A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report, 2023, Oka

[SNT Gatchaman]

A patient who recovered from post-COVID myalgic encephalomyelitis/chronic fatigue syndrome: a case report.
Oka T

Background: Some patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complain of persistent fatigue, dyspnea, pain, and cognitive dysfunction. These symptoms are often described as "long COVID". Whether a patient with long COVID might develop myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is of interest, as is the treatment and management of ME/CFS in a post-COVID patient. Here I report a patient, who, after an infection with SARS-CoV-2, developed ME/CFS and recovered after treatment.

Case presentation: The patient was a previously healthy 55-year-old woman who worked as a nurse and became ill with COVID-19 pneumonia. She then presented with severe fatigue, post-exertional malaise, dyspnea, pain, cognitive dysfunction, tachycardia, and exacerbation of fatigue on physical exertion, which persisted for more than 6 months after her recovery from COVID-19 pneumonia. She was bedridden for more than half of each day. The patient was treated from multiple perspectives, which included (1) instructions on eating habits and supplements; (2) cognitive and behavioral modifications for coping with physical, emotional, and cognitive fatigue; (3) instructions on conditioning exercises to improve deconditioning due to fatigue and dyspnea; and (4) pharmacotherapy with amitriptyline and hochuekkito, a Japanese herbal (Kampo) medicine. The patient made a complete recovery after completing the prescribed regimen and was able to return to work as a nurse.

Conclusions: To the best of my knowledge, this is the first detailed report on a patient infected with SARS-CoV-2 followed by long COVID with the signs/symptoms of ME/CFS who recovered after treatment. I hope this case report will be helpful to health care practitioners by its presentation of some of the therapeutic options for alleviating disabling signs/symptoms in patients with post-COVID ME/CFS.

Link | PDF

 

[SNT Gatchaman]

To date, there is no single treatment that can cure every patient with ME/CFS, which might be accounted for by the fact that many abnormalities are thought to be involved in this illness. Therefore, my patients are usually treated from multiple perspectives to resolve as many abnormalities as possible with the aim of providing treatment that exerts a synergistic effect. For this case, I focused on four aspects.

The first was to minimize the effects of oxidative stress.
The second aspect was to maximize adaptive coping and self-management skills.
The third aspect was reverse deconditioning.
The fourth aspect was pharmacotherapy.

The role of physical exercise in the treatment of ME/CFS remains debatable, whereas the importance of multidisciplinary rehabilitation is stressed in treating long COVID. As was suggested for the treatment of long COVID, it was thought that treating the deconditioning of this patient was important because she had been completely bedridden for longer than a week because of pneumonia. Her signs/symptoms such as dyspnea, weakness, and tachycardia on exertion might have been derived, at least partly, from deconditioning.

Hochuekkito is a Japanese herbal medicine for improving “ki-kyo”, i.e., a low-energy state, according to traditional Japanese (Kampo) medicine [24, 25]. Hochuekkito has been found to ameliorate fatigue in patients with such chronic diseases as cancer, chronic obstructive pulmonary disease, and ME/CFS [26, 27]. It has also been found to improve hypocortisolemia and decreased heart rate variability [28] and, furthermore, to inhibit neuroinflammation [29]. Together, amitriptyline and hochuekkito may have acted synergistically to ameliorate the patient’s ME/CFS.

it might be that the apparent beneficial effects of the treatment protocol were actually a reflection of the natural process of recovery. However, the patient had been almost bed-ridden for longer than 6 months and started to feel better as early as 2 weeks after the start of treatment. Therefore, even if she was in the process of natural recovery, the interventions may have facilitated her recovery.

 

[SNT Gatchaman]

I haven't looked at them but if interested, the available English references given for Hochuekkito are —

Efficacy and Safety of a Traditional Herbal Medicine, Hochu-ekki-to in the Long-term Management of Kikyo (Delicate Constitution) Patients with Atopic Dermatitis: A 6-month, Multicenter, Double-blind, Randomized, Placebo-controlled Study (2010)
Basic pharmacological mechanisms and clinical evidence of the efficacy of hochuekkito against infectious diseases and its potential for use against COVID-19 (2020)
Bojungikki-tang for cancer-related fatigue: a pilot randomized clinical trial (2010)
Neuroinflammation, Oxidative Stress, and Neurogenesis in a Mouse Model of Chronic Fatigue Syndrome, and the Treatment with Kampo Medicine (2020)

 

[Hutan]

It's deeply frustrating that here we are, trying to discern if there is any scrap of relevance in an anecdote about someone recovering from Long Covid at around the 6 month mark, when the odds of recovery from persistent symptoms following a covid-19 infection must surely be high.

