A U.S. National Study of Family Resilience During the COVID-19 Pandemic.

The COVID-19 pandemic has significantly disrupted the lives of children and their caregivers. Recent research has examined the impact of the pandemic on child and caregiver functioning but there is a paucity of work examining the impact of the pandemic on the broader family system. The current study examined family resilience during the COVID-19 pandemic across three aims: Aim 1 tested whether meaning, control, and emotion systems form a unitary family adaption factor, Aim 2 evaluated a concurrent model of family resilience, and Aim 3 examined whether parent gender and vaccination status moderated paths in the final model. A nationally representative sample of U.S. parents (N = 796; 51.8% fathers, M age = 38.87 years, 60.3% Non-Hispanic White) completed a cross-sectional survey about themselves and one child (5-16 years old) between February-April 2021, including measures of COVID-19 family risk and protective factors, pre-existing family health vulnerabilities, race, COVID-19 stressors, and family adaptation. Confirmatory Factor Analysis demonstrated that the meaning (i.e., family making meaning of COVID-19), control (i.e., stability in routines), and emotional (i.e., family support) facets of family adaptation are unique but related. A path model revealed that there were concurrent effects from COVID-19 exposure, pre-existing vulnerabilities, and racial diversity status to the family protective, vulnerability, and adaptation variables. Additionally, parent COVID-19 vaccination status altered the association between pre-existing family health vulnerabilities and the family protective factor. Overall, results underscore the importance of examining pre-existing and concurrent risk and protective factors for family resilience during a stressful, global, and far-reaching event.

COVID-19 vaccine hesitancy, vaccination, and mental health: A national study among U.S. parents.

The COVID-19 pandemic led to increased mental health concerns among parents. Emerging studies have shown links between COVID-19 vaccine hesitancy and psychological distress, including among parents. The primary aim of this study was to extend these emerging findings by examining the role of COVID-19 vaccine hesitancy in mental health functioning in a national sample of U.S. parents, accounting for the effects of COVID-19 vaccination status and underlying medical conditions increasing COVID-19 risk. A nationally representative sample of U.S. parents (N = 796) completed a cross-sectional survey between February-April 2021, including measures of depressive, anxiety, and COVID-19 acute stress symptoms; COVID-19 vaccination status; underlying medical conditions increasing COVID-19 risk; and COVID-19 vaccine hesitancy. The sample consisted of 51.8% fathers, Mage=38.87 years, 60.3% Non-Hispanic white, 18.1% Hispanic/Latinx, 13.2% Non-Hispanic Black/African American, 5.7% Asian, and 2.8% Other Race. Hierarchical regression models adjusted for demographic covariates revealed that greater COVID-19 vaccination hesitancy and presence of an underlying medical condition were consistently associated with higher levels of depressive, anxiety, and COVID-19 acute stress symptoms among parents. Having had at least one COVID-19 vaccination dose was associated with greater levels of COVID-19 acute stress, but was not associated with depressive or anxiety symptoms. Results add new evidence from the U.S. in support of the link between COVID-19 vaccine hesitancy and psychological distress, point to the potential utility of behavioral health care workers in helping reduce vaccine hesitancy, and provide tentative data suggesting that COVID-19 vaccination for parents alone may not have provided mental health relief.

Characterisation of infection-induced SARS-CoV-2 seroprevalence amongst children and adolescents in North Carolina.

Few prospective studies have documented the seropositivity among those children infected with severe acute respiratory syndrome coronavirus 2. From 2 April 2021 to 24 June 2021, we prospectively enrolled children between the ages of 2 and 17 years at three North Carolina healthcare systems. Participants received at least four at-home serological tests detecting the presence of antibodies against, but not differentiating between, the nucleocapsid or spike antigen. A total of 1,058 participants were enrolled in the study, completing 2,709 tests between 1 May 2021 and 31 October 2021. Using multilevel regression with poststratification techniques and considering our assay sensitivity and sensitivity, we estimated that the seroprevalence of infection-induced antibodies among unvaccinated children and adolescents aged 2-17 years in North Carolina increased from 15.2% (95% credible interval, CrI 9.0-22.0) in May 2021 to 54.1% (95% CrI 46.7-61.1) by October 2021, indicating an average infection-to-reported-case ratio of 5. A rapid rise in seropositivity was most pronounced in those unvaccinated children aged 12-17 years, based on our estimates. This study underlines the utility of serial, serological testing to inform a broader understanding of the regional immune landscape and spread of infection.

