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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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OPINION STATEMENT Substance use disorders (SUD) can be considered developmental disorders in light of their frequent origins in substance initiation during adolescence. Cross-sectional functional magnetic resonance imaging (fMRI) studies of adolescent substance users or adolescents with SUD have indicated aberrations in brain structures or circuits implicated in motivation, self-control, and mood-regulation. However, attributing these differences to the neurotoxicological effects of chronic substance use has been problematic in that these circuits are also aberrant in at-risk children, such as those with prenatal substance exposure, externalizing disorders (such as conduct disorder), or prodromal internalizing disorders such as depression. To better isolate the effects of substance exposure on the adolescent brain, the newly-launched Adolescent Brain Cognitive Development (ABCD) study, funded by the National Institutes of Health, will follow the neurodevelopmental trajectories of over 11,000 American 9/10-year-olds for 10 years, into emerging adulthood. This study will provide a rich open-access dataset on longitudinal interactions of neurodevelopment, environmental exposures, and childhood psychopathology that confer addiction risk. The ABCD twin study will further clarify genetic versus experiential influences (e.g., substance use) on neurodevelopmental and psychosocial outcomes. Neurocircuitry thought to regulate mood and behavior has been directly normalized by administration of psychoactive medications and by cognitive therapies in adults. Because of this, we contend that ABCD project data will be a crucial resource for prevention and treatment of SUD in adolescence because its cutting-edge neuroimaging and childhood assessments hold potential for discovery of additional targetable brain differences earlier in development that are prognostic of (or aberrant in) SUD. The ABCD sample size will also have the power to illuminate how sex differences, environmental interactions and other individual differences interact with neurodevelopment to inform treatment in different groups of adolescents.

Key PointsQuestionDoes provision of pharmacogenomic testing for drug-gene interactions affect selection of antidepressant medication and response of depressive symptoms in patients with major depressive disorder (MDD)?FindingsIn this randomized clinical trial that included 1944 patients with MDD, provision of pharmacogenomic tests for drug interactions compared with usual care resulted in prescriptions with no predicted drug-gene interactions in 45% vs 18%, respectively, a difference that was statistically significant. Remission of symptoms reached a maximum difference of 16.5% vs 11.2% at 12 weeks but was not significantly different at 24 weeks.MeaningPharmacogenomic testing for drug-gene interactions in MDD reduced prescription of medications with predicted drug-gene interactions but had small and nonpersistent effects on symptom remission.