That said:
Hochuekkito, a Japanese Herbal Medicine, Restores Metabolic Homeostasis between Mitochondrial and Glycolytic Pathways Impaired by Influenza A Virus Infection (2017)
Maybe it's worth looking at?

 

[Hutan]

Just as an aside:

She initially complained of insomnia and non- restorative sleep; however, these symptoms gradually resolved. Her complaints satisfied the 1994 Fukuda case definition of CFS [5]. Before her visit to our department, her complaints to other physicians also satisfied the 2003 Canadian clinical case definition of myalgic encephalo- myelitis (ME)/CFS [10]. However, because her sleeping problems gradually resolved, she did not quite satisfy the Canadian clinical case definition at the time of her visit to our department.

That quote illustrates the difficulties with the 'sleep problems' or 'non-restorative sleep' criteria of the more demanding ME/CFS criteria. The patient seems to have PEM; her illness sounds very much like ME/CFS. And yet, different interpretations of the sleep criteria can potentially see someone excluded from a CCC compliant diagnosis (and probably IOM and ICC compliant diagnoses too). Sometimes, I wake up in the morning noting that I feel awful, but most days, it's just more of the same, and often an afternoon sleep is restorative, in that I can get going again, to make dinner or something. I think 'sleep issues' as part of ME/CFS criteria creates unnecessary confusion.

 

[Hutan]

There's an awful lot of fluff there, with not one, but two vicious cycle diagrams and a lot of what I find to be awfully patronising. Perhaps the clinician was able to offer some useful advice, although we just have their word for it.

First, her cop- ing strategies against fatigue and her beliefs and feelings behind them were evaluated. She believed that she should not give in to fatigue but had to endure and over- come it. This idea seemed to derive, at least partly, from the fact that when she was young she was athletic and trained herself to overcome fatigue without complain- ing in order to become stronger. She used this strat- egy not only when she felt fatigued but also when she had pain and cognitive problems. It was obvious that these coping strategies resulted in exhaustion and PEM and exacerbated her symptoms. Furthermore, because of her concerns for other people she prioritized help- ing others instead of resting, even when she felt fatigue. Her beliefs and feelings might have made it difficult for her to accept adaptive coping strategies.

Did the patient actually improve? I think that's arguable. She did report lower fatigue at the end, but she seemed to be learning how to manage her illness, as most of us do over time, regardless of whether we are given instructions about how to improve our coping approaches. If anything, the increase in heart rate on standing got worse. Much was made about axillary temperature, suggesting what I think is quite a normal temperature initially was high, and that the subsequent decrease was indicative of an improvement in health. To the contrary, the final axillary temperature might be tending towards being too low, and, in any case, one measurement doesn't prove much.

At the fourth visit (11 weeks later), she said she was in good shape and her fatigue was almost zero when she was at rest; however, she did not have enough endurance for shopping. Therefore, she was instructed to gradually increase her exercise to improve deconditioning. At the sixth visit (21 weeks later), she said she had become able to practice the activities of daily living without medication and that her physical and mental condition had recovered to almost the same level as that before she became ill. She reported that she was planning to return to work, and her treatment was terminated.

So, the conclusion that the woman had recovered was based pretty much on her self-reported symptoms, while she was still not working. At the final appointment , she reported that she was planning to return to work, but we don't hear how that went - and that would be a better test of whether she had recovered. I myself reported to my GP at one point that I was better, I hoped it was true, and even got her to sign a form that I had recovered, so that I would be allowed to complete a project I was working on (which I never did finish). My son returned to school full time - and ended up worse than he had ever been.

So, I'm not convinced the woman permanently recovered; the information we are given seems compatible with someone learning how to manage their illness, and perhaps recovering a bit naturally over time, perhaps reporting improvements out of politeness and wishful thinking. If you were a clinician looking to promote your clinic, the logical thing to do is write the paper about recovery before the patient tries to resume their pre-illness activities.

That said, is there anything in the treatments?

Oral amitriptyline (10 mg before sleep) and hochuekkito, a Japanese herbal (Kampo) medicine (7.5 g before every meal) were prescribed.

I think we can discount the fluff about a good diet and vitamin C; too many other people have been there and done that, with no benefit. But I think it might be worth looking at amitriptyline and hochuekkito, to see if there is any reason to think they might be useful. (Not that I'm suggesting trying them; I assume amitriptyline at least could be dangerous.)

 

[Sean]

To date, there is no single treatment that can cure every patient with ME/CFS,

To date, there is no specific treatment for ME/CFS.

 

[SNT Gatchaman]

Much was made about axillary temperature, suggesting what I think is quite a normal temperature initially was high, and that the subsequent decrease was indicative of an improvement in health.