Estimated COVID-19 vaccine effectiveness against seroconversion from SARS-CoV-2 Infection, March-October, 2021.

BACKGROUND: Monitoring the effectiveness of COVID-19 vaccines against SARS-CoV-2 infections remains important to inform public health responses. Estimation of vaccine effectiveness (VE) against serological evidence of SARS-CoV-2 infection might provide an alternative measure of the benefit of vaccination against infection. METHODS: We estimated mRNA COVID-19 vaccine effectiveness (VE) against development of SARS-CoV-2 anti-nucleocapsid antibodies in March-October 2021, during which the Delta variant became predominant. Participants were enrolled from four participating healthcare systems in the United States, and completed electronic surveys that included vaccination history. Dried blood spot specimens collected on a monthly basis were analyzed for anti-spike antibodies, and, if positive, anti-nucleocapsid antibodies. We used detection of new anti-nucleocapsid antibodies to indicate SARS-CoV-2 infection, and estimated VE by comparing 154 case-participants with new detection of anti-nucleocapsid antibodies to 1,540 seronegative control-participants matched by calendar period. Using conditional logistic regression, we estimated VE ≥ 14 days after the 2nd dose of an mRNA vaccine compared with no receipt of a COVID-19 vaccine dose, adjusting for age group, healthcare worker occupation, urban/suburban/rural residence, healthcare system region, and reported contact with a person testing positive for SARS-CoV-2. RESULTS: Among individuals who completed a primary series, estimated VE against seroconversion from SARS-CoV-2 infection was 88.8% (95% confidence interval [CI], 79.6%-93.9%) after any mRNA vaccine, 87.8% (95% CI, 75.9%-93.8%) after BioNTech vaccine and 91.7% (95% CI, 75.7%-97.2%) after Moderna vaccine. VE was estimated to be lower ≥ 3 months after dose 2 compared with < 3 months after dose 2, and among participants who were older or had underlying health conditions, although confidence intervals overlapped between subgroups. CONCLUSIONS: VE estimates generated using infection-induced antibodies were consistent with published estimates from clinical trials and observational studies that used virologic tests to confirm infection during the same period. Our findings support recommendations for eligible adults to remain up to date with COVID-19 vaccination.

Reflex cardioinhibitory syncope potentially related to SARS-CoV-2 infection: a case report / Síncope cardioinibitória reflexa potencialmente relacionada à infecção por SARS-CoV-2: um relato de caso

Autonomic dysfunction related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is increasingly described in the literature. We report the case of a 30-year-old male with a background of asthma and migraine who experienced a second episode of SARS-CoV-2 infection characterized by mild respiratory symptoms. Twenty-four days after the symptom onset, he developed acute syncope. A tilt test revealed a neuromediated cardioinhibitory response with asystole (Vasovagal Syncope International Study ­ VASIS type 2B). The temporal association between SARS-CoV-2 infection and syncope seems to indicate a probable causal relationship, which requires corroboration by future studies.

Disfunção autonômica relacionada à infecção por coronavírus-2 da síndrome respiratória aguda grave (SARS-CoV-2) vem sendo cada vez mais descrita na literatura. Relatamos o caso de um homem de 30 anos de idade, com histórico de asma e enxaqueca, que apresentou um segundo episódio de infecção por SARS-CoV-2 caracterizado por sintomas respiratórios leves. Vinte e quatro dias após o início dos sintomas, desenvolveu um quadro agudo de síncope. Um teste de inclinação revelou uma resposta cardioinibitória neuromediada com assistolia (Vasovagal Syncope International Study ­ VASIS tipo 2B). A associação temporal entre infecção por SARS-CoV-2 e síncope parece indicar uma provável relação causal, a qual requer corroboração por estudos futuros.

Race, Ethnicity, and Health Disparities in US Children With COVID-19: A Review of the Evidence and Recommendations for the Future.

