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1.
J Clin Med ; 11(24)2022 Dec 07.
Article in English | MEDLINE | ID: covidwho-2155157

ABSTRACT

Obesity is associated with long-term morbidity and mortality, but it is unclear if obesity affects goals of care determination and intensive care unit (ICU) resource utilization during hospitalization under a general medicine service. In a cohort of 5113 adult patients admitted under general medicine, 15.3% were obese. Patients with obesity were younger and had a different comorbidity profile than patients who were not obese. In age-adjusted regression analysis, the distribution of goals of care categories for patients with obesity was not different to patients who were not obese (odds ratio for a lower category with more limitations, 0.94; 95% confidence interval [CI]: 0.79-1.12). Patients with obesity were more likely to be directly admitted to ICU from the Emergency Department, require more ICU admissions, and stayed longer in ICU once admitted. Hypercapnic respiratory failure and heart failure were more common in patients with obesity, but they were less likely to receive mechanical ventilation in favor of non-invasive ventilation. The COVID-19 pandemic was associated with 16% higher odds of receiving a lower goals of care category, which was independent of obesity. Overall hospital length of stay was not affected by obesity. Patients with obesity had a crude mortality of 3.8 per 1000 bed-days, and age-adjusted mortality rate ratio of 0.75 (95% CI: 0.49-1.14) compared to patients who were not obese. In conclusion, there was no evidence to suggest biased goals of care determination in patients with obesity despite greater ICU resource utilization.

2.
Clinical Laboratory News ; 47(8):4-5, 2021.
Article in English | CINAHL | ID: covidwho-1481517
3.
Intern Med J ; 52(5): 755-762, 2022 05.
Article in English | MEDLINE | ID: covidwho-1440763

ABSTRACT

BACKGROUND: Conversion from paper-based to electronic medical records (EMR) may affect the quality and timeliness of the completion of Goals-of-Care (GOC) documents during hospital admissions and this may have been further impacted by the COVID-19 pandemic. AIMS: To determine the impact of EMR and COVID-19 on the proper completion of GOC forms and the factors associated with inpatient changes in GOC. METHODS: We conducted a cross-sectional study of adult general medicine admissions (August 2018-September 2020) at Dandenong Hospital (Victoria, Australia). We used interrupted time series to model the changes in the rates of proper GOC completion (adequate documented discussion, completed ≤2 days) after the introduction of EMR and the arrival of COVID-19. RESULTS: We included a total of 5147 patients. The pre-EMR GOC proper completion rate was 27.7% (overall completion, 86.5%). There was a decrease in the proper completion rate by 2.21% per month (95% confidence interval (CI): -2.83 to -1.58) after EMR implementation despite an increase in overall completion rates (91.2%). The main reason for the negative trend was a decline in adequate documentation despite improvements in timeliness. COVID-19 arrival saw a reversal of this negative trend, with proper completion rates increasing by 2.25% per month (95% CI: 1.35 to 3.15) compared with the EMR period, but also resulted in a higher proportion of GOC changes within 2 days of admission. CONCLUSIONS: EMR improved the timeliness and overall completion rates of GOC at the cost of a lower quality of documented discussion. COVID-19 reversed the negative trend in proper GOC completion but increased the number of early revisions.


Subject(s)
COVID-19 , Adult , COVID-19/epidemiology , Cross-Sectional Studies , Electronic Health Records , Goals , Humans , Pandemics , Victoria
4.
Proc Natl Acad Sci U S A ; 118(23)2021 06 08.
Article in English | MEDLINE | ID: covidwho-1238060

ABSTRACT

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.


Subject(s)
Antigen Presentation , COVID-19/immunology , Down-Regulation/immunology , Histocompatibility Antigens Class I/immunology , Immune Evasion , SARS-CoV-2/immunology , Viral Proteins/immunology , Animals , Autophagy/genetics , Autophagy/immunology , COVID-19/genetics , Chlorocebus aethiops , HEK293 Cells , Histocompatibility Antigens Class I/genetics , Humans , Lysosomes/genetics , Lysosomes/immunology , Lysosomes/virology , Mice , Mice, Transgenic , SARS-CoV-2/genetics , Vero Cells , Viral Proteins/genetics
5.
Signal Transduct Target Ther ; 6(1): 189, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1226420

ABSTRACT

Since the outbreak of coronavirus disease 2019 (COVID-19), it has become a global pandemic. The spike (S) protein of etiologic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specifically recognizes human angiotensin-converting enzyme 2 (hACE2) as its receptor, which is recently identified as an interferon (IFN)-stimulated gene. Here, we find that hACE2 exists on the surface of exosomes released by different cell types, and the expression of exosomal hACE2 is increased by IFNα/ß treatment. In particular, exosomal hACE2 can specifically block the cell entry of SARS-CoV-2, subsequently inhibit the replication of SARS-CoV-2 in vitro and ex vivo. Our findings have indicated that IFN is able to upregulate a viral receptor on the exosomes which competitively block the virus entry, exhibiting a potential antiviral strategy.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Exosomes/metabolism , Interferon-alpha/pharmacology , Interferon-beta/pharmacology , SARS-CoV-2/physiology , Virus Internalization/drug effects , Virus Replication/drug effects , Angiotensin-Converting Enzyme 2/genetics , Animals , Chlorocebus aethiops , Exosomes/genetics , Exosomes/virology , HEK293 Cells , Humans , Mice , Mice, Transgenic , Vero Cells
6.
Immunity ; 53(6): 1315-1330.e9, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-967948

ABSTRACT

Various vaccine strategies have been proposed in response to the global COVID-19 pandemic, each with unique strategies for eliciting immune responses. Here, we developed nanoparticle vaccines by covalently conjugating the self-assembled 24-mer ferritin to the receptor binding domain (RBD) and/or heptad repeat (HR) subunits of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) spike (S) protein. Compared to monomer vaccines, nanoparticle vaccines elicited more robust neutralizing antibodies and cellular immune responses. RBD and RBD-HR nanoparticle vaccinated hACE2 transgenic mice vaccinated with RBD and/or RBD-HR nanoparticles exhibited reduced viral load in the lungs after SARS-CoV-2 challenge. RBD-HR nanoparticle vaccines also promoted neutralizing antibodies and cellular immune responses against other coronaviruses. The nanoparticle vaccination of rhesus macaques induced neutralizing antibodies, and T and B cell responses prior to boost immunization; these responses persisted for more than three months. RBD- and HR-based nanoparticles thus present a promising vaccination approach against SARS-CoV-2 and other coronaviruses.


Subject(s)
Bacterial Proteins/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Ferritins/immunology , Helicobacter pylori/metabolism , Recombinant Fusion Proteins/immunology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/immunology , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antibodies, Neutralizing/metabolism , Antibodies, Viral/metabolism , Bacterial Proteins/chemistry , COVID-19 Vaccines/chemistry , Ferritins/chemistry , Humans , Macaca mulatta , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Pandemics , Protein Binding , Spike Glycoprotein, Coronavirus/chemistry , Vaccination
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