COVID-19 Vaccines
 December 15, 2020 /  Charles W. Lapp, MD /  Ask The Doctor
Q: Should I take the COVID-19 vaccine when it becomes available?
A:            Many PWCs (Persons with CFS or FM) have developed a flare or relapse after vaccination with live viruses, so we have always recommended avoiding immunization with influenza vaccine, the MMR, and Hepatitis B, if feasible. The question is:  how safe are the COVID-19 vaccines?
                Currently there are at least 52 COVID vaccines in clinical trials according to the WHO, two of which will be imminently available in the USA.  These are produced by Pfizer and Moderna here in America.  Products by Astra-Zeneca and Johnson & Johnson are not far behind.   
                The Pfizer and Moderna products are not made from live virus, so they are not likely to cause flares or relapses in our PWCs. They both require two doses 21 to 28 days apart.  It takes about 2-3 weeks to develop a 50% level of immunity after the first dose, and that level persists for just a few weeks so the second immunization is necessary.  The vaccines are about 90-95% effective, but there is no data yet on how long such immunity will last.  Side effects of the vaccination include injection site soreness and fever in most cases, increased fatigue (up to 60%), headache (up to 50%), muscle aches (37%), and chills (32%), especially after the second jab. These symptoms resolve in 24 to 48 hours, and a minority of individuals has to take Tylenol or other remedies for them.
                Our concern is not the short term effects, but long term.  The Pfizer and Moderna vaccines have been administered safely to thousands of individuals already, but new issues are likely to arise after millions of individuals have been immunized.  Time will tell.  This is currently a moot point since the vaccines will be provided first to medical providers, health care workers, nursing home residents, prison inmates, and first responders.  It will probably be many months before they will be available to the public, so we will probably have a much better idea about long term effects by then.
                Because COVID-19 is such a severe disease we currently recommend that high risk individuals strongly consider vaccination. These include individuals with high blood pressure, diabetes, obesity, asthma or pulmonary disease, cardiovascular disease, and immune deficiency.  The vaccines have not been adequately tested in pregnant or lactating women, or in children under 16 years. 
                Since PWCs frequently suffer immune dysregulation, many wonder if they should be considered “immune deficient.”   Our opinion is that many patients have an UP-regulated immune system and fend off viruses readily, so they rarely fall ill.  If you are the type of individual who “catches every virus that comes along,” then you are probably in the minority of DOWN-regulated patients and should highly consider the vaccination when it is available.
                Despite immunization there is still a small but significant chance one could contract COVID-19; therefore, prevention is KEY.  Dr. Lapp has just reviewed dozens of past epidemics and one point is clear: frequent washing, hand sanitizing, face masks, and isolation are crucial for avoiding infection.


Dr. Bateman, from the Bateman Horne Center recommends the following:

"We [the world] certainly need COVID-19 vaccines desperately and everyone who is healthy enough for the vaccine should get vaccinated, starting with those at highest risk of COVID exposure.  This includes healthy family members of vulnerable people. For the ME/CFS/FM population, my advice is to stay safely quarantined and wait a couple of months while the vaccine is distributed and broadly administered.   Because of the large numbers and close monitoring, we should know fairly quickly how people do with the vaccines.  This advice will apply as each new branded vaccine is approved and rolled out.  In general, the people who should be most cautious are those who have previously had allergic reactions to vaccines or are prone to severe allergic reactions in general.   If you decide to get the vaccine, be rested and stable prior to the vaccine, and plan on resting/relaxing for at least 72 hours afterward.  Supportive care will include anything you usually do for flu symptoms, PEM, allergy flares, worsened orthostatic intolerance, etc.  If anything, including a vaccine, makes you sick enough that you are unable to maintain adequate fluids and nutrition, or results in fluid and electrolyte losses (sweating, diarrhea, etc), it is always appropriate to seek IV fluids as a primary intervention."

A Piece of My Mind November 11, 2020
Reflections of a COVID-19 Long Hauler
Jeffrey N. Siegelman, MD1
JAMA. Published online November 11, 2020. doi:10.1001/jama.2020.22130
I awoke on a Monday morning with a headache, and I am not a headache person. Fever followed, and the next morning my blueberry yogurt tasted of nothing. Thick emptiness. I knew I had it. Now, after more than 3 months of living with coronavirus disease 2019 (COVID-19) and the fatigue that has kept me couch-bound, I have had ample time to reflect on what it means to be a patient, how an illness ripples through family and community, and how I will use this experience to be a better physician. Here is what I have learned.
Mild Illness Can Have Dramatic Effects
I have what is referred to as a “mild” case. I have no preexisting conditions, was never hospitalized, had minimal respiratory symptoms, and even managed to do limited office work throughout the acute illness. For this, I am grateful because I have seen first-hand how awful COVID-19 can be for others. And yet, living with this has been anything but mild. I quarantined in the basement for 40 days, staying isolated from my family because low-grade fevers continued, and the Centers for Disease Control and Prevention guidance was unclear for people like me. I talked to my children only through FaceTime or walkie-talkies and saw my wife only by looking up between the balusters of the stairwell. Embraces were out of the question when what I needed most was human connection. Aside from my isolation, the effects on my family were also isolating. Even after they quarantined, my family continued to worry about whether they would become ill, whether I would get better, and whether others would be too afraid to be around them because of my illness. And, my parents, 600 miles away, were also struck with anxiety and an inability to help. These were but a few of the severe effects of a mild disease.
The Lack of Objective Data Does Not Preclude Illness
As an emergency medicine physician, I am trained to develop a hypothesis and to look for objective evidence in support to quickly identify the cause of a patient’s suffering. In the absence of objective data—laboratory tests, imaging, examination findings—we are often left to reassure patients and discharge them with a recommendation for outpatient follow-up, an outcome that too easily can feel dismissive and unsatisfying for the patient and unfulfilling for the physician. My test results were normal: nasopharyngeal swabs for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), imaging, laboratory results, oxygen saturation were all fine. But I did not feel fine, and still do not. I have had a rotating constellation of symptoms, different each day and worse each evening: fever, headache, dizziness, palpitations, tachycardia, and others. As a result, I have been reminded of the need to listen to the patient first, even in the absence of conclusive testing. The next time I care for someone with vague abdominal pain, or fatigue, or paresthesia, or any of the myriad conditions that are uncomfortable on the inside but look fine on the outside, I will remember that these symptoms are real and impactful for patients. There is a marked difference between tests being within normal limits and a patient being well.
It Is Hard to Ask for Help
My family and I have been so fortunate to have the support of friends and family, near and far, who have helped us with messages, calls, meals, puzzles, books, and more. So many have asked, “What can we do?” But, coming from a profession focused on helping others, it was hard to accept help. I could not bear to see emails activating my colleagues who were on-call to cover my shifts day after day. In fact, I asked the department to reconsider its practice of emailing the entire faculty with the name of the person seeking coverage to assuage the guilt I was feeling. Still, as difficult as it has been to accept help, long illness is even worse without help. If people had not insisted on helping, had my colleagues not been so supportive in covering my clinical work, these 3 months would have been marked by an overwhelming amount of additional stress.
Patients Need Validation
With each negative test, my worry increased that my employer would ask me to go back to work too soon or that my primary care physician would rule out COVID-19 despite strong clinical evidence otherwise. I doubted myself multiple times—thinking if I just pushed myself harder maybe I could go back to work and to my regular life, to move on. Then I would eat something without taste, would feel my heart pounding uncontrollably for hours, or would get so dizzy that I could not even write a simple letter. Each evening as my symptoms peaked, I was reminded that my diagnosis was not in question. I am so grateful that, instead of my worries manifesting, quite the opposite was the case. Instead of doubting the diagnosis, my doctor sent me the latest medical literature on long COVID-19 and patiently empathized. My employer clearly understood the inaccuracies of current testing, focusing on symptoms instead. My wife reminded me that she knew what I was experiencing was real. This validation was critical, allowing me to find peace and focus on healing.
I Am Lucky
My experience is not typical. I have a home with a well-equipped basement where I could safely and completely isolate. I have a wife and children who have approached my illness with endless strength and compassion. I have an employer that recognized the need to use a symptom-based approach for making return to work decisions and that provides a generous salary continuation benefit. And, I have long-term disability insurance should this affect me beyond 6 months.
This is not the case for most patients, many of whom cannot isolate from family and cannot afford to miss even a day or 2 of work. I have not had to live with the financial and health worries that accompany a COVID-19 diagnosis for so many in this country. I am also privileged by my race, whereas so many people of color are disproportionately suffering from this disease and others due to the many manifestations of institutional racism in this country. Recognizing this fact, I know how important it will be to continue to offer help and support to others less fortunate than me who are affected by COVID-19 and other chronic illnesses.
As I continue to live with uncertainty, fear, and a certain degree of continued isolation, the silver lining is the hope that my future patient interactions will allow me to provide greater comfort and validation, even when I cannot offer objective answers or concrete healing.
Section Editor: Preeti Malani, MD, MSJ, Associate Editor.
Corresponding Author: Jeffrey N. Siegelman, MD, Department of Emergency Medicine, Emory University School of Medicine, 49 Jesse Hill Jr Dr SE, Atlanta, GA 30303 (jsiegelman@emory.edu).
​

