The Centers for Disease Control and Prevention (CDC) estimates that nearly one out of every five American adults who have had COVID-19 continue to battle with long COVID, but experts are calling the validity of this claim into question.
Citing methodological flaws in how studies on the lingering symptoms of the virus have been conducted, a group of experts from the US, UK and Denmark, claim that the risk of long COVID, also known as post-acute sequelae of COVID-19 (PASC), has been overestimated.
“Many scientific publications overestimate PASC prevalence because of overly broad definitions, lack of control groups, inappropriate control groups, and other methodological flaws,” authors of the new paper, published Monday in BMJ, wrote. “This problem is further compounded by inclusion of poorly conducted studies into systematic reviews and meta-analyses that overstate the risk.”
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An imperfect definition of long COVID
One aspect of long COVID the experts take issue with is the way that it is defined, noting that its current definition is “imprecise” and too broad. Even the CDC says that long COVID is “broadly defined” as “signs, symptoms, and conditions that continue or develop after acute COVID-19 infection.”
To date, there have been more than 200 symptoms linked to long COVID. Some of the symptoms and conditions that fall under the long COVID umbrella, including weakness, brain fog and shortness of breath, are also associated with post-intensive care syndrome (post-ICU syndrome) , post-pneumonia respiratory compromise and the recovery period following other severe respiratory infections. This makes it difficult to determine whether a person’s symptoms are a direct result of COVID.
Unclear long COVID timelines
The authors also highlight the inconsistent timelines that studies and prominent health organizations have used to describe long COVID.
The CDC classifies any symptom that lasts longer than four weeks after the initial phase of an infection to be linked to the virus; the World Health Organization (WHO) uses an eight-week time frame, and other relevant institutions, such as the UK’s National Institute for Health and Care Excellence (NICE) require that symptoms last for at least 12 weeks.
The same inconsistencies can be found in research, with some studies lending more flexibility to the time when patients began to experience symptoms.
Control groups, or lack thereof
Control groups in medical research offer experts a way to gauge a treatment’s effectiveness. Healthy controls who are similar to an experimental group — in this case, a group of people with long COVID symptoms — in terms of age, gender, lifestyle and overall health risks are often used in research to determine how well an intervention does or does not work.
Many studies on the condition did not utilize control groups. The authors pointed to a recent systematic review of long COVID that included studies that lacked healthy controls. In that review, just 22 out of 194 studies included a control group
The authors note that control groups are especially beneficial “when the definition of a condition is vague and includes numerous common symptoms,” such as those used to define long COVID.
Sampling bias
Randomized controlled trials are the gold standard of clinical research, according to the National Institutes of Health (NIH). Randomization of participants offers insight into how a treatment will work for a diverse group of people and reduces the possibility of bias in trial results.
“Study results may also be biased towards poorer health outcomes if participants are recruited by advertising the study as pertaining to COVID-19 recovery or long COVID,” the authors explain. “People who are experiencing lasting symptoms after COVID-19 may be motivated to participate, potentially because they believe doing so may provide insight into their own condition or help others experiencing similar symptoms.”
In other words, sampling bias prevents a study’s results from being relevant to a larger, more diverse — racially, economically and medically — population.
Well-designed studies provide reliable results
The authors did highlight a number of studies that have been well designed, noting that the results from such studies are most often encouraging when it comes to long COVID.
They said that the goal of their paper was to bring awareness to some of the pitfalls in medical research that can cause the public to misunderstand and often “overestimate” the actual risks of long COVID.
“Ultimately, biomedicine must seek to aid all people who are suffering. In order to do so, the best scientific methods and analysis must be applied,” the authors wrote. “Inappropriate definitions and flawed methods do not serve those whom medicine seeks to help.”
