A randomized double-blinded trial to assess recurrence of systemic allergic reactions following COVID-19 mRNA vaccination.

BACKGROUND: Systemic allergic reactions (sARs) following coronavirus disease 2019 (COVID-19) mRNA vaccines were initially reported at a higher rate than after traditional vaccines. OBJECTIVE: We aimed to evaluate the safety of revaccination in these individuals and to interrogate mechanisms underlying these reactions. METHODS: In this randomized, double-blinded, phase 2 trial, participants aged 16 to 69 years who previously reported a convincing sAR to their first dose of COVID-19 mRNA vaccine were randomly assigned to receive a second dose of BNT162b2 (Comirnaty) vaccine and placebo on consecutive days in a blinded, 1:1 crossover fashion at the National Institutes of Health. An open-label BNT162b2 booster was offered 5 months later if the second dose did not result in severe sAR. None of the participants received the mRNA-1273 (Spikevax) vaccine during the study. The primary end point was recurrence of sAR following second dose and booster vaccination; exploratory end points included biomarker measurements. RESULTS: Of 111 screened participants, 18 were randomly assigned to receive study interventions. Eight received BNT162b2 second dose followed by placebo; 8 received placebo followed by BNT162b2 second dose; 2 withdrew before receiving any study intervention. All 16 participants received the booster dose. Following second dose and booster vaccination, sARs recurred in 2 participants (12.5%; 95% CI, 1.6 to 38.3). No sAR occurred after placebo. An anaphylaxis mimic, immunization stress-related response (ISRR), occurred more commonly than sARs following both vaccine and placebo and was associated with higher predose anxiety scores, paresthesias, and distinct vital sign and biomarker changes. CONCLUSIONS: Our findings support revaccination of individuals who report sARs to COVID-19 mRNA vaccines. Distinct clinical and laboratory features may distinguish sARs from ISRRs.

Pandemic-Related Post-traumatic Stress Symptomatology in COVID-19 Patients with and without Post-COVID Conditions.

Trauma and stressor-related symptoms have been frequently reported during the COVID-19 pandemic. Few studies compare post-traumatic stress symptoms (PTSS) between patients and non-infected controls. Using data from an ongoing natural history study of COVID-19, this study compared PTSS between patients infected with SARS-CoV-2 during the first year of the pandemic and controls. Within the COVID-19 patient cohort, we also compared PTSS between patients with and without post-COVID conditions, also known as post-acute sequelae of SARS-CoV-2 infection (PASC). This study also examined the association of PTSS with trait resilience and prior trauma exposure. PTSS were assessed using the Impact of Event Scaled-Revised (IES-R), which has a validated probable PTSD cutoff (score ≥33). The results showed that patients (n=131) reported significantly higher IES-R scores than controls (n=82) and had significantly higher odds of having scores indicative of PTSD [AOR: 4.17 p: 0.029]. IES-R scores among PASC patients (n=68) were significantly elevated compared to patients without PASC (n=63) and PASC patients did not have higher odds for probable PTSD [AOR: 2.60; p: 0.14]. Trait resilience was associated with lower PTSS. These findings help characterize the mental health impact of the COVID-19 illness experience and highlight elevated PTSS in patients with persistent post-COVID conditions.

Changes in Serum Concentration of Antidepressants After Bariatric Surgery and Recommendations for Postbariatric Surgery Antidepressant Therapy.

BACKGROUND: Bariatric surgery affects the absorption of medications including antidepressants, but data regarding these effects are limited. OBJECTIVES: Our objectives were to review publicly available data regarding changes in antidepressant serum concentration following bariatric surgery in order to develop medication dosing recommendations in this patient population. METHODS: A comprehensive literature review was performed utilizing key search terms in Pubmed. Additional data were retrieved from the Food and Drug Administration and DrugBank Online resources. RESULTS: A total of twelve published articles were included in addition to the publicly available data from the Food and Drug Administration and DrugBank. The serum concentration of antidepressants following bariatric surgery demonstrated considerable variability between and within drug classes due to unique pharmacokinetic features, drug preparation, and formulation. Recommendations were developed from published data regarding changes in serum concentration and drug-specific pharmacokinetic data. CONCLUSIONS: To our knowledge, this is the first study to propose medication dose-adjustment recommendations for patients on antidepressants undergoing bariatric surgery. We were limited by the relatively small amount of data available and recommend monitoring patients and use of clinical judgment along with this guidance.

Pediatric Consultation-Liaison (C-L) Psychiatry Training Pathways.

This perspective piece reviews the current training pathways for pediatric consultation-liaison psychiatry. Significant workforce shortages of child and adolescent psychiatry over the past 3 decades have led to the creation of new training pathways between pediatrics and child and adolescent psychiatry training programs to care for children whose medical and psychiatric management has become increasingly complex. There are now several options available to receive excellent training in pediatric consultation-liaison. Efforts to foster continued interactions and shared education between adult and pediatric consultation-liaison providers are likely to be beneficial to both disciplines given the astonishing advances in technology over the years that have allowed many patients with complex childhood medical disorders to survive into adulthood today.

