This the End of the Pandemic? 

First, it’s important to understand the difference between a pandemic and an epidemic, Vasan says. An epidemic is the spreading of a disease that outpaces what would be expected within a certain time and location. A pandemic is an epidemic that spreads across various continents and regions of the world.

COVID-19 is a new virus, which makes things tricky. “Before 2020, our baseline was zero because COVID-19 didn’t exist,” says Vasan. “So, the question we can’t really answer from an epidemiologic standpoint is – ‘is it still a pandemic?’ Well, is it circulating beyond what’s to be expected? I think we’re going to have to figure out what those expectations are at baseline.”

Jim Versalovic, MD, pathologist-in-chief at Texas Children’s Hospital, deems this a “post-pandemic” period, since the virus isn’t impacting us as dramatically as it did in 2020 and 2021. This is thanks to the successful efforts “to diagnose, treat, and prevent COVID-19,” along with collective immunity after many being exposed and infected with the virus, he says.

Some experts believe that declaring the pandemic “over” is a long shot. Rather, it’s likely that we are changing to more of an endemic status, according to Natascha Tuznik, DO, an infectious disease specialist at the University of California, Davis. It’s best to view COVID-19 as a “permanently established infection” in both humans and animals, she says. So we should treat it like the seasonal flu and continue to be careful to update vaccinations. 

“Vaccine uptake, overall, is still insufficient,” says Tuznik, “It’s important to not let our guard down and believe the problem no longer exists.”

The impact the pandemic has had on communities of color, frontline workers, and the health care system more broadly is also not to be forgotten, says Gil. “While the number of COVID-19 cases is subsiding, the invisible impact of the pandemic will continue to emerge in the coming years,” she says. 

What Worries You Now About COVID-19? 

Complacency can be an issue with any viral infection, says Versalovic, and it’s critical to continue to treat COVID-19 with extreme caution. For example, the U.S. will always need to track COVID-19 trends.

“It has become one of our major respiratory viruses affecting mankind around the globe,” he says. “Certainly, in the medical profession, we’re going to have to do our best to communicate and emphasize to everyone that these viruses aren’t going to disappear, and we need to continue to be aware and vigilant.”

Don’t forget that people still die from this virus every day, says Tuznik. “COVID-19 has killed over 1 million Americans and over 6.8 million people globally,” she says. “While the rates of death have declined, they have not stopped.”

Vasan poses another critical question: “What pieces are in place to ensure that we have a strong health system prepared to respond to COVID-19 changes or if another epidemic or pandemic illness arrives?” 

Examples could include ensuring tests, vaccines, and treatments are deployed in a quick, strategic manner, and building a public health system that can make that happen, without failing to support health care workers, he says.

Challenges like staffing shortages and hazardous work conditions have resulted in mental health-related issues and burnout among health care workers, Gil says. Many have reported skyrocketing rates of PTSD, anxiety, depression, and stress. Some have chosen to leave the health care workforce entirely.

“Investing in our health care workforce by providing mental health and wellness resources is essential,” says Gil. “We must also equally address the underlying issues by enforcing safe staffing standards and investing in long-term solutions that aim to improve the work environment.”

Has the Pandemic Changed Your Relationship to Medicine? 

The COVID-19 crisis has altered the health care world, likely for posterity. For many, like Vasan, the last 3 years have been a shining example of how fragile our health care system is. 

“We continually spend on things that don’t deliver on health,” he says, referring specifically to the $4 trillion spent on health care, with only a small fraction of that dedicated to disease prevention efforts. “Had we spent more on prevention, fewer would have died from COVID. We need to have a reckoning in this country about whether we are willing not to design for health care and medicine, but to design for health.” 

And while COVID-19 certainly brought to light the major – and minor – flaws in the health care system, the knowledge we’ve learned along the way is a silver lining for many doctors. Versalovic says that the chaos and anxiety forced those in medicine to rapidly refine their approaches to diagnostics, from in-hospital testing to drive-thru and at-home testing. Along the way, he says, there has also been a renewed gratitude for treatments like monoclonal antibodies and the preventive powers of RNA vaccines. 

