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2.
Sci Rep ; 12(1): 18506, 2022 Nov 02.
Article in English | MEDLINE | ID: covidwho-2096786

ABSTRACT

SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithelial cell line infected with a clinical isolate of SARS-CoV-2. This identified 20 approved drugs that act synergistically with remdesivir, many with favorable pharmacokinetic and safety profiles. Strongest effects were observed with established antivirals, Hepatitis C virus nonstructural protein 5A (HCV NS5A) inhibitors velpatasvir and elbasvir. Combination with their partner drugs sofosbuvir and grazoprevir further increased efficacy, increasing remdesivir's apparent potency > 25-fold. We report that HCV NS5A inhibitors act on the SARS-CoV-2 exonuclease proofreader, providing a possible explanation for the synergy observed with nucleoside analog remdesivir. FDA-approved Hepatitis C therapeutics Epclusa® (velpatasvir/sofosbuvir) and Zepatier® (elbasvir/grazoprevir) could be further optimized to achieve potency and pharmacokinetic properties that support clinical evaluation in combination with remdesivir.


Subject(s)
COVID-19 , Hepatitis C , Humans , SARS-CoV-2 , Antiviral Agents/therapeutic use , Sofosbuvir/pharmacology , Nucleosides/pharmacology , COVID-19/drug therapy , Adenosine Monophosphate , Alanine , Hepacivirus , Hepatitis C/drug therapy , Lung
3.
Can J Anaesth ; 69(10): 1248-1259, 2022 10.
Article in English | MEDLINE | ID: covidwho-2060083

ABSTRACT

PURPOSE: During the first wave of the COVID-19 pandemic, restricted visitation policies were enacted at acute care facilities to reduce the spread of COVID-19 and conserve personal protective equipment. In this study, we aimed to describe the impact of restricted visitation policies on critically ill patients, families, critical care clinicians, and decision-makers; highlight the challenges faced in translating these policies into practice; and delineate strategies to mitigate their effects. METHOD: A qualitative description design was used. We conducted semistructured interviews with critically ill adult patients and their family members, critical care clinicians, and decision-makers (i.e., policy makers or enforcers) affected by restricted visitation policies. We transcribed semistructured interviews verbatim and analyzed the transcripts using inductive thematic analysis. RESULTS: Three patients, eight family members, 30 clinicians (13 physicians, 17 nurses from 23 Canadian intensive care units [ICUs]), and three decision-makers participated in interviews. Thematic analysis was used to identify five themes: 1) acceptance of restricted visitation (e.g., accepting with concerns); 2) impact of restricted visitation (e.g., ethical challenges, moral distress, patients dying alone, intensified workload); 3) trust in the healthcare system during the pandemic (e.g., mistrust of clinical team); 4) modes of communication (e.g., communication using virtual platforms); and 5) impact of policy implementation on clinical practice (e.g., frequent changes and inconsistent implementation). CONCLUSIONS: Restricted visitation policies across ICUs during the COVID-19 pandemic negatively affected critically ill patients and their families, critical care clinicians, and decision-makers.


RéSUMé: OBJECTIF: Au cours de la première vague de la pandémie de COVID-19, des politiques de visite restreintes ont été adoptées dans les établissements de soins aigus afin de réduire la propagation de la COVID-19 et d'économiser les équipements de protection individuelle. Dans cette étude, nous avons cherché à décrire l'impact des politiques de visite restreintes sur les patients gravement malades, les familles, les intensivistes et les décideurs, ainsi qu'à souligner les difficultés rencontrées dans la mise en pratique de ces politiques et à définir des stratégies pour en atténuer les effets. MéTHODE: Une méthodologie de description qualitative a été utilisée. Nous avons mené des entretiens semi-structurés avec des patients adultes gravement malades et les membres de leur famille, les intensivistes et les décideurs (c.-à-d. les stratèges ou les responsables de l'application de la loi) touchés par les politiques de visite restreintes. Nous avons transcrit textuellement les entretiens semi-structurés et analysé les transcriptions à l'aide d'une analyse thématique inductive. RéSULTATS: Trois patients, huit membres de leur famille, 30 cliniciens (13 médecins, 17 infirmières de 23 unités de soins intensifs canadiennes) et trois décideurs ont participé à ces entrevues. L'analyse thématique a été utilisée pour identifier cinq thèmes : 1) l'acceptation des visites restreintes (p. ex., accepter avec des préoccupations); 2) l'impact des visites restreintes (p. ex., défis éthiques, détresse morale, patients mourant seuls, charge de travail accrue); 3) la confiance dans le système de santé pendant la pandémie (p. ex., méfiance à l'égard de l'équipe clinique); 4) les modes de communication (p. ex., communication à l'aide de plateformes virtuelles); et 5) l'incidence de la mise en œuvre des politiques sur la pratique clinique (p. ex., changements fréquents et mise en œuvre incohérente). CONCLUSION: Les politiques de visite restreintes dans les unités de soins intensifs pendant la pandémie de COVID-19 ont eu un impact négatif sur les patients gravement malades et leurs familles, les intensivistes et les décideurs.


