Sleep Issues Amongst People With ME – A Conversation with Professor Dorothy Bruck

by Bronc

Just before Xmas 2010 I was overcome by a bout of Swine Flu. After the holiday, which was a complete blur due to sickness, I went back to work in January feeling very weak. Over the course of the next 8 months, up until my diagnosis of ME, I was afflicted by a bewildering variety of symptoms which caused a great deal of physical and mental suffering. The symptoms which affected me the most in some respects were the unrefreshing sleep and acute insomnia which made me fear that I would lose my job. I was working over 50 hours a week in a very stressful and physically demanding job which I increasingly struggled to keep onto partly due to the lack of sleep/unrefreshing sleep. I noticed a considerable decline in my ability to do some of the basics of my job as I struggled to concentrate and felt increasingly unable to keep up with the very demanding target driven regime at work. Trying to teach a class of 30 teenagers can be hard work at the best of times but when you’re getting 4 hours of unrefreshing sleep it can be a nightmare. Once I received my diagnosis of ME one of the first things I asked my GP for was a course of sleeping tablets to help me overcome the worst of the insomnia.

Since my diagnosis unrefreshing sleep and insomnia have been my constant companions. Sadly, none of the health professionals and scientists I’ve spoken to over the years have been able to offer much insight as to what is causing this and what might help treat it.

There is lack of research into this important aspect of ME. As we all know sleep is the foundation stone of good health for anyone. Those of us who live with dysfunctional sleep all the time it can be very debilitating and have a considerable knock on effect on the other symptoms of our illness.

I recently spoke with Professor Dorothy Bruck about her insights into some of the sleep issues which affect people with ME.

Emeritus Professor Bruck’s main area of research interest and expertise is sleep and sleep health. She has been thinking about, and working with, many aspects of sleep for about 40 years. Professor Bruck has had a long academic career at Victoria University in Melbourne, with particular expertise in sleep/wake behaviour, mental health, chronic fatigue syndrome, waking thresholds and human behaviour in emergencies. She has an international research reputation, with over 120 peer-reviewed full-length publications, $2.5 million in competitive grant income, dozens of invited international and national professional speaking engagements, and numerous awards. Professor Bruck’s research has been regularly featured in the media, including Time Magazine and New Scientist. Apart from her academic work Professor Bruck has worked as a sleep psychologist and most recently she was Chair of the Sleep Health Foundation (Australia). She is now semi-retired and lives in the Far South of Tasmania, Australia.

Q1. How did you get involved in the field of M.E. research?

I have been a sleep researcher since undertaking my Honours degree in 1978, with a particular interest in disorders of excessive daytime sleepiness such as narcolepsy.  In 2010 my teenage son was diagnosed with ME/CFS, which left him bed and recliner bound for about 10 of the next 15 years. Remarkably he has now improved sufficiently to hold a job with flexible hours.  While he was very sick I met ME/CFS clinicians and researchers in Melbourne and we managed to obtain funding for a series of studies focussing on sleep and gut microbes.  We have since published this research with Melinda Jackson and Amy Wallis as the first authors.

Q2. In October 2021 the National Institute for Clinical Excellence in the UK issued a new guideline for the treatment and care of people with M.E. This guideline recognised that for a diagnosis of M.E. to be made people had to suffer from four key symptoms. Unrefreshing sleep or non-restorative sleep is recognised as one of the core symptoms of the illness. The sleep disturbance experienced by pwME can be broken down into two categories: disturbed sleep patterns and unrefreshing sleep. Despite this, there is remarkably little research being conducted into this core symptom of the illness. Amongst the limited studies that have been done into this issue there appears to be no consensus as to what is causing the sleep dysfunction among pwME. How would you explain the sleep dysfunction experienced by pwME?

I think the dichotomy between disturbed sleep patterns and unrefreshing sleep is quite useful, keeping in mind however, that a pwME/CFS may have both.  Neither are unique to ME/CFS.

Disturbed sleep patterns (where the person is unable to sleep when they want to) may arise from co-morbidities with ME/CFS, such as sleep apnea, insomnia and circadian rhythm disorders. Sometimes the latter two disorders may begin with, or be perpetuated by, behavioural changes in sleep/wake behaviours that lead to disturbed sleep.

