Act 1
An app based Covid-symptom study reveals 60,000 people in the UK are experiencing prolonged, excruciating symptoms for more than three months after acute Covid-19 infection. Pivotal to the recognition are the ‘Long Haulers’ themselves, courageously speaking out. And crucial to getting ahead are the relatively small group of scientists pioneering in post-viral ME/CFS research.
Surviving a virus can be the ‘beginning of the end’ as Paul Garner, infectious diseases specialist articulates in the BMJ, ‘Don’t try to dominate this virus, accommodate it.’ Professor Garner is one of our UK health professionals talking openly about his personal experience with Long Covid, the ‘illness resembling ME/CFS.’
After six months of persistent post-viral symptoms an ME/CFS diagnosis is heavily pencilled, if not penned.
After mulling over Garner’s judicious piece, I noted Matt Hancock our UK Health Secretary acted by putting almost £10m into research of the long-term effects following Covid-19. Despite driving research in the right direction in relation to post-viral debilitation, my cause for concern persists and does not bode well for Long Covid patients, nor does it look promising for those burdened with an ME/CFS diagnosis prior to this pandemic.
When I break down my TV scripts as an Actress, I often use a single word or sentence to sum up each “episode.” Act 1 is synopsised, “I am worried.”
I am worried for the Long Haulers inevitably left to navigate post-viral fatigue in the dark. Long Covid patients are dipping their toe into the sea of medical gaslighting which the ME/CFS community has endured for decades. And here is why I am on tender hooks. Current “management” for post-infectious illness is alarmingly constrained. I do not write accusatively. My intention is to be part of the solution and not part of the problem.
Who and what will ensure the proposed “Long Covid Clinics” are radically distinct from the “Chronic Fatigue Clinics” which have failed many post viral patients over the years? My agony breeds with perturbation. Should there be improvement in regard to what is offered to post-viral patients affected by Covid-19 will the people who have been left disabled by other types of viral infection before 2020 be included? If so, how? I want to protect, validate and guide those who will inevitably struggle with this diagnosis. The two communities, Long Covid and ME/CFS, must unite sooner rather than later, for there is strength in numbers.
As projections develop into reality it is evident that whilst Covid-19 is a new virus, severe post-viral complications are not new. ‘Covid-Fatigue’ is proving no exception to the rule; viral infection can trigger long-term complications with the haunting capability to avalanche into a lifetime of ill health, for a significant portion of people.
A Producer is 'a person responsible for the financial and managerial aspects of the making of a film or broadcast or for staging a play, opera, etc.' And a Director is ‘a person who supervises the actors and the other staff in a film, play or similar production.’ Post viral damage will have a radical sweeping effect on our citizens and economy for years, not just months. It is currently deprived of appropriate supervision, management and funding. Who is directing this tragedy?
Covid-19 basks centre stage, Long Covid accrues in the wings and ME/CFS skulks backstage.
With no unified biomarker we must be mindful as to how we deal with the clinical problems and cautious to which labels we commit, agreed, but labels aside; we are talking about individuals; mothers, brothers, aunties, uncles, children. Some of our loved ones lucky enough to survive this virus may never be able to return to full health and the number is set to increase.
Determined to adhere to helping us push forward with the proper scientific research for post-viral debilitation, ‘Long Covid’ plagues the forefront of my mind as do the millions missing with ME/CFS. An open and honest dialogue regarding how the medical community have mishandled post-viral fatigue, ME/CFS to date is on the cards. And if 'accountability' is not possible then for now what is most important, is for us to listen and to learn.
Listen to the people who are debilitated with Long Covid. And learn from those disabled by ME/CFS. Everyone has their story. Many of the answers are here, within our public, who are far too regularly underestimated and dismissed. My focus is on the handful of innovative scientists and specialists to date who have the potential to uncover that which has somehow managed to continually slip under the radar.
To assist this article in my attempt to bring my readers up to speed, I reached out to Neuroscientist Fellow Michael VanElzakker, Microbiologist Amy Proal, Autonomic Neurologist Dr Blitsheyn and molecular
virologist Bhupesh K Prusty; a special thanks to each for taking the time to talk to me.