But for Tuznik, the pandemic has given her an entirely newfound appreciation for her career path. 

“The infectious diseases community really came together as a tour de force during the pandemic, and it was humbling to be a part of such a mass effort and collaboration,” she says. 

What Have the Last 3 Years Taught You?

COVID-19 has forced us all to learn new and often difficult lessons about ourselves, our relationships, and how we each fit into the world. 

It’s a line we’ve heard over and over again: These are unprecedented times. A large part of that has been the extreme politicization of science and the growing divisiveness across the country. But despite what feels like unyielding friction in the medical community and beyond, people were still able to come together and tackle the pandemic’s challenges. 

Vasan says that our ability to work together on life-saving treatments and prevention strategies is “a testament to human endeavor, ingenuity, collaboration, in the face of an existential threat.”

For nurses, the pandemic brought about pervasive burnout and fatigue. But that’s not the end of the story. 

“Personally, it has driven me to go back to school to gain the research and analytical skills necessary to develop evidence-based policies and programs that aim to improve health care delivery,” says Gil. “Now, more than ever, nurses are key stakeholders at the policy and decision-making table.”

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COVID at 3 Years: Where Are We Headed?

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March 15, 2023 – Three years after COVID-19 rocked the world, the pandemic has evolved into a steady state of commonplace infections, less frequent hospitalization and death, and continued anxiety and isolation for older people and those with weakened immune systems.

After about 2½ years of requiring masks in health care settings,  the CDC lifted its recommendation for universal, mandatory masking in hospitals in September 2022.

Some statistics tell the story of how far we have come. COVID-19 weekly cases dropped to nearly 171,000 on March 8, a huge dip from the 5.6 million weekly cases reported in January 2022. COVID-19 deaths, which peaked in January 2021 at more than 23,000 a week, stood at 1,862 per week on March 8.

Where We Are Now

Since Omicron is so infectious, “we believe that most people have been infected with Omicron in the world,” says Christopher J.L. Murray, MD, a professor and chair of health metrics sciences at the University of Washington and director of the Institute for Health Metrics and Evaluation in Seattle. Sero-prevalence surveys — or the percentage of people in a population who have antibodies for an infectious disease, or the Omicron variant in this case — support this rationale, he says.

“Vaccination was higher in the developed world but we see in the data that Omicron infected most individuals in low income countries,” says Murray. For now, he says, the pandemic has entered a “steady state.”

At New York University Langone Health System, clinical testing is all trending downward, and hospitalizations are low, says Michael S. Phillips, MD, an infectious disease doctor and chief epidemiologist at the health system. 

In New York City, there has been a shift from pandemic to “respiratory viral season/surge,” he says. 

The shift is also away from universal source control – where every patient encounter in the system involves masking, distancing, and more – to a focus on the most vulnerable patients “to ensure they’re well-protected,” Phillips says. 

Johns Hopkins Hospital in Baltimore has seen a “marked reduction” of the number of people coming to the intensive care unit because of COVID, says Brian Thomas Garibaldi, MD, a critical care doctor and director of the Johns Hopkins Biocontainment Unit.

“That is a testament to the amazing power of vaccines,” he says. 

The respiratory failures that marked many critical cases of COVID in 2020 and 2021 are much rarer now, a shift that Garibaldi calls “refreshing.”

“In the past 4 or 5 weeks, I’ve only seen a handful of COVID patients. In March and April of 2020, our entire intensive care unit – in fact, six intensive care units – were filled with COVID patients.”

Garibaldi sees his own risk differently now as well. 

“I am not now personally worried about getting COVID, getting seriously ill, and dying from it. But if I have an ICU shift coming up next week, I am worried about getting sick, potentially having to miss work, and put that burden on my colleagues. Everyone is really tired now,” says Garibaldi, who is also an associate professor of medicine and physiology in the Division of Pulmonary and Critical Care Medicine at Johns Hopkins University School of Medicine. 

What Keeps Experts Up at Night?

