Public Health Measures Enacted by the Norwegian Political Leadership to Protect the Elderly in Response to the SARS-CoV-2 Pandemic Crisis

The SARS-CoV-2 pandemic crisis is ongoing, and the elderly are still affected by the virus, sometimes with fatal consequences. The political leaders are, inter alia, focussed on protecting citizens, including this vulnerable group. This article aims to describe the response of the Norwegian political leadership, with a focus on the public health measures enacted to protect the elderly during the SARS-CoV-2 pandemic crisis in the years 2020 and 2021. This study has a descriptive qualitative research design using thematic-content analysis as a methodology to evaluate data collected from official documents, national statistics and public health documents from Norway. Statistics show that the elderly mortality rate per 100,000 person-weeks during the first wave of the SARS-CoV-2 pandemic was 2.69 in Norway;during the second wave of the pandemic, it was 1.43. The public health measures the Norwegian political leadership instigated were more effective in containing the crisis when compared to other European countries, and this paper investigates the reasons. The results of our study provide public health policy decision-makers with insights into analytical material showing the usefulness of different measures enacted by the Norwegian government. The Norwegian government's responses to the crisis, such as the public health measures, restrictions, social consequences for vulnerable groups such as the elderly, as well as cross-government and cross-community cooperation, will need further in-depth analysis. © 2023 Miroslava Tokovska et al., published by Sciendo 2023.

Using R programming to inform and improve case notification procedures in a local public health unit : Henrique Barrilaro Ruas

Issue/Problem COVID-19 was declared a pandemic in March 2020. Information systems, particularly those related to laboratory testing notification, became extremely important as a mechanism of fast identification of cases. In Portugal, any test performed in a professional setting is of mandatory notification. For a local public health unit in northern Portugal, much like in other regions worldwide, challenges related to lack of human and material resources were felt over the course of the pandemic. Description of the problem In 2021, an intensive surveillance strategy was implemented using up to date notification database analysis through R programming, focusing on simplified data availability for contact tracing team members and accuracy of notifications submitted by laboratories, including verification of individual identifying information. Results Some laboratories were identified has having lower data completion rate, which had negative effects on contact tracing timeliness, while others failed to notify tests conducted. Public Health workers warned partners of these failures and worked with them to develop solutions. Interventions included facilitation of access to technologies to notify test results, as well as revision of internal processes to ensure correct patient identification. During the intervention, successful notification rates were increased, and new informal and formal partnerships were developed, leading to faster identification of clusters. Lessons Establishing partnerships with stakeholders and developing support systems is beneficial towards epidemiological surveillance efforts. Adequate analysis of notification procedures was an important step towards standardization and correctness of information required for epidemiological surveillance. Key messages Resilient information systems are important for surveillance, especially during a pandemic. Partnerships with community stakeholders are essential to timely and adequate epidemiological response.

SARS-CoV-2 Infection is Associated with Greater Neutralizing Antibody Response Compared to Three Doses of Mrna-1273 Vaccine in Solid Organ Transplant Recipients