  • For example, the fatigue associated with ME/CFS may lead to irregular sleep patterns where the person sleeps episodically (i.e. naps) across the 24 hour period and the circadian (24 hour) rhythm becomes confused. The person’s sleep quality suffers because they are no longer getting their main sleep period in a single block at the time the body clock expects it. A different pattern that we may see in ME./CFS is Delayed Sleep Phase Disorder, where the person is very much an ‘evening’ type, going to bed late and getting up late. People who get insufficient outdoor light during the daytime are particularly susceptible to this.  Sometimes their body clock begins to ‘free run’ and each night they may go to bed later than the previous night, so their ‘day’ may be 25 hours instead of 24 hours.
  • Behavioural changes that may precipitate insomnia include decreased sleep drive (or sleep pressure) arising from reduced activity, significant napping during the day, reduced exposure to daytime light, worry at night about the consequences of having ME/CFS, and/or longer time in bed trying to sleep than the actual sleep duration that person may need. For example, due to boredom and/or feelings of fatigue, turning lights off from 9pm to 8am each night (i.e. 11 hours trying to sleep) when the person may only need 8 hours of actual sleep.  Best if lights-out time equals sleep time required.  The research shows quite clearly that treatment with Cognitive Behavioural Therapy for Insomnia can provide significant improvements in people whose sleep has been impaired by such behavioural factors and online programs are available.

On the other hand, disturbed sleep patterns in pwME/CFS may arise, not from behavioural factors, but from factors associated with ME/CFS itself, such as impaired melatonin secretion or other imbalances in the many hormonal or metabolic or neurological factors that we are only now beginning to understand affect sleep patterns.  Such imbalances may, in fact lead to either disturbed sleep patterns or unrefreshing sleep.

Unrefreshing sleep occurs across the population, both in people with a range of clinical conditions and sometimes in people with no diagnosed medical problem.  It is usually described by self-report. It is likely to be a very heterogenous phenomenon. A study by El-Mekkawy Leqaa et al (2022) noted a significant change in delta wave power (deep sleep) in the temporal brain region in those with unrefreshing sleep arising from sleep apnea, compared to controls. In our review of sleep patterns in ME/CFS (Jackson and Bruck, 2012) we concluded that technological advances in the assessment/monitoring of sleep may lead to further understanding of how the micro-structure of sleep may differ between those with self-reported unrefreshing sleep compared to quality sleep.

Q3. Anecdotal evidence from some pwME and a few research studies suggest that the sleep disturbance that people experience can have a significant impact on their cognitive abilities. How prevalent is this? What may be causing the sleep disturbance to impact people’s cognitive function?

Any ongoing sleep disturbance will affect a person’s cognitive abilities. Attention, concentration, memory and reaction time may all be affected in some way depending on (a) their overall health (physical and/or mental) and (b) individual differences in how poor sleep quality affects an individual.  It seems reasonable to think that a pwME/CFS that includes the symptom of brain fog would be affected by the cognitive impairments we associate with poor sleep in an additive way.

Q.4 Is there any evidence that non-restorative sleep is impacting other symptoms which pwME experience such as pain?

I believe that ANY ongoing poor quality sleep, whether it is unrestorative sleep or disturbed sleep will affect a range of ME/CFS symptoms, possibly all.  Pain and brain fog are likely to be particularly affected.

With regard to pain we know that sleep loss increases the experience of pain.  Krause et al (2019) showed that acute sleep deprivation amplifies pain reactivity within the human primary somatosensory cortex, lowers pain thresholds and that ‘even modest nightly changes in sleep quality within an individual determine consequential day-to-day changes in experienced pain’.

Q5. Having a clearer understanding about the pathophysiology of non-restorative sleep in pwME may lead to better treatment options for patients. Are you aware of any clinical trials which are exploring treatment issues for non-restorative sleep in pwME?

Unfortunately not.

Q6. Many people with M.E. report that there is a direct link between the degree of their non-restorative sleep and the depth of the fatigue they experience the next day. What research has been done into this particular issue and what were their findings?