Subject(s)
COVID-19 , Critical Illness , Adult , Canada , Critical Care , Critical Illness/therapy , Decision Making , Family , Humans , Intensive Care Units , Pandemics/prevention & control , Policy , Qualitative Research
4.
PLoS One ; 17(9): e0275310, 2022.
Article in English | MEDLINE | ID: covidwho-2054375

ABSTRACT

BACKGROUND: Family visitation in intensive care units (ICU) has been impacted by the severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic. While studies report on perceptions of families completely restricted from ICUs, little is known about the burden experienced by designated family caregivers allowed to visit their critically ill loved one. This study sought the perspectives of family caregivers of critically ill patients on the impact of one-person designated visitor policies mandated in ICUs during the COVID-19 pandemic. METHODS: Throughout the study period a restricted visitation policy was mandated capturing the first (April 2020) and second (December 2020) waves of the pandemic that allowed one designated family caregiver (i.e., spouses or adult children) per patient to visit the ICU. Designated family caregivers of critically ill patients admitted to ICU September 2020 to November 2020 took part in individual 60-minute, semi-structured interviews at 6-months after discharge from the index ICU admission. Themes from family interviews were summarized with representative quotations. RESULTS: Key themes identified following thematic analysis from six participants included: one visitor rule, patient advocate role, information needs, emotional distress, strategies for coping with challenges, practicing empathy, and appreciation of growth. CONCLUSION: Designated family caregivers of critically ill patients admitted to ICU during the COVID-19 pandemic perceived a complex and highly stressful experience. Support from ICU family liaisons and psychologists may help ameliorate the impact.


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , Caregivers/psychology , Child , Critical Illness , Family , Humans , Intensive Care Units , Pandemics , Qualitative Research
5.
Microbiol Spectr ; 10(5): e0333122, 2022 Oct 26.
Article in English | MEDLINE | ID: covidwho-2053144

ABSTRACT

Three directly acting antivirals (DAAs) demonstrated substantial reduction in COVID-19 hospitalizations and deaths in clinical trials. However, these agents did not completely prevent severe illness and are associated with cases of rebound illness and viral shedding. Combination regimens can enhance antiviral potency, reduce the emergence of drug-resistant variants, and lower the dose of each component in the combination. Concurrently targeting virus entry and virus replication offers opportunities to discover synergistic drug combinations. While combination antiviral drug treatments are standard for chronic RNA virus infections, no antiviral combination therapy has been approved for SARS-CoV-2. Here, we demonstrate that combining host-targeting antivirals (HTAs) that target TMPRSS2 and hence SARS-CoV-2 entry, with the DAA molnupiravir, which targets SARS-CoV-2 replication, synergistically suppresses SARS-CoV-2 infection in Calu-3 lung epithelial cells. Strong synergy was observed when molnupiravir, an oral drug, was combined with three TMPRSS2 (HTA) oral or inhaled inhibitors: camostat, avoralstat, or nafamostat. The combination of camostat plus molnupiravir was also effective against the beta and delta variants of concern. The pyrimidine biosynthesis inhibitor brequinar combined with molnupiravir also conferred robust synergistic inhibition. These HTA+DAA combinations had similar potency to the synergistic all-DAA combination of molnupiravir plus nirmatrelvir, the protease inhibitor found in paxlovid. Pharmacodynamic modeling allowed estimates of antiviral potency at all possible concentrations of each agent within plausible therapeutic ranges, suggesting possible in vivo efficacy. The triple combination of camostat, brequinar, and molnupiravir further increased antiviral potency. These findings support the development of HTA+DAA combinations for pandemic response and preparedness. IMPORTANCE Imagine a future viral pandemic where if you test positive for the new virus, you can quickly take some medicines at home for a few days so that you do not get too sick. To date, only single drugs have been approved for outpatient use against SARS-CoV-2, and we are learning that these have some limitations and may succumb to drug resistance. Here, we show that combinations of two oral drugs are better than the single ones in blocking SARS-CoV-2, and we use mathematical modeling to show that these drug combinations are likely to work in people. We also show that a combination of three oral drugs works even better at eradicating the virus. Our findings therefore bode well for the development of oral drug cocktails for at home use at the first sign of an infection by a coronavirus or other emerging viral pathogens.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Antiviral Agents/pharmacology , COVID-19/drug therapy , Protease Inhibitors/pharmacology , Drug Combinations , Pyrimidines
6.
The Journal of adolescent health : official publication of the Society for Adolescent Medicine ; 2022.
Article in English | EuropePMC | ID: covidwho-2046977

