RIC in COVID-19-a Clinical Trial to Investigate Whether Remote Ischemic Conditioning (RIC) Can Prevent Deterioration to Critical Care in Patients with COVID-19.

PURPOSE: Coronavirus disease 19 (COVID-19) has, to date, been diagnosed in over 130 million persons worldwide and is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several variants of concern have emerged including those in the United Kingdom, South Africa, and Brazil. SARS-CoV-2 can cause a dysregulated inflammatory response known as a cytokine storm, which can progress rapidly to acute respiratory distress syndrome (ARDS), multi-organ failure, and death. Suppressing these cytokine elevations may be key to improving outcomes. Remote ischemic conditioning (RIC) is a simple, non-invasive procedure whereby a blood pressure cuff is inflated and deflated on the upper arm for several cycles. "RIC in COVID-19" is a pilot, multi-center, randomized clinical trial, designed to ascertain whether RIC suppresses inflammatory cytokine production. METHODS: A minimum of 55 adult patients with diagnosed COVID-19, but not of critical status, will be enrolled from centers in the United Kingdom, Brazil, and South Africa. RIC will be administered daily for up to 15 days. The primary outcome is the level of inflammatory cytokines that are involved in the cytokine storm that can occur following SARS-CoV-2 infection. The secondary endpoint is the time between admission and until intensive care admission or death. The in vitro cytotoxicity of patient blood will also be assessed using primary human cardiac endothelial cells. CONCLUSIONS: The results of this pilot study will provide initial evidence on the ability of RIC to suppress the production of inflammatory cytokines in the setting of COVID-19. TRIAL REGISTRATION: NCT04699227, registered January 7th, 2021.

PCSK9 Inhibition During the Inflammatory Stage of SARS-CoV-2 Infection.

BACKGROUND: The intensity of inflammation during COVID-19 is related to adverse outcomes. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is involved in low-density lipoprotein receptor homeostasis, with potential influence on vascular inflammation and on COVID-19 inflammatory response. OBJECTIVES: The goal of this study was to investigate the impact of PCSK9 inhibition vs placebo on clinical and laboratory outcomes in patients with severe COVID-19. METHODS: In this double-blind, placebo-controlled, multicenter pilot trial, 60 patients hospitalized for severe COVID-19, with ground-glass opacity pneumonia and arterial partial oxygen pressure to fraction of inspired oxygen ratio ≤300 mm Hg, were randomized 1:1 to receive a single 140-mg subcutaneous injection of evolocumab or placebo. The primary endpoint was death or need for intubation at 30 days. The main secondary endpoint was change in circulating interleukin (IL)-6 at 7 and 30 days from baseline. RESULTS: Patients randomized to receive the PCSK9 inhibitor had lower rates of death or need for intubation within 30 days vs placebo (23.3% vs 53.3%, risk difference: -30%; 95% CI: -53.40% to -6.59%). Serum IL-6 across time was lower with the PCSK9 inhibitor than with placebo (30-day decline: -56% vs -21%). Patients with baseline IL-6 above the median had lower mortality with PCSK9 inhibition vs placebo (risk difference: -37.50%; 95% CI: -68.20% to -6.70%). CONCLUSIONS: PCSK9 inhibition compared with placebo reduced the primary endpoint of death or need for intubation and IL-6 levels in severe COVID-19. Patients with more intense inflammation at randomization had better survival with PCSK9 inhibition vs placebo, indicating that inflammatory intensity may drive therapeutic benefits. (Impact of PCSK9 Inhibition on Clinical Outcome in Patients During the Inflammatory Stage of the COVID-19 [IMPACT-SIRIO 5]; NCT04941105).

Do pandemic COVID 19 and business cycle influence the Indonesia composite index?

