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2.
Cureus ; 14(9), 2022.
Article in English | EuropePMC | ID: covidwho-2092493

ABSTRACT

Introduction: In a challenging time for the healthcare workforce responding to the coronavirus disease 2019 (COVID-19) pandemic, it is critical to identify factors contributing to team members' feelings of “belonging” in the workplace. The Institute for Healthcare Improvement’s Quintuple Aim’s principle of improving healthcare worker well-being could be applied to explore the implications of the increased turnover and stress, which connect to components of belonging. This study applies a qualitative approach to the organizational issues impacting healthcare teams, particularly during a complex and uncertain time. Methods: To elucidate factors contributing to belonging, we conducted a series of semi-structured interviews with an interdisciplinary cross-sectional sample of healthcare workers. Interviews were conducted with 23 total staff members in two clinical settings, the emergency department and hospital medicine groups at a large urban teaching hospital, to evaluate team members’ perspectives of the work environment. Results: Participants discuss their degree of inclusion, excitement, challenges, and respective needs from the organization. Perspectives of workers representing varied professional roles of the healthcare team were gathered to provide robust and unique insights into initiatives that can enhance belonging in the clinical workplace. Conclusion: Our findings provide a preliminary framework to identify strategies that can potentially reinforce collective team member belonging and consequently improve staff well-being, morale, and retention.

3.
Int J Environ Res Public Health ; 19(17)2022 Aug 23.
Article in English | MEDLINE | ID: covidwho-1997620

ABSTRACT

Individuals' vulnerability to the risk of COVID-19 infection varies due to their health, socioeconomic, and living circumstances, which also affect the effectiveness of implementing non-pharmacological interventions (NPIs). In this study, we analysed socioeconomic-related inequalities in COVID-19 vulnerability using data from the nationally representative South African General Household Survey 2019. We developed a COVID-19 vulnerability index, which includes health and social risk factors for COVID-19 exposure and susceptibility. The concentration curve and concentration index were used to measure socioeconomic-related inequalities in COVID-19 vulnerability. Recentred influence function regression was then utilised to decompose factors that explain the socioeconomic-related inequalities in COVID-19 vulnerability. The concentration index estimates were all negative and highly significant (p < 0.01), indicating that vulnerability to COVID-19 was more concentrated among the poor. According to the decomposition analysis, higher income and education significantly (p < 0.01) positively impacted lowering socioeconomic-related COVID-19 vulnerability. Living in an urban region, being Black, and old all had significant (p < 0.01) positive impacts on increasing socioeconomic-related COVID-19 vulnerability. Our findings contribute to a better understanding of socially defined COVID-19-vulnerable populations in South Africa and the implications for future pandemic preparedness plans.


Subject(s)
COVID-19 , COVID-19/epidemiology , Humans , Income , Prevalence , Socioeconomic Factors , South Africa/epidemiology
4.
Epidemiol Infect ; 149: e183, 2021 07 23.
Article in English | MEDLINE | ID: covidwho-1947139

ABSTRACT

The feasibility of non-pharmacological public health interventions (NPIs) such as physical distancing or isolation at home to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in low-resource countries is unknown. Household survey data from 54 African countries were used to investigate the feasibility of SARS-CoV-2 NPIs in low-resource settings. Across the 54 countries, approximately 718 million people lived in households with ⩾6 individuals at home (median percentage of at-risk households 56% (95% confidence interval (CI), 51% to 60%)). Approximately 283 million people lived in households where ⩾3 people slept in a single room (median percentage of at-risk households 15% (95% CI, 13% to 19%)). An estimated 890 million Africans lack on-site water (71% (95% CI, 62% to 80%)), while 700 million people lacked in-home soap/washing facilities (56% (95% CI, 42% to 73%)). The median percentage of people without a refrigerator in the home was 79% (95% CI, 67% to 88%), while 45% (95% CI, 39% to 52%) shared toilet facilities with other households. Individuals in low-resource settings have substantial obstacles to implementing NPIs for mitigating SARS-CoV-2 transmission. These populations urgently need to be prioritised for coronavirus disease 2019 vaccination to prevent disease and to contain the global pandemic.