ABSTRACT

databases. The analysis used negative binomial regression with robust standard errors to compare hospitalization counts in the months preceding and following the World Health Organization pandemic declaration (March 11, 2020). Results Hospitalizations due to pediatric AN increased by 63% and 132% at SickKids (p < .001) and ACH (p < .001), respectively, in the first year of the pandemic compared to the previous six years. The total number of non-ED hospitalizations decreased by 29.3% and 2.4% at SickKids and ACH, respectively. Discussion This is the first Canadian study to show a rise in pediatric hospitalizations over one year due to AN in two tertiary care hospitals following the onset of the pandemic, confirming the impact that the pandemic has had on children and adolescents with AN in Canada.

7.
Commun Biol ; 5(1): 958, 2022 09 14.
Article in English | MEDLINE | ID: covidwho-2028733

ABSTRACT

Hydroxychloroquine (HCQ), a drug used to treat lupus and malaria, was proposed as a treatment for SARS-coronavirus-2 (SARS-CoV-2) infection, albeit with controversy. In vitro, HCQ effectively inhibits viral entry, but its use in the clinic has been hampered by conflicting results. A better understanding of HCQ's mechanism of actions in vitro is needed. Recently, anesthetics were shown to disrupt ordered clusters of monosialotetrahexosylganglioside1 (GM1) lipid. These same lipid clusters recruit the SARS-CoV-2 surface receptor angiotensin converting enzyme 2 (ACE2) to endocytic lipids, away from phosphatidylinositol 4,5 bisphosphate (PIP2) clusters. Here we employed super-resolution imaging of cultured mammalian cells (VeroE6, A549, H1793, and HEK293T) to show HCQ directly perturbs clustering of ACE2 receptor with both endocytic lipids and PIP2 clusters. In elevated (high) cholesterol, HCQ moves ACE2 nanoscopic distances away from endocytic lipids. In cells with resting (low) cholesterol, ACE2 primarily associates with PIP2 clusters, and HCQ moves ACE2 away from PIP2 clusters-erythromycin has a similar effect. We conclude HCQ inhibits viral entry through two distinct mechanisms in high and low tissue cholesterol and does so prior to inhibiting cathepsin-L. HCQ clinical trials and animal studies will need to account for tissue cholesterol levels when evaluating dosing and efficacy.


Subject(s)
Angiotensin-Converting Enzyme 2 , COVID-19 , Animals , COVID-19/drug therapy , Cell Culture Techniques , Cholesterol , HEK293 Cells , Humans , Hydroxychloroquine/pharmacology , Lipids , Mammals , Peptidyl-Dipeptidase A , SARS-CoV-2
8.
Journal of LGBT Youth ; : 1-34, 2022.
Article in English | Academic Search Complete | ID: covidwho-2017491