To my knowledge this issue has not yet been investigated in pwME/CFS.  However, cognitive fatigue as measured on a range of working memory tests (Benkirane et al, 2022) found that the main effect of sleep fragmentation was to increase subjectively reported fatigue rather than reduce cognitive test performance.  This study, using healthy participants, highlights the difficulties in objectively measuring fatigue, as many people can rally their mental resources for short-term testing in a research setting.  This may have little to do with how fatigue is experienced in real-life settings.

Q7. What further research is required to investigate the causes of non-restorative sleep and the impact this has on cognitive function, fatigue and pain in pwME?

There are so many unanswered questions.  The first step for any such research is to have a standard definition of non-restorative sleep.  Is it a certain level of sleep fragmentation? Sleep disruption? Lower EEG delta power? Subjective report in the light of an otherwise normal sleep diary?  Is reported non-restorative sleep the same for someone with sleep apnea, vivid dreaming or ME/CFS?

The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study

Abstract:

Long Covid-19 syndrome (LCS) manifests with a wide range of clinical symptoms, yet the factors associated with LCS remain poorly understood. The current study aimed to investigate the relationships that demographic characteristics, clinical history, laboratory indicators, and the frequency of HLA-I alleles have with the likelihood of developing LCS.

We extracted the demographic characteristics and clinical histories from the medical records of 88 LCS cases (LCS+ group) and 96 individuals without LCS (LCS− group). Furthermore, we evaluated the clinical symptoms, serum levels of interleukin (IL)-6 and tumor necrosis factor-α, laboratory parameters, and the frequencies of HLA-I alleles.

Following this we used multiple logistic regression to investigate the association these variables had with LCS. Subjects in the LCS+ group were more likely to have experienced severe Covid-19 symptoms and had higher body mass index (BMI), white blood cell, lymphocyte counts, C-reactive protein (CRP), and IL-6 levels than those in the LCS− group (for all: P < 0.05).

Moreover, the frequencies of the HLA-A*11, -B*14, -B*38, -B*50, and -C*07 alleles were higher in the LCS+ group (for all: P < 0.05). After adjusting for the most important variables, the likelihood of suffering from LCS was significantly associated with BMI, CRP, IL-6, the HLA-A*11, and -C*07 alleles, as well as a positive history of severe Covid-19 (for all: P < 0.05).

Our study showed that a history of severe Covid-19 during the acute phase of the disease, the HLA-A*11, and -C*07 alleles, higher BMI, as well as elevated serum CRP and IL-6 levels, were all associated with an increased likelihood of LCS.

Source: Torki, E., Hoseininasab, F., Moradi, M. et al. The demographic, laboratory and genetic factors associated with long Covid-19 syndrome: a case–control study. Clin Exp Med 24, 1 (2024). https://doi.org/10.1007/s10238-023-01256-1 https://link.springer.com/article/10.1007/s10238-023-01256-1 (Full text)

Long COVID in pediatrics-epidemiology, diagnosis, and management

Abstract:

This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID — at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities.

Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.

Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions.

Source: Toepfner N, Brinkmann F, Augustin S, Stojanov S, Behrends U. Long COVID in pediatrics-epidemiology, diagnosis, and management. Eur J Pediatr. 2024 Jan 27. doi: 10.1007/s00431-023-05360-y. Epub ahead of print. PMID: 38279014. https://link.springer.com/article/10.1007/s00431-023-05360-y (Full text available as PDF file)

The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability

Highlights:

  • Though a common symptom, fatigue is difficult to define and investigate, and occurs in a wide variety of disorders, with differing pathological causes.
  • This review aims to guide clinicians in how to approach fatigue and to suggest that neurophysiological tests may allow an understanding of its origin and severity.
  • The effectiveness of neurophysiological tests as cost-effective objective biomarkers for the assessment of fatigue has been summarised.

Abstract

Though a common symptom, fatigue is difficult to define and investigate, occurs in a wide variety of neurological and systemic disorders, with differing pathological causes. It is also often accompanied by a psychological component. As a symptom of long-term COVID-19 it has gained more attention.