The impact of the Covid 19 pandemic on the Indonesian economy was worse than the impact of the global financial crisis in 2008. We can see the business cycle from the contraction of economic growth, volatility of the exchange rate, and inflation. The shocks to these business cycles could create systemic risks and influence financial system stability. Financial system stability is more sensitive to shocks from changes in one of the macroprudential indicators, namely the Indonesia Composite Index (ICI). This study will examine the effect of the Covid 19 pandemic and the business cycle on ICI. This research was conducted in Indonesia using quarterly secondary data from 2008-2021. The data was obtained from Bank Indonesia. The model used is the Auto Regressive Distributed Lag (ARDL) model. The purpose of using this model is to see the long-term and short-term relationships between the variables studied. The results show that the Covid 19 pandemic and business cycle variables such as;economic growth, exchange rate, and inflation have a relationship on the ICI both in the short and long term. The decline in economic growth during a crisis is difficult to avoid. However, the government must continue to accelerate the economic growth so it does not decline sharply during the crisis. Monetary authorities must also maintain exchange rate stability and inflation so it does not fluctuate unsteadily. © The Authors, published by EDP Sciences.

Evaluation of Urban Sustainability in Cities of The French Way of Saint James (Camino de Santiago Francés) in Castilla y León according to The Spanish Urban Agenda

The emblematic French Way of Saint James (Camino de Santiago Francés) crosses towns, cities, and Spanish regions to the Cathedral of Santiago de Compostela (Galicia, Spain), However, where is The French Way of Saint James going with respect to the urban sustainability of its host cities? As each city is unique and urban sustainability favors the revitalization and transition of urban areas, to know where to go, it is first necessary to establish a diagnosis that makes the different urban situations visible. In this article, the behavior of urban sustainability is analyzed in the six host cities of The French Way of Saint James in the Autonomous Community of Castilla y León, a region characterized by its link with the rural environment and its current depopulation problems. The data and indicators used are officially provided by the Spanish Urban Agenda, which, through the normalization of its values, are able to territorialize the SDGs at the local level and reflect the realities of the cities of Burgos, Astorga, Cacabelos, León, Ponferrada, and Valverde de la Virgen. The results make it possible to diagnose and compare these host cities, identifying weaknesses, skills, and opportunities that favor the promotion of action plans, local or joint (favored by The French Way of Saint James), in the multiple aspects of sustainability. In addition, they show that Valverde de la Virgen is the city with the best performance in terms of urban sustainability.

The effect of COVID-19 on transplant function and development of CLAD in lung transplant patients: A multicenter experience.

BACKGROUND: Concerns have been raised on the impact of coronavirus disease (COVID-19) on lung transplant (LTx) patients. The aim of this study was to evaluate the transplant function pre- and post-COVID-19 in LTx patients. METHODS: Data were retrospectively collected from LTx patients with confirmed COVID-19 from all 3 Dutch transplant centers, between February 2020 and September 2021. Spirometry results were collected pre-COVID-19, 3- and 6-months post infection. RESULTS: Seventy-four LTx patients were included. Forty-two (57%) patients were admitted, 19 (26%) to the intensive care unit (ICU). The in-hospital mortality was 20%. Twelve out of 19 ICU patients died (63%), a further 3 died on general wards. Patients with available spirometry (78% at 3 months, 65% at 6 months) showed a significant decline in mean forced expiratory volume in 1 second (FEV1) (ΔFEV1 138 ± 39 ml, p = 0.001), and forced vital capacity (FVC) (ΔFVC 233 ±74 ml, p = 0.000) 3 months post infection. Lung function improved slightly from 3 to 6 months after COVID-19 (ΔFEV1 24 ± 38 ml; ΔFVC 100 ± 46 ml), but remained significantly lower than pre-COVID-19 values (ΔFEV1 86 ml ± 36 ml, p = 0.021; ΔFVC 117 ± 35 ml, p = 0.012). FEV1/FVC was > 0.70. CONCLUSIONS: In LTx patients COVID-19 results in high mortality in hospitalized patients. Lung function declined 3 months after infection and gradually improved at 6 months, but remained significantly lower compared to pre-COVID-19 values. The more significant decline in FVC than in FEV1 and FEV1/FVC > 70%, suggested a more restrictive pattern.