The potential for a stronger SARS-CoV-2 variant to emerge concerns some experts.  

A new Omicron  subvariant could emerge, or a new variant altogether could arise.  

One of the main concerns is not just a variant with a different name, but one that can escape current immune protections. If that happens, the new variant could infect people with immunity against Omicron. 

If we do return to a more severe variant than Omicron, Murray says, “then suddenly we’re in a very different position. 

Keeping an Eye on COVID-19, Other Viral Illnesses

We have better genomic surveillance for circulating strains of SARS-CoV-2 than earlier in the pandemic, Phillips says. More reliable, day-to-day data also helped recently with the respiratory syncytial virus (RSV) outbreak and for tracking flu cases.

 Wastewater surveillance as an early warning system for COVID-19 or other respiratory virus surges can be helpful, but more research is needed, Garibaldi says. And with more people testing at home, test positivity rates are likely an undercount. So, hospitalization rates for COVID and other respiratory illnesses remain one of the more reliable community-based measures, for now, at least. 

One caveat is that sometimes, it is unclear if COVID-19 is the main reason someone is admitted to the hospital vs. someone who comes in for another reason and happens to test positive upon admission. 

Phillips suggests that using more than one measure might be the best approach, especially to reduce the likelihood of bias associated with any single strategy. “You need to look at a whole variety of tests in order for us to get a good sense of how it’s affecting all communities,” he says. In addition, if a consensus emerges among different measures – wastewater surveillance, hospitalization and test positivity all trending up – “that’s clearly a sign that things are afoot and that we would need to modify our approach accordingly.”

Where We Could Be Heading

Murray predicts a steady pace of infection with “no big changes.” But waning immunity remains a concern. 

That means if you have not had a recent infection – in the last 6 to 10 months – you might want to think about getting a booster, Murray says “The most important thing for people, for themselves, for their families, is to really think about keeping their immunity up.” 

Phillips hopes the improved surveillance systems will help public health officials make more precise recommendations based on community levels of respiratory illness. 

When asked to predict what might happen with COVID moving forward, “I can’t tell you how many times I’ve been wrong answering that question,” Garibaldi says.

 Rather than making a prediction, he prefers to focus on hope. 

“We weathered the winter storm we worried about in terms of RSV, flu, and COVID at the same time. Some places were hit harder than others, especially with pediatric RSV cases, but we haven’t seen anywhere near the level we saw last year and before that,” he says. “So, I hope that continues.”

“We’ve come very far in just 3 years. When I think about where we were in March 2020 taking care of our first round of COVID patients in our first unit called a biocontainment unit,” Garibaldi says. 

Murray addresses whether the term “pandemic” still applies at this point. 

“In my mind, the pandemic is over,” he says, because we are no longer in an emergency response phase. But COVID in some form is likely to be around for a long time, if not forever.  

“So, it depends on how you define pandemic. If you mean an emergency response, I think we’re out of it. If you mean the formal definition you know of an infection that goes all over the place, then we’re going to be in it for a very long time.”

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‘Breakthrough’ Study: Diabetes Drug Helps Prevent Long COVID

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March 9, 2023 – Metformin appears to play a role in preventing long COVID when taken early during a COVID-19 infection, according to a new preprint study from The Lancet. The preprint hasn’t yet been peer-reviewed or published in a journal.

In particular, metformin led to a 42% drop in long COVID among people who had a mild to moderate COVID-19 infection. 

“Long COVID affects millions of people, and preventing long COVID through a treatment like metformin could prevent significant disruptions in people’s lives,” says lead author Carolyn Bramante, MD, an assistant professor of internal medicine and pediatrics at the University of Minnesota.

Between January 2021 and February 2022, Bramante and colleagues tested three oral medications – metformin (typically used to treat type 2 diabetes), ivermectin (an antiparasitic), and fluvoxamine (an antidepressant) – in a clinical trial across the U.S. called COVID-OUT. The people being studied, investigators, care providers, and others involved in the study were blinded to the randomized treatments. The trial was decentralized, with no in-person contact with participants.