In this review, we begin by differentiating fatigue, a perception, from fatigability, quantifiable through biomarkers. Central and peripheral nervous system and muscle disorders associated with these are summarised. We provide a comprehensive and objective framework to help identify potential causes of fatigue and fatigability in a given disease condition. It also considers the effectiveness of neurophysiological tests as objective biomarkers for its assessment. Among these, twitch interpolation, motor cortex stimulation, electroencephalography and magnetencephalography, and readiness potentials will be described for the assessment of central fatigability, and surface and needle electromyography (EMG), single fibre EMG and nerve conduction studies for the assessment of peripheral fatigability.

The purpose of this review is to guide clinicians in how to approach fatigue, and fatigability, and to suggest that neurophysiological tests may allow an understanding of their origin and interactions. In this way, their differing types and origins, and hence their possible differing treatments, may also be defined more clearly.

Source: Tankisi H, Versace V, Kuppuswamy A, Cole J. The role of clinical neurophysiology in the definition and assessment of fatigue and fatigability. Clin Neurophysiol Pract. 2023 Dec 18;9:39-50. doi: 10.1016/j.cnp.2023.12.004. PMID: 38274859; PMCID: PMC10808861. https://www.sciencedirect.com/science/article/pii/S2467981X23000367 (Full text)

Confirmation of COVID-19 infection status and reporting of Long COVID symptoms in a population-based birth cohort: No evidence of a nocebo effect

Abstract:

Some patients with COVID-19 develop symptoms after the acute infection, known as ‘Long COVID’. We examined whether or not confirmation of COVID-19 infection status could act as a nocebo, using data from questionnaires distributed to the Avon Longitudinal Study of Parents and Children cohort.
We examined associations between confirmation of COVID-19 infection status (confirmed by a positive test vs unconfirmed) and reporting of Long COVID symptoms. We explored the roles of sex and anxiety as potential moderators.
There was no clear evidence of a strong association between confirmation of COVID-19 infection status and the Long COVID composite score, physical or psychological symptoms or duration of symptoms. There was no clear evidence of moderation by sex or anxiety. We therefore found no evidence of a nocebo effect. Our data suggest that this psychological mechanism does not play a role in the medical symptomatology experienced by patients with Long COVID.
Source: 1.
Macleod-Hall CI, Munafò MR, Dyer ML. Confirmation of COVID-19 infection status and reporting of Long COVID symptoms in a population-based birth cohort: No evidence of a nocebo effect. Journal of Health Psychology. 2024;0(0). doi:10.1177/13591053241228711 https://journals.sagepub.com/doi/10.1177/13591053241228711

A suffering body, hidden away from others: The experience of being long-term bedridden with severe myalgic encephalomyelitis/chronic fatigue syndrome in childhood and adolescence

Abstract:

In this article, we present findings from a qualitative study examining how young women experience being long-term bedridden with myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), during childhood and adolescence. The aim is to explore how young women who fell ill with ME/CFS during childhood and adolescence look back on their lived experience of being long-term bedridden from the vantage point of being fully or partially recovered.

Informed by a phenomenological theoretical perspective, the researchers applied a narrative methodological approach involving the analysis of interviews with 13 women, aged 16–29 years at the time of the interview. Attention was particularly paid to how participants structured their narratives and to the events (telling moments) they identified as important.

Four major storylines were developed: Ambivalent responses to the presence of others; A body on the edge of life; An eternity in the dark; and Recasting painful memories of being bedridden and alone.

Based on our findings, we argue that the experience of being long-term bedridden with ME/CFS during childhood and adolescence can be understood and communicated as a plot in which individuals find themselves pushed to the extreme limit of suffering and loneliness.

Source: Krabbe, S. H., Bjorbækmo, W. S., Mengshoel, A. M., Sveen, U., & Groven, K. S. (2024). A suffering body, hidden away from others: The experience of being long-term bedridden with severe myalgic encephalomyelitis/chronic fatigue syndrome in childhood and adolescence. Nursing Inquiry, e12625. https://doi.org/10.1111/nin.12625 https://onlinelibrary.wiley.com/doi/10.1111/nin.12625 (Full text)

Chronic Fatigue Syndrome, Viruses and Related Conditions in Women: The Liver Link

Abstract:

Chronic Fatigue Syndrome (CFS) can be triggered by different factors and create a complex health situation. In the last decades incidence has been increasing. This situation is a clear example of how humans, viruses, and the environment are all connected.
In the 90s cases related to CFS, complaints about a feeling of chronic fatigue, inability for everyday tasks, dull pain, cephalalgia, de-pression, anxiety, poor concentration. Clinical tests for EBV, HHV, CMV, IgG, IgM, T4 and T8 subsets were tested, along with hormones and hemogram tests. Most of the cases were women. The timeline of the medical history showed also myomas, breast lumps, premenstrual syndrome previously to CFS development. The nature of these conditions promoted the idea of a possible common link among them and CFS. Some cases also suffered from allergies, food intolerances, candidiasis, intestinal impairment, thyroid implications, endometriosis.
As an initial working hypothesis, The Liver Link (TLL) was proposed in order to understand those different conditions affecting body, mind and emotional wellbeing. Considering liver implication can make a difference in treatment and recovery. Low grade inflammatory conditions are related to Th2 predominance and liver functions. Functional disharmonies are very important because they usually still do not appear in any conventional tests.
In 2002, TLL was presented as a framework to explain the concomitance of CFS and other conditions and the relationship with some viruses such as EBV, HHV, CMV, as a lecture in a congress at the University of Westminster (London). When SARS-CoV-2 outbroke, TLL helped to warn about the post-covid syndrome more likely to occur in specific individuals.
Source: Lorite-Ayán, N. Chronic Fatigue Syndrome, Viruses and Related Conditions in Women: The Liver Link. Preprints 2024, 2024011654. https://doi.org/10.20944/preprints202401.1654.v1 https://www.preprints.org/manuscript/202401.1654/v1 (Full text available as PDF file)

Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn’s Disease and chronic fatigue syndrome

Abstract:

Background: Patients with Crohn’s disease (CD) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) exhibit elevated antibody responses against gut microbiota flagellins. However, flagellin-specific antibody repertoires and functional roles in the diseases remain incompletely understood. Bacterial flagellins can be categorized into three types depending on their interaction with toll-like receptor 5 (TLR5): (1) “stimulator” and (2) “silent” flagellins, binding TLR5 through a conserved N-terminal motif, with only stimulators activating TLR5 due to a specific C-terminal domain; (3) “evader” flagellins of pathogens, which circumvent TLR5 activation via mutated N-terminal TLR5 binding motifs. Here we studied the characteristics, epitope binding, and sequence (dis)similarity of anti-flagellin antibody responses in CD and ME/CFS.
Methods: Since conventional antibody profiling methods like enzyme-linked immunosorbent assays [ELISAs] do not allow for large-scale measurements of antibody repertoires, we leveraged phage-display immunoprecipitation sequencing (PhIP-Seq) to characterize 344,000 rationally selected peptide antigens in 256 patients with CD, 40 patients with ME/CFS and in two equally sized groups of age- and sex-matched healthy controls from population-based cohorts in the Netherlands and U.K., respectively. Different sequence alignment strategies were employed to compare flagellin peptide structures with observed antibody-bound flagellin peptide reactivity.
Results: Both patients with CD and ME/CFS exhibited elevated antibody responses against distinct regions of flagellin peptides compared to healthy individuals (P<0.001). N-terminal binding to Lachnospiraceae flagellins was comparable in both diseases, while C-terminal binding was more prevalent in CD. N-terminal antibody-bound flagellin sequences were similar across CD and ME/CFS, resembling ‘stimulator’ and ‘silent’ flagellins more than evaders. However, C-terminal antibody-bound flagellins showed higher resemblance to stimulator than to silent flagellins in CD, but not in ME/CFS. This group of antibody-bound flagellins was exclusively identified in a subset (10-20%) of patients with CD and characterized by its strong overrepresentation (exceeding 20-fold), underscoring its potential significance in distinguishing pathophysiologic subtypes of CD.
Conclusion: Antibody binding to the N-terminal domain of stimulator and silent flagellins may impact TLR5 activation in both CD and ME/CFS patients. Furthermore, elevated antibody binding to the C-terminal domain of stimulator flagellins in CD may explain pathophysiological differences between diseases. Our results highlight the diagnostic potential of these antibody responses and their impact on innate/adaptive immunity balance.