ABSTRACT

Literature has discussed the intersectionality between autism and transgender and gender diverse (TGD) identities. Research has also identified the importance of protective factors, which are experiences that enhance positive outcomes in the face of potentially negative experiences. This exploratory quantitative survey study seeks to identify school and community-based protective factors that relate to psychological well-being and life satisfaction among 31 TGD Autistic youths between the ages of 13 to 17. The authors utilized adapted and full-forms of validated measures including the KID-SCREEN 27, Brief Multidimensional Students’ Life Satisfaction Survey Peabody Treatment Progress Battery, Adolescent Resilience Questionnaire, Perceived Coronavirus Threat Questionnaire, and Autism-Spectrum Quotient. Results suggest that community connectedness, school support, family availability, and self-identification of sexual orientation as queer were identified as protective factors. Implications for research and practice are discussed. [ FROM AUTHOR] Copyright of Journal of LGBT Youth is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

9.
Preprint in English | bioRxiv | ID: ppbiorxiv-507833

ABSTRACT

Identifying host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to reveal novel drug targets and further our understanding of coronavirus disease 2019 (COVID-19). We previously performed a genome-wide CRISPR/Cas9 screen to identify pro-viral host factors for highly pathogenic human coronaviruses. Very few host factors were required by diverse coronaviruses across multiple cell types, but DYRK1A was one such exception. Although its role in coronavirus infection was completely unknown, DYRK1A encodes Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A and regulates cell proliferation, and neuronal development, among other cellular processes. Interestingly, individuals with Down syndrome overexpress DYRK1A 1.5-fold and exhibit 5-10x higher hospitalization and mortality rates from COVID-19 infection. Here, we demonstrate that DYRK1A regulates ACE2 and DPP4 transcription independent of its catalytic kinase function to support SARS-CoV, SARS-CoV-2, and MERS-CoV entry. We show that DYRK1A promotes DNA accessibility at the ACE2 promoter and a putative distal enhancer, facilitating transcription and gene expression. Finally, we validate that the pro-viral activity of DYRK1A is conserved across species using cells of monkey and human origin and an in vivo mouse model. In summary, we report that DYRK1A is a novel regulator of ACE2 and DPP4 expression that may dictate susceptibility to multiple highly pathogenic human coronaviruses. Whether DYRK1A overexpression contributes to heightened COVID-19 severity in individuals with Down syndrome through ACE2 regulation warrants further future investigation.

10.
Nat Biomed Eng ; 6(8): 944-956, 2022 08.
Article in English | MEDLINE | ID: covidwho-1991606

ABSTRACT

Rapid nucleic acid testing is central to infectious disease surveillance. Here, we report an assay for rapid COVID-19 testing and its implementation in a prototype microfluidic device. The assay, which we named DISCoVER (for diagnostics with coronavirus enzymatic reporting), involves extraction-free sample lysis via shelf-stable and low-cost reagents, multiplexed isothermal RNA amplification followed by T7 transcription, and Cas13-mediated cleavage of a quenched fluorophore. The device consists of a single-use gravity-driven microfluidic cartridge inserted into a compact instrument for automated running of the assay and readout of fluorescence within 60 min. DISCoVER can detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in saliva with a sensitivity of 40 copies µl-1, and was 94% sensitive and 100% specific when validated (against quantitative PCR) using total RNA extracted from 63 nasal-swab samples (33 SARS-CoV-2-positive, with cycle-threshold values of 13-35). The device correctly identified all tested clinical saliva samples (10 SARS-CoV-2-positive out of 13, with cycle-threshold values of 23-31). Rapid point-of-care nucleic acid testing may broaden the use of molecular diagnostics.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/diagnosis , COVID-19 Testing , Humans , RNA, Viral/genetics , SARS-CoV-2/genetics , Saliva
11.
Cell Rep ; 36(8): 109591, 2021 08 24.
Article in English | MEDLINE | ID: covidwho-1370154

ABSTRACT

The relationship between B cells and CD4 T cells has been carefully studied, revealing a collaborative effort in which B cells promote the activation, differentiation, and expansion of CD4 T cells while the so-called "helper" cells provide signals to B cells, influencing their class switching and fate. Interactions between B cells and CD8 T cells are not as well studied, although CD8 T cells exhibit an accelerated contraction after certain infections in B-cell-deficient mice. Here, we find that B cells significantly enhance primary CD8 T cell responses after vaccination. Moreover, memory CD8 numbers and function are impaired in B-cell-deficient animals, leading to increased susceptibility to bacterial challenge. We also show that interleukin-27 production by B cells contributes to their impact on primary, but not memory, CD8 responses. Better understanding of the interactions between CD8 T cells and B cells may aid in the design of more effective future vaccine strategies.


