The post-exertional malaise displayed by patients who have not recovered from COVID is a common symptom among patients who have not recovered from COVID. It is also consistent with a standard feature of another chronic illness: myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).
At six months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression, found a study in The Lancet. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations
Kaiser Permanente writes that the post-exertional malaise displayed by patients who have not recovered from COVID is a common symptom among patients who have not recovered from COVID. It is also consistent with a standard feature of another chronic illness: myalgic encephalomyelitis, also known as chronic fatigue syndrome (ME/CFS).
Four weeks after San Diego paediatric nurse Jennifer Minhas fell ill with COVID-19 last March, her cough and fever had resolved, but new symptoms had emerged: chest pain, an elevated heart rate and crushing fatigue. Her primary care physician told her she was just anxious, and that none of her other COVID patients had those issues. “That wasn’t what I needed to hear,” Minhas said.
At times, she’s been too exhausted to hold up her head. “I was kind of a zombie for months, shuffling around unable to do much of anything.”
ME/CFS patients also report cognitive impairment – “brain fog” – and orthostatic intolerance, in which standing upright produces a racing heart rate and light-headedness. Minhas has experienced these symptoms, as have many other “long haulers,” the tens of thousands of post-COVID patients who haven’t recovered.
The percentage of COVID patients who become long haulers is hard to pin down – in part because many early COVID patients were not tested in time to detect the virus. But “long COVID” is potentially an enormous problem.
A recent study of 1,733 COVID patients in Wuhan, China, found three-quarters of them still had symptoms six months after being released from the hospital.
As of January, doctors had documented more than 21m cases of COVID-19 in the US. “If just 5% develop lingering symptoms” – about 1m cases – “and if most of those with symptoms have ME/CFS, we would double the number of Americans suffering from ME/CFS in the next two years,” Harvard Medical School professor Dr Anthony Komaroff wrote recently.
The report says the cause of ME/CFS is unknown, but multiple studies have found it follows acute infections with viruses – everything from the 1918 “Spanish” flu to Ebola. “A certain percentage of people don’t recover,” said Leonard Jason, a researcher at DePaul University.
Scientists are trying to figure out the mechanisms of the disease and why it develops in certain people and not others. According to the US Centres for Disease Control and Prevention, ME/CFS shares certain characteristics with autoimmune diseases, in which the immune system attacks healthy tissue in the body. Multiple studies are underway to explore this and other potential causes.
Doctors who specialize in treating ME/CFS are beginning to pivot to long-COVID patients, the report says. Dr Peter Rowe, whose clinic at Johns Hopkins is one of the country’s leading centres for ME, has so far seen four long haulers at his practice. “All of them meet the criteria for ME/CFS,” he said.
Despite years of research, there is no biomarker for ME/CFS, so blood tests are ineffective as a diagnostic tool. Rowe’s approach is to tease apart which symptoms may have identifiable causes and treatments, and address those. One example: A 15-year-old boy Rowe was treating for ME/CFS was so sick that even sitting upright a few hours a day exhausted him and made schoolwork virtually impossible. The boy’s heart rate while lying down was 63; when he stood up it skyrocketed to 113. This effect is known as postural orthostatic tachycardia syndrome, or POTS.
Rowe knew from interviews with the boy’s mother that he had an extraordinary appetite for salt. So much so that he kept a shaker at his bedside and would regularly sprinkle salt on his hand and lick it off.
Rowe hypothesised that he was dealing with a sodium retention problem. To counter it, he prescribed the steroid fludrocortisone, which promotes sodium resorption in the kidneys. Three weeks later, the boy had recovered so dramatically he was helping a neighbour with a landscaping project, pushing rocks around in a wheelbarrow. “He was a different kid,” Rowe said.
Such a course of treatment would not be applicable in a typical case, Rowe said, “but it does emphasise the potential for patients to get a substantial improvement in their CFS symptoms if we address the orthostatic intolerance.”
The report says beginning in the 1980s, many doctors treating ME/CFS prescribed a combination of cognitive behavioural therapy and an exercise regimen based on a now discredited assertion that the illness had no biomedical origin. That approach proved ineffective – patients often got demonstrably worse after pushing beyond their physical limits. It also contributed to a belief within the medical establishment that ME/CFS was all in your head, a narrative that has largely been refuted.
“ME/CFS was never a mostly behavioural problem, although it has been cast as that,” Rowe said.
Answers have been slow to arrive, but, the report says, attitudes about the illness are beginning to change. Advocates of patients point to a 2015 report by the Institute of Medicine that called ME/CFS “a serious, chronic, complex, systemic disease” and acknowledged that many doctors are poorly trained to identify and treat it.
The problem is exacerbated by a reluctance to provide health care coverage to patients whose illnesses aren’t easily diagnosed, said Joe Dumit, a medical anthropologist at the University of California-Davis. “Making patients prove they are not just suffering, but suffering from a documented illness, saves money. So, I worry about the way in which COVID long haulers will be treated as the numbers rise.” The best treatment in many cases may be rest or reduced workload, “which translates into some form of disability coverage,” he said.
But since long haulers typically sicken immediately after having had a testable viral infection, perhaps they won’t be disbelieved, Rowe said – after all, their illness “starts as a ‘real’ illness.’’
The report says long haulers may also help researchers better understand the onset of the illness because they are being studied as their symptoms emerge, while ME/CFS patients often aren’t seen until they’ve been ill for two or more years, he said.
“There’s no question that this legitimises in many ways the experience of people with ME/CFS who have felt they weren’t believed,” DePaul’s Jason said.
