Symptom Scoring Framework Paves the Way for Long COVID Definition

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Analysis of symptoms present six months or more after SARS-CoV-2 infection was used to develop a composite scoring framework for identifying postacute sequelae of SARS-CoV-2 infection (PASC) as a new condition.

Investigators took a step toward formally identifying postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, as a new condition with an analysis of self-reported symptoms across multiple organ systems present at six months or more after infection.

The study, published in JAMA, looked at data from 9764 patients who participated in the National Institutes of Health’s Researching COVID to Enhance Recovery (RECOVER) Initiative, including 8,646 infected with SARS-CoV-2. Investigators identified 37 symptoms that were more often present after COVID, with frequency of 2.5% or greater and adjusted odds ratio of 1.5 or greater.

Twelve symptoms were included in a composite scoring framework for identifying PASC. Symptoms include postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain and abnormal movements. Each symptom was assigned a value to determine a composite PASC score, with higher scores associated with worse well-being.

“A framework for identifying PASC cases based on symptoms is a first step to defining PASC as a new condition. These findings require iterative refinement that further incorporates clinical features to arrive at actionable definitions of PASC,” the authors, led by Tanayott Thaweethai, PhD, of Massachusetts General Hospital and Harvard Medical School, wrote.

Participants were enrolled in the study in 33 states, Washington, D.C., and Puerto Rico. A total of 71% of study participants were female; 16% Hispanic/Latino; and 15% non-Hispanic Black. The median age was 47.

Overall, 1990, or 23%, of all infected participants scored PASC positive along with 41 of 1118, or 3.7%, of uninfected participants. Most common symptoms were postexertional malaise, reported among 87% of PASC-positive participants, fatigue (85%), brain fog (64%), dizziness (62%), GI (59%), and palpitations (57%).

Investigators reported results in three subcohorts: acute Omicron, postacute pre-Omicron and postacute Omicron. Among them, 2231 were first infected with SARS-CoV-2 on or after Dec. 1, 2021, and enrolled in the study within 30 days. Based on the symptom framework, the study identified 224, or 10%, as PASC positive at six months.

Participants who were infected before the Omicron variant of SARS-CoV-2 became dominant were more likely to be PASC positive with more severe manifestation, with 35% of those in the postacute pre-Omicron subgroup scoring PASC positive. However, the authors noted that those infected earlier may have been more likely to enroll in RECOVER because of PASC. Those with recurrent infections during the Omicron era also were more likely to be PASC positive, and vaccination was associated with a modest reduction in PASC.

“Given the heterogeneity of PASC symptoms, determining whether PASC represents one unified condition or reflects a group of unique phenotypes is important,” the authors wrote. “Recent evidence supports the presence of PASC phenotypes, although characterization of these phenotypes is inconsistent and largely dependent on available data.”

Limitations of the study include that the symptoms included in the framework may not reflect the impact of other symptoms, selection bias was likely as symptoms may have affected study participation and uninfected participants may have had previous asymptomatic infections.

The authors described the PASC scoring system as a launching point for further investigations andnoted that a definition of a classification rule for PASC requires a more detailed algorithm that incorporates biological features.

“The research exemplifies the benefits of multidisciplinary collaboration informed by extensive input from patient representatives,” Robert Gross, MD, MSCE, and Vincent Lo Re III, MD, MSCE, wrote in an editorial comment. “These efforts will continue to be needed to determine whether this phenomenon represents one entity with a single definition or multiple phenotypes that arise after COVID-19 infection requiring separate case definitions (ie, E unibus pluram [from one, many]). Addressing this question and finalizing the definitions of these postacute sequelae should facilitate more robust research that ultimately leads to high-quality care and treatment for patients with late effects of SARS-CoV-2 infection.”

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