Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8
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T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
We describe the establishment and current content of the ImmuneCODE™ database, which includes hundreds of millions of T-cell Receptor (TCR) sequences from over 1,400 subjects exposed to or infected with the SARS-CoV-2 virus, as well as over 135,000 high-confidence SARS-CoV-2-specific TCRs. This database is made freely available, and the data contained in it can be downloaded and analyzed online or offline to assist with the global efforts to understand the immune response to the SARS-CoV-2 virus and develop new interventions.
The paper addresses several issues pertinent to the characteristics and treatment of separation anxiety in children and adults. The rationale for separating separation anxiety from other childhood anxiety conditions rests on clinical observations of its relationship to panic disorder and its response to drug treatment. The psychopharmacological treatment of separation anxiety is reviewed, with special emphasis on the use of tricyclic antidepressants. The literature relevant to a possible association between separation anxiety and adult panic disorder is presented. The prevalence of separation anxiety disorder in adult outpatients with panic disorder is discussed. Data are presented to address the issue of treatment response in adult panic disorders with and without separation anxiety.
Sixty-six children received individual reading instruction for 18 weeks, in combination with methylphenidate (mean daily dose 44.2 mg/day) or a placebo. Assignment to medication was random and double blind. Children were re-evaluated at the end of treatment, and two and eight months later. Only occasional and weak methylphenidate effects were obtained on measures of reading performance. Highly significant improvement in some tests of mathematics was found. No treatment differences occurred at follow-up. The results do not support the hypothesis that the enhancement of attention with stimulant treatment facilitates the acquisition of reading skills in children with pure reading disorders.
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