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1.
Virus Res ; 301: 198464, 2021 08.
Article in English | MEDLINE | ID: covidwho-1246220

ABSTRACT

The spread of SARS-CoV-2 and the increasing mortality rates of COVID-19 create an urgent need for treatments, which are currently lacking. Although vaccines have been approved by the FDA for emergency use in the U.S., patients will continue to require pharmacologic intervention to reduce morbidity and mortality as vaccine availability remains limited. The rise of new variants makes the development of therapeutic strategies even more crucial to combat the current pandemic and future outbreaks. Evidence from several studies suggests the host immune response to SARS-CoV-2 infection plays a critical role in disease pathogenesis. Consequently, host immune factors are becoming more recognized as potential biomarkers and therapeutic targets for COVID-19. To develop therapeutic strategies to combat current and future coronavirus outbreaks, understanding how the coronavirus hijacks the host immune system during and after the infection is crucial. In this study, we investigated immunological patterns or characteristics of the host immune response to SARS-CoV-2 infection that may contribute to the disease severity of COVID-19 patients. We analyzed large bulk RNASeq and single cell RNAseq data from COVID-19 patient samples to immunoprofile differentially expressed gene sets and analyzed pathways to identify human host protein targets. We observed an immunological profile of severe COVID-19 patients characterized by upregulated cytokines, interferon-induced proteins, and pronounced T cell lymphopenia, supporting findings by previous studies. We identified a number of host immune targets including PERK, PKR, TNF, NF-kB, and other key genes that modulate the significant pathways and genes identified in COVID-19 patients. Finally, we identified genes modulated by COVID-19 infection that are implicated in oncogenesis, including E2F transcription factors and RB1, suggesting a mechanism by which SARS-CoV-2 infection may contribute to oncogenesis. Further clinical investigation of these targets may lead to bonafide therapeutic strategies to treat the current COVID-19 pandemic and protect against future outbreaks and viral escape variants.


Subject(s)
COVID-19/immunology , Immunity , Pandemics , SARS-CoV-2/immunology , COVID-19/drug therapy , COVID-19/epidemiology , COVID-19/virology , Carcinogenesis , Cytokines/immunology , High-Throughput Nucleotide Sequencing , Humans , SARS-CoV-2/genetics , Up-Regulation
2.
JMIR Cardio ; 5(1): e25277, 2021 May 05.
Article in English | MEDLINE | ID: covidwho-1217018

ABSTRACT

BACKGROUND: Virtual care has historically faced barriers to widespread adoption. However, the COVID-19 pandemic has necessitated the rapid adoption and expansion of virtual care technologies. Although the intense and prolonged nature of the COVID-19 pandemic has renewed people's interest in health systems resilience, which includes how services adapt or transform in response to shocks, evidence regarding the role of virtual care technologies in health systems resilience is scarce. OBJECTIVE: At Toronto General Hospital in Ontario, Canada, the rapid virtualization of cardiac care began on March 9, 2020, as a response to the pandemic. The objective of this study was to understand people's experiences with and the barriers and facilitators of the rapid virtualization and expansion of cardiac care resulting from the pandemic. METHODS: A single-case study was conducted with 3 embedded units of analysis. Patients, clinicians, and staff were recruited purposively from an existing mobile, phone-based telemonitoring program at a heart function clinic in Toronto, Canada. Individual, semistructured phone interviews were conducted by two researchers and transcribed verbatim. An inductive thematic analysis at the semantic level was used to analyze transcripts and develop themes. RESULTS: A total of 29 participants were interviewed, including patients (n=16), clinicians (n=9), and staff (n=4). The following five themes were identified: (1) patient safety as a catalyst for virtual care adoption; (2) piecemeal virtual care solutions; (3) confronting new roles and workloads; (4) missing pieces in virtual care; and (5) the inequity paradox. The motivation to protect patient safety and a piecemeal approach to virtual care adoption facilitated the absorptive and adaptive resilience of cardiac care during the COVID-19 pandemic. However, ad hoc changes to clinic roles and workflows, challenges in building relationships through remote methods, and widened inequities were barriers that threatened virtual care sustainment. CONCLUSIONS: We contend that sustaining virtual care hinges upon transformative actions (rather than adaptive actions) that strengthen health systems so that they can face the dynamic and emergent challenges associated with COVID-19 and other shocks. Based on the barriers and facilitators we identified, we present the lessons we learned and recommend transformations for sustaining virtual care during and beyond the COVID-19 pandemic.

