Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a highly debilitating disease with heterogeneous constitutional and neurological complaints. Infection-like symptoms often herald disease onset, but no pathogen or immune defect has been conclusively linked.
In this issue of the JCI, Mandarano et al. illuminate bioenergetic derangements of ME/CFS T cell subsets. CD4+ and CD8+ T cells had impaired resting glycolysis. CD8+ cells additionally showed activation-related metabolic remodeling deficits and decreased mitochondrial membrane potential; a subset had increased resting mitochondrial mass.
Immune senescence and exhaustion paradigms offer only partial explanations. Hence, unique mechanisms of disrupted immunometabolism may underlie the complex neuroimmune dysfunction of ME/CFS.
Cardiff University medical student Emilia Allwright tells us about her research project:
In October 2019, I presented a poster for my project at the National RCGP conference. This was a wonderful opportunity to highlight ME/CFS and hopefully lead to changes in care.
As part of my medical degree, in Spring 2019, I spent 6 weeks looking at ‘TheRole of the GP in caring for patients with ME/CFS’.
I was touched by the response of the ME/CFS community and so grateful to WAMES for helping me to find participants.
I was able to complete 10 telephone interviews- each participant shared their personal story which provided an amazing volume of data to use.
I went through each interview and identified key ideas and themes that formed my results:
Patients would appreciate having a single healthcare practitioner who would offer consistent care
All but one participant had experienced feeling dismissed by a GP
There were examples of positive relationships with GPs where both the patient and GP benefited through working together, but also where relationships had broken down
“They just need to be honest and kind and respectful and together we’ll figure out what the best way forward is.”
“You hope to have a supportive GP because he will help you, even if he can’t treat you, he will help you.”
“And I just found it too upsetting to keep going because nothing was happening.”
“He’s just been sympathetic to what I’m going through which is a big thing.”
Conclusion:
Overall, my results emphasised the idea that a supportive GP who is honest and open with patients can make a significant impact, regardless of their ability to cure the patient.
What do people with ME need to know about Covid-19 and self-isolating? updated 10 April 2020
The Health Minister for Wales has confirmed that people over 70 and people with a range of health conditions, including neurological conditions, should self-isolate. People with a cough and/or high temperature are asked to self isolate for 7 days. Those who have had contact with someone with confirmed Covid-19 should self-isolate for 14 days. Everybody should stay at home except for essential shopping, short daily exercise a day, essential medical needs, travelling to and from essential work, but only where this cannot be done from home. Social distancing is required by all people when outside the home.
Many people with ME have been self-isolating to some extent for years, because they have been too ill to mix with others. They will be practised in ensuring they have enough food, cleaning products, personal care items, ‘distractions’ and medications, but the coronavirus Covid-19 poses some extra problems and questions.
Much is still not known about this new virus, but some clues are emerging from US research and from the badly affected countries of China and Italy.
People don’t have to have symptoms to be infectious
symptoms appear 2-14 days after infection
infection can last weeks, up to 37 days (China)
people can be infectious before & after symptoms are apparent, or without symptoms
it is uncertain how many have no obvious symptoms and are spreading the virus
no symptoms doesn’t necessarily mean less able to spread the virus
Regular flu has similar symptoms to COVID-19. However, COVID-19 is more likely to cause shortness of breath and other respiratory symptoms. Some people have only mild symptoms while others are very ill and struggle to breathe.
Early indications in China and Italy was that the majority of people who died were over 60 with certain underlying health conditions, (but anyone can catch and pass on the virus):
heart disease
diabetes
hypertension – high blood pressure
chronic lung disease
some cancers
It has now become clear that younger people with no known health conditions can also be at risk.
It is unknown to what extent people with ME are at greater risk but Dr Nancy Klimas believes we could be, as ‘one of the underlying problems is that the cells protecting you against viruses are less functional because overworked.’ Dr Charles Shepherd says: ‘an infection such as this will almost certainly cause a relapse, or significant exacerbation of symptoms’.
Public health England’s updated list of those at risk & requiring social distancing, which includes Neurological Conditions, the obese and pregnant women.
What distance is safe when social distancing?
It may not be possible to avoid close contact with people giving you care, or for whom you care, but all sources say where possible stay 2 metres or 6 feet away from other people. If people are moving (cyclists or runners) it may be wise to stay up to 10m away. Face masks won’t stop you catching the virus, but they may reduce the likelihood of passing it on to others.
Prof Hugh Pennington adds: “This virus needs 15 minutes of close contact with someone carrying it for you to have a reasonable chance of contracting it…But if someone who is infected coughs or sneezes on you directly then the droplets can infect you — that will be a much higher risk.”