I have a feverish indignation to teach that which needs to be taught. My extensive reading to date on this topic is broad, but it is nowhere near enough. Combined with a deeply personal experience with severe viral infection I am confident I can inform a greater audience with succour and precision. It’s time to bridge the gap between the medical community and those suffering.
Before you read Act 2, hang out here for a history lesson…
Act 2
In Vikings my character Judith, a dark ages Queen, uses leaches and compressed herbs to treat her dying son, King Alfred. Are some of the ways in which we assess (and manage) patients with post-viral chronic illness in 2020 as steadfast and dependable as this archaic methodology I was scripted to use on set? A spooky concept considering we are in a pandemic driven by viral infection. I am being facetious, but my point holds weight.
There are two words I choose to define Act 2, “Catch up.”
Microbiologist Amy Proal supports some of my rationale, ‘often the pathogen that starts a post-viral syndrome does not seem to clear from all body sites (even if it is no longer in blood it may still be found elsewhere) for example in Post-Ebola syndrome the Ebola virus was found capable of persisting for years in breast milk and semen.’
Proal further enlightens me with a study which shows the ‘Zika virus could persist in the cerebrospinal fluid (CSF) and lymph nodes of infected rhesus monkeys for months after it has cleared from the blood and urine.’ And furthermore highlights ‘persistent coronaviruses have been found in the brains of MS patients.’
Surely we must investigate beyond the common blood test before deeming a patient clear of the virus, if the virus itself could be persisting in tissues? Also if an infectious agent persists, is the term “post” viral entirely accurate? Further investigation is incongruously curbed and ‘persistent infection’ overlooked. For a medical community so pernickety when it comes to labelling, this is a slap dash approach to ‘branding.'
Proal expresses passionately that she (like me) is determined to change things and is interested to see, ‘if the pathogens connected to post-viral syndromes can persist in the central nervous system/tissues of certain patients.’ The persistence of infection in the central nervous system and the tissues of certain patients is something which has fascinated me for a while in relation to post-viral-fatigue, ME/CFS, and now Long Covid too.
Proal made me aware of an article emphasising, ‘the coronavirus that causes COVID-19 can sometimes hijack brain cells, using the cells' internal machinery to copy itself, according to a new study.’
For further reading here it is - https://www.livescience.com/brain-invasion-coronavirus.html
One important clarification about the aforementioned article is that ALL viruses do exactly this; they hijack host cells and use their machinery to copy themselves. It's how viruses work! Viruses and their ability to infect the brain is another personal topic of interest. And Neuroscientist Michael VanElzakker accentuates, ‘it's important and valuable to study the severity of infection - viral load plus what tissues within the body were penetrated by the virus.’
Both Proal and VanElzakker agree more specifically that single cell sequencing has huge potential. Talking to Proal and VanElzakker boosted my confidence that the cogs are turning across the pond and one day we will most definitely see the results with minds like theirs on side.
For longitudinal studies VanElzakker explains that you can pick one particular cell type and follow how it changes its activity over time. Talking about post-viral fatigue syndrome on a cellular level excites me because it brings us closer to the truth. Every time I get a script for a character I try to find the truth at the core of each scene. And I suppose my search for what's real bleeds into the way I observe chronic illness and infection.
Proal adds ‘I would like to use single cell TCR sequencing to see if T cells that activate in response to COVID-19 continue to stay active towards the virus in the cerebrospinal fluid of patients who develop Long Covid symptoms. The goal would be to test the possibility that in such patients, the virus may have cleared from the blood/lungs, but is able to persist in the central nervous system in a latent state where it can drive chronic symptoms.’
On the subject of Covid-19 in particular, Proal is currently in discussion with some teams about ‘studying how, if a patient already has Epstein Barr virus, Borrelia, or other persistent pathogens, that could change the way their immune systems are able to respond to COVID-19 in a way that could contribute to the development of some Long Covid cases.’ This ties into the conversation I had with Bhupesh K Prusty.