Source: A R Bourgonje, N V Hörstke, M Fehringer, G Innocenti, T Vogl, DOP27 Systemic antibody responses against gut microbiota flagellins implicate shared and divergent immune reactivity in Crohn’s Disease and chronic fatigue syndrome, Journal of Crohn’s and Colitis, Volume 18, Issue Supplement_1, January 2024, Page i122, https://doi.org/10.1093/ecco-jcc/jjad212.0067 https://academic.oup.com/ecco-jcc/article/18/Supplement_1/i122/7586226 (Full text available as PDF file)

Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS

Abstract:

Post-COVID Syndrome (PCS) refers to a diverse array of symptoms that persist beyond 3 months of the acute phase of a SARS-CoV-2 infection. The most frequent symptom is fatigue, which can manifest both mentally and physically. In this study, handgrip strength (HGS) parameters were determined as an objective measure of muscle fatigue and fatigability. HGS parameters were correlated with other frequent symptoms among 144 female PCS patients suffering from fatigue, exertional intolerance, and cognitive impairment.

Seventy-eight patients met the Canadian Consensus Criteria (CCC) for post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The severity of disability and key symptoms were evaluated utilizing self-reported questionnaires.

Notably, patients diagnosed with ME/CFS exhibited a higher overall severity of symptoms, including lower physical function (p < 0.001), a greater degree of disability (p < 0.001), more severe fatigue (p < 0.001), post-exertional malaise (p < 0.001), and autonomic dysfunction (p = 0.004). While HGS was similarly impaired in both PCS and ME/CFS patients, the associations between HGS and the severity of symptoms and disability revealed striking differences.

We observed significant correlations of HGS parameters with physical function across all patients, but with the key symptoms PEM, fatigue, cognitive impairment, and autonomic dysfunction in ME/CFS patients only. This points to a common mechanism for these symptoms in the ME/CFS subtype, distinct from that in other types of PCS. Further HGS provides an objective marker of disease severity in ME/CFS.

Source: Anna Paffrath, Laura Kim, Claudia Kedor, Elisa Stein, Rebekka Rust, Helma Freitag, Uta Hoppmann, Leif G Hanitsch, Judith Bellmann-Strobl, Kirsten Wittke, Carmen Scheibenbogen, Franziska Sotzny. Repeated Hand Grip Strength is an Objective Marker for Disability and Severity of Key Symptoms in Post-COVID ME/CFS.
medRxiv 2024.01.25.24301776;  https://www.medrxiv.org/content/10.1101/2024.01.25.24301776v1 (Full text available as PDF file)

Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms

Abstract:

Purpose: Treatments for myalgic encephalomyelitis and chronic fatigue syndrome can be adapted for post-COVID-19 condition. Our aim was to compare treatments in patients from our post-COVID-19 clinic.

Methods: We conducted a retrospective cohort study and included consecutive patients enrolled in our post-COVID-19 clinic. We included patients who received low-dose naltrexone, amitriptyline, duloxetine, and physical therapy, and evaluated improvements in fatigue, pain, dyspnea, and brain fog recorded in the electronic health record. We calculated the adjusted relative hazard of improvement using Cox proportional models. We adjusted for demographic characteristics, comorbidities, and prior COVID-19 hospitalization.

Findings: We included the first 108 patients with post-COVID-19 enrolled in the clinic. Most of the patients received amitriptyline. The relative hazard of improvement for those taking low-dose naltrexone was 5.04 (95% CI, 1.22-20.77; P = 0.02) compared with physical therapy alone. Both fatigue and pain were improved in patients taking low-dose naltrexone; only fatigue was improved in patients taking amitriptyline.

Implications: Post-COVID-19 condition symptoms may improve in patients taking medications adapted from myalgic encephalomyelitis and chronic fatigue syndrome. Randomized controlled trials should evaluate these medications and translational studies should further evaluate their mechanisms of action.

Source: Tamariz L, Bast E, Klimas N, Palacio A. Low-Dose Naltrexone Improves post-COVID-19 condition Symptoms. Clin Ther. 2024 Jan 23:S0149-2918(24)00003-1. doi: 10.1016/j.clinthera.2023.12.009. Epub ahead of print. PMID: 38267326. https://pubmed.ncbi.nlm.nih.gov/38267326/