Long-term Health Consequences of COVID-19
Carlos del Rio, MD1; Lauren F. Collins, MD1; Preeti Malani, MD, MSJ2,3
JAMA. Published online October 5, 2020. doi:10.1001/jama.2020.19719
With more than 30 million documented infections and 1 million deaths worldwide, the coronavirus disease 2019 (COVID-19) pandemic continues unabated. The clinical spectrum of severe acute respiratory syndrome coronavirus (SARS-CoV) 2 infection ranges from asymptomatic infection to life-threatening and fatal disease. Current estimates are that approximately 20 million people globally have “recovered”; however, clinicians are observing and reading reports of patients with persistent severe symptoms and even substantial end-organ dysfunction after SARS-CoV-2 infection. Because COVID-19 is a new disease, much about the clinical course remains uncertain—in particular, the possible long-term health consequences, if any.
Epidemiology
Currently, there is no consensus definition of postacute COVID-19. Based on the COVID Symptom Study, in which more than 4 million people in the US, UK and Sweden have entered their symptoms after a COVID-19 diagnosis, postacute COVID-19 is defined as the presence of symptoms extending beyond 3 weeks from the initial onset of symptoms and chronic COVID-19 as extending beyond 12 weeks.1 It is possible that individuals with symptoms were more likely to participate in this study than those without them.
Previously described, a postacute syndrome is well recognized in patients who are recovering from a serious illness, in particular an illness that required hospitalization and admission to the intensive care unit. In a 2016 study among 43 patients who had been discharged after intensive care unit stay (46% required mechanical ventilation), 36 (84%) reported impairment in cognition, mental health, or physical function that persisted for 6 to 12 months beyond hospital discharge, collectively known as post–intensive care syndrome.2 In a study from Italy that assessed COVID-19 symptom persistence among 143 patients discharged from the hospital, only 18 patients (12.6%) were completely free of any COVID-19–related symptoms after a mean of 60 days after initial symptom onset.3
However, postacute COVID-19 syndrome is not just observed among patients who had severe illness and were hospitalized. In a telephone survey conducted by the Centers for Disease Control and Prevention among a random sample of 292 adults (≥18 years) who had a positive outpatient test result for SARS-CoV-2 by reverse transcriptase–polymerase chain reaction, 35% of 274 symptomatic respondents reported not having returned to their usual state of health 2 weeks or more after testing, including 26% among those aged 18-34 years (n = 85), 32% among those aged 35-49 years (n = 96), and 47% among those aged 50 years or older (n = 89).4 Older than 50 years and the presence of 3 or more chronic medical conditions were associated with not returning to usual health within 14 to 21 days after receiving a positive test result. Notwithstanding, 1 in 5 individuals aged 18-34 years without chronic medical conditions had not yet achieved baseline health when interviewed at a median of 16 days from the testing date.
Manifestations
The most commonly reported symptoms after acute COVID-19 are fatigue and dyspnea. Other common symptoms include joint pain and chest pain.3 In addition to these general symptoms, specific organ dysfunction has been reported, involving primarily the heart, lungs, and brain. From a pathogenesis standpoint, these complications could be the consequence of direct tissue invasion by the virus (possibly mediated by the presence of angiotensin-converting enzyme 2 receptor), profound inflammation and cytokine storm, related immune system damage, the hypercoagulable state described in association with severe COVID-19, or a combination of these factors.

Cardiovascular
Myocardial injury, as defined by an increased troponin level, has been described in patients with severe acute COVID-19, along with thromboembolic disease. Myocardial inflammation and myocarditis, as well as cardiac arrhythmias, have been described after SARS-CoV-2 infection. In a German study of 100 patients who recently recovered from COVID-19, cardiac magnetic resonance imaging (performed a median of 71 days after COVID-19 diagnosis) revealed cardiac involvement in 78% and ongoing myocardial inflammation in 60%.5 The presence of chronic comorbidities, duration and severity of acute COVID-19 illness, and time since original diagnosis did not correlate with these findings. However, the sample was not random and likely biased toward patients with cardiac findings. Nevertheless, among 26 competitive college athletes who received a diagnosis of COVID-19 by reverse transcriptase–polymerase chain reaction, none of whom required hospitalization and the majority without reported symptoms, 12 (46%) had evidence of myocarditis or prior myocardial injury by cardiac magnetic resonance imaging routinely performed for positive testing results (range, 12-53 days later).6 The durability and consequences of such imaging findings are not yet known and longer follow-up is needed. However, an increased incidence of heart failure as a major sequela of COVID-19 is of concern, with considerable potential implications for the general population of older adults with multimorbidity, as well as for younger previously healthy patients, including athletes.
Pulmonary
In a study of 55 patients with COVID-19, at 3 months after discharge, 35 (64%) had persistent symptoms and 39 (71%) had radiologic abnormalities consistent with pulmonary dysfunction such as interstitial thickening and evidence of fibrosis.7 Three months after discharge, 25% of patients had decreased diffusion capacity for carbon monoxide. In another study of 57 patients, abnormalities in pulmonary function test results obtained 30 days after discharge, including decreased diffusion capacity for carbon monoxide and diminished respiratory muscle strength, were common and occurred in 30 patients (53%) and 28 patients (49%), respectively.8 If compounded on cardiovascular comorbidity, either preexisting or incident from COVID-19, persistent decline in lung function could have major adverse cardiopulmonary consequences.

