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9% (-21.6, -8.1), and lowest prevalence and largest decline in the oldest group (>74 years) at -39.0% (-50.8, -27.2). The decline from June to September 2020 was largest in those who did not report a history of COVID-19 at -64.0% (-75.6, -52.3), compared to -22.3% (-27.0, -17.7) in those with SARS-CoV-2 infection confirmed on PCR.
A large proportion of the population remained susceptible to SARS-CoV-2 infection in England based on naturally acquired immunity from the first wave. Widespread vaccination is needed to confer immunity and control the epidemic at population level.
This work was funded by the Department of Health and Social Care in England.
This work was funded by the Department of Health and Social Care in England.
Over the past decade in England the rate of alcohol and opioid-related hospitalisation has increased alongside a simultaneous reduction in people accessing specialist addiction treatment. We aimed to determine the hospitalisation patterns of people presenting to addiction treatment with problematic use of alcohol or opioids, and estimate how individual sociodemographic characteristics and hospital admission diagnoses are associated with the rate of hospitalisation, death and successful completion of addiction treatment.
A national record linkage between Hospital Episode Statistics (HES) and the National Drug Treatment Monitoring System (NDTMS) captured lifetime hospital admission profiles of people presenting to addiction services in England in 2018/19. Latent class analysis assigned individuals to clusters based on the ICD-10 diagnosis coded as primary reason for admission. Negative binomial, and multilevel logistic regression models determined if outcomes differed due to sociodemographic characteristicsage, and increased odds of death, future work should focus on targeting appropriate interventions, to improve their health outcomes and prevent unnecessary hospital readmission.
The work was funded by the Medical Research Council (MRC).
The work was funded by the Medical Research Council (MRC).
Pregnant women are at increased risk for severe outcomes from coronavirus disease 2019 (COVID-19), but the pathophysiology underlying this increased morbidity and its potential effect on the developing fetus is not well understood.
We assessed placental histology, ACE2 expression, and viral and immune dynamics at the term placenta in pregnant women with and without respiratory severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.
The majority (13 of 15) of placentas analyzed had no detectable viral RNA. ACE2 was detected by immunohistochemistry in syncytiotrophoblast cells of the normal placenta during early pregnancy but was rarely seen in healthy placentas at full term, suggesting that low ACE2 expression may protect the term placenta from viral infection. Using immortalized cell lines and primary isolated placental cells, we found that cytotrophoblasts, the trophoblast stem cells and precursors to syncytiotrophoblasts, rather than syncytiotrophoblasts or Hofbauer cells, are most vulnerable to SARS-CoV-2 infection
. To better understand potential immune mechanisms shielding placental cells from infection
, we performed bulk and single-cell transcriptomics analyses and found that the maternal-fetal interface of SARS-CoV-2-infected women exhibited robust immune responses, including increased activation of natural killer (NK) and Tcells, increased expression of interferon-related genes, as well as markers associated with pregnancy complications such as preeclampsia.
SARS-CoV-2 infection in late pregnancy is associated with immune activation at the maternal-fetal interface even in the absence of detectable local viral invasion.
NIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) and Fast Grant funding support from Emergent Ventures at the Mercatus Center.
NIH (T32GM007205, F30HD093350, K23MH118999, R01AI157488, U01DA040588) and Fast Grant funding support from Emergent Ventures at the Mercatus Center.
The COVID-19 pandemic caused by the novel SARS-CoV-2 coronavirus has drastically altered the global realities. Harnessing national scale data from the COVID-19 pandemic may better inform policy makers in decision making surrounding the reopening of society. We examined country-level, daily-confirmed, COVID-19 case data from the World Health Organization (WHO) to better understand the comparative dynamics associated with the ongoing global pandemic at a national scale.
Observational study.
We included data from 20 countries in Europe, the Americas, Africa, Eastern Mediterranean and West Pacific regions, and obtained the aggregated daily new case data for the European Union including 27 countries. We utilized an innovative analytic approach by applying statistical change point models, which have been previously employed to model volatility in stock markets, changes in genomic data, and data dynamics in other scientific disciplines, to segment the transformed case data. This allowed us to identify possiblet potential widespread extension of the pandemic.
Our models describe the behavior of COVID-19 prevalence at a national scale and identify changes in national disease burden as relating to chronological changes in restrictive societal activity. Globally, social distancing measures may have been most effective in smaller countries with single governmental and public health organizational structures. Further research examining the impact of heterogeneous governmental responses to pandemic management appears warranted.
Our models describe the behavior of COVID-19 prevalence at a national scale and identify changes in national disease burden as relating to chronological changes in restrictive societal activity. Globally, social distancing measures may have been most effective in smaller countries with single governmental and public health organizational structures. Further research examining the impact of heterogeneous governmental responses to pandemic management appears warranted.