How long does it last on surfaces?
When self isolating we will need to receive post, groceries etc. Are they safe? US researchers measured how long the virus stays active on various surfaces:
up to 24 hours on cardboard
up to 2 or 3 days on plastic and stainless steel.
it remained viable in aerosols—attached to particles that stay aloft in the air—for up to 3 hours.
Accept goods from outside, then put away perishables without contaminating other items. Either thoroughly wash the outside of the items or leave them until they are safe to touch. Wash your hands and don’t touch your face!!
Can you become re-infected?
it is uncertain if or how long immunity lasts
it appears to be possible to relapse, though numbers are small
there are 2 variations of the virus and potentially it could mutate, though probably unlikely
in some countries testing for the presence of the virus may not be reliable so people only think they have recovered
most people recover but some experience reduced lung function following recovery, which will require some rehab
The UK is stepping up testing of frontline workers but still only wants to test those whose symptoms become serious due to shortage of tests – if experiencing severe symptoms ring 111 anywhere in Wales. (Don’t press any numbers, just hold to be connected to NHS Wales, rather than NHS England)
Information on what it means to self-isolate in your home, or in a room within your home can be found on the UK Government website. Increasingly local support schemes are being set up by concerned citizens to make it possible for people to self-isolate, even when they don’t have friends or family nearby, or access to online deliveries.
For info about how to get or give support, find your COVID-19 Facebook support group here Some Council & AVO websites list local sources of help and delivery services. Age Cymru and RVS provide support.
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is prevalent (1%–2%) in adolescents and nearly two-thirds of patients report moderate or severe pain
Pain is associated with worse fatigue and poorer physical function in adolescents with CFS/ME.
What this study adds?
Despite the prevalence and impact of pain in children with CFS/ME few treatment studies have measured pain as an outcome and no interventions targeted pain.
There is insufficient evidence to suggest that the treatment of fatigue also improves pain in paediatric CFS/ME.
Patients who recover from CFS/ME appear to have less pain at follow-up than those who do not recover.
Research abstract:
Background Paediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is common (prevalence 1%-2%). Two-thirds of children experience moderate or severe pain, which is associated with increased fatigue and poorer physical function. However, we do not know if treatment for CFS/ME improves pain.
Objective
Identify whether specialist treatment of paediatric CFS/ME improves pain.
Methods
We conducted a detailed search in MEDLINE, EMBASE, PsycINFO and the Cochrane Library. Two researchers independently screened texts published between 1994 and 24 January 2019 with no language restrictions. Inclusion criteria were (1) randomised controlled trials and observational studies; (2) participants aged <19 years with CFS/ME; and (3) measure of pain before and after an intervention.
Results
Of 1898 papers screened, 26 studies investigated treatment for paediatric CFS/ME, 19 of which did not measure pain at any time point. Only five treatment studies measured pain at baseline and follow-up and were included in this review. None of the interventions were
specifically targeted at treating pain. Of the included studies, two showed no improvement in pain scores, one suggested an improvement in one subgroup and two studies identified improvements in pain measures in ‘recovered’ patients compared with ‘non-recovered’ patients.
Conclusions
Despite the prevalence and impact of pain in children with CFS/ME surprisingly few treatment studies measured pain. In those that did measure pain, the treatments used focused on overall management of CFS/ME and we identified no treatments that were targeted specifically at managing pain. There is limited evidence that treatment helps improve pain scores. However, patients who recover appear to have less pain than those who do not recover. More studies are needed to determine if pain in paediatric CFS/ME requires a specific treatment approach, with a particular focus on patients who do not recover following initial treatment.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling multisystem chronic disease. The etiology and pathogenesis of ME/CFS are unknown. Infections of cytomegalovirus (CMV), Epstein‐Barr virus (EBV) and human herpesvirus‐6 (HHV‐6) are suspected as etiological agents for ME/CFS.
This study aims to estimate prevalence and type (active/latent) of EBV, CMV and HHV‐6 infections in Bulgarian ME/CFS patients. In the study were included 58 ME/CFS patients and 50 healthy controls.
Virus‐specific antibodies were detected by ELISA and viral genomic sequences in PBMCs and plasma samples ‐ by nPCR. We did not observe any significant differences in virus specific IgG and IgM positivity rates between ME/CFS patients and control group. In ME/CFS plasma samples EBV DNA was found in 24.1%, CMV DNA – in 3.4% and HHV‐6 DNA in 1.7% of samples. EBV DNA was detected in 4%, CMV and HHV‐6 DNA were not found in plasma samples of controls.