Subject(s)
COVID-19 , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/prevention & control , Housing , Humans , Sanitation , Social Conditions
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-329670

ABSTRACT

New therapeutic targets are a valuable resource in the struggle to reduce the morbidity and mortality associated with the COVID-19 pandemic, caused by the SARS-CoV-2 virus. Genome-wide association studies (GWAS) have identified risk loci, but some loci are associated with co-morbidities and are not specific to host-virus interactions. Here, we identify and experimentally validate a link between reduced expression of EXOSC2 and reduced SARS-CoV-2 replication. EXOSC2 was one of 332 host proteins examined, all of which interact directly with SARS-CoV-2 proteins;EXOSC2 interacts with Nsp8 which forms part of the viral RNA polymerase. Lung-specific eQTLs were identified from GTEx (v7) for each of the 332 host proteins. Aggregating COVID-19 GWAS statistics for gene-specific eQTLs revealed an association between increased expression of EXOSC2 and higher risk of clinical COVID-19 which survived stringent multiple testing correction. EXOSC2 is a component of the RNA exosome and indeed, LC-MS/MS analysis of protein pulldowns demonstrated an interaction between the SARS-CoV-2 RNA polymerase and the majority of human RNA exosome components. CRISPR/Cas9 introduction of nonsense mutations within EXOSC2 in Calu-3 cells reduced EXOSC2 protein expression, impeded SARS-CoV-2 replication and upregulated oligoadenylate synthase (OAS) genes, which have been linked to a successful immune response against SARS-CoV-2. Reduced EXOSC2 expression did not reduce cellular viability. OAS gene expression changes occurred independent of infection and in the absence of significant upregulation of other interferon-stimulated genes (ISGs). Targeted depletion or functional inhibition of EXOSC2 may be a safe and effective strategy to protect at-risk individuals against clinical COVID-19.

6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-313759

ABSTRACT

Background: : The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. Methods: : We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. Results: : A total of 97 adults with an opioid-use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. Conclusions: : The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. Trial Registration : NCT04530591

7.
NPJ Vaccines ; 6(1): 50, 2021 Apr 09.
Article in English | MEDLINE | ID: covidwho-1387358

ABSTRACT

The development of an effective AIDS vaccine remains a challenge. Nucleoside-modified mRNAs formulated in lipid nanoparticles (mRNA-LNP) have proved to be a potent mode of immunization against infectious diseases in preclinical studies, and are being tested for SARS-CoV-2 in humans. A critical question is how mRNA-LNP vaccine immunogenicity compares to that of traditional adjuvanted protein vaccines in primates. Here, we show that mRNA-LNP immunization compared to protein immunization elicits either the same or superior magnitude and breadth of HIV-1 Env-specific polyfunctional antibodies. Immunization with mRNA-LNP encoding Zika premembrane and envelope or HIV-1 Env gp160 induces durable neutralizing antibodies for at least 41 weeks. Doses of mRNA-LNP as low as 5 µg are immunogenic in macaques. Thus, mRNA-LNP can be used to rapidly generate single or multi-component vaccines, such as sequential vaccines needed to protect against HIV-1 infection. Such vaccines would be as or more immunogenic than adjuvanted recombinant protein vaccines in primates.

8.
Harm Reduct J ; 18(1): 75, 2021 07 23.
Article in English | MEDLINE | ID: covidwho-1322939

ABSTRACT

BACKGROUND: The incidence of opioid-related overdose deaths has been rising for 30 years and has been further exacerbated amidst the COVID-19 pandemic. Naloxone can reverse opioid overdose, lower death rates, and enable a transition to medication for opioid use disorder. Though current formulations for community use of naloxone have been shown to be safe and effective public health interventions, they rely on bystander presence. We sought to understand the preferences and minimum necessary conditions for wearing a device capable of sensing and reversing opioid overdose among people who regularly use opioids. METHODS: We conducted a combined cross-sectional survey and semi-structured interview at a respite center, shelter, and syringe exchange drop-in program in Philadelphia, Pennsylvania, USA, during the COVID-19 pandemic in August and September 2020. The primary aim was to explore the proportion of participants who would use a wearable device to detect and reverse overdose. Preferences regarding designs and functionalities were collected via a questionnaire with items having Likert-based response options and a semi-structured interview intended to elicit feedback on prototype designs. Independent variables included demographics, opioid use habits, and previous experience with overdose. RESULTS: A total of 97 adults with an opioid use history of at least 3 months were interviewed. A majority of survey participants (76%) reported a willingness to use a device capable of detecting an overdose and automatically administering a reversal agent upon initial survey. When reflecting on the prototype, most respondents (75.5%) reported that they would wear the device always or most of the time. Respondents indicated discreetness and comfort as important factors that increased their chance of uptake. Respondents suggested that people experiencing homelessness and those with low tolerance for opioids would be in greatest need of the device. CONCLUSIONS: The majority of people sampled with a history of opioid use in an urban setting were interested in having access to a device capable of detecting and reversing an opioid overdose. Participants emphasized privacy and comfort as the most important factors influencing their willingness to use such a device. TRIAL REGISTRATION: NCT04530591.


