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ds or greater compared with patients without COVID-19.
In this cohort study, COVID-19 infection was independently associated with significant mean QTc prolongation at days 5 and 2 of hospitalization compared with day 0. More patients with COVID-19 had QTc of 500 milliseconds or greater compared with patients without COVID-19.
A significant proportion of COVID-19 transmission occurs silently during the presymptomatic and asymptomatic stages of infection. Children, although important drivers of silent transmission, are not included in the current COVID-19 vaccination campaigns.
To estimate the benefits of identifying silent infections among children as a proxy for their vaccination.
This study used an age-structured disease transmission model, parameterized with census data and estimates from published literature, to simulate the estimated synergistic effect of interventions in reducing attack rates during the course of 1 year among a synthetic population representative of the US demographic composition. The population included 6 age groups of 0 to 4, 5 to 10, 11 to 18, 19 to 49, 50 to 64, and 65 years or older based on US census data. https://www.selleckchem.com/products/3po.html Data were analyzed from December 12, 2020, to February 26, 2021.
In addition to the isolation of symptomatic cases within 24 hours of symptom onset, vaccination of adults was implemented to ren the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. These findings suggest that without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.
In this simulation modeling study of a synthetic US population, in the absence of vaccine availability for children, a targeted approach to rapidly identify silent COVID-19 infections in this age group was estimated to significantly mitigate disease burden. These findings suggest that without measures to interrupt transmission chains from silent infections, vaccination of adults is unlikely to contain the outbreaks in the near term.
The incidence of mother-to-newborn SARS-CoV-2 transmission appears low and may be associated with biological and social factors. However, data are limited on the factors associated with neonatal clinical or viral testing outcomes.
To ascertain the percentage of neonates who were born to mothers with positive SARS-CoV-2 test results during the birth hospitalization, the clinical and sociodemographic factors associated with neonatal test result positivity, and the clinical and virological outcomes for newborns during hospitalization and 30 days after discharge.
This multicenter cohort study included 11 academic or community hospitals in Massachusetts and mother-neonate dyads whose delivery and discharge occurred between March 1, 2020, and July 31, 2020. Eligible dyads were identified at each participating hospital through local COVID-19 surveillance and infection control systems. Neonates were born to mothers with positive SARS-CoV-2 test results within 14 days before to 72 hours after delivery, and neonaforts of ongoing surveillance of the virus and long-term follow-up.
The findings emphasize the importance of both biological and social factors in perinatal SARS-CoV-2 infection outcomes. Newborns exposed to SARS-CoV-2 were at risk for both direct and indirect adverse health outcomes, supporting efforts of ongoing surveillance of the virus and long-term follow-up.
Hospitalizations for infections among nursing home (NH) residents remain common despite national initiatives to reduce them. Cognitive impairment, which markedly affects quality of life and caregiving needs, has been associated with hospitalizations, but the association between infection-related hospitalizations and long-term cognitive function among NH residents is unknown.
To examine whether there are changes in cognitive function before vs after infection-related hospitalizations among NH residents.
This cohort study used data from the Minimum Data Set 3.0 linked to Medicare hospitalization data from 2011 to 2017 for US nursing home residents aged 65 years or older who had experienced an infection-related hospitalization and had at least 2 quarterly Minimum Data Set assessments before and 4 or more after the infection-related hospitalization. Analyses were performed from September 1, 2019, to December 21, 2020.
Infection-related hospitalization lasting 1 to 14 days.
Using an event study approach,on may help to ensure that their care needs are addressed to prevent further cognitive decline.
In this cohort study, infection-related hospitalization was associated with immediate and persistent cognitive decline among nursing home residents, with the largest increase in CFS scores among older residents, those with ADRD, and those who had experienced sepsis. Identification of NH residents at risk of worsened cognition after an infection-related hospitalization may help to ensure that their care needs are addressed to prevent further cognitive decline.
Negative symptoms are a core aspect of psychopathology in schizophrenia. Currently available pharmacological agents have proven minimally efficacious for remediating negative symptoms. A promising treatment avenue is the intranasal administration of the neuropeptide oxytocin. However, there have been inconsistencies in effects of oxytocin on negative symptoms throughout the literature and factors leading to inconsistent effects are unclear.
