Project description:RNA was extracted from whole blood of subjects collected in Tempus tubes prior to COVID-19 mRNA booster vaccination. D01 and D21 correspond to samples collected at pre-dose 1 and pre-dose 2 respectively. RNA was also extracted from blood collected at indicated time points post-vaccination. DB1, DB2, DB4 and DB7 correspond to booster day 1 (pre-booster), booster day 2, booster day 4 and booster day 7 respectively. The case subject experienced cardiac complication following mRNA booster vaccination. We performed gene expression analysis of case versus controls over time.
Project description:ObjectiveThis study examined how the COVID-19 pandemic differently affected households of children with versus without special healthcare needs. We compared caregivers' and children's emotional well-being (Aim 1), the utilization of preventive healthcare services for young children (Aim 2), and the promotive effects of social support on well-being outcomes (Aim 3) during the pandemic between the two groups.MethodsData were drawn from an ongoing, large, longitudinal, and national survey that assessed the pandemic impact on households of young children (0-5). Analyses for Aims 1 and 2 were based on 10,572 households, among which 10.96% had children with special healthcare needs. Analyses for Aim 3 were based on a subsample of 821 families, among which 12.54% had children with special healthcare needs.ResultsCaregivers of children with special healthcare needs exhibited more emotional distress and reported higher levels of household children's behavioral problems during the pandemic. The percentages of missed preventive healthcare visits and vaccinations were also higher in families of children with special healthcare needs due to structural barriers. Lastly, emotional social support was indirectly related to children's decreased behavioral problems through caregivers' reduced emotional distress, only among households of children without special healthcare needs. In other words, social support alone was not sufficient in promoting caregivers' and children's better well-being outcomes among households of children with special healthcare needs.ConclusionsThe pandemic has caused extensive burdens on families of children with special healthcare needs. Actions from policymakers and early intervention service providers are urgently needed to mitigate these impacts.
Project description:Purpose: This study aims to characterize the early innate and adaptive responses induced by SARS-CoV-2 infection in children and adults over time up to 8 weeks post symptoms onset (POS). We report the gene signature of COVID-19 over the course of the disease in both age groups. The kinetic of infection was divided in 5-time intervals according to the calculated days POS: interval 1 (0-5), interval 2 (6-14), interval 3 (15-22), interval 4 (23-35), and interval 5 (36-81). Methods: RNA extraction was performed automatically via the PAXgene Blood miRNA Kit and the QIAcube instrument (Qiagen) following the manufacturer’s protocol. RNA concentration and quality were assessed by using the Qubit instrument (Invitrogen) and the Agilent 2100 Bioanalyzer, respectively. The Stranded Total RNA Ribo-Zero Plus kit from Illumina was used for the library preparation with 100 ng of total RNA as input. Library molarity and quality were assessed with the Qubit and Tapestation using a DNA High sensitivity chip (Agilent Technologies). Libraries were pooled at 2 nM for clustering and sequenced on an Illumina HiSeq 4000 sequencer for a minimum of 30 million single-end 100 reads per sample. Main results: (I) we observed an antiviral-IFN-signature and innate-cell-activation within the first 5 days post symptoms onset (POS), while genes associated with CD4 T-cell responses, plasma cells and immunoglobulin were upregulated in both age groups during the first two weeks POS, indicative of SARS-CoV-2-specific adaptive immune responses; (II) in adults, genes associated with IFN antiviral responses and activated dendritic cells were maintained during the second week of disease, and subsided only after 14 days. By contrast, those transcriptome changes subsided already after 5 days in children.
Project description:BACKGROUND. Coronavirus disease 2019 (COVID-19) is more benign in children compared with adults for unknown reasons. This contrasts with other respiratory viruses where disease manifestations are often more severe in children. We hypothesize that a more robust early innate immune response to SARS coronavirus 2 (SARS-CoV-2) protects against severe disease. METHODS. Clinical outcomes, SARS-CoV-2 viral copies, and cellular gene expression were compared in nasopharyngeal swabs obtained at the time of presentation to the emergency department from 12 children and 27 adults using bulk RNA sequencing and quantitative reverse-transcription PCR. Total protein, cytokines, and anti–SARS-CoV-2 IgG and IgA were quantified in nasal fluid. We used a subset of 21 samples for RNAseq analysis. RESULTS. SARS-CoV-2 copies, angiotensin-converting enzyme 2 (ACE2), and TMPRSS2 gene expression were similar in children and adults, but children displayed higher expression of genes associated with IFN signaling, NLRP3 inflammasome, and other innate pathways. Higher levels of IFN-α2, IFN-γ, IP-10, IL-8, and IL-1β protein were detected in nasal fluid in children versus adults. Children also expressed higher levels of genes associated with immune cells, whereas expression of those associated with epithelial cells did not differ in children versus adults. Anti–SARS-CoV-2 IgA and IgG were detected at similar levels in nasal fluid from both groups. None of the children required supplemental oxygen, whereas 7 adults did (P = 0.03); 4 adults died. CONCLUSION. These findings provide direct evidence of a more vigorous early mucosal immune response in children compared with adults and suggest that this contributes to favorable clinical outcomes.