The COVID-19 agent, SARS-CoV-2, is conspecific with SARS-CoV, the causal agent of the severe acute respiratory syndrome epidemic in 2002-03. Although the viruses share a completely homologous repertoire of proteins and use the same cellular entry receptor, their transmission efficiencies and pathogenetic traits differ. We aimed to compare interferon antagonism by SARS-CoV and SARS-CoV-2.
For this functional study, we infected Vero E6 and Calu-3 cells with strains of SARS-CoV and SARS-CoV-2. We studied differences in cell line-specific replication (Vero E6
Calu-3 cells) and analysed these differences in relation to TMPRSS2-dependent cell entry based on inhibition with the drug camostat mesilate. We evaluated viral sensitivity towards type I interferon treatment and assessed cytokine induction and type I interferon signalling in the host cells by RT-PCR and analysis of transcription factor activation and nuclear translocation. Based on reverse genetic engineering of SARS-CoV, we investigated the contribusuppression was less efficient than that by SARS-CoV ORF6. Mutagenesis showed that charged amino acids in residues 51 and 56 shift the phenotype towards more efficient interferon antagonism, as seen in SARS-CoV.
SARS-CoV-2 ORF6 interferes less efficiently with human interferon induction and interferon signalling than SARS-CoV ORF6. CD437 Because of the homology of the genes, onward selection for fitness could involve functional optimisation of interferon antagonism. Charged amino acids at positions 51 and 56 in ORF6 should be monitored for potential adaptive changes.
Bundesministerium für Bildung und Forschung, EU RECOVER project.
Bundesministerium für Bildung und Forschung, EU RECOVER project.
Patterns of medication administration prior to in-hospital cardiac arrest (I-HCA) and the potential impact of these on patient outcomes is not well-established. Accordingly, types of medications administered in the 72 h prior to I-HCA were examined in relation to initial rhythms of I-HCA and survival.
A retrospective, pilot study was conducted among 96 patients who experienced I-HCA. Clinical characteristics and treatments including medications were extracted from electronic health records. Relative risk (RR) of medications or class of medications associated with the initial rhythms of I-HCA and return of spontaneous circulation (ROSC) were calculated.
Two distinct sub-groups were identified that did not survive to hospital discharge (n = 31) 1) those who received either vasopressin/desmopressin (n = 16) and 2) those who received combinations of psychotherapeutic agents with anxiolytics, sedatives, and hypnotics (n = 15) prior to I-HCA. The risk of pulseless electrical activity and asystolic arrest was high in patients who received sympathomimetic agents alone or in combination with β-Adrenergic blocking agents, (RR = 1.40, 1.41, respectively). Vasopressin and a combination of vasopressin and fentanyl were associated with risk of unsuccessful ROSC (RR = 2.50, 2.38, respectively).
The types of medications administered during inpatient care may serve as a surrogate marker for identifying patients at risk of specific initial rhythms of I-HCA and survival.
The types of medications administered during inpatient care may serve as a surrogate marker for identifying patients at risk of specific initial rhythms of I-HCA and survival.
Determine changes in rapid response team (RRT) activations and describe institutional adaptations made during a surge in hospitalizations for coronavirus disease 2019 (COVID-19).
Using prospectively collected data, we compared characteristics of RRT calls at our academic hospital from March 7 through May 31, 2020 (COVID-19 era) versus those from January 1 through March 6, 2020 (pre-COVID-19 era). We used negative binomial regression to test differences in RRT activation rates normalized to floor (non-ICU) inpatient census between pre-COVID-19 and COVID-19 eras, including the sub-era of rapid COVID-19 census surge and plateau (March 28 through May 2, 2020).
RRT activations for respiratory distress rose substantially during the rapid COVID-19 surge and plateau (2.38 (95% CI 1.39-3.36) activations per 1000 floor patient-days v. 1.27 (0.82-1.71) during the pre-COVID-19 era; p=0.02); all-cause RRT rates were not significantly different (5.40 (95% CI 3.94-6.85) v. 4.83 (3.86-5.80) activations per 1000 floor patient-days, respectively; p=0.52). Throughout the COVID-19 era, respiratory distress accounted for a higher percentage of RRT activations in COVID-19 versus non-COVID-19 patients (57% vs. 28%, respectively; p=0.001). During the surge, we adapted RRT guidelines to reduce in-room personnel and standardize personal protective equipment based on COVID-19 status and risk to providers, created decision-support pathways for respiratory emergencies that accounted for COVID-19 status uncertainty, and expanded critical care consultative support to floor teams.
Increased frequency and complexity of RRT activations for respiratory distress during the COVID-19 surge prompted the creation of clinical tools and strategies that could be applied to other hospitals.
Increased frequency and complexity of RRT activations for respiratory distress during the COVID-19 surge prompted the creation of clinical tools and strategies that could be applied to other hospitals.