The researchers included patients who were ages 30-85 with overweight or obesity, had documentation of a confirmed COVID-19 infection, had fewer than 7 days of symptoms, had no known prior infection, and joined the study within 3 days of their positive test. The study included monthly follow-up for 300 days, and participants indicated whether they received a long COVID diagnosis from a medical doctor, which the researchers confirmed in medical records after participants gave consent.

The medications were pre-packaged into pill boxes for fast delivery to participants and to ensure they took the correct number of each type of pill. The packages were sent via same-day courier or overnight shipping.

The metformin doses were doled out over 14 days: with 500 milligrams on the first day, 500 milligrams twice a day for the next 4 days, and then 500 milligrams in the morning and 1,000 milligrams in the evening for the remaining 9 days.

Among the 1,323 people studied, 1,125 agreed to do long-term follow-up for long COVID, including 564 in the metformin group and 561 in the blinded placebo group. The average age was 45, and 56% were women, including 7% who were pregnant. 

The average time from the start of symptoms to starting medication was 5 days, and 47% began taking the drug within 4 days or less. About 55% had received the primary COVID-19 vaccination series, including 5.1% who received an initial booster, before enrolling in the study.

Overall, 8.4% of participants reported that a medical provider diagnosed them with long COVID. Of those who took metformin, 6.3% developed long COVID, compared to 10.6% among those who took the identical-matched placebo.

The risk reduction for metformin was 42% versus the placebo, which was consistent across subgroups, including vaccination status and different COVID-19 variants.

When metformin was started less than 4 days after COVID-19 symptoms started, the effect was potentially even greater, with a 64% reduction, as compared with a 36% reduction among those who started metformin after 4 or more days after symptoms.

Neither ivermectin nor fluvoxamine showed any benefits for preventing long COVID.

At the same time, the study authors caution that more research is needed. 

“The COVID-OUT trial does not indicate whether or not metformin would be effective at preventing long COVID if started at the time of emergency department visit or hospitalization for COVID-19, nor whether metformin would be effective as treatment in persons who already have long COVID,” they wrote. “With the burden of long COVID on society, confirmation is urgently needed in a trial that addresses our study’s limitations in order to translate these results into practice and policy.”

Several risk factors for long COVID emerged in the analysis. About 11.1% of the women had a long COVID diagnosis, as compared with 4.9% of the men. Also, those who had received at least the primary vaccine series had a lower risk of developing long COVID, at 6.6%, as compared with 10.5% among the unvaccinated. Only one of the 57 people who received a booster shot developed long COVID.

Notably, pregnant and lactating people were included in this study, which is important given that pregnant people face higher risks for poor COVID-19 outcomes and are excluded from most non-obstetric clinical trials, the study authors wrote. In this study, they were randomized to metformin or placebo but not ivermectin or fluvoxamine due to limited research about the safety of those drugs during pregnancy and lactation.

The results are now under journal review but show consistent findings from other recent studies. Also, in August 2022, the authors published results from COVID-OUT that showed metformin led to a 42% reduction in hospital visits, emergency department visits, and deaths related to severe COVID-19.

“Given the lack of side effects and cost for a 2-week course, I think these data support use of metformin now,” says Eric Topol, MD, founder and director of the Scripps Research Translational Institute and editor-in-chief of Medscape, WebMD’s sister site for health care professionals. 

Topol, who wasn’t involved with this study, has been a leading voice on COVID-19 research throughout the pandemic. He noted the need for more studies, including a factorial design trial to test metformin and Paxlovid, which has shown promise in preventing long COVID. Topol also wrote about the preprint in Ground Truths, his online newsletter.

“As I’ve written in the past, I don’t use the term ‘breakthrough’ lightly,” he wrote. “But to see such a pronounced benefit in the current randomized trial of metformin, in the context of it being so safe and low cost, I’d give it a breakthrough categorization.”

Another way to put it, Topol wrote, is that based on this study, he himself would take metformin if he became infected with COVID-19. 