Neurologic
SARS-CoV-2 can penetrate brain tissue via viremia and also by direct invasion of the olfactory nerve, leading to anosmia. To date, the most common long-term neurologic symptoms after COVID-19 are headache, vertigo, and chemosensory dysfunction (eg, anosmia and ageusia). Although stroke is a serious albeit uncommon consequence of acute COVID-19, encephalitis, seizures, and other conditions such as major mood swings and “brain fog” have been reported up to 2 to 3 months after initial illness onset.9 Past pandemics involving viral pathogens (such as SARS-CoV-1, Middle East respiratory syndrome coronavirus [MERS], and influenza) have involved neuropsychiatric sequelae that could linger for months in “recovered” patients, which can seriously threaten cognitive health, overall well-being, and day-to-day functional status.
Emotional Health and Well-being
In addition to symptom persistence and clinical sequelae that may last far beyond the initial COVID-19 illness, the extent of emotional and behavioral concerns and general distress for those affected has yet to be determined. A diagnosis of COVID-19, and subsequent need for physical distancing, has been associated with feelings of isolation and loneliness.10 COVID-19–related stigma has also become pervasive and can result in a sense of hopelessness. Increasing reports of lingering malaise and exhaustion akin to chronic fatigue syndrome may leave patients with physical debility and emotional disturbance. Compounded by the psychological toll of the pandemic experienced population wide, individuals recovering from COVID-19 may be at even greater risk of depression, anxiety, posttraumatic stress disorder, and substance use disorder. These combined effects have the potential to result in a global health crisis, considering the sheer number of COVID-19 cases worldwide.

Conclusions
Granted that no long-term data of substantial numbers of patients with various presenting symptoms exist and with comparison groups, and that it is still early in the COVID-19 pandemic, it is possible that large numbers of patients will experience long-term sequelae. Outpatient post–COVID-19 clinics are opening in many localities where large outbreaks have occurred, and the term “long-haulers” has been suggested to refer to these patients. It is imperative that the care of this vulnerable patient population take a multidisciplinary approach, with a thoughtfully integrated research agenda, to avoid health system fragmentation and to allow the comprehensive study of long-term health consequences of COVID-19 on multiple organ systems and overall health and well-being. Furthermore, such an approach will provide the opportunity to efficiently and systematically conduct studies of therapeutic interventions to mitigate the adverse physical and mental health effects among hundreds of thousands, if not millions, of people who recover from COVID-19. Longer-ranging longitudinal observational studies and clinical trials will be critical to elucidate the durability and depth of health consequences attributable to COVID-19 and how these may compare with other serious illnesses.