Apparently there's psychogenic fever. From the same author —

Psychogenic fever: how psychological stress affects body temperature in the clinical population (2015)

Psychogenic fever is a stress-related, psychosomatic disease especially seen in young women. Some patients develop extremely high core body temperature (Tc) (up to 41°C) when they are exposed to emotional events, whereas others show persistent low-grade high Tc (37–38°C) during situations of chronic stress. The mechanism for psychogenic fever is not yet fully understood.

and different Japanese authors, recently referencing that paper —
Psychogenic fever and postural tachycardia syndrome among school-aged children and adolescents with fever of unknown origin (2022)

the latter concluding with:

Psychogenic fever was a common cause of fever of unknown origin in pediatric patients, and postural tachycardia was prevalent among children with psychogenic fever. Enhanced sympathetic response to stress might play an important role in both psychogenic fever and postural tachycardia.

Although the underlying reason remains unknown, we speculate that the high comorbidity rate of postural tachycardia syndrome (POTS) might have partially accounted for the increased preponderance of female pediatric patients with [psychogenic fever] in the current study.

Those delicate teenage girls... This is the first time I've come across PUO (pyrexia of unknown origin) which is a common childhood referral problem being explained with MUS-like psychologisation.

 

[Hutan]

Axillary temperature at first visit 37.2 degrees
Axillary temperature at last visit 36.3 degrees

Average body temperature can vary between 95.7ºF (35.4ºC) and 98.9ºF (37.2ºC), but a high temperature is only considered to be a fever when the temperature under the armpit (the axillary temperature) is higher than 100.4ºF (38ºC). This is because temperatures between 98.9 and 100.4ºF can be easily achieved when it’s very hot outside or when you have many layers of clothes on.

A lot more weight than seems warranted is given to two measurements of temperature, that really aren't very extraordinary.

I think we may have commented about Oka before, the psychogenic fever idea rings a bell.
Ah yes, here:
Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial 2022 Oka et al
Oka (I'm assuming it's the same one) has a track record of publishing with a Japanese traditional medicine company.

 

[Milo]

View attachment 19136

Axillary temperature at first visit 37.2 degrees
Axillary temperature at last visit 36.3 degrees



A lot more weight than seems warranted is given to two measurements of temperature, that really aren't very extraordinary.

I think we may have commented about Oka before, the psychogenic fever idea rings a bell.
Ah yes, here:
Clinical effects of wasabi extract containing 6-MSITC on myalgic encephalomyelitis/chronic fatigue syndrome: an open-label trial 2022 Oka et al
Oka (I'm assuming it's the same one) has a track record of publishing with a Japanese traditional medicine company.

Axilla temperature is the least reliable measurement of them all. It is typically only performed on newborns.

 

[Peter T]

So, the conclusion that the woman had recovered was based pretty much on her self-reported symptoms, while she was still not working. At the final appointment , she reported that she was planning to return to work, but we don't hear how that went - and that would be a better test of whether she had recovered.

ME/CFS is a very variable condition between and within patients. I am sure we can all share anecdotes of people dramatically cutting back their activity levels and seemingly improving dramatically, perhaps attributing that improvement to whichever intervention they were doing at the time, be it diet, gentle exercise, psychotherapy, positive thinking.

One I cite is someone who went on holiday on a Greek island and felt much improved, so she left her job and sold everything she had to raise enough money to return to the island for over six months. With a healthy Mediterranean diet, gentle walking, swimming, lots of rest and sunbathing she believed this resulted in a total recovery. Then returning to full time but temporary job in the UK, within a few days she experienced a major relapse leaving her unable to work again. Having previously left her permanent post she had no entitlement to ill health retirement just general state benefits.

We desperately need good longitudinal data for a reasonable sized cohort. The single case reported here may have recovered or she may simply have learned to manage her symptoms to avoid triggering PEM, but we have no idea if that could be sustained when returning to premorbid activity levels.

 

[rvallee]

To the best of my knowledge, this is the first detailed report on a patient infected with SARS-CoV-2 followed by long COVID with the signs/symptoms of ME/CFS who recovered after treatment

Uh, literally half recover, at least. Come on this is just weak. A freaking TV show about busting myths was more rigorous than this. And it was for entertainment. Why are entertainers more serious about a freaking TV show than actual medical doctors about their actual job?

Do they literally don't know anything about the overall picture? I mean for years people have insisted that most recover, therefore it's very likely to randomly find people who will recover. Unless this clinician has only treated this patient, this is one case out of who knows?

Of course those claims about everyone recovering were largely aspirational hopium and in fact many do not, but on a year-span most do, this is what was expected given the probabilities.

Why is medicine so bad at statistics and probabilities? And I mean just absolutely catastrophically awful in ways that are hard to put into proper context.

It's a good thing we will have medical and research AIs to allow us to bypass this broken system. Because it is completely broken and unable to commit a competent effort.