Subject(s)
B-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Immunologic Memory , Interleukin-27/immunology , Interleukin-27/metabolism , T-Lymphocytes, Helper-Inducer/immunology , Vaccines, Subunit/immunology , Animals , B-Lymphocytes/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , COVID-19/immunology , Humans , Lymphocyte Count , Mice , Mice, Inbred C57BL , Receptors, Virus/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , Vaccination
12.
Nat Commun ; 13(1): 4503, 2022 08 03.
Article in English | MEDLINE | ID: covidwho-1972603

ABSTRACT

The COVID-19 pandemic is exacting an increasing toll worldwide, with new SARS-CoV-2 variants emerging that exhibit higher infectivity rates and that may partially evade vaccine and antibody immunity. Rapid deployment of non-invasive therapeutic avenues capable of preventing infection by all SARS-CoV-2 variants could complement current vaccination efforts and help turn the tide on the COVID-19 pandemic. Here, we describe a novel therapeutic strategy targeting the SARS-CoV-2 RNA using locked nucleic acid antisense oligonucleotides (LNA ASOs). We identify an LNA ASO binding to the 5' leader sequence of SARS-CoV-2 that disrupts a highly conserved stem-loop structure with nanomolar efficacy in preventing viral replication in human cells. Daily intranasal administration of this LNA ASO in the COVID-19 mouse model potently suppresses viral replication (>80-fold) in the lungs of infected mice. We find that the LNA ASO is efficacious in countering all SARS-CoV-2 "variants of concern" tested both in vitro and in vivo. Hence, inhaled LNA ASOs targeting SARS-CoV-2 represents a promising therapeutic approach to reduce or prevent transmission and decrease severity of COVID-19 in infected individuals. LNA ASOs are chemically stable and can be flexibly modified to target different viral RNA sequences and could be stockpiled for future coronavirus pandemics.


Subject(s)
COVID-19 , SARS-CoV-2 , Administration, Intranasal , Animals , Humans , Mice , Oligonucleotides, Antisense/pharmacology , Oligonucleotides, Antisense/therapeutic use , Pandemics/prevention & control , RNA, Viral/genetics
13.
Nat Genet ; 54(8): 1078-1089, 2022 08.
Article in English | MEDLINE | ID: covidwho-1960394

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a range of symptoms in infected individuals, from mild respiratory illness to acute respiratory distress syndrome. A systematic understanding of host factors influencing viral infection is critical to elucidate SARS-CoV-2-host interactions and the progression of Coronavirus disease 2019 (COVID-19). Here, we conducted genome-wide CRISPR knockout and activation screens in human lung epithelial cells with endogenous expression of the SARS-CoV-2 entry factors ACE2 and TMPRSS2. We uncovered proviral and antiviral factors across highly interconnected host pathways, including clathrin transport, inflammatory signaling, cell-cycle regulation, and transcriptional and epigenetic regulation. We further identified mucins, a family of high molecular weight glycoproteins, as a prominent viral restriction network that inhibits SARS-CoV-2 infection in vitro and in murine models. These mucins also inhibit infection of diverse respiratory viruses. This functional landscape of SARS-CoV-2 host factors provides a physiologically relevant starting point for new host-directed therapeutics and highlights airway mucins as a host defense mechanism.


Subject(s)
COVID-19 , Animals , COVID-19/genetics , Clustered Regularly Interspaced Short Palindromic Repeats , Epigenesis, Genetic , Humans , Mice , Mucins/genetics , SARS-CoV-2
14.
Journal of Emergency Management ; 19(9):159-168, 2021.
Article in English | Scopus | ID: covidwho-1847539