We conducted a systematic review and meta-analysis of RCTs to compare the effectiveness of oxytocin to placebo for the treatment of negative symptoms and determine moderators of treatment effect. Random effects meta-analyses and dose-response meta-analysis were performed on mean changes in negative symptoms.
In an initial analysis of all 9 identified RCTs intranasal oxytocin showed no significant effect on negative symptoms. For higher doses (> 40 to 80 I.U.), a beneficial effect on negative symptoms was found with a moderate effect size, but this effect disappearcious. If future studies are conducted, an effort to reach adequate CNS concentrations for a sufficient duration is required.Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
To evaluate upstream and downstream regulators leading to macrophage activation and subsequent cytokine storm in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-associated interstitial lung disease (ILD).
We conducted an integrated miRNA-mRNA association analysis using circulating monocytes from 3 patients with anti-MDA5-associated ILD and 3 healthy controls and identified disease pathways and a regulator effect network by Ingenuity Pathway Analysis (IPA). The expression of relevant genes and proteins was verified using an independent validation cohort, including 6 patients with anti-MDA5-associated ILD, 5 with anti-aminoacyl tRNA synthetase antibody-associated ILD, and 6 healthy controls.
IPA identified 26 matched pairs of downregulated miRNA and upregulated mRNAs and revealed that canonical pathways mediated by type I IFN signaling and C-C motif ligand 2 (CCL2) were responsible for the pathogenic process (P < 0.05 for all pathways). The regulatory network model identified IFN-β; Toll-like receptors 3, 7, and 9; and PU.1 as upstream regulators, while the downstream effect of this network converged at the inhibition of viral infection. mRNA and protein expression analysis using validation cohort showed a trend towards the increased expression of relevant molecules identified by IPA in patients with anti-MDA5-associated ILD compared with those with anti-aminoacyl tRNA synthetase antibody-associated ILD or healthy controls. The expression of all relevant genes in monocytes and serum levels of CCL2 and IFN-β declined after treatment in survivors with anti-MDA5-associated ILD.
An antiviral proinflammatory network orchestrated primarily by activated monocytes/macrophages might be responsible for cytokine storm in anti-MDA5-associated ILD.
An antiviral proinflammatory network orchestrated primarily by activated monocytes/macrophages might be responsible for cytokine storm in anti-MDA5-associated ILD.To investigate cross-ancestry genetics of complex traits, we conducted a phenome-wide analysis of loci with heterogeneous effects across African, Admixed-American, Central/South Asian, East Asian, European, and Middle Eastern participants of UK Biobank (N = 441 331). Testing 843 phenotypes, we identified 82 independent genomic regions mapping variants showing genome-wide significant (GWS) associations (P less then 5 × 10-8) in the trans-ancestry meta-analysis and GWS heterogeneity among the ancestry-specific effects. These included i) loci with GWS association in one ancestry and concordant but heterogeneous effects among the other ancestries; ii) loci with a GWS association in one ancestry group and an experiment-wide significant discordant effect (P less then 6.1 × 10-4) in at least another ancestry. Since the trans-ancestry GWS associations were mostly driven by the European-ancestry sample size, we investigated the differences of allele frequency (ΔAF) and linkage-disequilibrium regulome tagging (ΔLD) between European populations and the other ancestries. Within loci with concordant effects, the degree of heterogeneity was associated with European-Middle Eastern ΔAF (P = 9.04 × 10-6) and ΔLD of European populations with respect to African, Admixed-American, and Central/South Asian groups (P = 8.21 × 10-4, P = 7.17 × 10-4, and P = 2.16 × 10-3, respectively). Within loci with discordant effects, ΔAF and ΔLD of European populations with respect to African and Central/South Asian ancestries was associated with the degree of heterogeneity (ΔAF P = 7.69 × 10-3 and P = 5.31 × 10-3, ΔLD P = 0.016 and P = 2.65 × 10-4, respectively). Considering the traits associated with cross-ancestry heterogeneous loci, we observed enrichments for blood biomarkers (P = 5.7 × 10-35) and physical appearance (P = 1.38 × 10-4). This suggests that these specific phenotypic classes may present considerable cross-ancestry heterogeneity due to large allele frequency and LD variation among worldwide populations.
