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1.
Theranostics ; 12(10): 4779-4790, 2022.
Article in English | MEDLINE | ID: covidwho-2203050

ABSTRACT

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are continuing to spread globally, contributing to the persistence of the COVID-19 pandemic. Increasing resources have been focused on developing vaccines and therapeutics that target the Spike glycoprotein of SARS-CoV-2. Recent advances in microfluidics have the potential to recapitulate viral infection in the organ-specific platforms, known as organ-on-a-chip (OoC), in which binding of SARS-CoV-2 Spike protein to the angiotensin-converting enzyme 2 (ACE2) of the host cells occurs. As the COVID-19 pandemic lingers, there remains an unmet need to screen emerging mutations, to predict viral transmissibility and pathogenicity, and to assess the strength of neutralizing antibodies following vaccination or reinfection. Conventional detection of SARS-CoV-2 variants relies on two-dimensional (2-D) cell culture methods, whereas simulating the micro-environment requires three-dimensional (3-D) systems. To this end, analyzing SARS-CoV-2-mediated pathogenicity via microfluidic platforms minimizes the experimental cost, duration, and optimization needed for animal studies, and obviates the ethical concerns associated with the use of primates. In this context, this review highlights the state-of-the-art strategy to engineer the nano-liposomes that can be conjugated with SARS-CoV-2 Spike mutations or genomic sequences in the microfluidic platforms; thereby, allowing for screening the rising SARS-CoV-2 variants and predicting COVID-19-associated coagulation. Furthermore, introducing viral genomics to the patient-specific blood accelerates the discovery of therapeutic targets in the face of evolving viral variants, including B1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), c.37 (Lambda), and B.1.1.529 (Omicron). Thus, engineering nano-liposomes to encapsulate SARS-CoV-2 viral genomic sequences enables rapid detection of SARS-CoV-2 variants in the long COVID-19 era.


Subject(s)
COVID-19 , Coronavirus Infections , Pneumonia, Viral , Animals , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/complications , COVID-19/diagnosis , Coronavirus Infections/prevention & control , Genomics , Humans , Liposomes , Microfluidics , Mutation , Pandemics/prevention & control , Peptidyl-Dipeptidase A/metabolism , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus
8.
Elife ; 92020 08 13.
Article in English | MEDLINE | ID: covidwho-2155738

ABSTRACT

As of 1 May 2020, there had been 6808 confirmed cases of COVID-19 in Australia. Of these, 98 had died from the disease. The epidemic had been in decline since mid-March, with 308 cases confirmed nationally since 14 April. This suggests that the collective actions of the Australian public and government authorities in response to COVID-19 were sufficiently early and assiduous to avert a public health crisis - for now. Analysing factors that contribute to individual country experiences of COVID-19, such as the intensity and timing of public health interventions, will assist in the next stage of response planning globally. We describe how the epidemic and public health response unfolded in Australia up to 13 April. We estimate that the effective reproduction number was likely below one in each Australian state since mid-March and forecast that clinical demand would remain below capacity thresholds over the forecast period (from mid-to-late April).


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Pandemics , Pneumonia, Viral/epidemiology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Australia/epidemiology , COVID-19 , Child , Child, Preschool , Communicable Disease Control/methods , Communicable Disease Control/organization & administration , Communicable Disease Control/statistics & numerical data , Coronavirus Infections/prevention & control , Female , Forecasting , Geography, Medical , Hospitalization/statistics & numerical data , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Public Health , Quarantine , SARS-CoV-2 , Travel , Young Adult
10.
Hypertension ; 76(5): 1368-1383, 2020 11.
Article in English | MEDLINE | ID: covidwho-2153222