ABSTRACT

The prolonged coronavirus-2019 (COVID-19) pandemic and co-occurring disasters during 2020 took a toll on everyone, taxing public health and disaster management personnel particularly. This initial study evaluated levels of exhaustion, cynicism, and professional efficacy among a broad array of the disaster workforce responding to these events through an online survey. Responses were compared to normative standards from an international dataset using a one-sample t-test and described using k-means cluster analysis. Results from 111 emergency management and disaster services, public health, healthcare, first responders, and other professionals and volunteers indicated high levels of emotional exhaustion and cynicism, along with high levels of personal efficacy compared to normative samples. Perceptions of the heightened risk of contracting COVID-19 were significantly associated with increased emotional exhaustion and cynicism. Cluster analysis results indicated three different patterns of burnout: half of the respondents were overextended (high levels of emotional exhaustion, cynicism, and efficacy) or burned out (high emotional exhaustion and cynicism, low efficacy), while 50 percent were engaged (low emotional exhaustion, low cynicism, and high personal efficacy). This suggests that despite the COVID-19 pandemic, a substantial proportion of the disaster response workforce is still thriving. However, a large proportion is burned out or at high risk (overextended). Limitations of this study include a lack of diversity in the sample, which, although similar to the demographic characteristics of the emergency manager population, may limit the generalizability of the study results. System-level planners can use this information to develop comprehensive workforce approaches, policies, and procedures to prevent burnout for these essential personnel working behind the scenes. © 2021 Weston Medical Publishing. All rights reserved.

15.
Preprint in English | bioRxiv | ID: ppbiorxiv-487988

ABSTRACT

The severity of disease following infection with SARS-CoV-2 is determined by viral replication kinetics and host immunity, with early T cell responses and/or suppression of viraemia driving a favourable outcome. Recent studies have uncovered a role for cholesterol metabolism in the SARS-CoV-2 life cycle and in T cell function. Here we show that blockade of the enzyme Acyl-CoA:cholesterol acyltransferase (ACAT) with Avasimibe inhibits SARS-CoV-2 entry and fusion independent of transmembrane protease serine 2 expression in multiple cell types. We also demonstrate a role for ACAT in regulating SARS-CoV-2 RNA replication in primary bronchial epithelial cells. Furthermore, Avasimibe boosts the expansion of functional SARS-CoV-2-specific T cells from the blood of patients sampled in the acute phase of infection. Thus, re-purposing of available ACAT inhibitors provides a compelling therapeutic strategy for the treatment of COVID-19 to achieve both antiviral and immunomodulatory effects.

16.
Int J Eat Disord ; 2022 Apr 05.
Article in English | MEDLINE | ID: covidwho-1772681

ABSTRACT

OBJECTIVE: A growing body of evidence suggests that individuals with eating disorders (EDs) have experienced deteriorating symptoms, increased isolation, and an increase in hospital admissions as a result of the COVID-19 pandemic. Despite this, no systematic reviews have been conducted examining the COVID-19 and ED peer-reviewed literature. Therefore, this systematic review aimed to synthesize the impact of the COVID-19 pandemic on individuals with EDs. METHOD: Database searches of the peer-reviewed literature were completed in the subsequent databases: CINAHL, Embase, MEDLINE, and PsycINFO (from November 2019 to October 20, 2021). All research reporting on the relationship between the COVID-19 pandemic on individuals with EDs were included. RESULTS: Fifty-three studies met the inclusion criteria, including 36,485 individuals with EDs. The pooled hospital admissions across the studies demonstrated on average a 48% (pre = 591, post = 876, n = 10 studies) increase in admissions during the pandemic compared to previous pre-pandemic timepoints. In this review, 36% of studies (n = 19) documented increases in eating disorder symptoms during the pandemic, this increase in eating disorder symptoms were documented in AN, BED, BN, and OFSED patients. Studies also demonstrated increases in anxiety (n = 9) and depression (n = 8), however patterns of change appeared to be diagnostic and timing specific (e.g., lockdowns). DISCUSSION: We found a large increase in the number of hospitalizations and an increase in ED symptoms, anxiety, depression, and changes to BMI in ED patients during the pandemic. However, these changes appeared to be diagnostic and timing specific. Many qualitative studies described deterioration in ED symptomatology due to decreased access to care and treatment, changes to routine and loss of structure, negative influence of the media, and social isolation. Future studies are needed to focus on pediatric populations, new ED diagnoses, and severity of illness at presentation. PUBLIC SIGNIFICANCE: The scientific literature suggests that individuals with eating disorders have experienced deteriorating symptoms, increased isolation, and an increase in hospital admissions as a result of the COVID-19 pandemic. This study synthesized 53 articles and explored the impact of the COVID-19 pandemic on patients with eating disorders. We found increases in eating disorder symptoms during the pandemic; this increase in eating disorder symptoms was documented in patients with common eating disorders including anorexia nervosa, binge-eating disorder, bulimia nervosa, and other specified feeding and eating disorders. This review also demonstrated changes in body mass index (an index used to classify underweight, overweight, and obesity in adults) and increases in anxiety and depression during the pandemic compared to previous timepoints; patterns of change appeared to be related to timing of lockdowns. This review provides important information on the impact of COVID-19 on the physical and mental health of individuals with eating disorders.