Jeremy Faust, MD, an emergency medicine doctor at Brigham and Women’s Hospital in Boston, also wrote about the study in his newsletter, Inside Medicine. He noted that the 42% reduction in long COVID means that 23 COVID-19 patients need to be treated with metformin to prevent one long COVID diagnosis, which is an “important reduction.”

“Bottom line: If a person who meets criteria for obesity or overweight status were to ask me if they should take metformin (for 2 weeks) starting as soon as they learn they have COVID-19, I would say yes in many if not most cases, based on this new data,” he wrote. “This is starting to look like a real win.”

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Long COVID Takes Toll on Already Stretched Health Care Workforce

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March 6, 2023 — The impact of long COVID – and its sometimes-disabling symptoms that can persist for more than a year — has worsened health care’s already severe workforce shortage. 

Hospitals have turned to training programs, traveling nurses, and emergency room staffing services. While the shortage of clinical workers continues, support workers are also in short supply, with no end in sight.

“Our clinical staff is the front line, but behind them, several layers of people do jobs that allow them to do their jobs,” says Joanne Conroy, MD, president of Dartmouth-Hitchcock Medical Center, a 400-bed hospital in New Hampshire. “Lab and radiology and support people and IT and facilities and housekeeping … the list goes on and on.” 

Long COVID is contributing to the U.S. labor shortage overall, according to research. But with no test for the condition and a wide range of symptoms and severity – and with some workers attributing their symptoms to something else — it’s difficult to get a clear picture of the impacts on the health care system.

Emerging research suggests long COVID is hitting the health care system particularly hard.

 The system has lost 20% of its workforce over the course of the pandemic, with hospital understaffing at hospitals resulting in burnout and fatigue among frontline medical professionals, according to the U.S. Bureau of Labor Statistics.

Other research spotlights the significant impacts on health care workers:

  • In New York, nearly 20% of long COVID patients are still out of work after a year, with high numbers among health care workers, according to a new study of workers compensation claims.  
  • A new study in the American Journal of Infection Control reports nurses in intensive care units and non-clinical workers are especially vulnerable. About 2% of nurses have not returned work after developing COVID-19, according to a 2022 survey by the National Nursing Association, which represents unionized workers.  
  • In the United Kingdom, long COVID symptoms impact the lives of 1.5 million people, according to the Office of National Statistics, which is monitoring the impact of COVID. Nearly 20% report their ability to engage in day-to-day activities had been “limited a lot,” according to data from February.

While long COVID brain fog, fatigue, and other symptoms can sometimes last just a few weeks or months, a percentage of those who develop the condition – on or off the job – go on to have chronic, long-lasting, disabling symptoms that may linger for years. 

Several recent research studies suggest the impacts of long COVID on health care workers, who interact more closely with COVID patients than others on the job, are greater than other occupations and are likely to have a continuing impact.

About 25% of those filing COVID-related workers compensation claims for lost time at work are health care workers, according to a study from the National Council on Compensation Insurance. That was more than any other industry. At the same time,  the study – which included data from nine states – found that worker compensation claims for acute COVID cases dropped from 11% in 2020 to 4% in 2021.  

Last year, Katie Bach wrote a study for the Brookings Institution on the impact of long COVID on the labor market. She said in an email that she still thinks it’s a problem for the health care workforce and the workforce in general. 

“It is clear that we have a persistent group of long COVID patients who aren’t getting better,” she says.

Hospitals Forced to Adapt

Dartmouth-Hitchcock Medical Center is the largest health system — and one of the largest employers — in New Hampshire with 400 beds and 1,000 employees at the flagship hospital and affiliate. Human resource staff here have been tracking COVID-19 infections among employees.

The hospital is treating fewer COVID cases, down from a high of about 500 a month to between 100 and 200 cases month. But at the same time, they are seeing an increase in staff are who calling in sick with a range of COVID-like symptoms or consulting with the occupational medicine department, says Aimee M. Claiborne, the head of human resources for the Dartmouth Health system. 

“Some of that might be due to long COVID; some if it might be due to flu or RSV or other viruses,” she says. “We are definitely looking at things like absenteeism and what people are calling in for.”

