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The Overexaggerated Threat of Long COVID

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Researchers have identified significant issues in long COVID studies, including overly broad definitions and a lack of proper comparison groups, leading to distorted risks and consequences like increased public anxiety and misdiagnoses. They stress the need for better-matched control groups and improved research standards, including more stringent criteria for defining long COVID. They suggest that the term ‘long COVID’ should be replaced with more specific terminology to accurately address different aftereffects and improve outcomes.

Researchers argue that excessively wide definitions and the absence of comparison groups have skewed perceptions of risk, resulting in heightened public anxiety, escalated healthcare spending, frequent misdiagnoses, and the misallocation of funds.

Overly general definitions and the absence of appropriate, or any, comparison groups, and other issues in research exploring the occurrence, frequency, and management of the condition—epidemiology—have skewed the perceived risks, according to the researchers.

This issue is exacerbated by the incorporation of substandard studies into systematic reviews and aggregated data analyses, which further exaggerate the risk, they add.

The likely consequences of this include, but aren’t limited to, increased public anxiety and healthcare spending; misdiagnoses; and diversion of funds from those who really do have other long-term conditions secondary to COVID-19 infection, suggest the researchers.

Common Symptoms and Inadequate Definitions

Many after-effects of COVID-19 infection include post-ICU syndrome—a constellation of health issues that are present when the patient is in intensive care and which persist after discharge home—and shortness of breath following pneumonia. Trouble is: these are common to many upper respiratory viruses, point out the researchers.

None of the working definitions of ‘long COVID’ used by influential health bodies, such as the US Centers for Disease Control and Prevention, the World Health Organization, the UK National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guidelines Network (SIGN), and the Royal College of General Practitioners requires a causal link between the virus responsible for COVID-19 (SARS-CoV2) and a range of symptoms. 

The Need for Proper Control Groups

Not only should comparator (control) groups be included in ‘long COVID’ studies, when they often aren’t, but they should also be properly matched to cases, ideally by age, sex, geography, socioeconomic status and, if possible, underlying health and health behaviours, which they rarely are, say the researchers.

During the early stages of the pandemic, when SARS-CoV-2 testing wasn’t widely available, studies were more likely to include a non-representative sample of SARS-CoV-2-positive patients by including fewer patients with mild or no symptoms.

This is known as sampling bias, which occurs when certain members of a population have a higher probability of being included in a study sample than others, potentially limiting the generalisability of a study’s findings, explain the researchers.

“Our analysis indicates that, in addition to including appropriately matched controls, there is a need for better case definitions and more stringent [‘long COVID’] criteria, which should include continuous symptoms after confirmed SARS-CoV-2 infection and take into consideration baseline characteristics, including physical and mental health, which may contribute to an individual’s post-COVID experience, “ they write, adding that the umbrella term ‘long COVID’ should be jettisoned in favor of different terms for specific after effects.

While the results of high-quality population studies on ‘long COVID’ in adults and children have been reassuring, they point out,  the body of research “is replete with studies with critical biases” they add, setting out common pitfalls.

“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. Inappropriate definitions and flawed methods do not serve those whom medicine seeks to help,” they insist.

“Improving standards of evidence generation is the ideal method to take long COVID seriously, improve outcomes, and avoid the risks of misdiagnosis and inappropriate treatment,” they include.

Reference: “How methodological pitfalls have created widespread misunderstanding about long COVID” by Tracy Beth Høeg, Shamez Ladhani and Vinay Prasad, 25 September 2023, BMJ Evidence-Based Medicine.
DOI: 10.1136/bmjebm-2023-112338

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