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 To investigate the relationships between psychological and physiologic measures of stress, mood and gestational age at delivery and preterm birth (PTB). METHODS This prospective cohort study recruited healthy women in the early second trimester, 18–45 years of age. Validated psychological measures of perceived stress, depressive symptoms, and anxiety were completed at 16, 22, 28, 34 and 40 weeks of gestation. Cortisol concentration was measured in maternal hair at 16, 28, and 40 weeks of gestation to approximate 1st, 2nd, and 3rd trimester levels of physiologic stress. Statistical methods included: analyses of variance (ANOVA), t-tests, Chi-square, Pearson correlations, regression modeling and mediation analysis as appropriate. Hair cortisol concentrations were natural log transformed to normalize values. RESULTS Eleven (12%) out of 90 included women had a spontaneous preterm birth or preterm premature rupture of the membranes. Perceived stress at 16 weeks of gestation correlated with both 2nd trimester cortisol concentration (r= 0.28, p=0.007) and earlier gestational age at delivery (r= −0.30, p< 0.01). Gestational age at delivery was also negatively correlated with cortisol concentration in the 2nd trimester (r= −0.25, p=0.02) and 2nd trimester cortisol concentration was higher in preterm (2.7 ± 0.4 LN pg/mg) vs term (2.0 ± 0.7 LN pg/mg, P<0.001) delivered women. Using mediation statistics, the association between the psychological measure, the physiologic measure, and gestational age at delivery was mainly driven by increased physiologic stress (hair cortisol concentration) in the 2nd trimester (difference in coefficients (standard error)= −0.05(0.02)),. CONCLUSION Higher perceived stress in the 2nd trimester is associated with both elevated 2nd trimester hair cortisol concentration and gestational age at delivery. Physiologic measure of stress in the 2nd trimester appears most strongly associated with preterm birth. Identification and amelioration of early pregnancy stressors may attenuate physiologic stress and ultimately affect preterm birth.
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