‘There are no small parts,’ and metaphorically speaking, there are other characters (viruses!) which may very well contribute to the bigger picture in relation to post-viral debilitation.
The Epstein Barr Virus (just as an example) has an ostensibly parallel capacity to floor it’s host with long-term post-viral fatigue (and a multitude of other symptoms) for months and in some cases years; fatigue, nausea, heart palpitations, breathlessness, digestive issues and post-exertional malaise, to name a few. These persistent (and unforgiving) symptoms might sound all too familiar to many Long Covid patients?
There are several other viruses I could mention which cause similar long-term issues, but it was my curiosity enveloping EBV which lead me to write to Molecular Virologist Dr Bhupesh K Prusty.
Prusty is interested in understanding the pathology of viruses like HHV-6, HHV-7 and other herpesviruses. HHV-6 and HHV-7 (like EBV) are common viruses which more often than not lay latent in the majority of us. These are viruses which ‘can reactivate under various types of stress including other pathogenic infections.’ Much of the time they reactivate and you are not even aware of it, other times you can fall quite seriously ill.
Every person is different and it is not all about the “survival of the fittest” when it comes to your body’s unique reaction to Covid-19, or any virus. Too much pressure is placed upon people to recover and get back to normality or work when something rather sinister could still be very much at play.
Now this is where the conversation vamped up a notch, correlating with Proal, Prusty said – ‘It is very much possible that SARS-Cov-2 infection directly or indirectly reactivate these viruses. They are highly neurotropic.’ This means they have a propensity to attack the human nervous system, ‘No wonder Long Covid patients share several clinical features with ME/CFS,’ he added.
It appears that other persistent pathogens, the nervous system and ME/CFS are forming an ensemble in our musical; a risky string quartet. Let’s call this stage drama, ‘The Pandemic And Me.’
To summarise, a person could fall sick with the Covid-19 infection, mild or severe, and it could in turn trigger the reactivation of other viruses which already lay latent in the body. This is a daunting concept. And the plot thickens.
Prusty is actually working with Covid-19 live in his laboratory in Germany. He kindly further explained, ‘under normal circumstances our immune system senses these viruses (HHV-6/HHV-7) and gets rid of these reactivation events after some time and then comes back to normalcy. But in some individuals the immune system remains active and senses the threat continuously.’
Be magnanimous if someone is unable to get back to full health for a long time after acute infection of Covid-19 or any virus for we have still got a lot to learn about post-viral fatigue and viral infection. As I fall deeper down the rabbit hole into the science behind infectious disease, I am reminded that there is a continual and complex interaction happening within us all and it’s this extraordinary and delicate balance which is almost absurd to attempt to contemplate once you begin to grasp it’s intricacies and workings of the human body.
Prusty went on to explain the role of the mitochondria in some patients who struggle to deactivate HHV-6/HHV-7. The function and metabolism of the mitochondria is altered and produces less energy. I took a moment to visualise the powerhouse of the cell under constant stress; the word ‘post-viral fatigue’ does not mean ‘tired’ in the way in which a healthy host might feel reduced, sleep and then feel better. As we near the end of Act 2, allow me to dig just a tad deeper, into some of the science behind the incapacitating ‘fatigue.’
Prusty spoke of a protein called C1q, which is part of the innate immune system and helps with the clearance of apoptotic cells by macrophages. Macrophages assist us to clear the dying and dead cells. This process is essential when we have a viral infection because it is a method used to eliminate virus-infected cells. C1q is also a protein which naturally depletes when a person does any form of physical exercise.
‘Interestingly… some of the EBV peptides can mimic C1q,’ Prusty shares ‘We for the first time show that many ME/CFS patients have high anti-C1q antibody levels. We argue that these antibodies might be a key feature of mitochondrial dysfunction in ME/CFS.’ This new evidence explains why a person with ME/CFS may find themselves in a critical state after exertion; diminished, bedridden, housebound. In Act 3 I will further explain the complexity of post-exertional malaise.
If the C1q is already lowered due to the anti-bodies/mimicry, then ‘exercise’ and arguably any exertion added to the lowering of the protein C1q could tip a ‘post-viral’ and/or actively infected patient over the edge.