The frequency of viral genome detection in PBMCs of patients and controls was 74% vs 78% for CMV, 81% vs 84% for EBV, and 82.8% vs 82% for HHV‐6. The difference in frequency of EBV active infection in ME/CFS and control group was statistically significant (p=0.0027). No ME/CFS and control individuals with active CMV and HHV‐6 infection were observed.
In conclusion, our study using both serological and PCR‐based techniques for distinguishing between active and latent infection, showed high rate of active EBV infection among ME/CFS patients indicating that at least in a subset of cases EBV is important factor for development of disease.
From IBS to ME – The dysbiotic march hypothesis, by Arnold Berstad, Olav Hauso, Ketil Berstad, Johanna ER Berstad in Medical Hypotheses Vol 140, July 2020, 109648 [https://doi.org/10.1016/j.mehy.2020.109648]
Research abstract:
Irritable bowel syndrome (IBS) is often associated with other unexplained complaints like chronic fatigue syndrome (CFS), fibromyalgia and myalgic encephalopathy (ME). The pathogenesis of the relationship is unknown.
Intestinal dysbiosis may be a common abnormality, but based on 1100 consecutive IBS patients examined over a nine years period, we hypothesize that the development of the disease, often from IBS to ME, actually manifests a “dysbiotic march”.
In analogy with “the atopic march” in allergic diseases, we suggest “a dysbiotic march” in IBS; initiated by extensive use of antibiotics during childhood, often before school age. Various abdominal complaints including IBS may develop soon thereafter, while systemic symptom like CFS, fibromyalgia and ME may appear years later.
Conclusion:
The main findings among 1100 consecutive patients with IBS are an extensive past medical history (on average 26 years), during which 80%–90% of the patients, in addition to IBS, developed joint/muscle pain and chronic fatigue, and 65% developed ME. The vast majority of the 200 patients (86%) who were asked, reported extensive treatment with antibiotics during childhood. The observations suggest that IBS and subsequent comorbidities represent “a dysbiotic march” in response to antibiotic-induced “missing microbes”
Hence, our hypothesis is that «the dysbiotic march” begins with antibiotic-induced “missing microbes”, via abdominal discomfort, food intolerance and IBS, then years later, joint/muscle pain and chronic fatigue may develop and ultimately progress to ME. The progress of the disease, i.e. the march from IBS to ME, may well be due to new microbes or other infectious agents invading and conquering the biofilm to exploit its growth conditions.
Patients with chronic fatigue have often difficulties to perform a maximal exercise test.
Maximal handgrip strength was used to predict maximal exercise performance.
We explored 98 severely fatigued patients, 66 of them with chronic fatigue syndrome.
Handgrip strength was correlated with peak values of oxygen uptake and work rate.
Thus, handgrip strength is helpful when an ergometric cycle test cannot be performed.
Research abstract:
Background: Maximal handgrip strength is used to predict exercise performance in healthy older subjects and in patients with chronic obstructive pulmonary disease, breast cancer or cirrhosis. Our objective was to evaluate the ability of maximal handgrip strength to predict maximal exercise performance in patients with chronic fatigue.
Methods: Sixty-six patients with myalgic encephalomyelitis/chronic fatigue syndrome and 32 patients with chronic fatigue but no diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome were included. The maximal physical performance was measured on a cycle ergometer to measure the peak oxygen uptake and the maximal work rate. We searched for linear regressions between maximal handgrip strength and maximal performances.
Findings:
No significant differences in slopes and ordinates of regression lines were noted between patients with or without a diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, allowing to pool the data. Maximal handgrip strength was significantly and positively correlated with peak oxygen uptake and maximal work rate in all patients with chronic fatigue.
Interpretation:
We conclude that handgrip strength can predict maximal exercise performance in patients with chronic fatigue.
Conclusion: when an ergometric cycle test cannot be easily performed, the simple, low cost MHGS measurement may be useful to evaluate the maximal physical performance of patients with chronic fatigue, including those with ME/CFS. However, in ME/CFS patients the sole MHGS measurement cannot replace the information given by a maximal exercise test that are the altered muscle membrane excitability and the associated increase in exercise induced oxidative stress. MHGS can be used as a screening tool for patients who need to undergo a maximal exercise test. The usefulness of MHGS in chronic fatigue possibly opens future ways of research.
Extracranial Doppler technique to measure cerebral blood flow is feasible during head-up tilt testing.
Cerebral blood flow in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients is reduced during head-up tilt testing compared to healthy volunteers.
Using a lower limit of normal of the cerebral blood flow reduction during head-up tilt testing of 13%, 90 percent of ME/CFS patients showed an abnormal cerebral blood flow reduction.