September 23, 2020
As Their Numbers Grow, COVID-19 “Long Haulers” Stump Experts
Rita Rubin, MA
JAMA. Published online September 23, 2020. doi:10.1001/jama.2020.17709
For 32-year-old Hanna Lockman of Louisville, Kentucky, it all started March 12. She was at work when she suddenly felt a stabbing pain in her chest.
“It just got worse and worse and worse, to the point I was crying from the pain,” she recalled in a recent interview. At 3 am, the pain sent her to the emergency department. “I had developed a dry cough, maybe a mild fever. I don’t remember.”
Five months, 16 emergency department trips, and 3 short hospitalizations later, Lockman can’t remember a lot of things. She places the blame squarely on coronavirus disease 2019 (COVID-19).
“I joke, ‘Well, COVID has eaten my brain, because I can’t remember how to remember words, keep track of medication,’” she said. “My brain just feels like there’s a fog.”
Lockman considers herself to be a “long hauler,” someone who still hasn’t fully recovered from COVID-19 weeks or even months after symptoms first arose. She serves as an administrator of 2 “Long Haul COVID Fighters” Facebook groups, whose members now number more than 8000.
The longer the pandemic drags on, the more obvious it becomes that for some patients, COVID-19 is like the unwelcome houseguest who won’t pack up and leave.
“Anecdotally, there’s no question that there are a considerable number of individuals who have a postviral syndrome that really, in many respects, can incapacitate them for weeks and weeks following so-called recovery and clearing of the virus,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in July during a COVID-19 webinar organized by the International AIDS Society.
That appeared to be the case with the first severe acute respiratory syndrome (SARS), which emerged in 2002 and was also caused by a coronavirus. Some people who were hospitalized with SARS still had impaired lung function 2 years after their symptoms began, according to a prospective study of 55 patients in Hong Kong. But only 8096 people were diagnosed with SARS worldwide—a fraction of the COVID-19 cases reported each day in the US alone.
In a recent JAMA research letter, 125 of 143 Italian patients ranging in age from 19 to 84 years still experienced physician-confirmed COVID-19–related symptoms an average of 2 months after their first symptom emerged. All had been hospitalized, with their stays averaging about 2 weeks; 80% hadn’t received any form of ventilation.
Physicians at a Paris hospital recently reported that they saw an average of 30 long haulers every week between mid-May, when the COVID-19 lockdown ended in France, and late July. The patients’ average age was around 40 years, and women outnumbered men 4 to 1.
As with SARS, many COVID-19 long haulers are health care workers who had massive exposure to the virus early in the pandemic, neuroimmunologist Avindra Nath, MD, of the National Institute of Neurological Disorders and Stroke (NINDS), noted in a recent editorial.
Overall, approximately 10% of people who’ve had COVID-19 experience prolonged symptoms, a UK team estimated in a recently published Practice Pointer on postacute COVID-19 management. And yet, the authors wrote, primary care physicians have little evidence to guide their care.
Puzzling Persistence
Adults with severe illness who spend weeks in intensive care, often intubated, can experience long-lasting symptoms, but that’s not unique to patients with COVID-19. What’s unusual about the long haulers is that many initially had mild to moderate symptoms that didn’t require lengthy hospitalization—if any—let alone intensive care.
“Most of the patients that I see who are suffering from [post–COVID-19] syndrome were not hospitalized,” Jessica Dine, MD, a pulmonary specialist at the University of Pennsylvania Perelman School of Medicine, said in an interview. “They were pretty sick, but still at home.”
Why some previously healthy, often young, adults still haven’t recovered from the disease has stymied physicians.
“We in the medical field are very accustomed to taking care of respiratory syncytial virus and other pneumoviruses in young adults,” Wesley Self, MD, MPH, an emergency medicine physician at Vanderbilt University Medical Center, said in an interview. With those infections, “people feel pretty sick for 2 to 3 days, and then they feel markedly better.”
But COVID-19 is another matter, Self and his coauthors found in a recent study of 292 individuals with the disease who did not require hospitalization. “One of the goals of this particular study was to understand those with mild symptoms,” Self said. “This was an understudied group.”
More than a third of them hadn’t returned to their usual state of health 2 to 3 weeks after testing positive, the researchers wrote in the Morbidity and Mortality Weekly Report. The older the patients, the more likely they were to say they their pre–COVID-19 health hadn’t come back. But even a quarter of the youngest, those aged 18 to 34 years, said they had not yet regained their health.
“That certainly was a surprise to us,” Self’s coauthor and Vanderbilt colleague William Stubblefield, MD, an emergency medicine specialist, said in an interview.
Self and others say they suspect that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers long-lasting changes in the immune system. In some organs, especially the lungs, those changes persist far past the point at which patients have stopped shedding the virus, Self said. “Frankly, we don’t know how long that lasts.” To help answer that question, Self and his coauthors are conducting a follow-up study to assess outpatients’ health 6 months after their COVID-19 diagnosis.
Sorting Through Symptoms
Just as acute COVID-19 has been found to affect every part of the body, so, apparently, do its persistent symptoms.
In the study of Italian patients, the most common symptoms reported at follow-up were fatigue, shortness of breath, joint pain, and chest pain, in that order. None of the patients had a fever or other sign or symptom of acute illness, but about 44% of them had a worsened quality of life. As the authors pointed out, though, patients with community-acquired pneumonia can also have persistent symptoms, so the findings might not be exclusive to COVID-19.
Less formal surveys have also turned up wide-ranging lingering effects. When the Body Politic COVID-19 Support Group conducted an online survey in the spring, about 91% of 640 respondents said they hadn’t fully recovered and were on day 40 of symptoms, on average. Most reported ongoing fatigue, chills and sweats, body aches, headaches, brain fog, and gastrointestinal issues. Anecdotally, some people have reported feeling better for days or weeks before relapsing with old or new symptoms, according to the organization, which started as a small Instagram group chat and has grown to more than 14 000 members.
Francis Collins, MD, PhD, director of the National Institutes of Health (NIH), blogged about the survey in September. “Because COVID-19 is such a new disease, little is known about what causes the persistence of symptoms, what is impeding full recovery, or how to help the long-haulers,” Collins wrote, noting that the Body Politic and its international Patient-Led Research for COVID-19 group are now conducting a second survey of long haulers.
A recent survey by the grassroots group COVID-19 “Survivor Corps” found that fatigue was the most common of the top 50 symptoms experienced by the more than 1500 long haulers who responded, followed by muscle or body aches, shortness of breath or difficulty breathing, and difficulty concentrating.
Cough is the most common persistent symptom seen at the new COVID-19 Recovery Clinic (CORE) at Montefiore Medical Center in New York, codirector Aluko Hope, MD, MSCE, said in an interview. Between Hope, a pulmonary and critical care specialist, and the clinic’s other director, general internist Seth Congdon, MD, the clinic sees a wide range of patients, including some who were never hospitalized. What the CORE patients have in common is that they haven’t yet returned to their pre–COVID-19 health. At least a few of them have been sick for 4 or 5 months, Hope said. Besides the persistent cough, which can also occur with other viruses, loss of taste and smell lingers for many long haulers.
Many of the clinic’s patients are also still short of breath. This could be due to the deconditioning seen with any lengthy illness, Hope said, or to infection-specific conditions, such as postviral reactive airways disease, lung fibrosis, or viral myocarditis. Hope said that he’s seen at least one patient with no history of heart disease who developed postviral heart failure.
Dine first noticed that some patients weren’t getting better through Penn’s COVID Watch outreach program, which texts those who are home sick with the disease twice a day until they’ve been symptom-free for a week to 10 days. She now sees so many people with persistent issues that she’s developed a flowchart to try to narrow down the reasons for their ill health: Is this a new symptom unrelated to COVID-19? Is it a complication of the disease, like a blood clot? Or is it a side effect of treatment? If she rules those out, she said there are just 2 options left: Either the patient is still infected with SARS-CoV-2 or they have postviral syndrome.
When the Fog Doesn’t Lift
Lockman and many other long haulers describe their most debilitating persistent symptom as impaired memory and concentration, often with extreme fatigue.
The effects are different from the cognitive impairment patients might experience after a critical illness, according to Hope. When it comes to COVID-19, “I do think there’s a subset of patients [who] weren’t even in the hospital who have a postviral brain fog,” he said.
At the end of May, Lockman took a 6-week leave of absence from her job at a human resources management company. Since that ended, she has been working part-time—4 hours on a good day. She moved her home office to her living room so she can rest on the couch. After a recent trip to the emergency department, she was so exhausted that she slept all but 3 hours the next day.
An intriguing idea is taking shape. During the July webinar, Fauci noted that some long haulers’ symptoms like brain fog and fatigue are “highly suggestive” of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
New York–based psychiatrist Mady Hornig, MD, a member of Columbia University Medical Center’s epidemiology faculty, has long studied the role of microbial, immune, and toxic factors in the development of brain conditions such as ME/CFS, whose etiology and pathogenesis are unknown. Now she’s looking at these relationships not only as a physician and scientist but also as a long hauler.
Hornig wrote off a throat tickle and cough in March as allergies. And she assumed that walking around her home shoeless caused the chilblains that later developed on her toes. It wasn’t until a 4 am fever awoke her on April 24 that she suspected she had contracted COVID-19. Although she takes 650 mg of aspirin daily for another condition, the fever persisted for 12 days, a longer stretch than any she had experienced since she had her tonsils removed at age 14, nearly 50 years ago.
Despite all the indicators, Hornig’s April 27 nasal swab test was negative for SARS-CoV-2. That’s likely because it was performed either too soon or too late—depending on whether the late April fever or the earlier cough or “COVID toes” were the first sign.
Her doctors told her they didn’t have a better explanation than COVID-19 for her symptoms, which have also included oxygen saturation levels as low as 88% and 8- to 10-minute tachycardia episodes that still send her heart rate to 115 to 135 beats per minute at least once a day and leave her breathless, even if she’s sitting down. Before COVID-19, Hornig was used to working 12- to 14-hour days. For weeks after becoming ill, tachycardia would leave her so fatigued that “I felt like I could not do anything further—my brain was just empty,” she said in an interview.
About 3 out of 4 people diagnosed with ME/CFS report that it began with what appeared to be an infection, often infectious mononucleosis caused by Epstein-Barr virus (EBV), Hornig noted. One ME/CFS International Classification of Diseases diagnosis code even calls the condition “post-viral fatigue syndrome.” Although EBV is a herpesvirus, not a coronavirus, Hornig speculated that SARS-CoV-2 infection might reactivate latent EBV, triggering the fatigue.
To explore the idea, she has designed prospective studies with the Solve ME/CFS Initiative. The nonprofit in July launched a registry and biobank, funded in part by the NIH, to collect data from COVID-19 long haulers, as well as people diagnosed with ME/CFS and healthy controls.
“Because of the large number of COVID-19 cases occurring simultaneously, we have a unique scientific window and a huge responsibility to investigate any long-term consequences and disabilities that COVID-19 survivors may face,” Hornig said in a statement announcing the registry and biobank. “Doing so will provide clues and potential treatment candidates for the millions of Americans already diagnosed with ME/CFS.”
Hornig and other scientists point to autonomic nervous system dysregulation as the possible explanation for long-haulers’ tachycardia, extreme fatigue, and other persistent symptoms. The system controls involuntary physiologic processes such as heart rate, blood pressure, respiration, and digestion.
Stanford University neurologist Mitchell Miglis, MD, who specializes in autonomic nervous system disorders such as postural orthostatic tachycardia syndrome (POTS), recently coauthored a case report about a previously healthy, 26-year-old emergency department nurse who developed classic POTS symptoms—fatigue, tachycardia—that hadn’t resolved 5.5 months after she was diagnosed with COVID-19 in March.
“One of the most common symptoms of POTS is brain fog,” Miglis noted. “It’s not clearly related to blood flow to the brain. It’s something else.”
With Lauren Stiles, JD, president of Dysautonomia International and research assistant professor of neurology at Stony Brook University School of Medicine, Miglis has developed an online survey that is being shared with COVID-19 survivor social media groups to gather more information about autonomic symptoms. He plans to resurvey respondents every 3 months for the next year to see how they progress. Miglis speculated that POTS, ME/CFS, and persistent COVID-19 may be different names for the same disorder, and patients’ diagnoses depend on their physicians’ subspecialty.
Nath, chief of the Section of Infections of the Nervous System at NINDS, is planning a prospective study of persistent ME/CFS-type symptoms among people who’ve had COVID-19. “I think we need to assure the public that we are aware of the syndrome,” he said in an interview. “We’re very keen to understand what it’s about.”
“Medical Gaslighting”
Many long haulers never had laboratory confirmation of COVID-19, which, they say, adds to some health care professionals’ skepticism that their persistent symptoms have a physiological basis.
Only about a quarter of the Body Politic survey’s respondents had tested positive for COVID-19, while nearly half were never tested—often because their request was denied. But everyone’s answers were included in the analysis. The main difference between those who received a positive or negative result was how early in their illness they were tested. “We believe future research must consider the experiences of all people with COVID-19 symptoms, regardless of testing status, in order to better understand the virus and underscore the importance of early and widespread testing,” the report’s authors wrote.
Lockman was not one of the survey respondents, but she exemplifies the Body Politic’s point. At her first trip to the emergency department, she was diagnosed with pneumonia and admitted to the hospital, where she received supplemental oxygen and intravenous antibiotics for 3 days. She suspected it was COVID-19 from the beginning. But she was told she wasn’t sick enough or old enough to get one of the then-scarce tests for SARS-CoV-2.
Three weeks after her symptoms began, and after testing negative for influenza and respiratory syncytial virus, Lockman was finally given a SARS-CoV-2 nasal swab test. She tested negative, likely because she had low virus levels by then, she said. In June, she was hospitalized again, this time with pulmonary emboli. A physician who reviewed her chart said she had no doubt that COVID-19 explained her symptoms.
Body Politic has acknowledged that its survey sample wasn’t representative of all people with COVID-19. But the organization expressed hope that the findings would inform public health professionals and future research. Toward that end, the founders of the Long Haul COVID Fighters recently launched a Medical and Scientific Collaboration group on Facebook, giving patients and researchers a place to exchange information.
One thing that’s clear, Miglis said, is that “these mystery diagnoses are real, and they’re not just in patients’ heads.”
Long haulers say they aren’t always taken seriously, though, especially if they’re women, harkening back to the era when “female troubles” were written off as hysteria.
“There is definitely gender bias,” Dine said. Women with persistent symptoms are more likely than men to be viewed as “dramatic and anxious,” she said. “One of the first steps is believing them and making them feel heard. That alone helps.”
“We’ve experienced so much medical gaslighting, basically doctors telling us, ‘That’s not what you have. It’s just anxiety,’” Lockman said. Despite her frustrations, she remains hopeful that her health will continue to improve, although she recognizes that there likely will be bumps along the way.
“I definitely feel better than I did a month ago,” she said in early August. “But I still wake up not knowing what I’m going to deal with today.”
September 24, 2020
Long Haul COVID-19 is an Endothelial Disease
Jacqueline Lopez, M.D. | California State Polytechnic University Pomona
COVID-19 is an endotheliopathy with protean manifestations. Attributing long-haul COVID-19 symptoms to poorly understood conditions such as CFS or POTS is a step in the wrong direction. Clinicians are using these wastebasket diagnoses because they are unfamiliar with endothelial disease. We need research to determine whether viral persistence and/or an aberrant immune response underlie the continued symptoms in long-haulers, but we also need to reeducate our medical workforce to recognize and treat endothelial dysfunction and dysautonomia.
September 24, 2020
Secondary Gain
John Kaplan, MD | Dr. John's Nutrition Health
How are you controlling for or factoring for people who may get a secondary gain in reporting persistent symptoms, with or without serologic or PCR-confirmed Covid- 19? Our dependent culture often gives status and/or or compensation to those reporting persistent symptoms. The cultural dislocation, financial stresses, and persistent political warfare over the SARS-CoV-2 pandemic must certainly provoke opportunistic complaints in a subset of patients with persistent somatic symptoms.
September 24, 2020
Post-Covid Asthenia
H Silverstein, MD (FACC) | Private Internal Medicine Practice
For almost all medical conditions there are identifiable risk factors. These may have to do with environmental factors, dietary exposures and lifestyle, mental status (resilience, depression, anxiety), strength of the viral attack and response, and genetic predispositions. There may be other predisposing entities. These need to be identified to define why the post Covid asthenia occurs and persists.
September 24, 2020
Postviral syndromes are not new
Emily Casanova, PhD, Biomedical Science | University of South Carolina
The recognition of postviral syndromes is not new to the chronic illness community and the clinicians who treat them and scientists who study them, nor is the extreme sex-skewed nature of these conditions. While an endotheliopathy may indeed be an important consideration, the extreme sex-skewed nature of this particular postviral syndrome suggests that, like its idiopathic counterparts, differences in immune activation between the sexes are likely key in many cases. For instance, innate immune/autoimmune disorders are often triggered by viral infection, severe injury, surgery, pregnancy, and even severe emotional stress. Therefore, viewing this postviral syndrome under the framework of othersyndromes such as ME/CFS, POTS, MCAD, etc., could still be useful to clinicians and scientists studying this subpopulation, at least during early days. Most of these idiopathic conditions are not considered primary disorders anyways and are undoubtedly very heterogeneous in nature, but they are useful labels that help direct patient care and predict outcomes.