They are also looking at “presenteeism” – where workers show up when they are not feeling well and they are not as productive, she says. 

Those who return to work can access the company’s existing disability programs to get accommodations – allowing people with low energy or fatigue or another disability to, for example, work shorter shifts or from home. Dartmouth-Hitchcock is also building more remote work into its system after trying the approach during the height of the pandemic, Claiborne says. 

Ultimately, some workers will not be able to return to work. Those who were infected on the job can also seek workers’ compensation, but coverage varies from employer to employer and state to state. 

On the other side of the country, Annette Gillaspie, a nurse in a small Oregon hospital, says she caught COVID – like many other health care workers – early in the pandemic before vaccines were available and protective measure were in place. 

She says she still hasn’t fully recovered 3 years later – she still has a cough as well as POTS (postural orthostatic tachycardia syndrome), a common post-COVID-19 condition of the automatic nervous system that can cause dizziness and fatigue when a sitting person stands up.

But she’s back at work and the hospital has made accommodations for her, like a parking space closer to the building. 

She remembers being exposed — she forgot to put on protective glasses. A few days later she was in bed with COVID. She says she never quite recovered. Gillaspie says she sees a lot of other people at work who seem to have some long COVID symptoms. 

“Some of them know it’s COVID related,” she says. “They’re doing just like I do — pushing through.”

They do it because they love their work, she says. 

Shortages Span the Country

Millions of people are living in what the federal government calls “health practitioner shortage areas” without enough dental, primary, and mental health practitioners. At hospitals, vacancies for nurses and respiratory therapists went up 30% between 2019 and 2020, according to an American Hospital Association (AHA) survey. 

Hospitals will need to hire to 124,000 doctors and at least 200,000 nurses per year to meet increased demand and to replace retiring nurses, according to the AHA. 

When the pandemic hit, hospitals had to bring expensive traveling nurses in to deal with the shortages driven by wave after wave of COVID surges. But as the AHA notes, the staffing shortfalls in health care existed before the pandemic.

The federal government, states, and health care systems have programs to address the shortage. Some hospitals train their own staff, while others may be looking at expanding the “scope of care” for existing providers, like physician assistants. Still others are looking to support existing staff who may be suffering from burnout and fatigue – and now, long COVID.

Long COVID numbers  — like the condition itself — are hard to measure and ever-changing. Between 10% and 11% of those who have had COVID have long COVID, according to the Household Pulse Survey, an ongoing Census Bureau data project.

A doctor in the U.K. recently wrote that she and others initially carried on working, believing they could push through symptoms. 

“As a doctor, the system I worked in and the martyr complex instilled by medical culture enabled that view. In medicine, being ill, being human, and looking after ourselves is still too often seen as a kind of failure or weakness,” she wrote anonymously in February in the journal BMJ.

Jeffrey Siegelman, MD, a doctor at Emory University Medical Center in the Atlanta, also wrote a journal article about his experiences with long COVID in 2020 in JAMA. More than 2 years later, he still has long COVID. 

He was out of work for 5 months, returned to practice part-time, and was exempt from night work – “a big ask,” he says, for an emergency department doctor. 

In general,  he feels like the hospital “bent over backwards” to help him get back to work. He is just about to return to work full-time with accommodations.

“I’ve been really lucky in this job,” Siegelman says. “That’s not what most patients with long COVID deal with.”

He led a support group for hospital employees who had long COVID – including clerks, techs, nurses, and doctors. Many people were trying to push through their symptoms to do their jobs, he says. A couple of people who ran through their disability coverage were dismissed.

He acknowledges that as a doctor, he had better disability coverage than others. But with no diagnostic test to confirm long COVID, he’s not exempt from self-doubt and stigma. 

Siegelman was one of the doctors who questioned the physiological basis for ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), a condition that mirrors long COVID and commonly appears in those who have lingering symptoms of an infection. He doesn’t anymore. 