3.
Intensive Care Med ; 47(3): 282-291, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-1092644

ABSTRACT

Coronavirus disease 19 (COVID-19) has posed unprecedented healthcare system challenges, some of which will lead to transformative change. It is obvious to healthcare workers and policymakers alike that an effective critical care surge response must be nested within the overall care delivery model. The COVID-19 pandemic has highlighted key elements of emergency preparedness. These include having national or regional strategic reserves of personal protective equipment, intensive care unit (ICU) devices, consumables and pharmaceuticals, as well as effective supply chains and efficient utilization protocols. ICUs must also be prepared to accommodate surges of patients and ICU staffing models should allow for fluctuations in demand. Pre-existing ICU triage and end-of-life care principles should be established, implemented and updated. Daily workflow processes should be restructured to include remote connection with multidisciplinary healthcare workers and frequent communication with relatives. The pandemic has also demonstrated the benefits of digital transformation and the value of remote monitoring technologies, such as wireless monitoring. Finally, the pandemic has highlighted the value of pre-existing epidemiological registries and agile randomized controlled platform trials in generating fast, reliable data. The COVID-19 pandemic is a reminder that besides our duty to care, we are committed to improve. By meeting these challenges today, we will be able to provide better care to future patients.


Subject(s)
COVID-19 , Critical Care/trends , Pandemics , Critical Care/organization & administration , Disaster Planning , Humans , Intensive Care Units/organization & administration , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Personal Protective Equipment , Surge Capacity , Telemedicine , Workflow
4.
J Gerontol B Psychol Sci Soc Sci ; 76(3): e75-e80, 2021 02 17.
Article in English | MEDLINE | ID: covidwho-1087754

ABSTRACT

OBJECTIVES: The aim of this evidence-based theoretically informed article was to provide an overview of how and why the COVID-19 outbreak is particularly detrimental for the health of older Black and Latinx adults. METHODS: We draw upon current events, academic literature, and numerous data sources to illustrate how biopsychosocial factors place older adults at higher risk for COVID-19 relative to younger adults, and how structural racism magnifies these risks for black and Latinx adults across the life course. RESULTS: We identify 3 proximate mechanisms through which structural racism operates as a fundamental cause of racial/ethnic inequalities in COVID-19 burden among older adults: (a) risk of exposure, (b) weathering processes, and (c) health care access and quality. DISCUSSION: While the ongoing COVID-19 pandemic is an unprecedented crisis, the racial/ethnic health inequalities among older adults it has exposed are longstanding and deeply rooted in structural racism within American society. This knowledge presents both challenges and opportunities for researchers and policymakers as they seek to address the needs of older adults. It is imperative that federal, state, and local governments collect and release comprehensive data on the number of confirmed COVID-19 cases and deaths by race/ethnicity and age to better gauge the impact of the outbreak across minority communities. We conclude with a discussion of incremental steps to be taken to lessen the disproportionate burden of COVID-19 among older Black and Latinx adults, as well as the need for transformative actions that address structural racism in order to achieve population health equity.


Subject(s)
African Americans/ethnology , Aging/ethnology , COVID-19/ethnology , Health Services Accessibility/statistics & numerical data , Healthcare Disparities/statistics & numerical data , Quality of Health Care/statistics & numerical data , Racism/ethnology , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/mortality , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Risk , United States/ethnology , Young Adult
5.
Oncotarget ; 11(46): 4201-4223, 2020 11 17.
Article in English | MEDLINE | ID: covidwho-948276

ABSTRACT

COVID-19 affects vulnerable populations including elderly individuals and patients with cancer. Natural Killer (NK) cells and innate-immune TRAIL suppress transformed and virally-infected cells. ACE2, and TMPRSS2 protease promote SARS-CoV-2 infectivity, while inflammatory cytokines IL-6, or G-CSF worsen COVID-19 severity. We show MEK inhibitors (MEKi) VS-6766, trametinib and selumetinib reduce ACE2 expression in human cells. In some human cells, remdesivir increases ACE2-promoter luciferase-reporter expression, ACE2 mRNA and protein, and ACE2 expression is attenuated by MEKi. In serum-deprived and stimulated cells treated with remdesivir and MEKi we observed correlations between pRB, pERK, and ACE2 expression further supporting role of proliferative state and MAPK pathway in ACE2 regulation. We show elevated cytokines in COVID-19-(+) patient plasma (N = 9) versus control (N = 11). TMPRSS2, inflammatory cytokines G-CSF, M-CSF, IL-1α, IL-6 and MCP-1 are suppressed by MEKi alone or with remdesivir. We observed MEKi stimulation of NK-cell killing of target-cells, without suppressing TRAIL-mediated cytotoxicity. Pseudotyped SARS-CoV-2 virus with a lentiviral core and SARS-CoV-2 D614 or G614 SPIKE (S) protein on its envelope infected human bronchial epithelial cells, small airway epithelial cells, or lung cancer cells and MEKi suppressed infectivity of the pseudovirus. We show a drug class-effect with MEKi to stimulate NK cells, inhibit inflammatory cytokines and block host-factors for SARS-CoV-2 infection leading also to suppression of SARS-CoV-2-S pseudovirus infection of human cells. MEKi may attenuate SARS-CoV-2 infection to allow immune responses and antiviral agents to control disease progression.

