March, 15, 2023 – More than 3 years into the pandemic, finding out how many Americans have long COVID – and what to do about it – has proved to be far harder than identifying those infected with the virus who have recovered or died from it.
How best to simply define, diagnose, measure, and treat it have remained elusive, putting patients and doctors in an impossible situation.
But what is clear is that even at the lowest estimates, the CDC said in June 2022 that 1 in 13 Americans (7.5%, or nearly 26 million) had long COVID. But some research suggests that figure underestimates the actual number of Americans who are affected.
The World Health Organization estimates between 10% and 20% of people infected with COVID-19 end up with symptoms lasting 3 months or longer.
The U.S. Census Bureau’s most recent Household Pulse Survey puts the current figure at close to 11% – down from nearly 19% last summer, and nearly 15% in October – among adults who had COVID-19.
And research published in January by the Scripps Research Translational Institute in San Diego estimated at least 1 in 10 Americans with COVID continue to have long-term symptoms.
But some experts believe the World Health Organization, Census Bureau, and Scripps estimates are in fact conservative, even as others say the true number is likely closer to 5%.
One reason for the disparity: There is still no standard definition for long COVID.
“It's still unclear to many people whether what's being described as long COVID is one condition or several distinct conditions that are all being lumped under that same umbrella term,” says Amesh Adalja, MD, a senior scholar an infectious disease specialist who studies COVID-19 at the Johns Hopkins University Center for Health Security.
Defining the 'Long' in Long COVID
One of the most confounding problems in understanding long COVID is finding out who actually has it by identifying symptoms of the condition and for how long people have had them.
The World Health Organization notes that more than 200 symptoms have been reported; it defines long COVID as the continuation or development of new symptoms 3 months after an initial infection, and lasting for at least 2 months with no other explanation. Some experts believe these parameters are too broad, while others think they are too narrow.
Long COVID researchers increasingly suspect that post COVID-19 symptoms may result from multiple causes – including inflammation, autoimmunity, and immune dysfunction – and they hope that identifying biomarkers (things about the body that tell you that a disease is present) will make diagnosing the condition easier.
But unlike acute COVID-19, which can be diagnosed with antigen tests that detect a viral protein, there is no clear diagnostic criteria or tool yet for long COVID conditions like fatigue or brain fog.
That leaves many people with long COVID undiagnosed and not knowing where to turn for help or treatment.
“A lot of the burden of long COVID right now is going unseen because people with long COVID don't know where to go for help, or how to get help, or when it's going to end, so they just suffer quietly at home,” says Sarah Wulf Hanson, PhD, a research scientist with the Institute for Health Metrics and Evaluation at the University of Washington.
Making matters more difficult is trying to parse whether certain symptoms, like anxiety or depression, are caused by the hardships of living through the pandemic, by a lingering COVID infection, or were preexisting in some people.
Manali Mukherjee, PhD, an immunologist and assistant professor with the Respirology Division of the Department of Medicine at McMaster University in Hamilton, Ontario, Canada, notes these realities make it hard to even study long COVID to answer these lingering questions.
Despite the lack of consensus on defining the condition, many public health agencies around the world cite fatigue, brain fog, memory and sleep issues, shortness of breath, anxiety and depression, dizziness, and joint or muscle pain among the most common symptoms that linger for at least 3 months after a COVID-19 infection.
Disability Definitions in Long COVID Patients
While most experts agree on the most common set of symptoms, they are at odds over how far to expand that list and how to factor in how crippling they are in some people. Some worry about who gets left out when certain symptoms are excluded or disability is not considered.
Adalja says it is important to separate crippling symptoms that interfere with activities of daily life from those that do not. But even that is no simple task.
Post-COVID symptoms can also disappear and relapse, making the condition even more complex. Doing more longitudinal follow-up studies – which observe the same people over a period of time – may be the best way to identify cases like these because they can help researchers detect changes in both the individual and the group as a whole. But few longitudinal studies have been done on long COVID.
Not all studies follow the World Health Organization’s 3 -month parameter either, and these differences account in part for why results are “all over the place,” says Mukherjee.
A recent study from George Washington University published in Emerging Infectious Diseases, for example, found that among 1,338 COVID-19 cases in university members in Washington, DC, 36% of students, faculty, and staff ended up with long COVID, a figure that stands in contrast with the latest household survey and even the World Health Organization. But the study, which also did not include a control group, conducted a follow up after 30 days following the initial positive test.
Despite these debates and conflicts, is it clear that for some long COVID patients, a wide variety of symptoms can be debilitating and linger for 12 months or even longer.
Another Confounding Factor: Research Challenges and Limits
Many of the largest studies of long COVID use electronic health record data, a highly valuable resource that can nonetheless introduce biases and equity issues, like a person's ability to access health care.
Another major flaw with some long COVID studies is the lack of a control group, according to Adalja.
A control group is important to confirm that a COVID infection, and not some other variable, is the cause. But long COVID researchers have highlighted the hurdles with recruiting people who have the right criteria.
Another complicating factor: Many studies use self-reported surveys to gather information, a process that can also be rife with biases, inaccuracies, and other issues.
While a number of studies use a positive COVID test to filter the data, for example, some researchers are more cautious. A COVID test assumes patients have equal access to testing – or that they would even test at all, especially when some may have been asymptomatic or did not know they were infected.
“And that's not a small number of people,” says Lisa McCorkell, a long COVID patient and co-founder and researcher with the Patient-Led Research Collaborative. She is one of the co-authors of the study published in Nature Reviews Microbiology in January that documents the impact of long COVID on different organ systems based on a comprehensive review of numerous studies.
As the pandemic enters its fourth year, the number of people who have never had COVID-19 has shrunk dramatically, making it more challenging to find a healthy group of controls to compare to those who have had COVID, some scientists point out. This impacts how control groups are defined and underscores the need for more research into finding biomarkers that can definitely flag long COVID.
Where Do We Go From Here?
For all of these reasons, long COVID cases may actually be under-reported, McCorkell says.
Julia Moore Vogel, PhD, a program director with the Scripps Research Translational Institute, worries that the overall public health messaging – and lack of it on long COVID – may also be hindering efforts to combat it.
“I wonder whether the narrative that the pandemic is over has caused people to miss when they have mild cases of COVID … and subsequently not recognize the appearance of long COVID,” she says.
The bottom line: Understanding the prevalence of long COVID symptoms will help put a spotlight on the urgency for more funding for studying diagnostic biomarkers and finding effective therapies, researchers say.
But in the meantime, long COVID needs to be considered a higher public health priority – in clinical trials, research, doctor’s offices, and among policymakers, experts argue.
“I worry that we’re going to keep going in circles on this definition and prevalence debate, when that's not necessarily helping us get closer to answers for the people who are experiencing the illness,” McCorkell says.