The Emotional and Personal Experiences of the COVID-19 Illness During the Early Pandemic: A Qualitative Study.

BACKGROUND: Several studies report the incidence of psychiatric symptoms and disorders among patients who recovered from coronavirus disease 2019 (COVID-19); however, little is known about the emotional impact of acute COVID-19 illness and recovery on these survivors. Qualitative methods are ideal for understanding the psychological impact of a novel illness. OBJECTIVE: To describe the emotional experience of the acute COVID-19 illness and recovery in patients who contracted the virus during the early months of the pandemic. METHODS: Semi-structured interviews conducted by consultation-liaison (C-L) psychiatrists were used to elicit participant responses about the emotional impact of the acute and recovery phases of the COVID-19 illness. Participants recruited from the Maryland, District of Columbia, and Virginia area were interviewed which was audio recorded between June 2020 and December 2020. The research team extracted qualitative themes from the recordings using the principles of thematic analysis. RESULTS: One hundred and one COVID-19 survivors (54 women; mean [SD] age, 50 [14.7] years) were interviewed at a mean of 5.16 months after their acute illness, and their responses were audio-recorded. Most participants were White (77%), non-Hispanic/Latino (86.1%), and not hospitalized for COVID-19 (87.1%). Coders identified 26 themes from participant responses. The most frequently coded themes included anxiety/worry (49), uncertainty (37), supportfrom others (35), alone/isolation (32), and positive reframe/positive emotions (32). CONCLUSIONS: Survivors who contracted severe acute respiratory syndrome coronavirus 2 during the early months of the pandemic described both negative and positive valence emotions. They experienced emotional distress and psychosocial stressors associated with the acute illness and recovery but also drew upon personal resiliency to cope. This report highlights the utility of qualitative research methods in identifying emotional responses to a novel illness that may otherwise go unnoted. Consultation-liaison psychiatrists may be uniquely positioned to work in collaboration with medical colleagues in developing a multidimensional approach to evaluating an emerging illness.

A Longitudinal Study of COVID-19 Sequelae and Immunity: Baseline Findings.

BACKGROUND: A substantial proportion of persons who develop COVID-19 report persistent symptoms after acute illness. Various pathophysiologic mechanisms have been implicated in the pathogenesis of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To characterize medical sequelae and persistent symptoms after recovery from COVID-19 in a cohort of disease survivors and controls. DESIGN: Cohort study. (ClinicalTrials.gov: NCT04411147). SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland. PARTICIPANTS: Self-referred adults with laboratory-documented SARS-CoV-2 infection who were at least 6 weeks from symptom onset were enrolled regardless of presence of PASC. A control group comprised persons with no history of COVID-19 or serologic evidence of SARS-CoV-2 infection, recruited regardless of their current health status. Both groups were enrolled over the same period and from the same geographic area. MEASUREMENTS: All participants had the same evaluations regardless of presence of symptoms, including physical examination, laboratory tests and questionnaires, cognitive function testing, and cardiopulmonary evaluation. A subset also underwent exploratory immunologic and virologic evaluations. RESULTS: 189 persons with laboratory-documented COVID-19 (12% of whom were hospitalized during acute illness) and 120 antibody-negative control participants were enrolled. At enrollment, symptoms consistent with PASC were reported by 55% of the COVID-19 cohort and 13% of control participants. Increased risk for PASC was noted in women and those with a history of anxiety disorder. Participants with findings meeting the definition of PASC reported lower quality of life on standardized testing. Abnormal findings on physical examination and diagnostic testing were uncommon. Neutralizing antibody levels to spike protein were negative in 27% of the unvaccinated COVID-19 cohort and none of the vaccinated COVID-19 cohort. Exploratory studies found no evidence of persistent viral infection, autoimmunity, or abnormal immune activation in participants with PASC. LIMITATIONS: Most participants with COVID-19 had mild to moderate acute illness that did not require hospitalization. The prevalence of reported PASC was likely overestimated in this cohort because persons with PASC may have been more motivated to enroll. The study did not capture PASC that resolved before enrollment. CONCLUSION: A high burden of persistent symptoms was observed in persons after COVID-19. Extensive diagnostic evaluation revealed no specific cause of reported symptoms in most cases. Antibody levels were highly variable after COVID-19. PRIMARY FUNDING SOURCE: Division of Intramural Research, National Institute of Allergy and Infectious Diseases.

Adaptations Made to Pediatric Consultation-Liaison Psychiatry Service Delivery During the Early Months of the COVID-19 Pandemic: A North American Multisite Survey.