Project description:Background: Influenza causes significant morbidity and mortality; the pandemic in 2009-2010 was a reminder of the potential for novel strains and antigenic changes. Studies have shown that vitamin D deficiency may be associated with poor vaccine immunogenicity, therefore we sought to determine if there was a correlation between 25-hydroxyvitamin D [25(OH)D] and influenza vaccine response.Methods: A retrospective observational study was conducted among young, healthy military members to evaluate the association between total 25(OH)D levels with post influenza vaccination antibody titers and healthcare encounters during the 2009-10 influenza season. Univariate analyses were performed to evaluate whether 25(OH)D levels are associated with baseline characteristics and post-vaccination antibody responses. Multivariable logistic regression models were utilized to determine the associations between antibody responses and 25(OH)D levels adjusting for possible confounders.Results: A total of 437 subjects were studied. Most participants were young adults (91% were 18-39 years of age), 50% were male, and 56% resided in the southern U.S. Overall, 152 (34.8%) were vitamin D deficient, 167 (38.2%) insufficient, and 118 (27.0%) with normal 25(OH)D levels. There were no demographic differences by 25(OH)D category. Only 224 (51.3%) demonstrated a seroprotective anti-influenza post-vaccination titer, which did not vary by categorical 25(OH)D levels [vitamin D deficient vs. normal: OR 1.10 (0.68-1.78) and insufficient vs. normal: OR 1.25 (0.78-2.01)] or continuous vitamin D levels [OR 0.98 (0.84-1.15)]. There were also no associations with increased influenza like illnesses, respiratory diagnoses and healthcare encounters between the vitamin D groups.Conclusion: Vitamin D insufficiency and deficiency were highly prevalent despite evaluating a young, healthy adult population. There were no significant associations between 25(OH)D levels and post-vaccination antibody titers to influenza vaccine. Further studies are required to discover strategies to improve vaccine efficacy as well as to determine the role of 25(OH)D in vaccine immunity.
Project description:Healthcare systems are belligerently responding to the new Coronavirus Disease 2019 (COVID-19). The severe acute respiratory syndrome (SARS co-V2) is a specific condition, whose distinctive features are severe hypoxemia associated with (>50% of cases) normal respiratory system compliance. When a patient requires intubation and invasive ventilation the outcome is poor and the length of stay in the intensive care unit (ICU) is usually two or three weeks. In this manuscript, authors will review several technological devices, which could support healthcare providers at the bedside to optimise the care for COVID-19 patients who are sedated, paralysed and ventilated. Particular attention is provided to the use of video-laryngoscopes (VL) because these can assist anaesthetists to perform a successful intubation outside the ICU while protecting healthcare providers from this viral infection. Authors will also review processed electroencephalographic (EEG) monitors which are used to better titrate sedation and the train of four monitors which are utilised to better titrate neuromuscular blocking agents in the view of sparing limited pharmacological resources. COVID-19 can rapidly exhaust human and technological resources too within the ICU. This review features a series of technological advancements that can significantly improve the care of patients requiring isolation. The working conditions in isolation could cause gaps or barriers in communication, fatigue and poor documentation of provided care. The available technology has several advantages including: a) facilitating appropriate paperless documentation and communication between all healthcare givers working in isolation rooms or large isolation areas; b) testing patients and staff at the bedside using smart point of care diagnostics (SPOCD) to confirm COVID-19 infection; c) allowing diagnostics and treatment at the bedside through point of care ultrasound (POCUS) and Thromboelastography (TEG); d) adapting the use of anaesthetic machines and the use of volatile anaesthetics. Implementing technologies for safeguarding healthcare providers as well as monitoring the limited pharmacological resources is paramount. Only by leveraging new technologies it will be possible to sustain and support healthcare systems during the expected long course of this pandemic.
Project description:Known words can guide visual attention, affecting how information is sampled. How do novel words, those that do not provide any top-down information, affect preschoolers' visual sampling in a conceptual task? We proposed that novel names can also change visual sampling by influencing how long children look. We investigated this possibility by analyzing how children sample visual information when they hear a sentence with a novel name versus without a novel name. Children completed a match-to-sample task while their moment-to-moment eye movements were recorded using eye-tracking technology. Our analyses were designed to provide specific information on the properties of visual sampling that novel names may change. Overall, we found that novel words prolonged the duration of each sampling event but did not affect sampling allocation (which objects children looked at) or sampling organization (how children transitioned from one object to the next). These results demonstrate that novel words change one important dynamic property of gaze: Novel words can entrain the cognitive system toward longer periods of sustained attention early in development.
Project description:Purpose: To understand the single cell transcriptional and epigenetic landscape of immune cells from infants and young children infected with COVID-19