To vaccinate or not to vaccinate: impact of a public health action on vaccine hesitancy

Background and importanceVaccine hesitancy is one of the top 10 threats to global health according to the World Health Organization.1 A part of the Swiss population is hesitant to vaccinate against COVID-19.2Aim and objectivesThe aim of this study was to conduct a public health action with hesitant to vaccination and measure its impact on vaccine hesitancy and on vaccination rate.Material and methodsVaccine hesitancy and barriers to vaccination were measured and identified using a pre-test questionnaire. Only non-vaccinated volunteer participants were included, and they were invited to a 1-hour online session using motivational interviewing techniques, animated by a physician and a pharmacist. Two weeks after the session, they were asked to fill a post-test and 2 months later, their vaccine status was requested. Data collection was conducted from April to August 2021.Results31 adults participated for a total of 11 online sessions (2.8 participants/session). Majority were women (68%, n=21) and aged between 35 and 60 years (71%). 10 (32.3%) were public health professionals and 21 (67.7%) were not. Prior to the study, 54.9% did not consider vaccines safe (19.4% post-study), 87.1% were concerned about vaccine side effects (64.5% post-study) and 51.6% considered vaccines to be effective (83.9% post-study). Before the study, participants were classified as certainly willing to vaccinate (3.2%), probably (9.7%), probably not (35.5%), certainly not (12.9%), do not know/other (38.8%) and the degree of confidence in vaccination was 4.5 ± 2.2 (scale 1–10). After the study, the confidence increased to 6.3 ± 2.4 (+29%). Following the study, 52% (n=14) were effectively vaccinated. Among reasons that motivated to vaccinate: vaccination will help with containing the pandemic (5/14) and benefit-risk ratio is positive for the vaccine (5/14). 48% (n=13) were not vaccinated mainly for the following reasons: doubt about the effectiveness (2/13) and fear of side effects (2/13). Opinion on vaccines was moved mainly by having personal questions answered and feeling not judged for having a different opinion on vaccination.Conclusion and relevanceIn this study we could reduce vaccine hesitancy by increasing the degree of confidence in the vaccine and our action effectively convinced half the participants to get vaccinated.References and/or acknowledgements1. https://www.who.int/news-room/spotlight/ten-threats-to-global-health-in-20192. https://sotomo.ch/site/wp-content/uploads/2021/02/6.-SRG-Corona-Monitor.pdfConflict of interestNo conflict of interest

Flu and pertussis vaccination during pregnancy in Geneva during the COVID-19 pandemic: A multicentric, prospective, survey-based study.

OBJECTIVE: To determine pertussis and influenza vaccination coverage during pregnancy among women delivering in all the maternities of Geneva (Switzerland), during the COVID-19 pandemic. METHODS: All women delivering in all the maternity centres of the canton of Geneva from 1st November 2020 to 30th November 2020 (beginning of the flu vaccination season) and from 8th March 2021 to 7th April 2021 (end of the flu vaccination season) had their records checked upon admission to the labour ward regarding pertussis and influenza vaccination during pregnancy. Reasons for non-vaccination were recorded. Univariate and multivariate analyses were done to identify predictors of vaccine uptake. RESULTS: 951 women delivered in Geneva during the two study periods, of which 950 were included in the study. 86.2% were vaccinated against pertussis, with no significant difference between the study periods (87.5% vs 85% at the beginning and end of the flu vaccination season respectively). 49.8% were vaccinated against influenza, with no significant difference between the study periods (48.8% vs 50.7% beginning and end of the flu vaccination season respectively). The influenza vaccine was 5 times more likely not to be proposed (8.9% vs. 1.7%) and 3 times more likely to be refused (26.6% vs. 8%) than the pertussis vaccine. Main reason for refusal was a lack of maternal desire for both vaccines, but not vaccine fear. Maternal parity ≥ 1 was significantly associated with pertussis vaccine uptake at univariate analysis. Women were significantly more likely to accept the influenza vaccine if they had a university degree or if they did not deliver in a midwife-only run delivery unit in both univariate and multivariate analysis. CONCLUSIONS: In Geneva, most gynaecologists offer pertussis immunization during antenatal care and uptake is high, but more efforts must be done to increase influenza vaccination coverage. Education level impacts maternal flu vaccination uptake, but other social disparities did not.

