Is Long COVID Really Chronic Fatigue Syndrome by Another Name?
Even after the World Health Organization declares the end of the global pandemic, COVID-19 will continue to cast a long shadow. By some estimates, nearly a third of people with a symptomatic infection still experience debilitating symptoms months later. Much about Post-Acute Sequelae of SARS-CoV-2 infection (PASC), the clinical term for what is commonly referred to as Long (or Long-haul) COVID, is unknown. However, one intriguing clue can be found in its similarity to myalgic encephalomyelitis, a disease also known as chronic fatigue syndrome or ME/CFS.
Mady Hornig, a Columbia Mailman School psychiatrist renowned for her research on ME/CFS, joined Walter J. Koroshetz, director of the National Institute of Neurological Disorders and Stroke (NINDS), for a late June panel discussion on post-acute COVID. The panel was part of WNYC Radio’s 2021 Health Convening, hosted by Nsikan Akpan, health and science editor at New York Public Radio.
Individuals with PASC/Long COVID rarely continue to test positive for an active infection (at least by standard tests) but continue to experience a constellation of symptoms, from fatigue to trouble with cognition and chest and abdominal pain. While the condition is most common in those with severe COVID, it is also seen in 19 percent of those with asymptomatic infections, according to an analysis by FAIR Health, although studies vary widely. But how the virus triggers these symptoms and why it happens in some people not others is so far unknown.
“We’re really dealing with a mystery right now,” said Koroshetz. Yet the similarities of Long COVID to ME/CFS are striking, starting with a significant overlap in the symptoms, notably fatigue, unrefreshing sleep or “post-exertional malaise”—a general sense of being unwell after even minor physical or cognitive exertion affecting a majority of those with long COVID, along with high rates of problems with memory and attention (“brain fog”). Pain is another feature in common. And the onset of both Long COVID and up to 75 percent of ME/CFS cases can be traced to a viral infection. Indeed, one might easily ask: could Long COVID and ME/CFS be one and the same?
Hornig, who contributed some of the most influential research on ME/CFS in the past decade, helping to establish it as a biological disease, not a psychological disorder, believes research into the overlap between ME/CFS and Long COVID could help millions. In an interview with Columbia Magazine last year, she said we could be looking at an unprecedented wave of ME/CFS-like illness over the next few years, with profound societal costs. Even before the pandemic, an estimated three million Americans were suffering from the disorder.
In the WNYC panel, Hornig gave a short account of her own experience with Long COVID (thankfully, now resolving) then enumerated the most pressing research questions, starting with how SARS-Cov-2 affects the nervous system, and whether it continues to lurk in the body invisible to tests for active infection. Her research into ME/CFS has shed light on how the condition may come about due to a hyperactive immune response in the early years of the disease, followed by a state of immune exhaustion of a type that is sometimes reported in chronic viral infections. In future studies of Long COVID, she also urged fellow researchers to examine markers of resilience by including those like herself who are nearing or have achieved a stable recovery. “As much as we need to know vulnerability and what makes us ill, we need to know what makes us better,” she said.
In fact, several large studies are already in planning stages. One will follow individuals with COVID-19 over time to see how body systems improve or don’t improve. Another will follow people with persistent systems and compare them to those who had Covid and recovered. Other avenues for study include separate analyses of autopsy reports and electronic medical records. The research is supported through $1.15 billion allocated by Congress to NINDS. “We have the opportunity to do this in a big way now,” said Koroshetz.
For her part, Hornig is serving as a liaison with patients to get their input on research priorities including the kinds of questions to ask in surveys. “You have to ask people questions that are going to be meaningful,” she says. Doing so requires researchers to start by “bringing everyone to the table,” including Black, Indigenous, and People of Color people who have seen higher rates of COVID than the population at large, with some suggestion that the persistent health issues of Long COVID/PASC may also be more likely.
Even if all the scientific answers aren’t immediately forthcoming, one of the biggest potential upsides of the planned research is a greater awareness among clinicians to post-acute COVID and ME/CFS alike, as well as new approaches to treat them. If research moves ahead quickly, Hornig envisions in a year’s time that we may be graced by “a cohort of docs who are educated in these manifestations and maybe have something in their toolkits.”
The proliferation of the extra-contagious Delta variant gives the threat of Long COVID new urgency. Severe cases are almost entirely confined to those who haven’t been vaccinated. But an unknown number of mild or asymptomatic “breakthrough” cases are seen in those who already got the jab—and new research suggests that these cases may be contributing to the spread of the disease. It’s also worth remembering that individuals with mild and asymptomatic infections are still at risk for Long COVID. Hornig says all these facts raise important questions: “Why aren’t we tracing breakthrough infections? Why don’t we ensure all physical barriers to transmission are in place? What should the public health messages be?”