Purpose: Prior studies suggest that two doses of mRNA vaccine in SOTR may result in lower antibody and T-cell responses relative to levels seen following natural SARS-CoV-2 infection. In this study, we evaluated whether three doses of mRNA-1273 vaccine result in immune responses more comparable to, or greater than, natural infection. Method(s): Serum was collected 4-6 weeks from symptom onset in n=74 SOTR recovered from SARS-CoV-2 infection, and in n=60 SOTR receiving a third dose of mRNA-1273. Disease severity in the infection cohort ranged from mild to severe, but no deaths were reported. Vaccinated SOTR all had negative anti-nucleoprotein antibody results to confirm absence of infection. SARS-CoV-2 serology was assessed using an anti-spike (S) receptor binding domain (RBD) immunoassay (Roche). Neutralizing antibodies (nAb) were assessed using a commercial surrogate virus neutralization test (SVNT) targeting wildtype (WT), alpha, beta and delta strains (GenScript). A subset of participants underwent spike-specific T-cell testing (infection n=50, three doses n=34). PBMCs were stimulated overnight with overlapping peptides and frequencies of S-specific polyfunctional CD4+ and CD8+ T-cells (expressing IFN-gamma and IL-2) were measured by intracellular cytokine staining. Mann Whitney U, and Chi-square tests were used for statistical comparisons;significance was defined at p<0.05. Result(s): Anti-S RBD antibodies in SOTR recovered from infection were similar to levels in those receiving three doses of mRNA-1273 (median U/mL [IQR]: 73.5 [14.9-240.1] vs. 313.8 [313.8-2191.0];p=0.17). Relative to SOTR recovered from infection, the proportion of SOTR positive for nAb after three doses of vaccine was significantly lower. This was true for WT (93.2% vs. 60.0%, p<0.0001) and all variants tested - alpha: 90.5% vs. 56.7%, p<0.0001;beta: 67.6% vs. 50%, p=0.039;and delta: 85.1% vs. 55%, p=0.0001. Spike-specific polyfunctional CD4+ T-cell frequencies were similar between infection and three doses of vaccine (median cell frequency [IQR]: 241.7 [50-539.7] vs. 432.4 [50-1226];p>0.05). Spike-specific polyfunctional CD8+ T-cells were uncommonly detected following infection or vaccination. Vaccinated participants were significantly older than infected SOTR (p<0.001), and some differences in type of transplant were found between groups. However, sex and type of immunosuppressive medications were similar between infected and vaccinated SOTR cohorts (p>0.05). Conclusion(s): Three doses of mRNA vaccine may be required to optimize binding antibody, and to a lesser extent, CD4+ T-cell immunity, to levels similar to natural infection. However, nAb responses to wild-type virus and variants of concern were highest in SOTR recovered from infection when compared to vaccinated patients. These data provide further evidence of impaired SARS-CoV-2 vaccine responses in SOTR.

Lemierre's syndrome: case report of "the forgotten disease" in current COVID-19 pandemic.

Lemierre's syndrome refers to infectious thrombophlebitis of the internal jugular vein developed as complication of an oropharyngeal infection. It is a rare syndrome, affecting otherwise healthy young adults, which may lead to sepsis complicated by septic embolization. Although there is a characteristic clinical picture, many modern physicians are unaware of this syndrome, leading it to be termed 'the forgotten disease'. The authors report a case of late diagnosis due to initial suspicion of COVID-19 and highlight the pitfalls on its diagnosis.

Lost in consolidation? Declining public investment, multiplier effects and alternatives to the path of fiscal consolidation in Portugal

This paper deals with one of the most pressing concerns that Eurozone periphery economies will face in the near future: how to achieve a sustained recovery from the COVID-19 crisis while dealing with growing public debt-to-GDP ratios. The paper assesses the macroeconomic relationship between public spending, economic growth and debt sustainability. We use a TSLS method to perform the econometric estimation of the public spending multiplier for a panel of 11 Eurozone economies over the 1995-2019 period. We find evidence that the multiplier is positive and close to 1,8, suggesting that the benefits of promoting public investment exceed its initial financing cost. As a result, we conclude that debt sustainability is not only compatible with, but in fact improved by a more expansive fiscal policy and present an alternative policy path for the Portuguese economy in the 2021-2025 period based on this conclusion.

Facing covid-19, administrative and legal aspects: Health systems in Brazil and Mexico

Objective: The fight against the pandemic by COVID-19 has been a challenge for all States, due to the high level of contagion and the requirement for intensive care supplies and beds for the care of the most serious cases. Brazil has been fighting, in addition to the health crisis, several administrative, legislative and judicial problems related to procedures to combat the virus. The research aims to raise the context of Brazil and Mexico in this challenge, addressing issues such as administration, governance and related lawsuits-the latter concerning Brazil. Thus, the research will investigate how these States are facing the pandemic in terms of management, emphasizing administrative and legal aspects. Methodology: The method used combines the case study (considering Brazil and Mexico) with the development of deductive reasoning, starting from administrative organization and legal regulation. The research is based on literature review, documental and secondary data analysis. Results: The results show that Brazil has expertise in carrying out vaccinations, but that political divergences have hampered the fight against COVID-19, and that the Brazilian State may undertake efforts for a more active participation of the population, in order to legitimize the actions to fight it. to COVID-19, with the help and strengthening of local governments, as did Mexico, where the analysis demonstrates the lessons learned in combating the pandemic by strengthening governance and vaccine management by Solidarity Support Networks for Neighbors and Local Residents, coordinated by the municipal government. Contributions: The main contribution of the research is to allow the analysis of the contexts, problems and actions developed by Brazil and Mexico in confronting the pandemic by COVID-19. © 2021, Centro Universitario Curitiba - UNICURITIBA. All rights reserved.