Reduction in cerebral blood flow is correlated with symptoms of orthostatic intolerance.
Research abstract:
Objective:
The underlying hypothesis in orthostatic intolerance (OI) syndromes is that symptoms are associated with cerebral blood flow (CBF) reduction. Indirect CBF measurements (transcranial Doppler flow velocities), provide inconsistent support of this hypothesis. The aim of the study was to measure CBF during a 30 min head-up tilt test (HUT), using
Doppler flow imaging of carotid and vertebral arteries, in individuals with chronic fatigue syndrome/myalgic encephalomyelitis (ME/CFS), a condition with a high prevalence of OI.
Methods:
429 ME/CFS patients were studied: 247 had a normal heart rate (HR) and blood pressure (BP) response to HUT, 62 had delayed orthostatic hypotension (dOH), and 120 had postural orthostatic tachycardia syndrome (POTS). We also studied 44 healthy controls (HC). CBF measurements were made at mid-tilt and end-tilt. Before mid-tilt, we
administered a verbal questionnaire to ascertain for 15 OI symptoms.
Results:
End-tilt CBF reduction was 7% in HC versus 26% in the overall ME/CFS group, 24% in patients with a normal HR/BP response, 28% in those with dOH, and 29% in POTS patients (all P<.0005). Using a lower limit of normal of 2SD of CBF reduction in HC (13% reduction), 82% of patients with normal HR/BP response, 98% with dOH and 100% with POTS showed an abnormal CBF reduction. There was a linear correlation of summed OI
symptoms with the degree of CBF reduction at mid-tilt (P<.0005).
Conclusions:
During HUT, extracranial Doppler measurements demonstrate that CBF is reduced in ME/CFS patients with POTS, dOH, and even in those without HR/BP abnormalities.
Significance:
This study shows that orthostatic intolerance symptoms are related to CBF reduction, and that the majority of ME/CFS patients (90%) show an abnormal cerebral flow reduction during orthostatic stress testing. This may have implications for the diagnosis and treatment of ME/CFS patients.
Background:
Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) has been emerging as a significant health issue worldwide. This study aimed to systemically assess the prevalence of CFS/ME in various aspects of analyses for precise assessment.
Methods: We systematically searched prevalence of CFS/ME from public databases from 1980 to December 2018. Data were extracted according to 7 categories for analysis: study participants, gender and age of the participants, case definition, diagnostic method, publication year, and country of the study conducted. Prevalence data were collected and counted individually for studies adopted various case definitions. We analyzed and estimated prevalence rates in various angles: average prevalence, pooled prevalence and meta-analysis of all studies.
Results:
A total of 1291 articles were initially identified, and 45 articles (46 studies, 56 prevalence data) were selected for this study. Total 1085,976 participants were enrolled from community-based survey (540,901) and primary care sites (545,075). The total average prevalence was 1.40 ± 1.57%, pooled prevalence 0.39%, and meta-analysis 0.68% [95% CI 0.48–0.97].
The prevalence rates were varied by enrolled participants (gender, study participants, and population group), case definitions and diagnostic methods. For example, in the meta-analysis; women (1.36% [95% CI 0.48–0.97]) vs. men (0.86% [95% CI 0.48–0.97]), community-based samples (0.76% [95% CI 0.53–1.10]) vs. primary care sites (0.63% [95% CI 0.37–1.10]), adults ≥ 18 years (0.65% [95% CI 0.43–0.99]) vs. children and adolescents < 18 years (0.55% [95% CI 0.22–1.35]), CDC-1994 (0.89% [95% CI 0.60–1.33]) vs. Holmes (0.17% [95% CI 0.06–0.49]), and interviews (1.14% [95% CI 0.76–1.72]) vs. physician diagnosis (0.09% [95% CI 0.05–0.13]), respectively.
Conclusions:
This study comprehensively estimated the prevalence of CFS/ME; 0.89% according to the most commonly used case definition CDC-1994, with women approximately 1.5 to 2 folds higher than men in all categories. However, we observed the prevalence rates are widely varied particularly by case definitions and diagnostic methods. An objective diagnostic tool is urgently required for rigorous assessment of the prevalence of CFS/ME.
What Do I Do?
As of today, there are no special recommendations for immune compromised people on how to avoid COVID-19 infection. Common sense suggests, though, that anyone with a compromised or wonky immune system should be extra careful. That includes people with ME or other immune illnesses, people over 65, people undergoing chemotherapy, etc. The good news is that you probably know at least one thing you can do to protect yourself from SARS-CoV-2 because you already know how to protect yourself from influenza, and the prevention measures are similar.