What Is Engineering and Who Are Engineers? Student Reflections from a Sustainability-Focused Energy Course

In the spring of 2021, the University of San Diego’s Department of Integrated Engineering taught the course, “Integrated Approach to Energy”, the second offering of a new required course, to nine second-year engineering students. The sociotechnical course covered modern energy concepts, with an emphasis on renewable energies and sustainability, and it exposed the students to other ways of being, knowing, and doing that deviated from the dominant masculine Western White colonial discourse. Following the course completion, we interviewed five students by using a semistructured protocol to explore how they perceived of and communicated about engineers and engineering. We sought to identify the takeaways from their course exposure to sustainability and the sociotechnical paradigm, which were central to the course. The findings suggest that the students were beginning to form sociotechnical descriptions, and that they were still developing their understanding and perceptions of engineers and engineering. Moreover, we observed that they were still wrestling with how best to integrate sustainability into those perceptions. There was an a-la-carte feel to the students’ conceptualizations of sustainability as it related to engineering, as in, “you can ‘do’ sustainability with engineering, but do not have to”. We argue that engineering students likely need these pedagogical paradigms (sociotechnical engineering and sustainability) woven through the entirety of their engineering courses if they are to fully accept and integrate them into their own constructs about engineers and engineering.

Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium.

Coronavirus disease 2019 (COVID-19) predisposes patients to thrombotic and thromboembolic events, owing to excessive inflammation, endothelial cell activation and injury, platelet activation and hypercoagulability. Patients with COVID-19 have a prothrombotic or thrombophilic state, with elevations in the levels of several biomarkers of thrombosis, which are associated with disease severity and prognosis. Although some biomarkers of COVID-19-associated coagulopathy, including high levels of fibrinogen and D-dimer, were recognized early during the pandemic, many new biomarkers of thrombotic risk in COVID-19 have emerged. In this Consensus Statement, we delineate the thrombotic signature of COVID-19 and present the latest biomarkers and platforms to assess the risk of thrombosis in these patients, including markers of platelet activation, platelet aggregation, endothelial cell activation or injury, coagulation and fibrinolysis as well as biomarkers of the newly recognized post-vaccine thrombosis with thrombocytopenia syndrome. We then make consensus recommendations for the clinical use of these biomarkers to inform prognosis, assess disease acuity, and predict thrombotic risk and in-hospital mortality. A thorough understanding of these biomarkers might aid risk stratification and prognostication, guide interventions and provide a platform for future research.

Incidence of thrombotic complications in COVID-19 : On behalf of ICODE: The International COVID-19 Thrombosis Biomarkers Colloquium.

A high incidence of thrombosis in hospitalised patients with COVID-19 was identified early during the pandemic. Accurately quantifying thrombotic risk may assist prognosis and guide appropriate thromboprophylaxis. Observational studies have estimated the rate of thrombosis in both hospitalised and non-hospitalised patients with COVID-19, and how this corresponds to the severity of illness. In this review, we provide an overview of the incidence and prevalence of arterial and venous thrombotic events in patients with COVID-19 and highlight the limitations in the studies to date. Asymptomatic individuals with COVID-19 and those with mild symptoms are at very low risk of thrombotic complications. However, rates of thrombosis are substantially increased in hospitalised patients, and are strikingly high in those patients who are critically-ill requiring treatment on the intensive care unit and especially those requiring extracorporeal membrane oxygenation. Clinicians managing such patients need to be aware of these risks and take appropriate steps with respect to thromboprophylaxis and heightened clinical vigilance. Large prospective observational studies will more accurately quantify thrombotic rate, and randomized controlled trials are currently investigating optimal thromboprophylactic strategies.

Screening for venous thromboembolism in patients with COVID-19.

