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SARS-CoV-2 infection depend on the binding of the viral Spike glycoprotein (S) to the human receptor Angiotensin Converting Enzyme 2 (ACE2) to induce virus-cell membrane fusion. S protein evolved diverse amino acid changes that are possibly linked to more efficient binding to human ACE2, which might explain part of the increase in frequency of SARS-CoV-2 Variants Of Concern (VOCs). In this work, we investigated the role of ACE2 protein variations that are naturally found in human populations and its binding affinity with S protein from SARS-CoV-2 representative genotypes, based on a series of in silico approaches involving molecular modelling, docking and molecular dynamics simulations. Our results indicate that SARS-CoV-2 VOCs bind more efficiently to the human receptor ACE2 than the ancestral Wuhan genotype. Additionally, variations in the ACE2 protein can affect SARS-CoV-2 binding and protein-protein stability, mostly making the interaction weaker and unstable in some cases. We show that some VOCs, such as B.1.1.7 and P.1 are much less sensitive to ACE2 variants, while others like B.1.351 appear to be specifically optimized to bind to the widespread wild-type ACE2 protein.Communicated by Ramaswamy H. Sarma.
ABSTRACT
Introduction: The treatment of COVID-19 is still challenge. So convalescent plasma can be an important alternative of treatment. Protocols with nursing care during infusion is very important to guide an effective and safety care. Objective: to analyze the evidence in the literature on the action of convalescent plasma, of the use of protocols with nursing care to use convalescent plasma and build a nursing care protocol for transfusion in patients with COVID-19. Methods: Methodological study carried out in two stages: scoping review. The search was done using the descriptors: convalescent plasma transfusion, convalescent plasma, and acute respiratory syndromes or COVID-19, to found protocols and effectiveness of convalescent plasm. Beside was done a specialist panel to build the protocol. Results: Low-evidence studies have shown improvement in the clinical signs of COVID-19 using Convalescent Plasma, reduction or elimination of viral load, benefits in the production of lymphocytes, decreases C-reactive protein, increases titers of anti-SARS-CoV-2 antibodies, positive evolution in lung involvement identified by X-rays, decrease in hospitalization. No studies were found in the databases on the protocol for clinical nursing care in plasma transfusion. Therefore, a protocol was developed with the description of clinical nursing care to be performed before, during and after the transfusion by plasma: checking of vital signs and indicative signs of transfusion reaction, measurement of oxygen saturation, assessment of venous access and checking of the level of consciousness. Conclusion: There are no evidence studies to support the use of plasma, nor anything related to bundles.
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BACKGROUND AND AIMS SARS‐CoV-2 represents a challenge for hemodialysis (HD) patients due to their diminished immune defenses in the setting of kidney disease, multiple comorbidities and older age. COVID-19 vaccines have brought hope but these patients’ reduced response to immunization with the hepatitis B and influenza vaccination raised concerns about a lower efficacy of the new vaccines. This study aimed at quantifying IgG in sequential samples from HD patients and compare its titers with those of a non-HD healthy population, after vaccination. METHOD We compared IgG titers using Abbott SARS-CoV-2 IgG II Quantitative Antibody Assay on the Alinity i system (Abbott Diagnostics, Chicago, US), 3–4 months after the Pfizer-BioNTech COVID-19 vaccine in 54 HD patients and 59 non-HD controls. This method is a two-step chemiluminescent microparticle immunoassay used for the quantitative determination of IgG antibodies to the receptor binding domain of the S1 subunit of the spike protein of SARS-CoV-2. HD patients performed their treatments at the HD unit of Felgueiras, a municipality in the district of Porto, Portugal, and were vaccinated in January/February 2021. The controls were healthcare workers from the hospital of Gaia. All HD patients received 2 vaccine doses even if they had previously had COVID-19 (N = 8) whereas controls only received 1 dose of the vaccine if they had been infected (N = 28). For 48 of the HD patients, we reassessed IgG levels 8 months after vaccination and compared it with the first measurements. Statistical analysis used SPSS®. Parametric variables were described with mean ± standard deviation and compared using independent and paired-samples t-tests. Non parametric variables were described with median ± interquartile range (IQR) and compared using Mann-Whitney U and Wilcoxon tests. RESULTS HD patients were older (67.6 ± 15.8 years of age) when compared to the healthy controls (42.4 ± 12.1 years of age). Only 1 HD patient had IgG below the positive cutoff after vaccination, all others seroconverted. Median values were significantly lower among HD patients compared to the controls (973 IQR 387–3306 versus 4809 IQR 2557–7746 AU/mL;p < 0.001). This difference remained significant even if those who had COVID-19 were removed from the analysis (p < 0.001). Those who had had COVID-19 before vaccination, showed significantly increased IgG levels compared to those who had not (6956 IQR 4810–13 101 versus 1520 IQR 554–3950 AU/mL;p < 0.001), a similar finding among HD and non-HD individuals. In HD patients for whom this data was available, IgG levels decayed from month 4 to month 8 (973 IQR 387–3306 versus 382 IQR 168–2071 AU/mL;p < 0.001). CONCLUSION HD patients seem to have an impaired immune response after the COVID-19 vaccines, similar to what happens with vaccines against other viruses. After the Pfizer-BioNTech COVID-19 vaccine 98% of the patients seroconverted. Although they were older which may have played a role, a limitation to the analysis, IgG titers were lower in HD-patients than in the control group. Antibodies declined over the next months. This decline may be associated with loss of neutralizing antibodies, cellular responses to SARS-CoV-2 and risk of reinfection.
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BACKGROUND: Digital technologies have been central to efforts to respond to the COVID-19 pandemic. In this context, a range of literature has reported on developments regarding the implementation of new digital technologies for COVID-19-related surveillance, prevention, and control. OBJECTIVE: In this study, scoping reviews of academic and nonacademic literature were undertaken to obtain an overview of the evidence regarding digital innovations implemented to address key public health functions in the context of the COVID-19 pandemic. This study aimed to expand on the work of existing reviews by drawing on additional data sources (including nonacademic sources) by considering literature published over a longer time frame and analyzing data in terms of the number of unique digital innovations. METHODS: We conducted a scoping review of the academic literature published between January 1, 2020, and September 15, 2020, supplemented by a further scoping review of selected nonacademic literature published between January 1, 2020, and October 13, 2020. Both reviews followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) approach. RESULTS: A total of 226 academic articles and 406 nonacademic articles were included. The included articles provided evidence of 561 (academic literature) and 497 (nonacademic literature) unique digital innovations. The most common implementation settings for digital innovations were the United States, China, India, and the United Kingdom. Technologies most commonly used by digital innovations were those belonging to the high-level technology group of integrated and ubiquitous fixed and mobile networks. The key public health functions most commonly addressed by digital innovations were communication and collaboration and surveillance and monitoring. CONCLUSIONS: Digital innovations implemented in response to the COVID-19 pandemic have been wide ranging in terms of their implementation settings, the digital technologies used, and the public health functions addressed. However, evidence gathered through this study also points to a range of barriers that have affected the successful implementation of digital technologies for public health functions. It is also evident that many digital innovations implemented in response to the COVID-19 pandemic are yet to be formally evaluated or assessed.