#1: Wash your hands.
Seriously, wash your hands. Use soap and water, and wash your hands for at least 20 seconds after using the bathroom or blowing your nose/sneezing. I also wash my hands before using a restroom in a public place. Edited to add: this is a fabulous video that demonstrates proper hand-washing technique. Wash your hands before eating. Wash your hands when you get home from a public place. If there is no soap and water available, use an alcohol-based sanitizer with at least 60% alcohol.
#2 Don’t touch your face.
If you are out in public, don’t touch your eyes, nose, or mouth. Once you start to pay attention to it, you will be amazed how many times you do this. But if you are in public–especially in a healthcare setting–don’t!
#3 Practice cough and sneeze etiquette.
Cough or sneeze into a tissue, and then throw the tissue away. Then wash or sanitize your hands. If you don’t have a tissue, try to cover your mouth with your elbow instead of your hand.
#4 Avoid sick (or potentially sick) people.
If someone you know is sick, especially with a respiratory illness, it’s better not to be in close contact with them. That can be hard if the sick person lives with you or is your carer, but try to minimize your exposure (and everybody should be washing their hands). It’s a good idea to avoid large numbers of people during flu season, if you can. Be especially careful to avoid coughing/sneezing people in healthcare settings. Don’t shake hands with people, either.
#5 Ask others to practice good hygiene/infection control.
People who visit you, live with you, or help care for you should all practice the same infection control measures. They should wash their hands upon entering your living space and before preparing your food. They should cough and sneeze into tissues, throw the tissues away, and then wash their hands. If they are sick–or if someone in their families is sick–then it is best for them to stay away. This is especially true for caregivers of severely ill ME patients. Caregivers must practice good hygiene and infection control measures.
#6 Sick people should wear masks.
CDC does not recommend that well people wear masks to protect themselves from SARS-CoV-2 (or influenza). However, people who are sick should wear masks to protect against infecting others. Note that commonly available surgical masks do not filter out most viruses because the particles are too small. The masks that are rated N95 or better will filter viruses, but they are hard to find (or the prices have been jacked up). N95 masks are also supposed to be fitted to the individual and then tested, and most people are not doing that.
#7 Have some supplies on hand, but don’t go crazy.
Some experts have recommended preparing the same way you would for a big storm: have nonperishable food and a two week supply of medications on hand. I wish one of them would tell my health insurance company that so I can actually get the two week supply ahead of schedule. Keeping easy to prepare food on hand is always a good idea for people with ME anyway, since we never know when a crash will make food shopping and prep impossible.
#8 Prepare for disruption of your routine.
I have personally found the angsting over quarantine to be a bit ableist, since millions of people with serious health conditions (including ME) are already living partially or entirely as if we are quarantined. Being told to stay at home is redundant for those of us that rarely leave it. However, restrictions on who can come to us, especially those who live alone and depend on outside help, would have a significant impact. Thinking through your backup plans in advance is a good idea. Can you get groceries delivered? What are your options for getting medications or other essential items if you can’t go out for a week or more? If the person/people who help you were unavailable, do you have backup help?
#9 Make a healthcare plan.
You may not be able to get to your doctor’s office easily even on a good day, if you have ME. If you are sick with an acute illness on top of ME, it will be even harder. Does your doctor offer any virtual services, such as video or phone consults? Make a plan with your primary care doctor or nearby urgent care so that you can get tested and treated if you have symptoms of any flu-like illness.
#10 Do not delay seeking healthcare.
Flu-like symptoms that might be of less concern in a healthy person can be very serious for people with ME, so consulting a healthcare provider should not be delayed if fever, cough, or congestion develop. The risk of complications is too high. In the past, I haven’t always bothered to call my doctor when I spiked a fever or had bad congestion. This year, I called my doctor the moment my temperature went up, and I was able to get treatment for suspected influenza that helped my recovery. If you get flu-like symptoms, call your doctor right away. Don’t wait and risk developing more severe illness.
#11 Stay informed, but in balance.
Use a reliable source to stay aware of developments in your area. You need to know if there are health advisories or local outbreaks that affect you. Once you have that information, though, stop. Unless you are a virus geek like me, the constant buzz of updates and breaking news may just wind you up. The bad weather analogy may be helpful here. You probably pay different levels of attention to storms that are 1,000 miles from you versus 100 miles versus 10 miles. The risk assessment for a viral outbreak is similar.
There is no way to virus-proof ourselves completely. However, if you follow these common sense public health recommendations, you will be better equipped to handle an infection if it comes. Do what you can to minimize disruptions to your routine. If you do get sick, take it seriously and seek healthcare.
