Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection

Abstract

ImportanceSARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals.ObjectiveTo develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections.Design, Setting, and ParticipantsProspective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling.ExposureSARS-CoV-2 infection.Main Outcomes and MeasuresPASC and 44 participant-reported symptoms (with severity thresholds).ResultsA total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included 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. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months.Conclusions and RelevanceA definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Postacute Sequelae of SARS-CoV-2 Infection—Reply

“…In Reply We agree with Dr Batra and colleagues that different manifestations of long COVID may arise due to different underlying pathological mechanisms of disease, which may be related to whether an individual was hospitalized during the acute phase of SARS-CoV-2 infection. However, we disagree that stratification by hospitalization status was needed to ensure the validity of the approach we used in our study …”

Postacute Sequelae SARS-CoV-2 Infection by Vaccination Status: A Six-Month Latent Class Analysis

“…Although data are still limited regarding the underlying pathophysiology of PASC (Nalbandian et al 2021), understanding the patient symptomatology and care needs after the acute stages of SARS-CoV-2 infection can lead to potential interventions addressing PASC. Furthermore, there are a paucity of data in identifying clusters of symptoms associated with PASC (Natarajan et al 2023, Priyal et al 2023, Thaweethai et al 2023, Yugar-Toledo et al 2023).…”

Postacute Sequelae of SARS-CoV-2 Infection

“…To the Editor A recent study developed a data-driven scoring framework to classify postacute sequelae of SARS-CoV-2 infection (PASC). As stated in the accompanying Editorial, prior to developing a case definition, it is important to determine whether PASC is a single entity or multiple entities.…”

“…While this study makes significant strides toward a unifying definition of PASC, the study design may have inadvertently excluded (or included) patients with an entirely separate disease entity and pathogenesis. We agree with the accompanying Editorial that erroneous case definitions and misclassifications could delay diagnosis, decrease the likelihood of discovering the underlying mechanisms of PASC, and hamper the ability to demonstrate efficacy of interventions or lead to misdirected treatments.…”

“…We believe that additional data analyses of this study, stratified according to the severity of acute COVID-19 and whether participants were hospitalized for COVID-19, would provide important information.…”