6.
Ann Glob Health ; 86(1): 70, 2020 06 29.
Article in English | MEDLINE | ID: covidwho-648198

ABSTRACT

Background: In December 2019, early cases of COVID-19 were identified in Wuhan, China. By late January 2020, it was evident that COVID-19 was rapidly spreading and represented a national health emergency. In order to contain the spread of COVID-19, China adopted a centralized treatment plan by appointing designated hospitals in each region. Shantou Central Hospital is a Grade A Class A general hospital in Guangdong Province. It was appointed as a provincial COVID-19 designated treatment hospital on January 21, 2020, to provide all COVID-19-related treatments for the city of Shantou. The nursing department at Shantou Central Hospital is fully responsible for hospital nursing administration, nursing human resource management, nursing quality management, and all nursing tasks related to hospital medical care, nursing, teaching, scientific research, preventive healthcare, and so on. Objective: To summarize the role of nursing management in transforming a general hospital into a designated hospital for treatment of COVID-19 patients. Methods: We undertook a series of nursing management measures in the strategic phase and the implementation phase. Findings: Through a series of nursing management measures, all COVID-19 patients admitted to our hospital were cured and discharged. All non-COVID-19 patients and staff hospitalized during the same period were not infected with the virus. During this period, our hospital completed 7,466 operations. Hence, our nursing management measures were effective. Conclusions: Our efficient nursing management system, first of all, effectively mobilized all available manpower; secondly, up-skilled and trained personnel within a very short period of time; thirdly, provided reliable logistical support for front-line protection equipments; and finally, motivated nurses during this very difficult time to make a significant positive contribution to the fight against COVID-19 pandemic.


Subject(s)
Communicable Disease Control/organization & administration , Coronavirus Infections/epidemiology , Coronavirus Infections/nursing , Hospitals, General/organization & administration , Nursing Staff, Hospital/organization & administration , Pneumonia, Viral/epidemiology , Pneumonia, Viral/nursing , Betacoronavirus , COVID-19 , China/epidemiology , Efficiency, Organizational , Humans , Pandemics , SARS-CoV-2
7.
Virol Sin ; 35(3): 311-320, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-617330

ABSTRACT

The mechanism of how SARS-CoV-2 causes severe multi-organ failure is largely unknown. Acute kidney injury (AKI) is one of the frequent organ damage in severe COVID-19 patients. Previous studies have shown that human renal tubule cells could be the potential host cells targeted by SARS-CoV-2. Traditional cancer cell lines or immortalized cell lines are genetically and phenotypically different from host cells. Animal models are widely used, but often fail to reflect a physiological and pathogenic status because of species tropisms. There is an unmet need for normal human epithelial cells for disease modeling. In this study, we successfully established long term cultures of normal human kidney proximal tubule epithelial cells (KPTECs) in 2D and 3D culture systems using conditional reprogramming (CR) and organoids techniques. These cells had the ability to differentiate and repair DNA damage, and showed no transforming property. Importantly, the CR KPTECs maintained lineage function with expression of specific transporters (SLC34A3 and cubilin). They also expressed angiotensin-converting enzyme 2 (ACE2), a receptor for SARS-CoV and SARS-CoV-2. In contrast, cancer cell line did not express endogenous SLC34A3, cubilin and ACE2. Very interestingly, ACE2 expression was around twofold higher in 3D organoids culture compared to that in 2D CR culture condition. Pseudovirion assays demonstrated that SARS-CoV spike (S) protein was able to enter CR cells with luciferase reporter. This integrated 2D CR and 3D organoid cultures provide a physiological ex vivo model to study kidney functions, innate immune response of kidney cells to viruses, and a novel platform for drug discovery and safety evaluation.


Subject(s)
Betacoronavirus/metabolism , Cell Culture Techniques/methods , Coronavirus Infections/virology , Coronavirus/metabolism , Epithelial Cells/virology , Kidney/virology , Pneumonia, Viral/virology , Angiotensin-Converting Enzyme 2 , Animals , Betacoronavirus/pathogenicity , COVID-19 , Cell Line , Coronavirus/pathogenicity , DNA Damage , Disease Models, Animal , Humans , Organoids , Pandemics , Peptidyl-Dipeptidase A/metabolism , Receptors, Cell Surface/metabolism , SARS Virus/metabolism , SARS Virus/pathogenicity , SARS-CoV-2 , Sodium-Phosphate Cotransporter Proteins, Type IIc/metabolism , Spike Glycoprotein, Coronavirus/metabolism
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