Pulmonary thromboembolism and deep venous thrombosis occur frequently in hospitalised patients with COVID-19, the prevalence increases on the intensive care unit (ICU) and is very high in patients on extracorporeal membrane oxygenation (ECMO). We undertook a literature review to assess the usefulness of screening for peripheral venous thrombosis or pulmonary thrombosis in patients admitted with COVID-19. Outside of the ICU setting, D-dimer elevation on presentation or marked increase from baseline should alert the need for doppler ultrasound scan of the lower limbs. In the ICU setting, consideration should be given to routine screening with doppler ultrasound, given the high prevalence of thrombosis in this cohort despite standard anticoagulant thromboprophylaxis. However, absence of lower limb thrombosis on ultrasound does not exclude pulmonary venous thrombosis. Screening with CT pulmonary angiography (CTPA) is not justified in patients on the general wards, unless there are clinical features and/or marked elevations in markers of COVID-19-associated coagulopathy. However, the risk of pulmonary embolism or pulmonary thrombosis in ICU patients is very high, especially in patients on ECMO, where studies that employed routine screening for thrombosis with CT scanning have uncovered up to 100% incidence of pulmonary thrombosis despite standard anticoagulant thromboprophylaxis. Therefore, in patients at low bleeding risk and high clinical suspicion of venous thromboembolism, therapeutic anticoagulation should be considered even before screening, Our review highlights the need for increased vigilance for VTE, with a low threshold for doppler ultrasound and CTPA in high risk in-patient cohorts, where clinical features and D-dimer levels may not accurately reflect the occurrence of pulmonary thromboembolism.

Impact of COVID-19 pandemic on sickness absence for mental ill health in National Health Service staff.

OBJECTIVE: To explore the patterns of sickness absence in National Health Service (NHS) staff attributable to mental ill health during the first wave of the COVID-19 epidemic in March-July 2020. DESIGN: Case-referent analysis of a secondary dataset. SETTING: NHS Trusts in England. PARTICIPANTS: Pseudonymised data on 959 356 employees who were continuously employed by NHS trusts during 1 January 2019 to 31 July 2020. MAIN OUTCOME MEASURES: Trends in the burden of sickness absence due to mental ill health from 2019 to 2020 according to demographic, regional and occupational characteristics. RESULTS: Over the study period, 164 202 new sickness absence episodes for mental ill health were recorded in 12.5% (119 525) of the study sample. There was a spike of sickness absence for mental ill health in March-April 2020 (899 730 days lost) compared with 519 807 days in March-April 2019; the surge was driven by an increase in new episodes of long-term absence and had diminished by May/June 2020. The increase was greatest in those aged >60 years (227%) and among employees of Asian and Black ethnic origin (109%-136%). Among doctors and dentists, the number of days absent declined by 12.7%. The biggest increase was in London (122%) and the smallest in the East Midlands (43.7%); the variation between regions reflected the rates of COVID-19 sickness absence during the same period. CONCLUSION: Although the COVID-19 epidemic led to an increase in sickness absence attributed to mental ill health in NHS staff, this had substantially declined by May/June 2020, corresponding with the decrease in pressures at work as the first wave of the epidemic subsided.

Evolution of a Bidirectional Pediatric Critical Care Educational Partnership in a Resource-Limited Setting.

Introduction: Children in resource-limited settings are disproportionately affected by common childhood illnesses, resulting in high rates of mortality. A major barrier to improving child health in such regions is limited pediatric-specific training, particularly in the care of children with critical illness. While global health rotations for trainees from North America and Europe have become commonplace, residency and fellowship programs struggle to ensure that these rotations are mutually beneficial and do not place an undue burden on host countries. We created a bidirectional, multimodal educational program between trainees in Manila, Philippines, and Baltimore, Maryland, United States, to improve the longitudinal educational experience for all participants. Program Components: Based on stakeholder input and a needs assessment, we established a global health training program in which pediatricians from the Philippines traveled to the United States for observerships, and pediatric residents from a tertiary care center in Baltimore traveled to Manila. Additionally, we created and implemented a contextualized simulation-based shock curriculum for pediatric trainees in Manila that can be disseminated locally. This bidirectional program was adapted to include telemedicine and regularly scheduled "virtual rounds" and educational case conferences during the COVID-19 pandemic. Providers from the two institutions have collaborated on educational and clinical research projects, offering opportunities for resource sharing, bidirectional professional development, and institutional improvements. Conclusion: Although creating a mutually beneficial global health partnership requires careful planning and investment over time, establishment of a successful bidirectional educational and professional development program in a limited-resource setting is feasible and benefits learners in both countries.

Ethnic differences in risk of severe Covid-19: To what extent are they driven by exposure?