On a separate note to clinicians, please be cautious about psychosomaticizing patients presenting with these symptoms as gas-lighting has the potential to cause significant harm to the patient that cannot be easily undone, both in terms of psychological trauma (many chronically ill patients suffer from medically-induced PTSD) and additional harm due to potentially inaccurate/incomplete psychiatric diagnoses that can follow a patient on her/his chart for years, permanently affecting her/his quality of care in future. This is an extremely common problem for many women, in particular, with chronic illnesses that we as clinicians and scientists need to take even greater caution to avoid.

As with many immune disorders, immune modulators can have significant neuroactive effects (e.g., febrile seizures as an extreme example, the result of IL-1 activity) and anxiety/depression can often be symptomatic of these chronic medical conditions. Therefore, we need to be cautious about interpreting these psychiatric symptoms as causal. Likewise, peripheral nerve damage is a common feature in these chronic conditions, which research suggests may have a lower threshold for excitation in reaction to neuromodulators than the healthy nerve. Therefore, physical symptoms may be easily top-down "neuroreactive" but not truly "psychosomatic." The pathology is still within the peripheral tissues, not the result of a psychiatric disorder.

In addition, any person who has suddenly lost her/his health, mobility, etc., would be pathological if she/he were NOT devastated and over-focused on her/his sudden disability. This is a normal, healthy reaction to a major and traumatic loss.
September 26, 2020
Commentary
Norman Ratliff, MD, FACC | Chief of Cardiology, Gila Regional Cardiology Services
This post-viral syndrome is real and incredibly debilitating. Yes, the endothelium is involved but so is the autonomic nervous system, mitochondrial function and immune system derangement to name a few others. The above comments do a disservice to the millions of patients suffering from this poorly understood disease.