Many people reading this will likely have experienced a certain level of ‘viral fatigue’ due to being infected with the common flu? Imagine, for a moment, that this is continuous and perhaps even lifelong. Imagine, for a moment, that this persists intermittently, comes and goes in waves, for weeks, months, years, decades...
Act 3
‘THE SECRET OF CHANGE IS TO FOCUS ALL OF YOUR ENERGY NOT ON FIGHTING THE OLD BUT ON BUILDING THE NEW,’ an ME/CFS research tip from Socrates?
This old saying inspires the four words for my final act, ‘Build on the new.’
Focusing on the research we have to date here is an interesting discovery regarding post-viral patients and post-exertional malaise, PEM, associated with post-viral fatigue; Dr Systrom’s observation is that some people with ME/CFS have Preload Failure (PLF) and he's proved it. Systrom is a Cardiologist and practises pulmonary and critical care at Brigham and Women’s hospital. He also teaches at Harvard Medical School. Systrom is one of the few specialists looking deeply into the pathophysiology of Chronic Fatigue Syndrome.
I watched an interview a couple of years back now, which I highly recommend. All GP’s and Infectious Diseases specialists (at least) need to be aware of this trial.
The Open Medicine Foundation support the clinical trial to test the exercise response to Mestinon in people with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and I look forward to updating the progress.
‘PLF is thought to come from an imbalance in the autonomic nervous system and results in reduced filling of the heart during exertion. Prior studies have shown symptomatic improvement in patients with PLF after treatment with Mestinon. Dr. Systrom intends to evaluate the short-term effects of Mestinon on the autonomic nervous system and neurovascular control in people with ME / CFS with PLF.’
Although not a cure, Mestinon Pyridostigmine is one of the few drugs which could conceivably offer some respite moving forward.
Bringing us back onto Covid-19 and Long Covid specifically, Neuroscientist Fellow Micheal VanElzakker (who actually works closely with Systrom in Boston) highlights, ‘We've learned that the SARS-CoV-2 virus is capable of infecting the brain but we know less about important related questions like: to what extent are neurological symptoms during acute and long COVID due to the virus itself as opposed to inflammation or lack of oxygen, and whether the virus is capable of persisting in the brain even after the most acute symptoms have subsided.’
Long Covid patients who go on to get an ME/CFS diagnosis may find Dr. Systrom’s research encouraging and can be grateful to the likes of VanElzakker who is studying the effect of viral infection on the brain and the vagus nerve.
We will get there; patience is crucial and supporting our researchers is key. As https://polybio.org/ reassures us, ‘Complex chronic inflammatory diseases are not mysterious or hopeless.’ There are new tools which must be utilised to study ‘pathogen activity, environmental exposures, microbiome imbalances, neuroinflammation, gene changes, and other issues in patients with such conditions.’
Personally, I am entranced by the neurological side effects caused by viral infection. In the long run it is becoming apparent that a viral infection can trigger a process which damages other important cell types including neurons causing secondary complications.
And on the matter of secondary complications, I arranged a chat with Neurologist Dr. Blitshteyn who is the Director of Dysautonomia Clinic in the United States and who specialises in Autonomic Neurology. There is an understudied medical condition called Dysautonomia, which often occurs in conjunction with post viral syndrome.
As pieces of this mammoth puzzle are sprawled out, there are crossovers which I feel could potentially help a lot of the Long Covid patients to know about. And moreover, there is prospective relief available, which needs to be more easily accessible.
Something as simple as drinking the right amount of water to salt ratio to increase blood volume might even bring a portion of patients enough to relief to get through a day with a better quality of life, but frustratingly most GP’s would not know this to advise! Cort Johnson writes an extremely informative article further explaining.
https://www.healthrising.org/blog/2020/09/15/saline-ors-oral-rehydration-pots-chronic-fatigue-syndrome/
And the skinny on compression stockings - thank you Cort!