Subject(s)
Naloxone/administration & dosage , Narcotic Antagonists/administration & dosage , Opiate Overdose/diagnosis , Opiate Overdose/drug therapy , Patient Acceptance of Health Care/statistics & numerical data , Wearable Electronic Devices/statistics & numerical data , Adolescent , Adult , Child , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Male , Naloxone/therapeutic use , Narcotic Antagonists/therapeutic use , Opiate Overdose/psychology , Patient Acceptance of Health Care/psychology , Philadelphia , Wearable Electronic Devices/psychology , Young Adult
9.
Front Psychol ; 12: 644600, 2021.
Article in English | MEDLINE | ID: covidwho-1295687

ABSTRACT

While the COVID-19 pandemic has presented an immediate risk to human life around the world, climate change poses an arguably greater-although less immediate-threat to our species' survival. Within the framework of life-history theory (LHT), this pre-registered study investigated whether extrinsic risk (i.e., external factors that pose a risk to an individual's life, e.g., COVID-19) and existential risk (i.e., risks with outcomes that threaten the existence of humans as a species, e.g., climate change) had similar or different relationships with reproductive decision-making. A UK representative sample of 325 participants between 18 and 35 years of age was asked to indicate their ideal number of children, ideal age to start having children, and whether their desire for a child had recently changed. Participants were asked about their experiences of COVID-19 and given a series of scales with which to assess their beliefs about climate change. In support of LHT, the study found evidence that knowing people who had been hospitalized with or died of COVID-19 was associated with a greater ideal number of children. Conversely, there was no clear evidence of a relationship between climate change beliefs and reproductive decision-making. The repercussions for understanding how we interpret and respond to different forms of mortality risk are discussed.

10.
Telemed J E Health ; 27(8): 915-918, 2021 08.
Article in English | MEDLINE | ID: covidwho-1276127

ABSTRACT

Background: Residents of nursing homes are among the most vulnerable to COVID-19. There is no standardized approach for integration with hospitals for outbreak response. Previously, we described collaboration between a hospital and regional facilities. As a component of our COVID-19 Outbreak Response, we describe the impact of virtual daily rounds as an efficient and effective tool for facility outbreak in Central Virginia. Methods: At this facility, 82 (60%) residents were infected. Our team rapidly deployed technology to support staff at the facility. Virtual daily rounds created a systematic approach for patient care. The goals of virtual daily rounds include (1) efficiently facilitating HIPAA-compliant communication between nursing and all licensed independent providers, (2) rapid identification of clinical decline, (3) facilitation of care escalation, (4) facilitating bidirectional transfers, and (5) rapid and efficient identification of patients appropriate for telemedicine pulmonary consultation. Results: The outbreak remained active 6 weeks; 82 of 136 (60%) residents were infected, and 36 (44%) COVID-19 positive residents were seen by telemedicine consultation. Fifty-seven (70%) residents remained in-facility for treatment. Twenty-one residents died (15%); 10 in facility, 11 in hospital. Of those seen in telemedicine consultation, 24 (69%) remained on the treat-in-place protocol with goal-concordant care. These hospitalization and mortality rates are significantly lower than similar outbreaks reported. Discussion and Conclusion: We have since instituted this system at seven other facilities. A model of virtual daily rounding holds promise for decreasing mortality/hospitalization in this vulnerable population through systematically identifying patients most appropriate for telemedicine and cultivating close collaboration between hospitals and nursing homes.


Subject(s)
COVID-19 , Telemedicine , Disease Outbreaks , Hospitals , Humans , SARS-CoV-2
11.
Future Microbiol ; 16(3): 135-142, 2021 02.
Article in English | MEDLINE | ID: covidwho-1110198

ABSTRACT

The ability of influenza A virus to evolve, coupled with increasing antimicrobial resistance, could trigger an influenza pandemic with great morbidity and mortality. Much of the 1918 influenza pandemic mortality was likely due to bacterial coinfection, including Staphylococcus aureus pneumonia. S. aureus resists many antibiotics. The lack of new antibiotics suggests alternative antimicrobials, such as bacteriophages, are needed. Potential delivery routes for bacteriophage therapy (BT) include inhalation and intravenous injection. BT has recently been used successfully in compassionate access pulmonary infection cases. Phage lysins, enzymes that hydrolyze bacterial cell walls and which are bactericidal, are efficacious in animal pneumonia models. Clinical trials will be needed to determine whether BT can ameliorate disease in influenza and S. aureus coinfection.


