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Objectives: The COVID-19 pandemic has highlighted the need for sustainable and resilient healthcare systems to protect population health. This requires measuring the relative progress of health systems towards becoming more sustainable and resilient. In this research, we design, construct and estimate a country-level healthcare system sustainability and resilience index (HSSRI) that reflects and combines the two dimensions. Method(s): The HSSRI aims to summarise the performance of a health system in the different domains contributing to its sustainability and resilience. These domains are: i) health system governance, ii) health system financing, iii) health system workforce, iv) medicines and technologies, v) health service delivery, vi) population health and social determinants, and vii) environmental sustainability. As part of our analyses, we conduct a rapid evidence assessment to identify indicators reflecting the domains included in the sustainability and resilience dimensions. We assess the domain indicators' suitability by the quantity and quality of the literature supporting their inclusion. The variables in each indicator are extracted from publicly available data sources, such as the OECD, World Bank, and others. The period covered is from 2000 to 2020. Weighted means of the indicators are used to construct the domains' indices in each dimension. We apply a geometric mean to combine the domain indices into one final index. Result(s): The HSSRI is piloted using data from five high-income countries, providing a credible instrument for measuring and reporting healthcare system sustainability and resilience. The results enable policy-makers and stakeholders to observe how different domains of sustainability and resilience have evolved across countries and time. Conclusion(s): The HSSRI will facilitate better understanding and monitoring of the healthcare system's relative weaknesses and strengths, and empower policy-makers to design interventions that improve its resilience and sustainability.Copyright © 2022
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Background & Aim: Due to its immunomodulatory potential, therapy based on the transfer of regulatory T cells (Tregs) has acquired great interest in the treatment of diseases in which it is necessary to restore immune homeostasis. Until now, autologous Treg cell therapy has proven to be safe, but the employment of blood as the source of Treg presents several limitations in terms of Treg recovery and the quality of the employed Tregs. Our group has developed a new technology to produce massive amounts of GMP Treg derived from the pediatric thymic tissue discarded in pediatric cardiac surgeries (thyTreg) that could overcome the main obstacles. Indeed, we are employing thyTreg cells with success in a clinical trial as autologous cell therapy in transplanted children. Given the large amounts of thyTreg that can be obtained from a single thymus, the main objective of this work is to evaluate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible the allogeneic use of this cellular therapy in order to treat a range of immune diseases and patients. Methods, Results & Conclusion: The thyTreg obtained in the laboratory using the protocol developed by our group exhibit high viability (>90%) and high purity (>80%) in terms of CD25+FoxP3+ expression. ThyTreg have been observed to express low levels of immunogenicity markers (CD40L, CD80, CD86) by flow cytometry. Moreover, in vitro models of thyTreg co-culture with allogeneic peripheral blood mononuclear cells (PBMC) from healthy donors have been performed to i) determine if thyTreg generate an immunogenic response on PBMC, and ii) evaluate the capacity of thyTreg to suppress the proliferation of allogeneic PBMC. Even that the HLA disparity in the allogeneic cocultures between thyTreg and PBMC was high (13 of the 21 typed pairs had HLA <4/12 concordance), thyTreg did not induce the expression of activation markers (CD25, CD69) nor the proliferation or the production of pro-inflammatory cytokines (IFN-g) by allogeneic PBMCs. Moreover, thyTreg greatly inhibit the proliferation of allogeneic CD4 and CD8 T cells, reaching levels of around 70% inhibition of proliferation at a 1: 1 ratio. The results suggest that allogenic thyTreg are not immunogenic and are capable of exerting their suppressive function in an allogeneic context, indicating their possible off-the-shelf use as a treatment for transplant rejection, graft-versus- host disease, autoimmune diseases or the cytokine release syndrome characteristic of severe COVID-19 patients.