‘Pharmalogical treatment options are available for patients’ Dr Blitzsheyn fortifies, ‘but it is important to individualise treatment, based on each case.’ Dr Blitshteyn expressed that off the back of Long Covid she is receiving a number of new patients with Dysautonomia (an umbrella term) and more specifically the common one, POTS ; postural orthostatic tachycardia syndrome.
The investigation behind a POTS diagnosis directly involves the heart rate and blood pressure, which can be measured by a tilt-table test of a 10-minute stand up test . Thankfully, because POTS is an objective diagnosis, this means that the medical community tend to take the diagnosis of POTS more seriously than an ME/CFS label alone. Disturbing, but true.
Orthostatic Intolerance is a hallmark of disorders of the autonomic nervous system which often crosses over with an ME/CFS diagnosis after viral infection. It is extremely debilitating because it directly affects a person’s ability to remain upright.
If you are suffering with Long Covid and would like more information on POTS, here’s a helpful link - https://www.potsuk.org/
Dr. Blitshteyn is one of the few specialist pioneering in this area. ‘Persistent dizziness, fatigue, exercise intolerance, headaches, nausea, sleep disturbance and difficulty concentrating,’ are just some of the symptoms of Dysautonomia Dr. Blitshteyn hears on a daily basis when patients come to her. When the vitals are taken supine and standing, the evidence becomes clear-cut that an abnormal increase in heart rate and sometimes a significant drop in blood pressure is the culprit of some of the disabling symptoms which are holding the person back from having a decent quality of life.
I particularly liked Dr. Blitshteyn’s attention to the ‘non- cardiovascular’ symptoms, such as the nausea, orthostatic neck pain, heavy legs, numbness and tingling. Anything that is positional where lying down relieves the symptoms should not be ignored.
To suitably manage post-viral illness, Long Covid and ME/CFS, we urgently need to FUND THE SCIENCE. And while we wait, we should be putting together a team of well-informed specialists for those affected. But as Systrom said, getting the specialists to communicate can be like ‘herding cats.’ I am the eldest girl of seven kids and herding cats sounds like the kind of challenge I would actually like to take on…
In an ideal world the proposed 'Long Covid Clinics' would do better to be called 'Post Viral & Post Trauma Clinics' with subsets, depending on what triggered the chronic debilitation. To individualise treatment for the disability associated with post viral complications it might be useful to include - a Cardiologist, an Autonomic Neurologist, an Infectious Diseases doctor, Virologist and Rheumatologist. This is a convoluted chronic disease which needs to be treated and acknowledged as such.
It is clear the body is not functioning as it should after infection and it is evident that one cannot ‘talk’ or ‘exercise’ the body’s cells to respond or reactivate accordingly.
But while the science catches up, we can utilise and redefine our post-viral management tools.
An appropriate person with an up to date education on post-viral debilitation should to be appointed to offer guidance on ‘Pacing’ using the ME/CFS literature. In the same way a Cancer patient is offered CBT to help cope with the brutality of the diagnosis, we must provide support for the patient (and their family members) to help them deal with the monstrosity and management of this long-term physical illness.
A Physiotherapist (with knowledge on post-viral illness specifically) might be useful to eventual begin to rehabilitate a post-viral patient but only when the timing is right and only in conjunction with ongoing investigations. Timing is absolutely critical. Each post-viral patient very much needs to be treated as individual with the understanding that there is likely something sinister at play which we do not know enough about, yet.
Restoring movement and strengthening a post-viral patient with the guidance of an expert will most likely need to be within the comfort of their own bed at home, at least initially. There cannot and there must not be an unhealthy focus on ‘exercise’ or any form of cardio before the focus on daily activity – such as reading, washing and taking telephone calls has been established and stabilised with consistency. As far-fetched as this may sound to a healthy person, this is the world of chronic fatigue for some people. And I can promise you that the level of disability can reach a point where even these suggestions are too much, physically and mentally.
First and foremost, rest and more rest. Rest and pace and do not push!
Additionally an MRI scan, a tilt table test or a 10-minute stand test for many patients with ongoing neurological symptoms following infection could prove beneficial but we must educate the medic looking at the results to ensure we do not miss anything obvious - let’s save the science behind the brain stem and viral infection for the grand finale shall we?