Coronavirus disease 2019 (COVID-19) is an important cause of morbidity in children in the United States (U.S.). Moreover, the U.S. has witnessed significant disparities affecting American Indian/Alaska Native, Black, and Hispanic/Latino children, stemming from systemic racism and social-structural inequalities and not differences in innate biological susceptibility. We review what is known on COVID-19 and health disparities in disease burden, access to care, pharmaceutical interventions, and clinical research in children, with a focus on the U.S. context. In addition, we propose strategies to communicate scientific data in ways that do not promote racism and biological susceptibility themes, and to address pediatric disparities in clinical infectious diseases research.

Self-Reported SARS-CoV-2 Vaccination Is Consistent with Electronic Health Record Data among the COVID-19 Community Research Partnership.

Introduction: Observational studies of SARS-CoV-2 vaccine effectiveness depend on accurate ascertainment of vaccination receipt, date, and product type. Self-reported vaccine data may be more readily available to and less expensive for researchers than assessing medical records. Methods: We surveyed adult participants in the COVID-19 Community Research Partnership who had an authenticated Electronic Health Record (EHR) (N = 41,484) concerning receipt of SARS-CoV-2 vaccination using a daily survey beginning in December 2020 and a supplemental survey in September-October 2021. We compared self-reported information to that available in the EHR for the following data points: vaccine brand, date of first dose, and number of doses using rates of agreement and Bland-Altman plots for visual assessment. Self-reported data was available immediately following vaccination (in the daily survey) and at a delayed interval (in a secondary supplemental survey). Results: For the date of first vaccine dose, self-reported "immediate" recall was within ±7 days of the date reported in the "delayed" survey for 87.9% of participants. Among the 19.6% of participants with evidence of vaccination in their EHR, 95% self-reported vaccination in one of the two surveys. Self-reported dates were within ±7 days of documented EHR vaccination for 97.6% of the "immediate" surveys and 92.0% of the "delayed" surveys. Self-reported vaccine product details matched those in the EHR for over 98% of participants for both "immediate" and "delayed" surveys. Conclusions: Self-reported dates and product details for COVID-19 vaccination can be a good surrogate when medical records are unavailable in large observational studies. A secondary confirmation of dates for a subset of participants with EHR data will provide internal validity.

Pharmacokinetic, Hemostatic, and Anticancer Properties of a Low-Anticoagulant Bovine Heparin.

Heparin is a centennial anticoagulant drug broadly employed for treatment and prophylaxis of thromboembolic conditions. Although unfractionated heparin (UFH) has already been shown to have remarkable pharmacological potential for treating a variety of diseases unrelated with thromboembolism, including cancer, atherosclerosis, inflammation, and virus infections, its high anticoagulant potency makes the doses necessary to exert non-hemostatic effects unsafe due to an elevated bleeding risk. Our group recently developed a new low-anticoagulant bovine heparin (LABH) bearing the same disaccharide building blocks of the UFH gold standard sourced from porcine mucosa (HPI) but with anticoagulant potency approximately 85% lower (approximately 25 and 180 Heparin International Units [IU]/mg). In the present work, we investigated the pharmacokinetics profile, bleeding potential, and anticancer properties of LABH administered subcutaneous into mice. LABH showed pharmacokinetics profile similar to HPI but different from the low-molecular weight heparin (LMWH) enoxaparin and diminished bleeding potential, even at high doses. Subcutaneous treatment with LABH delays the early progression of Lewis lung carcinoma, improves survival, and brings beneficial health outcomes to the mice, without the advent of adverse effects (hemorrhage/mortality) seen in the animals treated with HPI. These results demonstrate that LABH is a promising candidate for prospecting new therapeutic uses for UFH.

Active Surveillance With Seroprevalence-based Infection Rates Indicates Racial Disparities With Pediatric SARS-CoV-2 Requiring Hospitalization in Mississippi, March 2020-February 2021.

