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.

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Introduction Hypoplastic left heart syndrome (HLHS) is a severe cardiovascular malformation (CVM) associated with fetal growth abnormalities. Genetic and environmental factors have been identified that contribute to pathogenesis, but the role of the placenta is unknown. The purpose of this study was to systematically examine the placenta in HLHS with and without growth abnormalities. Methods HLHS term singleton births were identified from a larger cohort when placenta tissue was available. Clinical data were collected from maternal and neonatal medical records, including anthropometrics and placental pathology reports. Placental tissues from cases and controls were analyzed to assess parenchymal morphology, vascular architecture and leptin signaling. Results HLHS cases (n = 16) and gestational age-matched controls (n = 18) were analyzed. Among cases, the average birth weight was 2993 grams, including 31% that were small for gestational age. When compared with controls, gross pathology of HLHS cases demonstrated significantly reduced placental weight and increased fibrin deposition, while micropathology showed increased syncytial nuclear aggregates, decreased terminal villi, reduced vasculature and increased leptin expression in syncytiotrophoblast and endothelial cells. Discussion Placentas from pregnancies complicated by fetal HLHS are characterized by abnormal parenchymal morphology, suggesting immature structure may be due to vascular abnormalities. Increased leptin expression may indicate an attempt to compensate for these vascular abnormalities. Further investigation into the regulation of angiogenesis in the fetus and placenta may elucidate the causes of HLHS and associated growth abnormalities in some cases.