OBJETIVO: Un creciente conjunto de evidencia sugiere que las personas con trastornos de la conducta alimentaria (TCA) han experimentado síntomas de deterioro, mayor aislamiento y un aumento en los ingresos hospitalarios como resultado de la pandemia de COVID-19. A pesar de esto, no se han realizado revisiones sistemáticas que examinen la literatura revisada por pares de COVID-19 y TCA. Por lo tanto, esta revisión sistemática tuvo como objetivo sintetizar el impacto de la pandemia de COVID-19 en las personas con TCA. MÉTODO: Las búsquedas en las bases de datos de la literatura revisada por pares se completaron en las bases de datos posteriores: CINAHL, Embase, MEDLINE y PsycINFO (de noviembre de 2019 al 20 de octubre de 2021). Se incluyeron todos los informes de investigación sobre la relación entre la pandemia de COVID-19 en individuos con TCA. RESULTADOS: Cincuenta y tres estudios cumplieron los criterios de inclusión, incluyendo 36,485 individuos con TCA. Los ingresos hospitalarios agrupados en los estudios demostraron en promedio un aumento del 48% (antes = 591, después = 876, n = 10 estudios) en los ingresos durante la pandemia en comparación con los puntos de tiempo previos a la pandemia. En esta revisión, el 36% de los estudios (n = 19) documentaron aumentos en los síntomas del trastorno alimentario durante la pandemia, este aumento en los síntomas del trastorno de la conducta alimentaria se documentó en pacientes con AN, TpA, BN y OSFED. Los estudios también demostraron aumentos en la ansiedad (n = 9) y la depresión (n = 8), sin embargo, los patrones de cambio parecían ser diagnósticos y específicos del momento (por ejemplo, encierros). DISCUSIÓN: Encontramos un gran aumento en el número de hospitalizaciones y un aumento en los síntomas de TCA, ansiedad, depresión y los cambios en el IMC en pacientes con TCA durante la pandemia. Sin embargo, estos cambios parecían ser diagnósticos y específicos del momento. Muchos estudios cualitativos describieron un deterioro en la sintomatología del trastorno de la conducta alimentaria (TCA) debido a la disminución del acceso a la atención y el tratamiento, los cambios en la rutina y la pérdida de estructura, la influencia negativa de los medios de comunicación y el aislamiento social. Se necesitan estudios futuros para centrarse en las poblaciones pediátricas, los nuevos diagnósticos de TCA y la gravedad de la enfermedad al momento de la presentación. PALABRAS CLAVE: trastornos de la conducta alimentaria, pandemia, COVID-19.

17.
Journal of Corporation Law ; 47(2):277-331, 2022.
Article in English | ProQuest Central | ID: covidwho-1762308

ABSTRACT

This Article is the first to analyze a sea change in bank governance-the precipitous rise of lawyer-directors in the past two decades. Using novel empirical evidence, we show that lawyer-directors are associated with efficient changes in risk management and significant increases in bank value. Banks with lawyer-directors assume more risk in ordinary circumstances and less risk when a crisis arises, in each case making those banks more valuable. Understanding that change in governance is vital in light of the COVID-19 crisis, which has transformed the risks that banks face. IVe show that-beyond new regulation, as others have proposed-having a director who thinks like a lawyer is likely to make boards more effective in managing new risks. Lawyer-directors add value to boards by drawing on advocacy skills to analyze opposing points of view, an essential quality in managing risk. They are more likely to make complex information more accessible to a board and to build a consensus among different points of view. Lawyer-directors, of course, are also skilled at assessing litigation and regulatory risks, which have grown significantly in recent years. Our findings challenge the standard framing of the board. Improving board efficacy requires a more nuanced understanding than has happened to date of the effect on boards of board composition and directors skills. We use the example of bank lawyer-directors to begin addressing that shortcoming. Beyond banks, however, our findings underscore the need for a new approach to analyzing what really matters for boards and corporate governance.