BACKGROUND: Racial disparities in SARS-CoV-2 infection, hospitalization, and multisystem inflammatory syndrome in children (MIS-C) have been reported. However, these reports have been based on incomplete data relying on passive reporting, unknown catchment populations, and unknown infection prevalence. We aimed to characterize population-based incidence of MIS-C and COVID-19 hospitalizations among non-Hispanic Black and White children using active surveillance based on seroprevalence-based cumulative incidence of pediatric SARS-CoV-2 infection in a defined catchment 16-county area of Mississippi. METHODS: Active, population-based surveillance for MIS-C and acute COVID-19 hospitalizations meeting clinical and laboratory criteria was conducted by adjudicating clinicians at the major pediatric referral hospital for Mississippi, University of Mississippi Medical Center, from March 2020, to February 2021. Race-stratified SARS-CoV-2 seroprevalence was estimated using convenience samples from persons <18 years to calculate cumulative SARS-CoV-2 infections in the population. RESULTS: Thirty-eight MIS-C cases and 74 pediatric acute COVID-19 hospitalizations were identified. Cumulative incidence of MIS-C was 4.7 times higher among Black compared with White children (40.7 versus 8.3 cases per 100,000 SARS-CoV-2 infections). Cumulative incidence of COVID-19 hospitalization was 62.3 among Black and 33.1 among White children per 100,000 SARS-CoV-2 infections. CONCLUSIONS: From the same catchment area, active surveillance, and cumulative incidence of infection estimated by seroprevalence, we show strikingly higher incidence of SARS-CoV-2-hospitalization and MIS-C in non-Hispanic Black children compared with White children before COVID-19 vaccination introduction in children. These disparities in SARS-CoV-2 manifestations cannot be accounted for by differences in exposure or testing. Targeted vaccine interventions will lessen disparities observed with SARS-CoV-2 manifestations in children.

Behavioral, Affective, and Cognitive Parenting Mechanisms of Child Internalizing and Externalizing Problems during the COVID-19 Pandemic.

The COVID-19 pandemic has led to increased mental health concerns, including depression and anxiety among parents and internalizing and externalizing problems among youth. To better understand the mechanisms and moderators of child mental health during the pandemic, the current study tested two moderated mediation models in which parent depression and anxiety indirectly impacted child internalizing and externalizing problems through negative effects on multiple parenting variables, with these associations moderated by families' exposure to COVID-19-stressors. A national sample representative of U.S. parents (N = 796, 48.2% female, Mage = 38.87 years, 60.3% Non-Hispanic white, 18.1% Hispanic/Latinx, 13.2% Non-Hispanic Black/African-American, 5.7% Asian, 2.8% Other Race) completed a cross-sectional online survey in February-April 2021. Children ranged from 5-16 years old (Mage = 10.35 years, 59.8% Non-Hispanic white, 17.2% Hispanic/Latinx, 13.7% Non-Hispanic Black/African-American, 4.5% Asian, 4.8% Other Race). Parent depression/anxiety was directly and indirectly associated with child internalizing and externalizing problems. For both internalizing and externalizing problems, indirect associations occurred by means of increased parent hostility and inconsistent discipline and decreased routines and parent supportiveness. There were also specific indirect effects through decreased monitoring (internalizing problems) and parenting self-efficacy (externalizing problems). Multiple indirect effects were moderated by number of COVID-19-stressors experienced. Notably, COVID-19-stressors did not have direct effects on child mental health when other variables were considered. Findings highlight the buffering effects of parents for child mental health, the need to address parent depression/anxiety in child interventions, the utility of existing evidence-based parent interventions during the pandemic, and the need to assess families' level of exposure to COVID-19-stressors.

The use of intravenous palivizumab for treatment of persistent RSV infection in children with leukemia.

Palivizumab is a humanized monoclonal antibody used to decrease the threat of respiratory syncytial virus (RSV) infection among children at high risk. There are no standard guidelines due to conflicting data on palivizumab's use in the treatment of RSV lower respiratory tract infections. Intravenous (IV) palivizumab was shown to be well tolerated and associated with decreased mortality in high-risk children who have RSV disease. However, it did not prevent lower respiratory tract infections and did not affect the survival rate of allogeneic stem cell transplant recipients who had RSV infection. We present 2 children with acute lymphocytic leukemia (ALL) and persistent RSV infection while receiving chemotherapy. Patient A is a 4-year-old male with Down syndrome, ALL, and persistent RSV infection for at least 3 months. Patient B is a 3-year-old female with pre-B cell ALL whose chemotherapy intensification phase was delayed due to a month-long RSV infection. RSV infections were determined by using real-time polymerase chain reaction assays from nasopharyngeal swabs before IV palivizumab therapy; patient A was positive for RSV at 36 cycles and patient B was positive for RSV at 29 cycles. RSV infection was cleared in both patients within 72 hours after receiving IV palivizumab (patient A: 16 mg/kg; patient B: 15 mg/kg). IV palivizumab may be a treatment option for persistent RSV infection among immunocompromised patients.