Applying Exploratory Testing and Ad-Hoc Usability Inspection to Improve the Ease of Use of a Mobile Power Consumption Registration App: An Experience Report

As the number of mobile devices has increased, software development teams have focused on releasing mobile applications, allowing users to carry out transactions, access information and improve their lifestyle more efficiently. Nevertheless, even when providing useful means for carrying out daily tasks, users report dissatisfaction or frustration when using these applications. For energy companies, mobile applications that fail to provide both usefulness and ease of use may reduce their adoption and an increase in the company’s workload, as users will require company workers to solve problems they could solve on their own. In this paper, we report how we applied exploratory testing and ad-hoc usability inspection to identify improvement opportunities during the development of a mobile application that would allow users to measure their power consumption, supporting social distancing in the context of the COVID-19 pandemic. After identified a set of functional and usability problems, the development team redesigned the application, which was perceived as both useful and easy to use from the point of view of the managers that requested it. Also, we report lessons learned that are useful for practitioners willing to replicate this experience. © 2021, Springer Nature Switzerland AG.

Longitudinal antibody response and viral loads in COVID-infected organ transplant recipients

Purpose: The full spectrum of COVID-19 disease and the impact of disease severity on antibody response and viral shedding dynamics in transplant patients is unclear. The aims of this study were to determine the outcomes COVID-19 in SOT recipients, and correlate disease severity with antibody response and viral dynamics following SARS-CoV-2 infection. Methods: We performed a single-centre, prospective, observational study of adult SOT patients infected with COVID-19 and followed patients for 4 weeks. Severe disease was defined as either hospitalization attributable to COVID-19 or death. SARS-CoV-2 serology using available sera was assessed by a commercial antinucleoprotein (NP) assay (Abbott). Viral loads on serial nasopharyngeal swabs were assessed using real time RT-qPCR (Norgen Biotek). Results: Between March and November 2020, 55 SOT recipients had PCRconfirmed SARS-CoV-2 infection. 78.2% were male with a median age 55 years (IQR 43-65), median time post-transplantation of 6 years (IQR 1.6-11.5). Transplant types were kidney (53.7%), liver (20.4%), lung (13.0%), kidney-pancreas (9.3%) and heart (3.7%). The majority of patients (65.5%) had >=2 comorbidities other than transplantation. Hospitalization occurred in 55.6% and 33.6% required supplemental oxygen. Other outcomes were ICU admission (16.7%), mechanical ventilation (13.0%), ECMO (1.9%), and all-cause mortality (5.6%). All deaths were lung transplant recipients. On univariate analysis, factors significantly associated with severe disease were >=2 comorbidities (p=0.034), and African-American race (p=0.015). Immunosuppression was reduced in 66.7% of cases, most commonly the antiproliferative agent. A subgroup of patients (n=26) underwent SARS-CoV-2 antibody testing and 23/26 (88%) had antibodies by day 14 post-symptom onset. The three negative patients had mild disease. A subgroup of patients (n=23) had serial nasopharyngeal swabs for viral load. The median duration of positivity was 15 days (IQR 10-24) (Fig 1,2). The median peak VL measured was 4,669 copies/ mL (IQR 274 to 103,038 copies/mL). Peak viral load and duration of shedding were not significantly different between hospitalized and non-hospitalized groups (p=0.59 and p=0.52 respectively). Conclusions: SOT patients experience a spectrum of COVID-19 although mortality was low in our cohort likely due to greater capture of mild cases in the outpatient population. Virus is shed for long durations despite most transplant recipients generating SARS-CoV-2 directed antibody responses.