19.
Open Forum Infectious Diseases ; 8(SUPPL 1):S353, 2021.
Article in English | EMBASE | ID: covidwho-1746496

ABSTRACT

Background. Long-term care facility (LTCF) residents are at increased risk of severe COVID-19, with CMS data indicating > 20% mortality. BLAZE-1 trial noted lower hospitalization rates in high-risk patients receiving monoclonal antibody (mAb) vs placebo (4.2% vs 14.6%) for mild to moderate infections, making it a treatment option for LTCF residents;however, many LTCF lack staff to prepare and administer mAb therapy. To address this need, Region VII Disaster Health Response Ecosystem (R7DHRE) coordinated via NE Medical Emergency Operations Center (NEMEOC) an ASPR pilot project to facilitate infusion of COVID-19 mAb therapeutics for LTCF residents in the state. Methods. R7DHRE partnered with Great Plains Health, Nebraska DHHS, Nebraska Antimicrobial Stewardship Assessment and Promotion Program (ASAP) and Infection Control Assessment and Promotion Program (ICAP) to surveil cases in the state, establish distribution/administration pathways, and educate providers on mAb therapeutics. A multi-hub-and-spoke model was created to allow LTCF to work with regional hospitals or pharmacy services to administer drug in their facilities, reducing time to therapy and transmission risk associated with patient transport. A centralized request process was created using a REDCap platform and verification of patient eligibility by ASAP. This request link, informational documents, fact sheets, and custom-built order form templates were hosted on a dedicated ASAP webpage, and details were shared during weekly ICAP LTCF webinars. Outcomes data, including 14- and 28-day COVID-related hospitalizations and mortality, were collected using databases from Nebraska Health Information Initiative and Nebraska DHHS. Results. Through this program, 513 doses were administered to LTCF residents. Average time from symptom onset to infusion was 2.6 days. COVID- related hospitalization and mortality rates were lower than previously reported for LTCF residents (Table 1). Conclusion. By utilizing existing relationships with LTCFs in the region, we established a program to promptly distribute, prepare, and administer monoclonal antibody therapy to LTCF residents in need, preventing COVID-related hospitalizations and deaths.

20.
Critical Care Medicine ; 50(1 SUPPL):43, 2022.
Article in English | EMBASE | ID: covidwho-1692106

ABSTRACT

INTRODUCTION: The U.S. healthcare system remains vulnerable to crisis and troubled by resource inequities. Uneven distribution and scarcity of critical care (CC) clinicians is one example: COVID19 overwhelmed many hospitals with critically ill patients forcing some clinicians to provide care beyond their normal scope of practice and level of comfort. METHODS: The National Emergency Tele-Critical Care Network (NETCCN) was developed to address this problem by providing on-demand access to CC experts. NETCCN was funded by the Coronavirus, Aid, Relief, and Economic Security (CARES) Act;as a collaboration between the U.S. Army's Telemedicine and Advanced Technology Research Center (TATRC), the Department of Health and Human Services Assistant Secretary for Preparedness and Response (HHS ASPR), and the Society of Critical Care Medicine (SCCM). NETCCN focused on rapid development and deployment of technology platforms that were simple and user-friendly, cyber-secure, and HIPAA compliant, and only required a cellular connected mobile device. This federally funded resource allowed local non-CC caregivers to consult with CC experts. RESULTS: NETCCN has deployed to six states/territories, eight hospitals and cared for hundreds of patients in locations unfamiliar with managing critically-ill patients. While limited in scope, the NETCCN experience highlights key challenges and successes to address or sustain moving forward. Fear commonly prevented wider acceptance and use of NETCCN support. Clinicians fear judgment when asking questions;hospital administrators fear violating laws or disrupting “normal” practice patterns;and provider groups fear loss of market share. Despite laws that permit expedience during disaster conditions, major policy barriers, particularly local credentialing and privileging processes, hinder the use of tele-CC consultation solutions. Finally, lack of consistent federal, state, and local telehealth policies, especially for in-patient and e-consult services, caused confusion and prevented wider deployment of NETCCN. CONCLUSIONS: A federal capability that provides telemedicine support to hospitals or communities in crisis as part of a disaster response system is feasible, but policy barriers and cultural expectations impede rapid adoption.

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