BACKGROUND: The COVID-19 pandemic led to rapid changes in clinical service delivery across hospital systems nationally. Local realities and resources were key driving factors impacting workflow changes, including for pediatric consultation-liaison psychiatry service (PCLPS) providers. OBJECTIVE: This study aims to describe the early changes implemented by 22 PCLPSs from the United States and Canada during the COVID-19 pandemic. Understanding similarities and differences in adaptations made to PCLPS care delivery can inform best practices and future models of care. METHODS: A 20-point survey relating to PCLPS changes during the COVID-19 pandemic was sent to professional listservs. Baseline hospital demographics, hospital and PCLPS workflow changes, and PCLPS experience were collected from March 20 to April 28, 2020, and from August 18 to September 10, 2020. Qualitative data were collected from responding sites. An exploratory thematic analysis approach was used to analyze the qualitative data that were not dependent on predetermined coding themes. Descriptive statistics were calculated using Microsoft Excel. RESULTS: Twenty-two academic hospitals in the United States and Canada responded to the survey, with an average of 303 beds/hospital. Most respondents (18/22) were children's hospitals. Despite differences in regional impact of COVID-19 and resource availability, there was significant overlap in respondent experiences. Restricted visitation to one caregiver, use of virtual rounding, ongoing trainee involvement, and an overall low number of COVID-positive pediatric patients were common. While there was variability in PCLPS care delivery occurring virtually versus in person, all respondents maintained some level of on-site presence. Technological limitations and pediatric provider preference led to increased on-site presence. CONCLUSIONS: To our knowledge, this is the first multicenter study exploring pandemic-related PCLPS changes in North America. Findings of this study demonstrate that PCLPSs rapidly adapted to COVID-19 realities. Common themes emerged that may serve as a model for future practice. However, important gaps in understanding their effectiveness and acceptability need to be addressed. This multisite survey highlights the importance of establishing consensus through national professional organizations to inform provider and hospital practices.

Gene expression profiles predict emergence of psychiatric adverse events in HIV/HCV-coinfected patients on interferon-based HCV therapy.

BACKGROUND: The efficacy of pegylated interferon-α and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns before therapy to predict emergent IFN-PE among 28 HIV/HCV-coinfected patients treated with pegIFN-α2b/RBV. METHODS: Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE). Gene expression analysis (Affymetrix HG-U133A) was performed using peripheral blood mononuclear cells before and after initiation of treatment. Analysis of Variance, post hoc analysis based on pair-wise comparisons, and functional annotation analysis identified differentially expressed genes within and between groups. Prediction analysis for microarrays was used to test the predictive ability of selected genes. RESULTS: Twenty-four genes (16 upregulated and 8 downregulated) that were differentially expressed at baseline in patients who subsequently developed IFN-PE compared with the IFN-NPE group showed the ability to predict IFN-PE with an accuracy of 82%. In 16 patients with IFN-PE, 135 genes (117 upregulated; 18 downregulated) were significantly modulated after treatment. Of these, 10 genes have already been shown to be associated with neuropsychiatric illnesses and were significantly modulated only in patients who experienced IFN-PE. CONCLUSIONS: We describe a novel molecular diagnostic biomarker panel to predict emergent IFN-PE in HIV/HCV-coinfected patients undergoing pegIFN/RBV treatment, which may improve the identification of patients at greatest risk for IFN-PE and suggest candidate therapeutic targets for preventing or treating IFN-PE.

Mania: psychiatric manifestations of the antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is a prothrombotic condition characterized by recurrent vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies. Central nervous system (CNS) involvement is a prominent feature of APS, and many neurological manifestations have been described in published reports. There are limited data on psychiatric syndromes occurring in association with APS, and there have been no previous reports of mania associated with APS. METHOD: The authors present the case of a 31-year-old man who experienced an acute manic episode in association with APS. They review the literature on psychiatric manifestations of APS, discuss potential mechanisms of CNS pathogenesis, and consider diagnostic and treatment implications of the co-occurrence of APS and psychiatric symptoms.

Pediatric psychosomatic medicine: an annotated bibliography.

This annotated bibliography is intended to be a resource in the essentials of pediatric psychosomatic medicine for the psychosomatic-medicine fellow. The publication list provides practical references for multiple clinical issues relevant to children and adolescents with medical illness and includes major developmental considerations, familial interactions, diagnostic categories, and pharmacologic concerns. Although it encompasses a range of topics, the proposed bibliography is not an exhaustive resource for fellowship training, but rather a first step toward developing a standard curriculum in pediatric psychosomatic medicine.

Facilitating treatment of anxiety disorders in patients with comorbid medical illness.

Anxiety is a universal human response that usually is adaptive, allowing one to prepare for a perceived threat. This can be a normal coping mechanism when dealing with a medical illness that may require hospitalization, surgery, or painful procedures. It becomes maladaptive when it is persistent and leads to panic attacks, severe physical symptoms, and impairment in functioning. Most of these patients are treated by primary care providers who frequently fail to adequately recognize and treat anxiety disorders in their patients. This leads to increased health care costs and chronic disability. To reach this under-served group of patients, mental health practitioners need to collaborate with their primary care colleagues to provide screening tools and education on diagnosis and effective treatment of these disorders.