Deep sequencing reveals mixed infection with 2009 pandemic influenza A (H1N1) virus strains and the emergence of oseltamivir resistance.

Mixed infections with seasonal influenza A virus strains are a common occurrence and an important source of genetic diversity. Prolonged viral shedding, as observed in immunocompromised individuals, can lead to mutational accumulation over extended periods. Recently, drug resistance was reported in immunosuppressed patients infected with the 2009 pandemic influenza A (H1N1) virus within a few days after oseltamivir treatment was initiated. To better understand the evolution and emergence of drug resistance in these circumstances, we used a deep sequencing approach to survey the viral population from an immunosuppressed patient infected with H1N1/2009 influenza and treated with neuraminidase inhibitors. This patient harbored 3 genetic variants from 2 phylogenetically distinct viral clades of pandemic H1N1/2009, strongly suggestive of mixed infection. Strikingly, one of these variants also developed drug resistance de novo in response to oseltamivir treatment. Immunocompromised individuals may, therefore, constitute an important source of genetic and phenotypic diversity, both through mixed infection and de novo mutation.

Pharmacokinetics and pharmacodynamics of linezolid in children with cystic fibrosis.

UNLABELLED: Alternative antimicrobial regimens are needed for treatment of methicillin-resistant Staphylococcus aureus (MRSA)-associated pulmonary exacerbations in children with cystic fibrosis (CF). There are no published pharmacokinetic (PK) and pharmacodynamic (PD) data for linezolid in children with CF. OBJECTIVES: (1) To determine the PK and PD profile of linezolid among children with CF; (2) to characterize the effect of linezolid on MRSA infection; (3) to determine the effect of age and CF transmembrane regulator (CFTR) gene mutations on drug clearance. HYPOTHESES: Linezolid clearance is enhanced in children with CF requiring a higher dosage regimen. Age and CFTR gene mutations affect drug clearance. METHODS: This was a retrospective cohort study; medical records of children with MRSA-associated pulmonary exacerbations treated with linezolid (10 mg/kg/dose IV every 8h) were reviewed. Linezolid peak and trough concentrations in serum were determined by high performance liquid chromatography, PK profiles determined using standard noncompartmental method, and PD indices were evaluated. RESULTS: 10 children (mean +/- SD, 10.2 +/- 5.5 years) received 14 courses of linezolid at 10 +/- 0.4 mg/kg/dose every 8h for 15.4 +/- 3.2 days. Seven had homozygous DeltaF508 CFTR mutation. Peak and trough linezolid concentrations varied widely (range, 8.4-20.5 and 0.1-11.5 mcg/mL respectively). The PK profile of children <10 years differed significantly from older patients (>or=10 years). The PK indices of children with homozygous DeltaF508 differed marginally from those with heterozygous CFTR mutations, but there were too few subjects to allow separation of age and CFTR mutations effect. No patient achieved the target PD ratio of AUC/MIC >80. MRSA persisted in sputum or throat culture after treatment with linezolid. CONCLUSIONS: Additional PK and PD data are needed to optimize linezolid therapy in children with cystic fibrosis; it is likely that higher doses will be needed.

Healthcare epidemiology: active surveillance cultures and contact precautions for control of multidrug-resistant organisms: ethical considerations.

Infection control personnel are required to develop institutional guidelines for prevention of transmission of multidrug-resistant organisms, especially methicillin-resistant Staphylococcus aureus, within health care settings. Such guidelines include performance of active surveillance cultures for patients after admission to health care facilities or to high-risk-patient care units, to detect colonization with target multidrug-resistant organisms. Patients who are colonized with these potential pathogens are placed under contact precautions to prevent transmission to other patients. Such screening programs are labor and resource intensive and raise the following ethical considerations: (1) autonomy versus communitarianism, (2) indication for informed consent for obtainment of active surveillance cultures, and (3) identification of the appropriate payer. Relevant infection control, public health, and ethical principles are reviewed in an effort to provide guidance for ethical decision making when designing a multidrug-resistant organism control program that includes active surveillance cultures and contact precautions. We conclude that a program of active surveillance cultures and contact precautions is part of standard medical care that requires patient education but not a specific informed consent and that the cost for such programs should be assigned to the health care institution, not the individual patient.