Subject(s)
Bacteriophages/physiology , Coinfection/therapy , Influenza A virus/physiology , Influenza, Human/therapy , Phage Therapy , Pneumonia, Staphylococcal/therapy , Staphylococcus aureus/virology , Animals , Coinfection/microbiology , Coinfection/mortality , Coinfection/virology , Humans , Influenza A virus/genetics , Influenza, Human/mortality , Influenza, Human/virology , Pneumonia, Staphylococcal/microbiology , Pneumonia, Staphylococcal/mortality , Staphylococcus aureus/genetics , Staphylococcus aureus/physiology
12.
Nat Commun ; 12(1): 1162, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1091489

ABSTRACT

The durability of infection-induced SARS-CoV-2 immunity has major implications for reinfection and vaccine development. Here, we show a comprehensive profile of antibody, B cell and T cell dynamics over time in a cohort of patients who have recovered from mild-moderate COVID-19. Binding and neutralising antibody responses, together with individual serum clonotypes, decay over the first 4 months post-infection. A similar decline in Spike-specific CD4+ and circulating T follicular helper frequencies occurs. By contrast, S-specific IgG+ memory B cells consistently accumulate over time, eventually comprising a substantial fraction of circulating the memory B cell pool. Modelling of the concomitant immune kinetics predicts maintenance of serological neutralising activity above a titre of 1:40 in 50% of convalescent participants to 74 days, although there is probably additive protection from B cell and T cell immunity. This study indicates that SARS-CoV-2 immunity after infection might be transiently protective at a population level. Therefore, SARS-CoV-2 vaccines might require greater immunogenicity and durability than natural infection to drive long-term protection.


Subject(s)
Antibodies, Viral/immunology , Antibody Formation , COVID-19/immunology , Immunity, Cellular , Immunologic Memory , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , Humans , Immunoglobulin G/immunology , Longitudinal Studies , Models, Theoretical , Neutralization Tests , T-Lymphocytes, Helper-Inducer/immunology
13.
Telemed J E Health ; 27(1): 102-106, 2021 01.
Article in English | MEDLINE | ID: covidwho-1066235

ABSTRACT

Purpose: The vulnerability of postacute and long-term care (PA/LTC) facility residents to COVID-19 has manifested across the world with increasing facility outbreaks associated with high hospitalization and mortality rates. Systematic protocols to guide telehealth-centered interventions in response to COVID-19 outbreaks have yet to be delineated. This article is intended to inform PA/LTC facilities and neighboring health care partners how to collaboratively utilize telehealth-centered strategies to improve outcomes in facility outbreaks. Methods: The University of Virginia rapidly developed a multidisciplinary telehealth-centered COVID-19 facility outbreak strategy in response to a LTC facility outbreak in which 41 (out of 48) facility residents and 7 staff members tested positive. This strategy focused on supporting the facility team remotely using rapidly deployed technologic solutions. Goals included (1) early identification of patients who need their care escalated, (2) monitoring and treating patients deemed safe to remain in the facility, (3) care coordination to facilitate bidirectional transfers between the skilled nursing facility (SNF) and hospital, and (4) daily facility needs assessment related to technology, infection control, and staff well-being. To achieve these goals, a standardized approach centered on daily multidisciplinary virtual rounds and telemedicine consultation was provided. Results: Over a month since the outbreak began, 18 out of 48 (38%) facility residents required hospitalization and 6 (12.5%) died. Eleven facility residents have since returned back to the SNF after recovering from their hospitalization. No staff required hospitalization. Conclusions: Interventions that reduce hospitalizations and mortality are a critical need during the COVID-19 pandemic. The mortality and hospitalization rates seen in this PA/LTC facility outbreak are significantly lower than has been documented in other facility outbreaks. Our multidisciplinary approach centered on telemedicine should be considered as other PA/LTC facilities partner with neighboring health care systems in responding to COVID-19 outbreaks. We have begun replicating these services to additional PA/LTC facilities facing COVID-19 outbreaks.