Practice Practice Pointer   BMJ
Management of post-acute covid-19 in primary care
BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3026 (Published 11 August 2020)Cite this as: BMJ 2020;370:m3026
Trisha Greenhalgh, professor of primary care health sciences1,  et al
Correspondence to: T Greenhalgh trish.greenhalgh@phc.ox.ac.uk
What you need to know

• Management of covid-19 after the first three weeks is currently based on limited evidence
• Approximately 10% of people experience prolonged illness after covid-19
• Many such patients recover spontaneously (if slowly) with holistic support, rest, symptomatic treatment, and gradual increase in activity
• Home pulse oximetry can be helpful in monitoring breathlessness
• Indications for specialist assessment include clinical concern along with respiratory, cardiac, or neurological symptoms that are new, persistent, or progressive

Post-acute covid-19 (“long covid”) seems to be a multisystem disease, sometimes occurring after a relatively mild acute illness.1 Clinical management requires a whole-patient perspective.2 This article, intended for primary care clinicians, relates to the patient who has a delayed recovery from an episode of covid-19 that was managed in the community or in a standard hospital ward. Broadly, such patients can be divided into those who may have serious sequelae (such as thromboembolic complications) and those with a non-specific clinical picture, often dominated by fatigue and breathlessness. The specialist rehabilitation needs of a third group, covid-19 patients whose acute illness required intensive care, have been covered elsewhere.3
Defining post-acute covid-19
In the absence of agreed definitions, for the purposes of this article we define post-acute covid-19 as extending beyond three weeks from the onset of first symptoms and chronic covid-19 as extending beyond 12 weeks. Since many people were not tested, and false negative tests are common,4 we suggest that a positive test for covid-19 is not a prerequisite for diagnosis.
How common is it?
Around 10% of patients who have tested positive for SARS-CoV-2 virus remain unwell beyond three weeks, and a smaller proportion for months (see box 1).7 This is based on the UK COVID Symptom Study, in which people enter their ongoing symptoms on a smartphone app. This percentage is lower than that cited in many published observational studies,89 whose denominator populations were those admitted to hospital or attending specialist clinics. A recent US study found that only 65% of people had returned to their previous level of health 14-21 days after a positive test.10
Box 1
A patient’s account
My wife, kids, and I all had symptoms of presumed covid-19 in early April 2020. They were soon fine, but I was more unwell and ended up in bed extremely fatigued, lethargic, and without appetite for four days.
The only person whose symptoms persisted was myself, and the fatigue which I had experienced was still lingering in the background. From this point onwards, it became difficult to engage fully in day to day activities with my normal energy levels. Exercise, of which I do a fair amount, was not at all possible.
I continued to feel like this for another three weeks, before finally feeling completely overwhelmed. This happened very quickly and without warning, resulting in me heading for bed immediately as I felt so bad. For the next 72 hours, I felt unwell in a way that was bordering on not coping. I was feverish, soaked with sweat to the point of having to regularly towel myself down, and with a persistent headache that had no relief in spite of increased doses of paracetamol or ibuprofen.
My chest was painfully tight, and my breathing was slightly erratic; I began to experience a shortness of breath in random waves that didn’t leave me gasping for air but certainly made me uncomfortable and very worried. My glands were swollen to the point that it was physically challenging to swallow, and this was only possible with severe discomfort. I felt physically exhausted, mentally drained, and, for the first time in my life, began to consider asking for additional help.
It was at this point that I noticed I had also not had any sense of smell for the past week, and this has continued to be the case since.
Overall, I spent seven days feeling like I had been knocked sideways. I rarely get unwell, and if I do it’s a fleeting fling with something that is usually seasonal and easily self medicated. This felt very different and was particularly challenging as there were points during my sickness that I was completely overwhelmed.
As far as recovery goes, it has now taken a full seven to eight weeks to start feeling close to my normal self again. In the aftermath of this, I have continued to experience the following: fatigued to the point of having to sleep in the day, inability to exercise, continued shortness of breath both motionless and when exerting, small waves of anxiety, considerable depression, continued loss of smell. These are all post-symptoms that I have had no experience or medical history with, and so it has been difficult to wrestle with the unexpectedness of them.
I’m back out doing moderate exercise now and glad to be through what has been a very difficult 12 week cycle from start to end.
Why are some people affected?
It is not known why some people’s recovery is prolonged. Persistent viraemia due to weak or absent antibody response,11 relapse or reinfection,12 inflammatory and other immune reactions,1314 deconditioning,2 and mental factors such as post-traumatic stress1516 may all contribute. Long term respiratory, musculoskeletal, and neuropsychiatric sequelae have been described for other coronaviruses (SARS and MERS),171819202122 and these have pathophysiological parallels with post-acute covid-19.23
What are the symptoms?
Post-acute covid-19 symptoms vary widely. Even so-called mild covid-19 may be associated with long term symptoms, most commonly cough, low grade fever, and fatigue, all of which may relapse and remit.47 Other reported symptoms include shortness of breath, chest pain, headaches, neurocognitive difficulties, muscle pains and weakness, gastrointestinal upset, rashes, metabolic disruption (such as poor control of diabetes), thromboembolic conditions, and depression and other mental health conditions.424 Skin rashes can take many forms including vesicular, maculopapular, urticarial, or chilblain-like lesions on the extremities (so called covid toe).25 There seems to be no need to refer or investigate these if the patient is otherwise well.
What tests are required?
Blood tests should be ordered selectively and for specific clinical indications after a careful history and examination (see infographic); the patient may not need any. Anaemia should be excluded in the breathless patient. Lymphopenia is a feature of severe, acute covid-19. Elevated biomarkers may include C reactive protein (for example, acute infection), white cell count (infection or inflammatory response), natriuretic peptides (for example, heart failure), ferritin (inflammation and continuing prothrombotic state), troponin (acute coronary syndrome or myocarditis) and D-dimer (thromboembolic disease). Troponin and D-dimer tests may be falsely positive, but a negative result can reduce clinical uncertainty. Further research is likely to refine the indications for, and interpretation of, diagnostic and monitoring tests in follow-up of covid-19.
For patients who were not admitted to intensive care, British Thoracic Society guidance on follow-up of covid-19 patients who have had a significant respiratory illness proposes community follow-up with a chest x ray at 12 weeks and referral for new, persistent, or progressive symptoms.26 For those with evidence of lung damage (such as persistent abnormal chest x ray and oximeter readings), referral to a respiratory service is recommended; subsequent early referral to pulmonary rehabilitation probably aids recovery.