Researchers are beginning to link ME/CFS and other long-term problems to COVID and other infections, and research is underway to better understand what is known as post-infection illnesses. 

Hospitals are dealing with so much, Siegelman says, that he understands if there’s a hesitancy to acknowledge that people are working at a reduced capacity. 

“It’s important for managers in hospitals to talk about this with their employees and allow people to acknowledge if they are taking more time than expected to recover from an illness,” he says. 

In medicine, he says, you are expected to show up for work unless you are on a gurney yourself. Now, people are much more open to calling in if they have a fever – a good development, he says.

And while he prepared to return to work, symptoms linger. 

“I can’t taste still,” he says. “That’s a pretty constant reminder that there is something real going on here.” 

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Can ‘Radical Rest’ Help With Long COVID Symptoms?

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Jan. 18, 2023 – On March 18, 2020, Megan Fitzgerald was lying on the floor of her Philadelphia home after COVID-19 hit her like a ton of bricks. She had a fever, severe digestive issues, and she couldn’t stand on her own. Yet there she was, splayed out in the bathroom, trying both to respond to work emails and entertain her 3-year-old son, who was attempting to entice her by passing his toys through the door. 

She and her husband, both medical researchers, were working from home early in the pandemic with no child care for their toddler. Her husband had a grant application due, so it was all-hands-on-deck for the couple, even when she got sick. 

“My husband would help me up and down stairs because I couldn’t stand,” Fitzgerald says.

So, she put a mask on and tried to take care of her son, telling him, “Mommy’s sleeping on the floor again.” She regrets pushing so hard, having since discovered there may have been consequences. She often wonders: If she’d rested more during that time, would she have prevented the years of decline and disability that followed? 

There’s growing evidence that overexertion and not getting enough rest in that acute phase of COVID-19 infection can make longer-term symptoms worse. 

“The concept that I would be too sick to work was very alien to me,” Fitzgerald says. “It didn’t occur to me that an illness and acute virus could be long-term debilitating.” 

Her story is common among long COVID-19 patients, not just for those who get severely ill but also those who only have moderate symptoms. It’s why many medical experts and researchers who specialize in long COVID rehabilitation recommend what’s known as radical rest – a term popularized by journalist and long COVID advocate Fiona Lowenstein – right after infection as well as a way of coping with the debilitating fatigue and crashes of energy that many have in the weeks, months, and years after getting sick.

These sustained periods of rest and “pacing” – a strategy for moderating and balancing activity– have long been promoted by people with post-viral illnesses such as myalgic encephalomyelitis, or chronic fatigue syndrome (ME/CFS), which share many symptoms with long COVID.

That’s why researchers and health care providers who have spent years trying to help patients with ME/CFS and, more recently, long COVID, recommend they rest as much as possible for at least 2 weeks after viral infection to help their immune systems. They also advise spreading out activities to avoid post-exertional malaise (PEM), a phenomenon where even minor physical or mental effort can trigger a flare-up of symptoms, including severe fatigue, headaches, and brain fog.

An international study, done with the help of the U.S. Patient-Led Research Collaborative and published in The Lancet in 2021, found that out of nearly 1,800 long COVID patients who tried pacing, more than 40% said it helped them manage symptoms.

Burden on Women and Mothers

In another survey published last year, British researchers asked 2,550 long COVID patients about their symptoms and found that not getting enough rest in the first 2 weeks of illness, along with other things like lower income, younger age, and being female, were associated with more severe long COVID symptoms.

It’s also not lost on many investigators and patients that COVID’s prolonged symptoms disproportionately affect women – many of whom don’t have disability benefits or a choice about whether they can afford to rest after getting sick. 

“I don’t think it’s a coincidence, particularly in America, that women of reproductive age have been hit the hardest with long COVID,” says Fitzgerald. “We work outside the home, and we do a tremendous amount of unpaid labor in the home as well.”

How Does Lack of Rest Affect People With COVID?