Nevirapine-associated rash with eosinophilia and systemic symptoms in a child with human immunodeficiency virus infection.

Drug rash with eosinophilia and systemic symptoms (DRESS Syndrome) associated with nevirapine treatment has not been previously reported in children. These findings can mimic other common illnesses, and treatment options are limited. We describe a 12-year-old girl infected with human immunodeficiency virus who developed hypersensitivity to nevirapine therapy. She was successfully treated with intravenous immune globulin.

Successful medical treatment of cutaneous aspergillosis in a premature infant using liposomal amphotericin B, voriconazole and micafungin.

Treatment options for primary cutaneous aspergillosis in neonates are limited by the lack of pharmacokinetic and safety data of newer antifungal agents that are effective against Aspergillus spp. We report the successful treatment of cutaneous aspergillosis in an extremely low-birth-weight preterm infant with liposomal amphotericin B, voriconazole and micafungin, and provide pharmacokinetic profiles for voriconazole and micafungin.

Inhaled tobramycin solution-associated recurrent eosinophilia and severe persistent bronchospasm in a patient with cystic fibrosis: a case report.

BACKGROUND: Delivery of tobramycin by inhalation to the lungs of patients with cystic fibrosis (CF) who are infected with Pseudomonas aeruginosa has been proven to be effective and safe. The aerosol administration allows high concentrations of tobramycin to be delivered to the site of infection with limited systemic absorption. In rare patients, systemic absorption of inhaled tobramycin may be significant enough to produce toxic effects, such as renal and vestibular toxicities. CASE PRESENTATION: We report a patient with CF who developed recurrent eosinophilia and severe persistent bronchospasm following repeated administration of preservative-free tobramycin by inhalation, beginning at 16 months of age. Also, he developed similar signs and symptoms when he was administered tobramycin intravenously on one occasion at 5 1/2 years. The patient had a history of environmental allergies. Temporal sequence of his signs and symptoms after each administration of tobramycin (similar to re-challenge testing), and his improvement after discontinuation of the drug strongly suggest an adverse drug reaction. CONCLUSION: Hypersensitivity reaction should be considered in patients who develop recurrent eosinophilia and deterioration of pulmonary function following the use of tobramycin by inhalation or by intravenous administration.

Difficulty in recognizing multiple sulfatase deficiency in an infant.

We describe the difficulty in recognizing multiple sulfatase deficiency (MSD; Online Mendelian Inheritance in Man [OMIM] database No. 272200) in an infant. MSD is a rare autosomal recessive disorder that affects the posttranslational activation of various sulfatase enzymes. It is both biochemically and clinically variable. Currently, there are 12 known sulfatases in humans, and the clinical presentation of MSD is a unique composite of those individual enzyme defects. Here we report a black girl who presented with bilateral broad thumbs and great toes, both with angulation deformities at birth. Rubinstein-Taybi syndrome (OMIM No. 180849) was considered initially. The detection of inclusion bodies in her white blood cells at 37 months of age led to the appropriate diagnostic workups for lysosomal storage diseases. Elevation of urine mucopolysaccharides provided additional clues, and the fibroblast enzyme assays finally established the diagnosis. Broad thumbs and great toes are rare features of MSD, and to the best of our knowledge such a bilateral congenital anomaly with angulation deformities has never been reported before to be associated with MSD.

Transient neonatal jitteriness due to maternal use of sertraline (Zoloft).

We describe the occurrence of marked jitteriness and an enhanced startle response in a term infant after being exposed to sertraline in utero. An umbilical cord blood sample taken at the time of birth showed a sertraline concentration (<10 ng/mL) below the reference range. On the third day during the peak of the symptoms, sertraline plasma concentration was <10 ng/mL, while his serotonin level (6 ng/mL) was below the reference range. The neurologic symptoms resolved by the fifth day. To date, there are no reports of transient neonatal jitteriness with maternal use of sertraline documented with low cord and neonatal plasma samples consistent with withdrawal syndrome.