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Gene expression patterns in blood cells from SARS-CoV-2 infected individuals with different clinical phenotypes and body mass index (BMI) could help to identify possible early prognosis factors for COVID-19. We recruited patients with COVID-19 admitted in Hospital Universitari Son Espases (HUSE) between March 2020 and November 2021, and control subjects. Peripheral blood cells (PBCs) and plasma samples were obtained on hospital admission. Gene expression of candidate transcriptomic biomarkers in PBCs were compared based on the patients' clinical status (mild, severe and critical) and BMI range (normal weight, overweight, and obesity). mRNA levels of ADAM17, IFITM3, IL6, CXCL10, CXCL11, IFNG and TYK2 were increased in PBCs of COVID-19 patients (n = 73) compared with controls (n = 47), independently of sex. Increased expression of IFNE was observed in the male patients only. PBC mRNA levels of ADAM17, IFITM3, CXCL11, and CCR2 were higher in those patients that experienced a more serious evolution during hospitalization. ADAM17, IFITM3, IL6 and IFNE were more highly expressed in PBCs of patients with obesity. Interestingly, the expression pattern of ADAM17, IFITM3 and IFNE in PBCs was related to both the severity of COVID-19 evolution and obesity status, especially in the male patients. In conclusion, gene expression in PBCs can be useful for the prognosis of COVID-19 evolution.
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The novel coronavirus disease (COVID-19) outbreak was first declared in China in December 2019, and WHO declared the pandemic on 11 March 2020. A fast-rising number of confirmed cases has been observed in all continents, with Europe at the epicentre of the outbreak at this moment. Sexual and reproductive health (SRH) and rights is a significant public health issue during the epidemics. The novel coronavirus (SARS-CoV-2) is new to humans, and only limited scientific evidence is available to identify the impact of the disease COVID-19 on SRH, including clinical presentation and outcomes of the infection during pregnancy, or for persons with STI/HIV-related immunosuppression. Beyond the clinical scope of SRH, we should not neglect the impacts at the health system level and disruptions or interruptions in regular provision of SRH services, such as pre- and postnatal checks, safe abortion, contraception, HIV/AIDS and sexually transmitted infections. Furthermore, other aspects merit attention such as the potential increase of gender-based violence and domestic abuse, and effects of stigma and discrimination associated with COVID-19 and their effects on SRH clients and health care providers. Therefore, there is an urgent need for the scientific community to generate sound clinical, epidemiological, and psycho-social behavioral links between COVID-19 and SRH and rights outcomes.
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Background Since the first report of COVID-19 in December 2019, there have been significant concerns regarding the effects of the disease on pregnant and recently pregnant women. Quantifying prevalence, and identifying risk factors for severe COVID-19 in this population is key to planning and providing effective clinical maternal care. Objectives To identify rates of COVID-19 amongst pregnant and recently pregnant women and to identify maternal risk factors for severe COVID-19 and worsening clinical outcomes. Design To address the objectives using the developing evidence base we are using a 'Living systematic review' study design. Methods A systematic search of various databases and sources was conducted, including: Medline, Embase, Cochrane database, WHO COVID-19 database, CNKI, Wanfang databases, preprint servers, social media, reference lists of guidelines and included studies until the 6th of October 2020. Quality assessment of prevalence studies was done using the risk of bias tool by Hoy et al. and comparative cohorts using the Newcastle Ottawa Scale. Data extraction was completed with a pre-piloted form by two independent reviewers. The analysis is undertaken monthly and findings are regularly updated. Results are disseminated through our website: https://www.birmingham.ac.uk/research/who-collabora ting-centre/pregcov/index.aspx. The living systematic review process and collated database has given rise to distinct review questions, and the authors of this focused on prevalence and maternal risk factors. Random effects meta-analysis was used to determine prevalence of COVID-19 and the maternal risk factors associated with severe COVID-19. Results 192 studies were included. Overall, 10% (95% confidence interval 7% to 12%;73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed COVID-19. Increased maternal age (1.82, 1.27 to 2.63;I2 = 30.1%;7 studies;3561 women), high body mass index (2.37, 1.83 to 3.07;I2 = 0%;6 studies;3380 women), pre-existing maternal comorbidity (1.81, 1.49 to 2.20;I2 = 0%;3 studies;2634 women), chronic hypertension (2.0, 1.14 to 3.48;I2 = 0%;2 studies;858 women), pre-existing diabetes (2.12, 1.62 to 2.78;I2 = 0%;3 studies;3333 women), and pre-eclampsia (4.21, 1.26 to 14.0;I2 = 0%;4 studies;274 women) were associated with severe COVID-19 in pregnancy. Conclusions 1 in 10 pregnant or recently pregnant women attending or admitted to hospital are estimated to have COVID-19. Pre-existing co-morbidities, chronic hypertension, pre-eclampsia, pre-existing diabetes, high maternal age, and high BMI are risk factors for severe COVID-19.