Subject(s)
COVID-19/epidemiology , Remote Consultation/organization & administration , Residential Facilities/organization & administration , Subacute Care/organization & administration , Continuity of Patient Care , Humans , Infection Control/organization & administration , Needs Assessment/organization & administration , Pandemics , SARS-CoV-2 , Time Factors
14.
HERD ; 14(2): 38-48, 2021 04.
Article in English | MEDLINE | ID: covidwho-975844

ABSTRACT

OBJECTIVES, PURPOSES, OR AIM: To identify design strategies utilized in airborne infection isolation and biocontainment patient rooms that improve infection control potential in an alternative care environment. BACKGROUND: As SARS-CoV-2 spreads and health care facilities near or exceed capacity, facilities may implement alternative care sites (ACSs). With COVID-19 surges predicted, developing additional capacity in alternative facilities, including hotels and convention centers, into patient care environments requires early careful consideration of the existing space constraints, infrastructure, and modifications needed for patient care and infection control. Design-based strategies utilizing engineering solutions have the greatest impact, followed by medical and operational strategies. METHODS: This article evaluates infection control and environmental strategies in inpatient units and proposes system modifications to ACS surge facilities to reduce infection risk and improve care environments. RESULTS: Although adequate for an acute infectious disease outbreak, existing capacity in U.S. biocontainment units and airborne infection isolation rooms is not sufficient for widespread infection control and isolation during a pandemic. To improve patients' outcomes and decrease infection transmission risk in the alternative care facility, hospital planners, administrators, and clinicians can take cues from evidence-based strategies implemented in biocontainment units and standard inpatient rooms. CONCLUSIONS: Innovative technologies, including optimized air-handling systems with ultraviolet and particle filters, can be an essential part of an infection control strategy. For flexible surge capacity in future ACS and hospital projects, interdisciplinary design and management teams should apply strategies optimizing the treatment of both infectious patients and minimizing the risk to health care workers.


Subject(s)
Built Environment/organization & administration , COVID-19/epidemiology , COVID-19/prevention & control , Infection Control/organization & administration , Patients' Rooms/organization & administration , Built Environment/standards , Humans , Infection Control/standards , Pandemics , Patient Isolation/standards , Patients' Rooms/standards , SARS-CoV-2 , Ventilation/standards
15.
Science ; 370(6521)2020 12 04.
Article in English | MEDLINE | ID: covidwho-873450

ABSTRACT

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARS-CoV-2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.


Subject(s)
COVID-19/metabolism , Coronavirus Nucleocapsid Proteins/metabolism , Host Microbial Interactions , Mitochondrial Membrane Transport Proteins/metabolism , Protein Interaction Maps , SARS Virus/metabolism , SARS-CoV-2/metabolism , Severe Acute Respiratory Syndrome/metabolism , Conserved Sequence , Coronavirus Nucleocapsid Proteins/genetics , Cryoelectron Microscopy , Humans , Mitochondrial Membrane Transport Proteins/genetics , Phosphoproteins/genetics , Phosphoproteins/metabolism , Protein Conformation
16.
Hypertension ; 76(5): 1526-1536, 2020 11.
Article in English | MEDLINE | ID: covidwho-800953

ABSTRACT

ACE2 (angiotensin-converting enzyme 2) is a key component of the renin-angiotensin-aldosterone system. Yet, little is known about the clinical and biologic correlates of circulating ACE2 levels in humans. We assessed the clinical and proteomic correlates of plasma (soluble) ACE2 protein levels in human heart failure. We measured plasma ACE2 using a modified aptamer assay among PHFS (Penn Heart Failure Study) participants (n=2248). We performed an association study of ACE2 against ≈5000 other plasma proteins measured with the SomaScan platform. Plasma ACE2 was not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 was associated with older age, male sex, diabetes mellitus, a lower estimated glomerular filtration rate, worse New York Heart Association class, a history of coronary artery bypass surgery, and higher pro-BNP (pro-B-type natriuretic peptide) levels. Plasma ACE2 exhibited associations with 1011 other plasma proteins. In pathway overrepresentation analyses, top canonical pathways associated with plasma ACE2 included clathrin-mediated endocytosis signaling, actin cytoskeleton signaling, mechanisms of viral exit from host cells, EIF2 (eukaryotic initiation factor 2) signaling, and the protein ubiquitination pathway. In conclusion, in humans with heart failure, plasma ACE2 is associated with various clinical factors known to be associated with severe coronavirus disease 2019 (COVID-19), including older age, male sex, and diabetes mellitus, but is not associated with ACE inhibitor and angiotensin-receptor blocker use. Plasma ACE2 protein levels are prominently associated with multiple cellular pathways involved in cellular endocytosis, exocytosis, and intracellular protein trafficking. Whether these have a causal relationship with ACE2 or are relevant to novel coronavirus-2 infection remains to be assessed in future studies.