And once again, I stress, there will be some people who cannot even get to their hospital appointments. Whether mild, moderate, severe, consistent or inconsistent, ‘chronic fatigue syndrome’ and associated chronic illness is not to be taken lightly.
I do not want to overwhelm readers, but I do want to clarify that having a virus ain’t always as simple as catch a cold, get over it and carry on for some individuals.
My article in May pre-warned about post-viral fatigue and ME/CFS in relation to Covid-19 and I’d argue that the label is still being swept under the carpet but as we shuffle over the six month mark, it is time to stop pussy footing around and build on what we know, not debate on what we do not.
If a patient presents with cognitive disturbance after a viral infection, we must not be too quick to jump to a conclusion of anxiety or depression without further investigating.
‘Pathophysiology is not straightforward,’ Blitshteyn echoes. When the mechanisms are variable it is crucial to be well educated on the complexity. For example, ‘about 50% of patients with POTS have small fibre neuropathy, which should be looked for by the neurologist evaluating a patient with POTS”
Post-viral illness is like a spider’s web with different species of arachnoids making divergent patterns. When the right set of eyes stare on these forms for long enough, I am hoping that the answer might just pop out like some sort of optical illusion. I have always been a blind optimist. And nothing will change that for me.
As we creep towards the end of Act.3, there is one old cobweb which rises from the dead every now and then in relation to the longevity of illness. And that is the concept of ‘Deconditioning.’ Gratefully Blitshteyn and Systrom put this notion of 'Deconditioning' being the cause of Chronic Fatigue to sleep with science, ‘Could all these kids and adults with POTS/ME/CFS be simply deconditioned from being sick and bedridden for so long? We now know that’s not the answer. "Secondary deconditioning" may factor as consequences but is not the cause. A few years ago, an excellent study out of Harvard (invasive cardiopulmonary tests) showed specific abnormalities – low filling pressure in the right atrium rather than high filling pressure. High filling would be inherent to deconditioned, sedentary patients, according to Systrom’s research There’s something more going on.’ And in a nutshell Blitshteyn brings us full circle, complimenting Systrom’s work which I highlighted at the beginning of Act. 3.
It would be foolish not to mention secondary 'depression' which can end up as a consequence of any long-term illness, but again not the cause of ME/CFS. I have expressed in my earlier article(s) that it is absolutely essential to nurture mental health for everyone during these uncertain times and to some extent even more critical if you find yourself with a life altering disability like post-viral ME/CFS.
The way in which we can support the ME/CFS and Long Covid community is to educate, communicate and to continue to validate, without judgement. Loved ones (and Doctors) must have empathy and compassion when talking to a person who has to endure long-term post-viral disability. The physical complications can be vast, inexplainable and on-going. Post-viral illness is severe.
On a lighter note, I want to end my Act with applause and congratulations to Dr Chris Armstrong, PhD, who is studying the relationship between altered metabolism of nitrogen and ME/CFS! Dr Armstrong has recently been given a grant to further extend this research. The study of ‘metabolic features’ in general, confirm the biological truth of this complex and unjustly pilloried disease.
On the topic of metabolism, if you happen to have further interest in the science, have a read of this.
Someone else who cannot go without mention, is Ron Davis, PhD, professor of Biochemistry and Genetics and Director of the Stanford Genome Technology Center working day and night to offer a molecular-based diagnostic test for ME/CFS. This guy gets a standing ovation, without question. As does his son, Whitney Defoe, severely affected by ME/CFS and yet he somehow manages to continue to be a beacon of light and hope to us all.
Covid-19 will continue to bask centre stage but only for now, Long Covid will accrue in the wings but only for now and ME/CFS will skulk backstage but only for now.
‘This time shall pass.’
Here is a toast to Long Covid patients coming together with the ME/CFS community and to us finding a cure, once and for all.
*The above is based on conversations with medical experts, and a personal review and interpretation of dozens of websites that address the concept of pacing and rest for people suffering from chronic complex diseases such as ME/CFS and post-COVID.