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To analyze the clinical characteristics and outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with sarcoidosis from a large multicenter cohort from Southern Europe and to identify the risk factors associated with a more complicated infection. We searched for patients with sarcoidosis presenting with SARS-CoV-2 infection (defined according to the European Centre for Disease Prevention and Control guidelines) among those included in the SarcoGEAS Registry, a nationwide, multicenter registry of patients fulfilling the American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and Other Granulomatous Disorders 1999 classification criteria for sarcoidosis. A 2:1 age-sex-matched subset of patients with sarcoidosis without SARS-CoV-2 infection was selected as control population. Forty-five patients with SARS-CoV-2 infection were identified (28 women, mean age 55 years). Thirty-six patients presented a symptomatic SARS-CoV-2 infection and 14 were hospitalized (12 required supplemental oxygen, 2 intensive care unit admission and 1 mechanical ventilation). Four patients died due to progressive respiratory failure. Patients who required hospital admission had an older mean age (64.9 vs. 51.0 years, p = 0.006), a higher frequency of baseline comorbidities including cardiovascular disease (64% vs. 23%, p = 0.016), diabetes mellitus (43% vs. 13%, p = 0.049) and chronic liver/kidney diseases (36% vs. 0%, p = 0.002) and presented more frequently fever (79% vs. 35%, p = 0.011) and dyspnea (50% vs. 3%, p = 0.001) in comparison with patients managed at home. Age- and sex-adjusted multivariate analysis identified the age at diagnosis of SARS-Cov-2 infection as the only independent variable associated with hospitalization (adjusted odds ratio 1.18, 95% conficence interval 1.04-1.35). A baseline moderate/severe pulmonary impairment in function tests was associated with a higher rate of hospitalization but the difference was not statistically significant (50% vs. 23%, p = 0.219). A close monitoring of SARS-CoV-2 infection in elderly patients with sarcoidosis, especially in those with baseline cardiopulmonary diseases and chronic liver or renal failure, is recommended. The low frequency of severe pulmonary involvement in patients with sarcoidosis from Southern Europe may explain the weak prognostic role of baseline lung impairment in our study, in contrast to studies from other geographical areas.
Subject(s)
COVID-19/complications , Sarcoidosis/complications , Adult , Aged , Aged, 80 and over , COVID-19/mortality , COVID-19/physiopathology , COVID-19/therapy , Cohort Studies , Comorbidity , Female , France , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Registries , Sarcoidosis/mortality , Sarcoidosis/physiopathology , Sarcoidosis/therapy , Treatment OutcomeABSTRACT
BACKGROUND: The use of low dose radiotherapy (LD-RT) for the treatment of COVID-19 pneumonia is supported by biological rationale for its immunomodulatory effect. Some institutions have started to treat these patients showing encouraging results. To shorten procedure times is crucial for the comfort of symptomatic patients receiving respiratory support and to optimize institutional facilities. PATIENTS AND METHODS: At our institution, LD-RT is offered to hospitalized patients with COVID-19 pneumonia and signs of early cytokine-released syndrome on behalf of a multicenter study. We designed a coordinated process flow starting from the patient transfer to the simulation CT-scan (first-step), to the end of the LD-RT treatment (last step). The times spent on each step of the process flow were evaluated. RESULTS: Mean age of treated patients was 83 (72-91) years-old. The timing parameters of the first 10 consecutive patients were analyzed. Except for the first (dummy run), patients were managed from the first to the last step in a median of 38 min (25-58, SD 10.67). The most time-consuming sub-process was the contouring of the treatment volumes and dosimetry. CONCLUSIONS: LD-RT is not only an encouraging option for COVID-19 pneumonia patients, but a convenient and feasible procedure if performed in a coordinated way by reducing procedure times.