Subject(s)
Coronavirus Infections/epidemiology , Disease Outbreaks/statistics & numerical data , Disease Progression , Heart Failure/enzymology , Heart Failure/physiopathology , Peptidyl-Dipeptidase A/blood , Pneumonia, Viral/epidemiology , Academic Medical Centers , Analysis of Variance , Angiotensin-Converting Enzyme 2 , Biomarkers/metabolism , COVID-19 , Cohort Studies , Coronavirus Infections/prevention & control , Female , Humans , Linear Models , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Prognosis , Proportional Hazards Models , Proteomics/methods , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , United States
17.
West J Emerg Med ; 21(5): 1105-1113, 2020 Aug 19.
Article in English | MEDLINE | ID: covidwho-793145

ABSTRACT

The coronavirus disease (COVID-19) pandemic has had a significant impact on undergraduate medical education with limitation of patient care activities and disruption to medical licensing examinations. In an effort to promote both safety and equity, the emergency medicine (EM) community has recommended no away rotations for EM applicants and entirely virtual interviews during this year's residency application cycle. These changes affect the components of the EM residency application most highly regarded by program directors - Standardized Letters of Evaluation from EM rotations, board scores, and interactions during the interview. The Council of Residency Directors in Emergency Medicine Application Process Improvement Committee suggests solutions not only for the upcoming year but also to address longstanding difficulties within the process, encouraging residency programs to leverage these challenges as an opportunity for disruptive innovation.


Subject(s)
Betacoronavirus , Coronavirus Infections/prevention & control , Emergency Medicine/education , Internship and Residency/methods , Organizational Innovation , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , School Admission Criteria/trends , COVID-19 , Humans , SARS-CoV-2 , United States , Videoconferencing/organization & administration , Videoconferencing/trends
18.
Neurocrit Care ; 34(3): 748-759, 2021 06.
Article in English | MEDLINE | ID: covidwho-728269

ABSTRACT

BACKGROUND AND PURPOSE: While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS: We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS: During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION: We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.


Subject(s)
Anticoagulants/therapeutic use , COVID-19/complications , Hemorrhagic Stroke/epidemiology , Aged , Aged, 80 and over , COVID-19/drug therapy , COVID-19/mortality , Female , Hemorrhagic Stroke/diagnosis , Hemorrhagic Stroke/virology , Hospitalization , Humans , Male , Middle Aged , New York City , Retrospective Studies , Risk Factors , Survival Rate
19.
Cell ; 182(3): 685-712.e19, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-624826

ABSTRACT

The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions and killed hundreds of thousands of people worldwide, highlighting an urgent need to develop antiviral therapies. Here we present a quantitative mass spectrometry-based phosphoproteomics survey of SARS-CoV-2 infection in Vero E6 cells, revealing dramatic rewiring of phosphorylation on host and viral proteins. SARS-CoV-2 infection promoted casein kinase II (CK2) and p38 MAPK activation, production of diverse cytokines, and shutdown of mitotic kinases, resulting in cell cycle arrest. Infection also stimulated a marked induction of CK2-containing filopodial protrusions possessing budding viral particles. Eighty-seven drugs and compounds were identified by mapping global phosphorylation profiles to dysregulated kinases and pathways. We found pharmacologic inhibition of the p38, CK2, CDK, AXL, and PIKFYVE kinases to possess antiviral efficacy, representing potential COVID-19 therapies.


Subject(s)
Betacoronavirus/metabolism , Coronavirus Infections/metabolism , Drug Evaluation, Preclinical/methods , Pneumonia, Viral/metabolism , Proteomics/methods , A549 Cells , Angiotensin-Converting Enzyme 2 , Animals , Antiviral Agents/pharmacology , COVID-19 , Caco-2 Cells , Casein Kinase II/antagonists & inhibitors , Casein Kinase II/metabolism , Chlorocebus aethiops , Coronavirus Infections/virology , Cyclin-Dependent Kinases/antagonists & inhibitors , Cyclin-Dependent Kinases/metabolism , HEK293 Cells , Host-Pathogen Interactions , Humans , Pandemics , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Phosphorylation , Pneumonia, Viral/virology , Protein Kinase Inhibitors/pharmacology , Proto-Oncogene Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/metabolism , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , p38 Mitogen-Activated Protein Kinases/metabolism
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