Supporting recovery from covid-19
After excluding serious ongoing complications or comorbidities, and until the results of long term follow-up studies are available, patients should be managed pragmatically and symptomatically with an emphasis on holistic support while avoiding over-investigation.2 Fever, for example, may be treated symptomatically with paracetamol or non-steroidal anti-inflammatory drugs. Monitoring functional status in post-acute coivd-19 patients is not yet an exact science. A post-covid-19 functional status scale has been developed pragmatically but not formally validated27—a simplified version of this is reproduced in the supplementary material.
Referral to a specialist rehabilitation service does not seem to be needed for most patients, who can expect a gradual, if sometimes protracted, improvement in energy levels and breathlessness, aided by careful pacing, prioritisation, and modest goal setting. In our experience, most but not all patients who were not admitted to hospital recover well with four to six weeks of light aerobic exercise (such as walking or Pilates), gradually increasing in intensity as tolerated. Those returning to employment may need support to negotiate a phased return. Box 5 links to patient resources, including a comprehensive patient guide from Homerton University Hospital.28
Respiratory symptoms and support
Cough
The British Thoracic Society defines chronic cough as one that persists beyond eight weeks.26 Up to that time, and unless there are signs of super-infection or other complications such as painful pleural inflammation, cough seems to be best managed with simple breathing control exercises28 (see box 2) and medication where indicated (such as proton pump inhibitors if reflux is suspected).
Box 2
Breathing techniques
About 80% of the work of breathing is done by the diaphragm. After illness or general deconditioning, the breathing pattern may be altered, with reduced diaphragmatic movement and greater use of neck and shoulder accessory muscles. This results in shallow breathing, increasing fatigue and breathlessness, and higher energy expenditure. The “breathing control” technique is aimed at normalising breathing patterns and increasing the efficiency of the respiratory muscles (including the diaphragm) resulting in less energy expenditure, less airway irritation, reduced fatigue, and improvement in breathlessness.
The patient should sit in a supported position and breathe in and out slowly, preferably in through the nose and out through the mouth, while relaxing the chest and shoulders and allowing the tummy to rise. They should aim for an inspiration to expiration ratio of 1:2. This technique can be used frequently throughout the day, in 5-10 minute bursts (or longer if helpful).
Other breathing techniques—such as diaphragmatic breathing, slow deep breathing, pursed lip breathing, yoga techniques, Buteyko—are used in strategies to manage patients’ breathing patterns and breathlessness but require specialist advice to identify which technique best suits each patient.
RETURN TO TEXT
Breathlessness
A degree of breathlessness is common after acute covid-19. Severe breathlessness, which is rare in patients who were not hospitalised, may require urgent referral. Breathlessness tends to improve with breathing exercises (box 2). Pulse oximeters may be extremely useful for assessing and monitoring respiratory symptoms after covid-19, and we could find no evidence that their use in the home leads to increased anxiety (box 3).
Box 3
Use of pulse oximetry in post-acute covid-19
Hypoxia may reflect impaired oxygen diffusion and is a recognised feature of covid-19. It may be asymptomatic (so called silent hypoxia29) or symptomatic (reflecting increased work of breathing, or secondary pathology such as a bacterial pneumonia or thromboembolism). Oxygen saturation probes (pulse oximeters) have been used as part of a package of care for patients with covid-19 and are recommended as part of the assessment of acute covid-19 in national and local guidelines.303132
Self monitoring of oxygen saturations over three to five days may be useful in the assessment and reassurance of patients with persistent dyspnoea in the post-acute phase, especially those in whom baseline saturations are normal and no other cause for dyspnoea is found on thorough evaluation. An exertional desaturation test should be performed as part of baseline assessment for patients whose resting pulse oximeter reading is 96% or above but whose symptoms suggest exertional desaturation (such as light-headedness or severe breathlessness on exercise). In the absence of contraindications, such patients should be invited to repeat the oximeter reading after 40 steps on a flat surface (if self testing remotely) and then after spending one minute doing sit-to-stand as fast as they can (if supervised on site).33 A fall of 3% in the saturation reading on mild exertion is abnormal and requires investigation.33
Patients should be provided with a pulse oximeter and an observations diary and given instructions for how to self monitor.34 Typically, this would be a daily reading taken on a clean, warm finger without nail polish, after resting for 20 minutes; the device should be left to stabilise and the highest reading obtained should be recorded. While the range of commercially available oxygen saturation probes from healthcare suppliers and pharmacies seem to work within normal ranges (92% and above), smartphone apps that purport to measure oxygen saturations using the phone camera and torch should not be used.35
British Thoracic Society guidelines define the target range for oxygen saturation as 94-98% and a level of 92% or below as requiring supplementary oxygen (unless the patient is in chronic respiratory failure).36 In the context of a normal assessment (history, examination, and appropriate investigations) without red flags, an oxygen saturation of 96% or above and the absence of desaturation on exertional tests is very reassuring. Further investigation or referral in the first six weeks after covid-19 in such patients is rarely indicated, though regular support by telephone or video is likely to be appreciated. Oximeter readings persistently in the 94-95% range or below (indicating substantially farther down the oxygen-haemoglobin desaturation curve37) require assessment and investigation. The patient should be provided with safety-netting advice (such as contacting their general practice or NHS111) in the event of recurrent low saturation readings. Appropriate adjustments should be made for patients with lung disease and known hypoxia—in whom the range of 88-92% is considered acceptable.
Recovery after any severe debilitating illness may be prolonged.38 Survivors of covid-19 acute respiratory distress syndrome are at risk of long term impairment of lung function.394041 Serious interstitial lung disease seems to be rare in patients who are not hypoxic, though data on long term outcomes are not yet available.42
Pulmonary rehabilitation
Many patients are still recovering spontaneously in the first six weeks after acute covid-19 and do not generally require fast-track entry into a pulmonary rehabilitation programme. Those who have had significant respiratory illness may benefit from pulmonary rehabilitation, defined as “a multidisciplinary intervention based on personalised evaluation and treatment which includes, but is not limited to, exercise training, education, and behavioural modification designed to improve the physical and psychological condition of people with respiratory disease.”43 In the context of covid-19, rehabilitation is being delivered by various virtual models, including video linked classes and home education booklets with additional telephone support. We describe one such programme in the supplementary material on bmj.com.
Fatigue
The profound and prolonged nature of fatigue in some post-acute covid-19 patients shares features with chronic fatigue syndrome described after other serious infections including SARS, MERS, and community acquired pneumonia.19202244 We found no published research evidence on the efficacy of either pharmacological or non-pharmacological interventions on fatigue after covid-19. Patient resources on fatigue management45 and guidance for clinicians on return to exercise43 and graded return to performance for athletes (box 4) 46 in covid-19 are currently all based on indirect evidence.
Box 4
The sportsperson returning to exercise (summarised from Stanford-Hall statement43)

• After recovery from mild illness: 1 week of low level stretching and strengthening before targeted cardiovascular sessions
• Very mild symptoms: limit activity to slow walking or equivalent. Increase rest periods if symptoms worsen. Avoid high-intensity training
• Persistent symptoms (such as fatigue, cough, breathlessness, fever): limit activity to 60% maximum heart rate until 2-3 weeks after symptoms resolve
• Patients who had lymphopenia or required oxygen need respiratory assessment before resuming exercise
• Patients who had cardiac involvement need cardiac assessment before resuming

