Long COVID patients need scientific ambition, not defeatism
Post-viral illnesses have often been neglected by science. Insights into Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) show that this is the time to ramp up efforts.
- 13 February 2024
- 6 min read
- by Ravi Veriah Jacques , Kaelyn Lynch , Janna Moen , Chris Maddison
Long before 2020, governments and public health experts spent decades preparing for a pandemic along the lines of COVID-19. However, these models failed to anticipate that the virus would not only kill millions, but also trigger a wave of debilitating and disabling chronic illness, now known as Long COVID. Upwards of seven million Americans – including the four authors of this article – have fallen victim to this shadow pandemic, with half a million forced out of work.
Scientific efforts to understand Long COVID are still in their infancy. And yet some have proposed that biological investigations of Long COVID should be abandoned. Fifty years of research into a seemingly identical post-viral condition – myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) – have yielded little, so why would Long COVID be any different?
We must seize the grim opportunity Long COVID has presented us to finally untangle the biology behind the devastating chronic illnesses that infections can trigger.
This argument draws all the wrong lessons from the decades-long neglect of ME/CFS. Rather than give up, we must seize the grim opportunity Long COVID has presented us to finally untangle the biology behind the devastating chronic illnesses that infections can trigger.
Understanding Long COVID
Long COVID is no longer a medical mystery. Scientists around the world have already published hundreds of studies demonstrating fundamental biological changes in Long COVID patients.
Researchers have zeroed in on potential disease mechanisms. Autopsies and biopsies have revealed pieces of the SARS-CoV-2 virus stuck in the digestive tract and nervous system of both acute and Long COVID patients, suggesting that persistent viral infection could drive Long COVID symptoms. Animal models show that even mild COVID-19 infection induces long-lasting inflammation in the brain and nervous system. Other studies have implicated immune dysregulation following COVID-19 infection, finding self-targeted antibodies that could potentially drive autoimmunity.
This is all before the largest Long COVID research efforts get into full swing. The US National Institutes of Health-sponsored RECOVER initiative, funded to the tune of a billion dollars by Congress, has only just started publishing its key biomedical findings. Similar is true of research financed by the UK and German governments. The glacial pace of these initiatives has been deeply frustrating to patients who are desperate for treatments to emerge. But this is to be expected: science moves slowly. It often takes decades and billions in funding to piece apart complex conditions. Fifteen years passed between the first reported HIV case and the development of effective antiretrovirals in 1996, a straightforward intervention credited with saving millions of lives.
One of the great challenges facing Long COVID research is simply defining the condition. Long COVID is incredibly heterogenous, encompassing some 200-odd symptoms that vary significantly by patient. It overlaps with previously known infection-associated chronic conditions, including dysautonomia (autonomic nervous system dysfunction), mast-cell activation syndrome (an immune disorder), and most notably, ME/CFS, a highly debilitating disease that can be triggered by a number of different pathogens, such as Epstein-Barr Virus. SARS-CoV-2 appears particularly adept at inducing a similar constellation of symptoms – approximately half of Long COVID patients, but certainly far from all, meet the diagnostic criteria for ME/CFS.
Parallels with ME/CFS
Though Long COVID and ME/CFS share underlying mechanisms, from persistent immune activation to autonomic dysfunction, it's too early to discern the exact relationship between the two conditions.
Research into ME/CFS has been continually starved of funding. [It is] the most underfunded disease relative to its disease burden in the US, a pattern replicated across Europe.
Still, the human toll of ME/CFS is inarguable, with patients enduring extraordinary suffering. The disease is associated with a lower quality of life than almost any other medical condition, from renal failure to lung cancer. The most severely affected ME/CFS patients are left confined to their beds for years, with even the smallest daily activities leading to days or weeks of excruciating symptoms. There are still no effective treatments for ME/CFS, and once patients have been ill for more than three years, there's only a 5% chance of recovery.
Which begs the question: why, even before the pandemic, were approximately one million Americans left to live in this continual agony? The answer has more to do with decades of scientific and medical neglect than the nature of the disease itself.
Have you read?
Research into ME/CFS has been continually starved of funding. Prior to 2015, America's National Institutes for Health – the largest global bankroller of scientific research – allotted just US$ 5 million a year to ME/CFS. This has made it the most underfunded disease relative to its disease burden in the US, a pattern replicated across Europe.
This chronic underfunding has been compounded by a decades-long effort to dismiss the disease as psychological. While similar illnesses following viral infections have been reported for centuries, the name myalgic encephalomyelitis – which translates to painful inflammation of the head – was coined in the 1950s. Research articles reported neurological, endothelial and metabolic perturbations in these ME/CFS patients. The psychosomatic pushback began almost immediately, with a 1970 article in the British Medical Journal asserting that the London outbreak could be explained by "epidemic hysteria". The evidence? A "high attack rate in females compared with males".
This psychologisation persisted for decades. A biological basis for ME/CFS was dismissed by senior officials at the US Centers for Disease Control and Prevention (CDC), who successfully rebranded the disease as "chronic fatigue syndrome". Top scientists ensured ME/CFS was never assigned to an NIH institute and was instead delegated to the Office of Research on Women's Health, a division that does not directly fund or perform biomedical research.
Meanwhile, a group of psychiatrists in the UK began pushing a "biopsychosocial" model which held that the illness was perpetuated by "deconditioning and avoidance of activity". Their proposed treatments were graded exercise therapy alongside cognitive behavioural therapy to address "unhelpful cognitions" about the illness.
Shifting thinking
Over the past ten years, the psychosomatic argument has been largely discredited and debunked. The NIH, CDC and UK-based National Institute for Health and Care Excellence (NICE) have all reversed their previous positions, concluding based on overwhelming evidence that ME/CFS is biological. And yet, the decades of underfunding, institutional neglect and psychologisation have left lasting damage.
The emergence of Long COVID is an opportunity to right the wrongs of this history, to properly fund biomedical research into infection-associated chronic illnesses for the very first time. This research has significance well beyond Long COVID. Viruses are implicated in the development of some of humanity's most feared neurodegenerative diseases. A recent study demonstrated that the shingles vaccine helps prevent the development of dementia, while another large study found that infectious mononucleosis elevates the risk of developing multiple sclerosis by a factor of 32.
The medical establishment's failure to anticipate Long COVID signals that a paradigm shift is in the offing – for both science and sufferers. The last thing patients need and deserve is defeatism. Giving up at this early juncture would likely doom many Long COVID patients to the same fate ME/CFS sufferers have faced for decades: debilitating illness without end. We want our lives back, and the only path to that is scientific ambition.
Authors
Ravi Veriah Jacques; 2021 Schwarzman Scholar, Long COVID patient and advocate.
Kaelyn Lynch; journalist and documentary filmmaker, Long COVID patient and advocate.
Janna Moen, PhD; postdoctoral research scientist, Yale Department of Immunobiology; Long COVID patient and advocate.
Chris Maddison, PhD; Assistant Professor, University of Toronto Department of Computer Science; Long COVID patient and advocate.
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