Experts are still trying to understand the many symptoms and mechanisms behind long COVID. But until the science is settled, both rest and pacing are two of the most solid pieces of advice they can offer, says David Putrino, PhD, a neuroscientist and physical therapist who has worked with thousands of long COVID patients at Mount Sinai Hospital in New York. “These things are currently the best defense we have against uncontrolled disease progression,” he says.

There are many recommended guides for rest and pacing for those living with long COVID, but ultimately, patients need to carefully develop their own personal strategies that work for them, says Putrino. He calls for research to better understand what’s going wrong with each patient and why they may respond differently to similar strategies. 

There are several theories on how long COVID infection triggers fatigue. One is that inflammatory molecules called cytokines, which are higher in long COVID patients, may injure the mitochondria that fuel the body’s cells, making them less able to use oxygen. 

“When a virus infects your body, it starts to hijack your mitochondria and steal energy from your own cells,” says Putrino. Attempts to exercise through that can significantly increase the energy demands on the body, which damages the mitochondria, and also creates waste products from burning that fuel, kind of like exhaust fumes, he explains. It drives oxidative stress, which can damage the body.

“The more we look objectively, the more we see physiological changes that are associated with long COVID,” he says. “There is a clear organic pathobiology that is causing the fatigue and post-exertional malaise.”

To better understand what’s going on with infection associated with complex chronic illnesses such as long COVID and ME/CFS, Putrino’s lab is looking at things like mitochondrial dysfunction and blood biomarkers such as microclots. 

He also points to research by pulmonologist David Systrom, MD, director of the Advanced Cardiopulmonary Exercise Testing Program at Brigham and Women’s Hospital and Harvard Medical School. Systrom has done invasive exercise testing experiments that show that people with long COVID have a different physiology than people who have had COVID and recovered. His studies suggest that the problem doesn’t lie with the functioning of the heart or lungs, but with blood vessels that aren’t getting enough blood and oxygen to the heart, brain, and muscles.

Why these blood vessel problems occur is not yet known, but one study led by Systrom’s colleague, neurologist Peter Novak, MD, PhD, suggests that the small nerve fibers in people with long COVID are missing or damaged. As a result, the fibers fail to properly squeeze the big veins (in the legs and belly, for instance) that lead to the heart and brain, causing symptoms such as fatigue, PEM, and brain fog. Systrom has seen similar evidence of dysfunctional or missing nerves in people with other chronic illnesses such as ME/CFS, fibromyalgia, and postural orthostatic tachycardia syndrome (POTS).

“It’s been incredibly rewarding to help patients understand what ails them and it’s not in their head and it’s not simple detraining or deconditioning,” says Systrom, referring to misguided advice from some doctors who tell patients to simply exercise their way out of persistent fatigue. 

These findings are also helping to shape specialized rehab for long COVID at places like Mount Sinai and Brigham and Women’s hospitals, whose programs also include things like increasing fluids and electrolytes, wearing compression clothing, and making diet changes. And while different types of exercise therapies have long been shown to do serious damage to people with ME/CFS symptoms, both Putrino and Systrom say that skilled rehabilitation can still involve small amounts of exercise when cautiously prescribed and paired with rest to avoid pushing patients to the point of crashing. In some cases, the exercise can be paired with medication.

In a small clinical trial published in November, Systrom and his research team found that patients with ME/CFS and long COVID were able to increase their exercise threshold with the help of a POTS drug, Mestinon, known generically as pyridostigmine, taken off label.

As is the case of many people with long COVID, Fitzgerald’s recovery has had ups and downs. She now has more help with child care and a research job with the disability-friendly Patient-Led Research Collaborative. While she hasn’t gotten into a long COVID rehab group, she’s been teaching herself pacing and breathwork. In fact, the only therapeutic referral she got from her doctor was for cognitive behavioral therapy, which has been helpful for the toll the condition has taken emotionally. “But it doesn’t help any of the physical symptoms,” Fitzgerald says.

She’s not the only one who finds that a problem.

“We need to continue to call out people who are trying to psychologize the illness as opposed to understanding the physiology that is leading to these symptoms,” says Putrino. “We need to make sure that patients actually get care as opposed to gaslighting.”



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