There is much debate and controversy about the role of graded exercise in chronic fatigue generally (see patient responses to a recent Cochrane review47) and in covid-19 in particular (see a recent statement from the National Institute for Health and Care Excellence (NICE)48). Pending direct evidence from research studies, we suggest that exercise in such patients should be undertaken cautiously and cut back if the patient develops fever, breathlessness, severe fatigue, or muscle aches. Understanding, support, and reassurance from the primary care clinician are a crucial component of management.
Cardiopulmonary complications, assessment and management
Perhaps 20% of patients admitted with covid-19 have clinically significant cardiac involvement4950; occult involvement may be even commoner.5152 Cardiopulmonary complications include myocarditis, pericarditis, myocardial infarction, dysrhythmias, and pulmonary embolus; they may present several weeks after acute covid-19. They are commoner in patients with pre-existing cardiovascular disease,49 but they have also been described in young, previously active patients.435354 Various pathophysiological mechanisms have been proposed, including viral infiltration, inflammation and microthrombi, and down-regulation of ACE-2 receptors.515354
Chest pain
Chest pain is common in post-acute covid-19. The clinical priority is to separate musculoskeletal and other non-specific chest pain (for example, the symptom described by a large patient-led survey as “lung burn”4) from serious cardiovascular conditions. Clinical assessment of the post-acute covid-19 patient with chest pain should follow similar principles to that for any chest pain: a careful history, taking account of past medical history and risk factors, a physical examination, backed up as indicated by investigations (infographic).43 Where the diagnosis is uncertain, or the patient is acutely unwell, urgent cardiology referral may be needed for specialist assessment and investigations (including echocardiography, computed tomography of the chest, or cardiac magnetic resonance imaging).
Thromboembolism
Covid-19 is an inflammatory and hypercoagulable state,50 with an increased risk of thromboembolic events.5556 Many hospitalised patients receive prophylactic anticoagulation. Recommendations for anticoagulation after discharge vary, but higher risk patients are typically discharged from hospital with 10 days of extended thromboprophylaxis.57 If the patient has been diagnosed with a thrombotic episode, anticoagulation and further investigation and monitoring should follow standard guidelines.58 It is not known how long patients remain hypercoagulable following acute covid-19.
Ventricular dysfunction
Left ventricular systolic dysfunction and heart failure after covid-19 can be managed according to standard guidelines.59 Intense cardiovascular exercise must be avoided for three months in all patients after myocarditis or pericarditis; athletes are advised to take three to six months of complete rest from cardiovascular training followed by specialist follow-up, with return to sport guided by functional status, biomarkers, absence of dysrhythmias, and evidence of normal left ventricular systolic function.60
Neurological sequelae
Ischaemic stroke, seizures, encephalitis, and cranial neuropathies have been described after covid-19, but these all seem to be rare.61 A patient suspected of these serious complications should be referred to a neurologist. Common non-specific neurological symptoms, which seem to co-occur with fatigue and breathlessness, include headaches, dizziness, and cognitive blunting (“brain fog”).4 Until evidence based guidance appears on how to manage or when to refer such symptoms, we recommend supportive management and symptom monitoring in primary care.
The older patient
Covid-19 tends to affect older patients more severely.62 Those who survive are at high risk of sarcopenia, malnutrition, depression, and delirium.2 Post-covid-19 chronic pain may affect patients of any age but seems to be commoner in elderly patients.63 Physical symptoms add to the psychosocial impact of disrupted access to health care (such as arrangements for obtaining regular medication), core personal routines (such as walking to local shops), social interactions (such as meeting friends), and lay and professional support networks.64 Support should be personalised with input from the multi-professional team (for example, general practitioner, district nurse, social worker, rehabilitation teams, and occupational therapist as needed).
Mental health and wellbeing
Most publications on covid-19 and mental health have emphasised individual reactions to the pandemic such as anxiety, stress, and conditions related to broken routines, loneliness, and social isolation in uninfected individuals6566; the World Health Organisation has issued guidance on these.67 Lay accounts suggest that post-acute covid-19 is often associated with low mood, hopelessness, heightened anxiety, and difficulty sleeping.6 Post-traumatic stress disorder may occur, especially in healthcare workers and others with caring responsibilities.151643
While a minority of patients may benefit from referral to mental health services, it is important not to pathologise the majority. Physical manifestations of covid-19 may distort responses to assessment tools (such as the PHQ9) designed to measure anxiety and depression in a physically healthy population, though these complications may occur. Patient organisations emphasise wellbeing, mindfulness, social connection, self care (including diet and hydration), peer support, and symptom control. Mental illness is strongly associated with social determinants such as poverty, discrimination, and social exclusion; mental health and wellbeing are enhanced by increased social solidarity, informal social support, mutual aid, and other community based and collective measures.6869 Given how pervasive and unequal the impact of covid-19 has been,7071 community level, cross-sector collaborations may be needed to develop locally relevant solutions. A recent report from general practice in a deprived area of Glasgow describes the importance of accessible, relationship-based care for patients with complex needs, and of system-level interventions such as attached financial advisers and outreach mental health services.69
Social and cultural considerations
Covid-19 is more common and has a worse prognosis in the acute phase in people who are poor, elderly, and from certain minority ethnic groups (notably black, south Asian, and Jewish70). It is too early to say whether these sociodemographic patterns persist in post-acute covid-19. Our own experience suggests that patients with post-acute covid-19 are from diverse social and cultural backgrounds. Many have comorbidities including diabetes, hypertension, kidney disease, or ischaemic heart disease. Some have experienced family bereavements as well as job losses and consequent financial stress and food poverty. Strain on many carers has been high. For an important few, lockdown has worsened safeguarding concerns such as the risk of child or intimate partner abuse. A detailed discussion of all these issues is beyond the scope of this article, but there are strong arguments for working with other agencies to develop local, system-level solutions. Box 5 provides some links to covid-19 advice from specialist social care, lay care, and faith organisations.
Living with covid-19
BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3392 (Published 03 September 2020)Cite this as: BMJ 2020;370:m3392 
fgodlee@bmj.com
“Death is not the only adverse outcome of covid-19,” writes Nisreen Alwan, an epidemiologist who is experiencing a range of prolonged, fluctuating, and debilitating symptoms several months after her initial mild illness.1 Like a growing number of people around the world, she has what is being called post-acute or long covid.
While most people recover quickly and completely from the virus, stories of persistent and troubling symptoms have now moved from anecdote to the evidence of crowd sourced cohorts. Reports suggest that one in three people have not fully recovered several weeks after initial illness. A smaller but still substantial proportion have symptoms and difficulties that persist for months. These are not people who have been seriously ill in hospital, whose difficult journey to recovery is better understood.2 These are often physically fit, younger people who report persistent exercise intolerance, breathlessness and cough,3 anxiety, palpitations, and poor concentration. Paul Garner describes boom and bust—the illusion of recovery only to fall back into mental and physical exhaustion.4 These false dawns add to the burden for “long haulers,” he says, which for him includes intense fatigue, mood swings, muscle and joint pains, headaches, and brain fog.
One of the most distressing aspects of living with long covid, says Garner, is the dismissive attitude of some doctors. This may change as more doctors find themselves affected. So how should doctors respond to their patients struggling with this complex and worrying multisystem disorder? Trish Greenhalgh and colleagues recommend taking a whole person, pragmatic approach with symptom management that avoids overinvestigation.5 With so much uncertainty about the cause and course of long covid, a doctor’s key role is to be a witness, they say, “‘honouring the story’ of the patient whose protracted recovery is unexpected, alarming, and does not make sense.”
The challenge for those in charge of our public health response to covid-19 is to make sense of this emergent information. Policies and messaging must now reflect the risks to younger people of developing prolonged illness and multiple organ damage, especially in light of other new information about the risks of airborne transmission.67 For this, we need to be able to quantify the risks through proper population surveillance and to mitigate them with effective systems of rapid testing, tracing, isolation, and support.8 In the UK, at least, such crucial traditional public health approaches still seem a long way off.9
https://bmj.com/coronavirus/usage