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.

Objective We aimed to characterize the current and lifetime prevalence of comorbid psychiatric diagnoses and suicidality in treatment‐ and nontreatment‐seeking individuals with full and subthreshold avoidant/restrictive food intake disorder (ARFID). We also sought to examine unique associations between the three DSM‐5 ARFID profiles (i.e., sensory sensitivity, fear of aversive consequences, and lack of interest in food or eating) and specific categories of psychiatric diagnoses and suicidality. Method We conducted structured clinical interviews with 74 children and adolescents with full or sub threshold ARFID to assess the presence of comorbid psychiatric diagnoses, suicidality, and the severity of each of the three ARFID profiles. Results Nearly half of the sample (45%) met criteria for a current comorbid psychiatric diagnosis, and over half (53%) met criteria for a lifetime comorbid diagnosis. A total of 8% endorsed current suicidality and 14% endorsed lifetime suicidality. Severity in the sensory sensitivity profile was uniquely associated with greater odds of comorbid disorders in the neurodevelopmental, disruptive, and conduct disorders category; the anxiety, obsessive–compulsive, and trauma‐related disorders category; and the depressive and bipolar‐related disorders category. Severity in the fear of aversive consequences profile was associated with greater odds of disorders in the anxiety, obsessive–compulsive, and trauma‐related disorders category. Discussion Our findings underscore the severity of psychopathology among individuals with ARFID and related presentations, and also highlight the potential that shared psychopathology between specific ARFID profiles and other psychiatric disorders represent transdiagnostic constructs (e.g., avoidant behavior) that may be relevant treatment targets.

There are currently no evidence-based treatments for adults with avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the acceptability, feasibility, and proof-of-concept of cognitive-behavioral therapy for ARFID (CBT-AR) for adults. Males and females (ages 18–55 years) were offered 20–30 outpatient sessions of CBT-AR delivered by one of five therapists. Of 18 eligible adults offered CBT-AR, 15 chose to participate and 14 completed treatment. All patients endorsed high ratings of treatment credibility and expected improvement after the first session, and 93% of completers provided high ratings of satisfaction at the conclusion of treatment. Therapists rated the majority (80%) of patients as “much improved” or “very much improved.” Based on intent-to-treat analyses, ARFID severity on the Pica, ARFID, and Rumination Disorder Interview (PARDI) showed a large and significant decrease from pre- to post-treatment; and patients incorporated a mean of 18.0 novel foods. The underweight subgroup ( n = 4) gained an average of 11.38 pounds, showing a large and significant increase in mean BMI from the underweight to the normal-weight range. At post-treatment, 47% of patients no longer met criteria for ARFID. To our knowledge, this is the first prospective treatment study of ARFID in adults. The findings of this study provide preliminary evidence of feasibility, acceptability, and proof-of-concept of CBT-AR for heterogeneous presentations of ARFID in adults. Randomized controlled trials are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02963220 .

Objective: Little is known about the optimal treatment of avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate feasibility, acceptability, and proof-of-concept for cognitive-behavioral therapy for ARFID (CBT-AR) in children and adolescents. Method: Males and females (ages 10-17 years) were offered 20-30 sessions of CBT-AR delivered in a family-based or individual format. Results: Of 25 eligible individuals, 20 initiated treatment, including 17 completers and 3 dropouts. Using intent-to-treat analyses, clinicians rated 17 patients (85%) as "much improved" or "very much improved." ARFID severity scores (on the Pica, ARFID, and Rumination Disorder Interview) significantly decreased per both patient and parent report. Patients incorporated a mean of 16.7 (SD = 12.1) new foods from pre-to post-treatment. The underweight subgroup showed a significant weight gain of 11.5 (SD = 6.0) pounds, moving from the 10th to the 20th percentile for body mass index. At post-treatment, 70% of patients no longer met criteria for ARFID. Discussion: This is the first study of an outpatient manualized psychosocial treatment for ARFID in older adolescents. Findings provide evidence of feasibility, acceptability, and proof-of-concept for CBT-AR. Randomized controlled trials are needed.

Objectives-Fetal hemoglobin (HbF) induction involves NO-cGMP signaling pathways. Larginine, an NO precursor, and the phosphodiesterase (PDE) 5 inhibitor sildenafil, which potentiates cGMP, were studied in adults with sickle cell disease (SCD) who were stably on HU.Methods-24 courses of L-arginine (0.1-0.2 g/Kg divided TID) or sildenafil (25-100 mg TID), assigned based on gender due to concerns about sildenafil-related priapism, were successfully completed. Biochemical assays, pulmonary pressures, and cardiopulmonary exercise capacity are reported from patients in whom serial values are available. Hematologic responses are reported in 14 subjects with HbSS who had stable baseline HbF levels.Results and Conclusions-L-arginine increased plasma arginine and ornithine, but not citrulline, suggesting diversion by plasma arginase from NO, and citrulline, generation. Glutathione (GSH) increased only in patients on L-arginine. Sildenafil increased plasma cGMP and citrulline, but not other amino acids. Pulmonary pressures and 6-minute walk distances improved only in patients on sildenafil.In subjects with stable baseline HbF levels, HbF levels changed little from a normalized baseline on L-arginine, decreasing by 2.9±16.1%, n=6; p=n.s., but increased on sildenafil, by 7.5±11.7%, n=8, p<.05. Absolute reticulocyte counts initially decreased in patients on sildenafil.L-arginine, at doses that increase plasma arginine levels, altered redox potential in red cells. The lack of clinically detectable efficacy of L-arginine may be due to increased arginine metabolism in SCD patients.In vivo augmentation of the cyclic nucleotide pathway by PDE inhibition may induce HbF slightly, but strikingly improves hemodynamic and functional status in SCD †