The scientific community has taken a crucial step in long COVID research with the update of the research index based on data from the RECOVER-Adult project. This effort, reflected in a recent study published in JAMAoffers a more precise approach to identify and classify persistent symptoms associated with this complex condition, which affects a significant portion of those who have overcome the acute phase of SARS-CoV-2 infection.
Long COVID, defined by the National Academies of Sciences, Engineering and Medicine (NASEM), encompasses a broad spectrum of symptoms that persist for at least three months after the initial infection. Although inclusive, this definition lacked the specificity needed to support systematic research, prompting the creation of a structured index to enable advances in the identification of biomarkers and treatments.
The study included 13,647 participants from 83 sites in the United States and Puerto Rico, of whom 11,743 had a confirmed history of SARS-CoV-2 infection, while 1,904 had not been infected. These individuals were evaluated at least 4.5 months after their initial infection and no earlier than 30 days after reinfection, which allowed the evolution of their symptoms to be analyzed.
The analysis used a LASSO regression approach to assign scores to 44 initially reported symptoms, establishing an optimal threshold that minimizes false positives. Participants whose symptoms exceeded this threshold were classified as probable long COVID cases, while those with relevant symptoms but not meeting the threshold were considered possible cases.
Among the symptoms that make up the updated index are fatigue, mental confusion, dizziness, post-exertional discomfort, palpitations, chronic cough, changes in smell or taste, and difficulty breathing, among others. This refinement eliminated three symptoms present in the 2023 version of the index: abnormal movements, lack of sexual desire, and certain gastrointestinal symptoms.
The data revealed that with the new index, 20% of previously infected participants and 4% of uninfected participants showed evidence of long COVID. In addition, a new category was introduced, called “possible long COVID,” which covered 39% of patients with a history of infection.
A notable finding of the study was the identification of five symptom subtypes. Each subtype was associated with predominant characteristics: changes in smell or taste, chronic cough, mental confusion, palpitations, and multisystem symptoms such as dizziness and post-exertional malaise. In all, except the subtype focused on olfactory changes, fatigue was a common denominator.
Subtype five, which included multisystem symptoms, was highlighted by a significant impact on quality of life, physical health, and daily functioning. Demographic characteristics also varied between subtypes; For example, subtypes four and five had greater female representation, while subtype five was more common in unvaccinated people, of Hispanic or multiracial ancestry, and in those infected before the omicron wave.
The 2024 version of the index has several advantages over the 2023 version, such as a more precise classification of symptoms, better specificity, and the ability to differentiate between clinical subtypes. This advance not only optimizes the identification of highly symptomatic cases, but also opens new opportunities to understand the mechanisms of the disease and develop specific treatments.
At a time when the pandemic continues to leave lasting consequences, this index represents crucial progress for medical research and for those living with the consequences of COVID-19.
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