Introduction
On May 25, 2023, researchers published a study funded by the National Institutes of Health Researching COVID to Enhance Recovery (NIH RECOVER) Initiative in the Journal of the American Medical Association (JAMA). This study, titled “Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection,” attempted to identify the symptom-based criteria that can be used to identify long COVID. Alongside the publication of this study, the NIH released a glowing press release that hailed it as “an important step toward defining long COVID.” Unfortunately, this study advanced a harmful and exclusionary point-based framework that has received searing criticism from long COVID patients and advocates. On behalf of people living with long COVID, Pandemic Patients calls for this paper to be retracted and for the NIH to publish a news release that cautions against the operationalization of this study’s point-based framework.
Long COVID
Many people who are exposed to COVID-19 continue to experience symptoms of the disease for months, or years, following their infection. This condition, referred to as “long COVID,” or “post-acute sequelae of SARS-CoV-2 Infection (PASC),” is characterized by over 200 symptoms associated with several different vital organs, including the heart, kidneys, lungs, and brain. Many of these symptoms, like cognitive impairment and dysautonomia, can be severe and disabling. The U.S. Census Bureau estimates that approximately ten percent of adults infected with COVID-19 continue to experience long-term symptoms.
Being able to accurately identify and diagnose long COVID is an important objective because many long COVID symptoms overlap with other conditions. Further, without clear diagnostic criteria, healthcare practitioners may find it difficult to assess whether a patient’s long-term symptoms were caused by a prior COVID-19 infection, or something else. This can cause complications across several domains. For example, a patient may have challenges obtaining medications to manage their symptoms because their doctor may mischaracterize the cause of their symptoms as “deconditioning,” “anxiety,” or “malingering.” Additionally, a patient may be unable to access disability benefits or other safety net resources because their healthcare provider lacks the tools to establish a clear diagnosis in their medical record. As these examples illustrate, the diagnostic criteria used to evaluate long COVID patients can carry significant consequences.
RECOVER Study
The NIH RECOVER Initiative is a research program funded by Congress that aims to study the long-term effects of COVID-19 and how to predict, treat, and prevent the disease. This initiative represents the largest public investment in long COVID research. Accordingly, long COVID patients across the country have invested their hopes and dreams in this program, as the research it produces may serve as the foundation for a cure for long COVID. The first published study to analyze health data from the cohort of long COVID patients enrolled in the RECOVER Initiative falls far short of delivering on that promise.
While aiming to define long COVID, the RECOVER Study ultimately offers a regressive and blunt tool to diagnose this condition. The study authors analyzed data from nearly ten thousand adult participants in the adult RECOVER cohort and devised a list of twelve symptoms with corresponding scores that must add up to twelve points for a patient to meet the threshold of having long COVID. These symptoms, derived from a pre-selected list of 44 symptoms, represent those that differentiate infected vs. non-infected study participants. Based on their analysis, the study authors identified the following symptoms as those that can contribute to a long COVID diagnosis: lost of smell or taste, post-exertional malaise, chronic cough, brain fog, thirst, heart palpitations, chest pain, fatigue, dizziness, gastrointestinal symptoms, issues with sexual desire or capacity, and abnormal movements.
The study’s approach to identifying long COVID is inherently problematic because it does not provide a mechanism to account for variations in the severity of a patient’s symptoms. For example, a person’s chest pain and fatigue can be severe and debilitating, yet the scores associated with these symptoms by themselves would only total three. Consequently, their doctor could use this scoring framework to exclude them from a long COVID diagnosis, despite their symptoms being caused by a prior COVID-19 infection. The exclusionary effect of a point-based scoring framework for long COVID is damaging to patients.
This algorithmic approach to identifying long COVID ignores the tremendous variability in symptom presentation and severity among long COVID patients. This approach also fails to account for the heightened risk of severe health events that patients may face following an acute COVID-19 infection, including heart attack, stroke, blood clots, and diabetes, among others. The study’s framework is derived from an adult-only patient cohort, which is not discussed among the study’s limitations. This could cause complications if the framework is wrongfully applied to children.
This harmful diagnostic framework could be used haphazardly by employers, insurers, and government programs to impede patients’ access to workplace accommodations, health and welfare benefits, and safety net resources. This framework could impede access to disability benefits specifically, as the study authors suggest that “in general, the higher someone’s score was, the worse their ability to carry out every day activities . . . . Higher symptom scores also correlated with a lower quality of life.” Further, researchers and scientists could wrongfully rely on this scoring system to exclude significant numbers of long COVID patients from further research and clinical trials. The development of treatments and cures for long COVID, consequently, would be biased towards only those patients whose symptom profiles meet this study’s twelve-point threshold. The framework’s bias is further complicated by the fact that the patient cohort analyzed in this study is overwhelmingly female (71.4 percent) and white (59.1 percent). Utilizing this framework is risky because it may produce inequitable outcomes that unfairly favor this population.
Targeting further research and development exclusively towards this patient population is troubling because only 23 percent of infected study participants met the framework’s threshold for diagnosis, while nearly four percent of uninfected participants were miscategorized as “PASC positive” without a history of prior infection. Among the patients who did not meet the framework’s twelve-point threshold for diagnosis, 26 percent reported “fair” or “poor” quality of life and general physical health alongside difficulty carrying out everyday physical activities. This reveals that a notable percentage of study participants are experiencing symptoms that negatively affect their quality of life, physical health, and functional capacity, despite being excluded from the study’s definition of long COVID. A diagnostic framework characterized by this degree of imprecision cannot be implemented without harming patients.
The study authors carefully note that “iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.” However, mainstream media outlets like the Washington Post have already mischaracterized this study by hailing it as a “unified framework” for long COVID, which is an extreme oversimplification of this disease. CNBC published a statement from an author of the study claiming that “the proposed definition of long COVID could help develop a method for doctors to diagnose patients.” Additionally, CNN describes the study’s framework as “a list of 12 symptoms that can reliably classify someone as having long COVID,” further quoting a statement from an author of the study: “this is a group of people who we think have this condition, and we can then study them and understand what is going on in their bodies.” These statements are harmful because they suggest that the point-based framework should be used outside of a research context while also revealing that researchers participating in the RECOVER Initiative intend to focus their work exclusively on the population of patients that meet the framework’s threshold for diagnosis.
Conclusion
While the study’s authors assert that the “symptom-based PASC definition represents a first step for identifying PASC,” it is a dangerous tool that will leave patients behind if it is implemented. For the reasons mentioned above, Pandemic Patients calls for this study be retracted. Additionally, we request the NIH issue a news release that cautions against the operationalization of the study’s point-based framework.
UPDATE: On June 9, 2023, the NIH Recover Initiative released a “RECOVER Research Q&A” that responds to some of our concerns.