ABSTRACT

Telemedicine allows the remote exchange of medical data between patients and healthcare professionals. It is used to increase patients' access to care and provide effective healthcare services at a distance. During the recent coronavirus disease 2019 (COVID-19) pandemic, telemedicine has thrived and emerged worldwide as an indispensable resource to improve the management of isolated patients due to lockdown or shielding, including those with hypertension. The best proposed healthcare model for telemedicine in hypertension management should include remote monitoring and transmission of vital signs (notably blood pressure) and medication adherence plus education on lifestyle and risk factors, with video consultation as an option. The use of mixed automated feedback services with supervision of a multidisciplinary clinical team (physician, nurse, or pharmacist) is the ideal approach. The indications include screening for suspected hypertension, management of older adults, medically underserved people, high-risk hypertensive patients, patients with multiple diseases, and those isolated due to pandemics or national emergencies.


Subject(s)
Coronavirus Infections/prevention & control , Cross Infection/prevention & control , Hypertension/drug therapy , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Telemedicine/statistics & numerical data , Blood Pressure Determination/methods , COVID-19 , Coronavirus Infections/epidemiology , Disease Management , Evidence-Based Medicine , Female , Humans , Hypertension/diagnosis , Italy , Male , Occupational Health , Pandemics/statistics & numerical data , Patient Safety , Pneumonia, Viral/epidemiology , Severity of Illness Index
11.
Hypertension ; 76(5): 1526-1536, 2020 11.
Article in English | MEDLINE | ID: covidwho-2153220

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
12.
JMIR Public Health Surveill ; 7(4): e25500, 2021 04 07.
Article in English | MEDLINE | ID: covidwho-2141301

ABSTRACT

BACKGROUND: The COVID-19 pandemic, caused by a novel coronavirus termed SARS-CoV-2, has spread quickly worldwide. Convalescent plasma (CP) obtained from patients following recovery from COVID-19 infection and development of antibodies against the virus is an attractive option for either prophylactic or therapeutic treatment, since antibodies may have direct or indirect antiviral activities and immunotherapy has proven effective in principle and in many clinical reports. OBJECTIVE: We seek to characterize the latest advances and evidence in the use of CP for COVID-19 through a systematic review and quantitative analysis, identify knowledge gaps in this setting, and offer recommendations and directives for future research. METHODS: PubMed, Web of Science, and Embase were continuously searched for studies assessing the use of CP for COVID-19, including clinical studies, commentaries, reviews, guidelines or protocols, and in vitro testing of CP antibodies. The screening process and data extraction were performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Quality appraisal of all clinical studies was conducted using a universal tool independent of study designs. A meta-analysis of case-control and randomized controlled trials (RCTs) was conducted using a random-effects model. RESULTS: Substantial literature has been published covering various aspects of CP therapy for COVID-19. Of the references included in this review, a total of 243 eligible studies including 64 clinical studies, 79 commentary articles, 46 reviews, 19 guidance and protocols, and 35 in vitro testing of CP antibodies matched the criteria. Positive results have been mostly observed so far when using CP for the treatment of COVID-19. There were remarkable heterogeneities in the CP therapy with respect to patient demographics, donor antibody titers, and time and dose of CP administration. The studies assessing the safety of CP treatment reported low incidence of adverse events. Most clinical studies, in particular case reports and case series, had poor quality. Only 1 RCT was of high quality. Randomized and nonrandomized data were found in 2 and 11 studies, respectively, and were included for meta-analysis, suggesting that CP could reduce mortality and increase viral clearance. Despite promising pilot studies, the benefits of CP treatment can only be clearly established through carefully designed RCTs. CONCLUSIONS: There is developing support for CP therapy, particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. These studies provide important lessons that should inform the planning of well-designed RCTs to generate more robust knowledge for the efficacy of CP in patients with COVID-19. Future research is necessary to fill the knowledge gap regarding prevention and treatment for patients with COVID-19 with CP while other therapeutics are being developed.


Subject(s)
COVID-19/therapy , Coronavirus Infections , Coronavirus Infections/prevention & control , Coronavirus Infections/therapy , Humans , Immunization, Passive
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