BACKGROUND: This study quantifies the risk of Covid-19 among ethnic groups of healthcare staff during the first pandemic wave in England. METHODS: We analysed data on 959 356 employees employed by 191 National Health Service trusts during 1 January 2019 to 31 July 2020, comparing rates of Covid-19 sickness absence in different ethnic groups. RESULTS: In comparison with White ethnic groups, the risk of short-duration Covid-19 sickness absence was modestly elevated in South Asian but not Black groups. However, all Black and ethnic minority groups were at higher risk of prolonged Covid-19 sickness absence. Odds ratios (ORs) relative to White ethnicity were more than doubled in South Asian groups (Indian OR 2.49, 95% confidence interval (CI) 2.36-2.63; Pakistani OR 2.38, 2.15-2.64; Bangladeshi OR 2.38, 1.98-2.86), while that for Black African ethnicity was 1.82 (1.71-1.93). In nursing/midwifery staff, the association of ethnicity with prolonged Covid-19 sickness absence was strong; the odds of South Asian nurses/midwives having a prolonged episode of Covid-19 sickness absence were increased 3-fold (OR 3.05, 2.82-3.30). CONCLUSIONS: Residual differences in risk of short term Covid-19 sickness absences among ethnic groups may reflect differences in non-occupational exposure to SARS-CoV-2. Our results indicate ethnic differences in vulnerability to Covid-19, which may be only partly explained by medical comorbidities.

Cardiovascular disease and COVID-19: a consensus paper from the ESC Working Group on Coronary Pathophysiology & Microcirculation, ESC Working Group on Thrombosis and the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Heart Rhythm Association (EHRA).

The cardiovascular system is significantly affected in coronavirus disease-19 (COVID-19). Microvascular injury, endothelial dysfunction, and thrombosis resulting from viral infection or indirectly related to the intense systemic inflammatory and immune responses are characteristic features of severe COVID-19. Pre-existing cardiovascular disease and viral load are linked to myocardial injury and worse outcomes. The vascular response to cytokine production and the interaction between severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and angiotensin-converting enzyme 2 receptor may lead to a significant reduction in cardiac contractility and subsequent myocardial dysfunction. In addition, a considerable proportion of patients who have been infected with SARS-CoV-2 do not fully recover and continue to experience a large number of symptoms and post-acute complications in the absence of a detectable viral infection. This conditions often referred to as 'post-acute COVID-19' may have multiple causes. Viral reservoirs or lingering fragments of viral RNA or proteins contribute to the condition. Systemic inflammatory response to COVID-19 has the potential to increase myocardial fibrosis which in turn may impair cardiac remodelling. Here, we summarize the current knowledge of cardiovascular injury and post-acute sequelae of COVID-19. As the pandemic continues and new variants emerge, we can advance our knowledge of the underlying mechanisms only by integrating our understanding of the pathophysiology with the corresponding clinical findings. Identification of new biomarkers of cardiovascular complications, and development of effective treatments for COVID-19 infection are of crucial importance.

Changing patterns of sickness absence among healthcare workers in England during the COVID-19 pandemic.

BACKGROUND: Patterns of sickness absence shed useful light on disease occurrence and illness-related behaviours in working populations. METHODS: We analysed prospectively collected, pseudonymized data on 959 356 employees who were continuously employed by National Health Service trusts in England from 1 January 2019 to 31 July 2020, comparing the frequency of new sickness absence in 2020 with that at corresponding times in 2019. RESULTS: After exclusion of episodes directly related to COVID-19, the overall incidence of sickness absence during the initial 10 weeks of the pandemic (March-May 2020) was more than 20% lower than in corresponding weeks of 2019. Trends for specific categories of illness varied substantially, with a fall by 24% for cancer, but an increase for mental illness. A doubling of new absences for pregnancy-related disorders during May-July of 2020 was limited to women with earlier COVID-19 sickness absence. CONCLUSIONS: Various factors will have contributed to the large and divergent changes that were observed. The findings reinforce concerns regarding delays in diagnosis and treatment of cancers and support a need to plan for a large backlog of treatment for many other diseases. Further research should explore the rise in absence for pregnancy-related disorders among women with earlier COVID-19 sickness absence.