In July, the non-profit Solve ME/CFS launched an initiative aimed at understanding similarities between long haulers and patients with ME/CFS. Dubbed You+ME and underwritten by the National Institutes of Health, it includes an app that enables registrants to record their symptoms and their effects over time.
Such efforts may further diminish the tendency of doctors to ignore patients’ complaints of symptoms that seem to have no evident cause, said Lauren Nichols, 32, a long hauler with a long list of miseries – everything from severe gastrointestinal problems to shingles in her left eye.
“I was one of those people who falsely believed that if you can’t see the illness it’s psychosomatic,” said Nichols, who helps administer Body Politic, a support group for long-COVID patients that has found common cause with the ME/CFS community.
“Now I’m living it,” she said. “If I have one message for doctors, it’s ‘Believe your patients.’”
6-month consequences of COVID-19 in patients discharged from hospital: a cohort study
Chaolin Huang, Lixue Huang, Yeming Wang, Xia Li,Lili Ren, Xiaoying Gu, Liang Kang, Li Guo, Min Liu, Xing Zhou, Jianfeng Luo, Zhenghui Huang, Shengjin Tu, Yue Zhao, Li Chen, Decui Xu, Yanping Li, Caihong Li, Lu Peng, Yong Li, Wuxiang Xie, Dan Cui, Lianhan Shang, Guohui Fan, Jiuyang Xu, Geng Wang, Ying Wang, Jingchuan Zhong, Chen Wang, Jianwei Wang, Dingyu Zhang, Bin Cao
Published in The Lancet on 8 January 2021
The long-term health consequences of COVID-19 remain largely unclear. The aim of this study was to describe the long-term health consequences of patients with COVID-19 who have been discharged from hospital and investigate the associated risk factors, in particular disease severity.
We did an ambidirectional cohort study of patients with confirmed COVID-19 who had been discharged from Jin Yin-tan Hospital (Wuhan, China) between Jan 7, 2020, and May 29, 2020. Patients who died before follow-up, patients for whom follow-up would be difficult because of psychotic disorders, dementia, or re-admission to hospital, those who were unable to move freely due to concomitant osteoarthropathy or immobile before or after discharge due to diseases such as stroke or pulmonary embolism, those who declined to participate, those who could not be contacted, and those living outside of Wuhan or in nursing or welfare homes were all excluded. All patients were interviewed with a series of questionnaires for evaluation of symptoms and health-related quality of life, underwent physical examinations and a 6-min walking test, and received blood tests. A stratified sampling procedure was used to sample patients according to their highest seven-category scale during their hospital stay as 3, 4, and 5–6, to receive pulmonary function test, high resolution CT of the chest, and ultrasonography. Enrolled patients who had participated in the Lopinavir Trial for Suppression of SARS-CoV-2 in China received severe acute respiratory syndrome coronavirus 2 antibody tests. Multivariable adjusted linear or logistic regression models were used to evaluate the association between disease severity and long-term health consequences.
In total, 1733 of 2469 discharged patients with COVID-19 were enrolled after 736 were excluded. Patients had a median age of 57·0 (IQR 47·0–65·0) years and 897 (52%) were men. The follow-up study was done from June 16, to Sept 3, 2020, and the median follow-up time after symptom onset was 186·0 (175·0–199·0) days. Fatigue or muscle weakness (63%, 1038 of 1655) and sleep difficulties (26%, 437 of 1655) were the most common symptoms. Anxiety or depression was reported among 23% (367 of 1617) of patients. The proportions of median 6-min walking distance less than the lower limit of the normal range were 24% for those at severity scale 3, 22% for severity scale 4, and 29% for severity scale 5–6. The corresponding proportions of patients with diffusion impairment were 22% for severity scale 3, 29% for scale 4, and 56% for scale 5–6, and median CT scores were 3·0 (IQR 2·0–5·0) for severity scale 3, 4·0 (3·0–5·0) for scale 4, and 5·0 (4·0–6·0) for scale 5–6. After multivariable adjustment, patients showed an odds ratio (OR) 1·61 (95% CI 0·80–3·25) for scale 4 versus scale 3 and 4·60 (1·85–11·48) for scale 5–6 versus scale 3 for diffusion impairment; OR 0·88 (0·66–1·17) for scale 4 versus scale 3 and OR 1·77 (1·05–2·97) for scale 5–6 versus scale 3 for anxiety or depression, and OR 0·74 (0·58–0·96) for scale 4 versus scale 3 and 2·69 (1·46–4·96) for scale 5–6 versus scale 3 for fatigue or muscle weakness. Of 94 patients with blood antibodies tested at follow-up, the seropositivity (96·2% vs 58·5%) and median titres (19·0 vs 10·0) of the neutralising antibodies were significantly lower compared with at the acute phase. 107 of 822 participants without acute kidney injury and with estimated glomerular filtration rate (eGFR) 90 mL/min per 1·73 m2 or more at acute phase had eGFR less than 90 mL/min per 1·73 m2 at follow-up.
At 6 months after acute infection, COVID-19 survivors were mainly troubled with fatigue or muscle weakness, sleep difficulties, and anxiety or depression. Patients who were more severely ill during their hospital stay had more severe impaired pulmonary diffusion capacities and abnormal chest imaging manifestations, and are the main target population for intervention of long-term recovery.
National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, National Key Research and Development Program of China, Major Projects of National Science and Technology on New Drug Creation and Development of Pulmonary Tuberculosis, and Peking Union Medical College Foundation.
Full Kaiser Permanente report (Open access)
The Lancet study (Open access)
See also from the MedicalBrief archives:
The Lancet study (Open access)
The Lancet study (Open access)