A mechanistic evaluation to guide the optimal immunosuppression adjustment strategy in transplant patients with COVID-19

Purpose: The optimal management of immunosuppression in transplant patients infected with COVID-19 is unknown. Reduction in calcineurin inhibitors or antimetabolite doses is often performed in order to enhance immune responses, but there are minimal data to guide decisions. We performed an in vitro study to determine the effect of individual immunosuppressive agents and doses on SARSCoV- 2 specific T-cell cytokine expression. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from nine non-immunosuppressed patients diagnosed with COVID-19 at least 14 days prior. Cells were pre-incubated for four hours with clinically relevant, differing concentrations of immunosuppressive drugs (tacrolimus (TAC), mycophenolate (MPA), sirolimus, prednisone). PBMCs were then stimulated with SARS-CoV-2 spike and nucleoprotein peptide pools for 24 hours with appropriate positive and negative controls. Supernatants collected were analyzed by a 14-plex high sensitivity T-cell cytokine array (Eve Technologies). Results: PBMCs stimulation with SARS-CoV-2 peptides resulted in broad cytokine responses. In the presence of TAC at medium (6ng/ml) and high concentrations (24ng/ml) (both are commonly achieved trough/peak clinical concentrations respectively), there were significantly reduced levels of IL-2 (p=0.0078 for both), and at high concentrations, lower amounts of IFN-γ (p= 0.0391) in response to peptide stimulation. TAC (24ng/ml) also resulted in a skewing of the response from a TH1 to a TH2 phenotype as indicated by lower IFN-γ: IL-13 ratio (p=0.0273), and IFN-γ: IL-4 ratio (p=0.0234). In contrast, differing clinically relevant concentrations of MPA and prednisone did not appear to influence the cytokine response postpeptide stimulation. Interestingly, Sirolimus at medium (4ng/ml) and high (16ng/ ml) concentrations was found to be significantly associated with pro-inflammatory cytokine release in response to SARS-CoV-2 peptides;TNF-α (p=0.0078 for both), IL-6 (p=0.0234 for both) and IL-1β (p=0.0156 and p=0.0078, respectively). When expressed as a pro- vs. anti-inflammatory ratio (with IL-10 as the anti-inflammatory cytokine), this finding remained consistent. Conclusions: These in-vitro results could help guide clinical decisions. Greater concentrations of TAC led to an inhibition of Th1 responses, whereas sirolimus led to an unexpected proinflammatory response, and MPA was neutral. This suggests that for transplant patients with COVID-19, a reduction of TAC may be of greater benefit than MPA. For those on sirolimus, reduction should be considered if evidence of an inflammatory phase.

T-cell responses in solid organ transplant recipients with SARSCOV- 2 infection

Purpose: Preliminary data suggest solid organ transplant (SOT) recipients may be at high-risk for developing severe COVID-19. This may be due in part to alterations in T-cell physiology owing to use of immunosuppressive agents to prevent rejection. In this study we evaluated convalescent T-cell responses against SARS-CoV-2 in SOT recipients who had COVID-19. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from peripheral blood of 20 SOT recipients and 15 non-transplant controls (NTCs), all of whom had COVID >=14 days prior (convalescent samples). A total of 106 PBMCs were stimulated for 16 hours with megapools of overlapping 15mer peptides corresponding to the spike (S), nucleoprotein (NP) or membrane (Mb) protein of SARS-CoV-2 (each peptide at 5 μg/mL). After incubation, flow cytometry was performed for intracellular cytokines (IFN-γ, TNF-α, IL-2) and cell-surface T-cell exhaustion markers (CTLA4, PD-1, TIM-3). Total and SARS-CoV-2 antigen-specific CD4+ and CD8+ T-cells were identified. Polyfunctional T-cells were defined as those expressing ≥ 2 of the cytokines investigated. Results: The median age among SOT recipients was 54 years (range 24-86). The majority (15/20) were male, and kidney (12/20) transplant recipients. The majority (60.0%) of SOT recipients were hospitalized with COVID-19;three (15.0%) required ICU admission and mechanical ventilation. SOT recipients had significantly lower total CD4+ T-cells (51.6% vs. 62.2%, p=0.002) but significantly higher proportions of total CD8+ T-cells relative to NTCs (41.9% vs. 31.2% of live CD3+ cells, p=0.0016). SOT recipients also had significantly higher proportions of PD-1 on total CD4 (15.2% vs. 3.7%, p<0.0001) and CD8 T-cells (9.4% vs. 4.1% of live CD3+ cells, p=0.014). The majority of SOT recipients and NTCs generated S, NP and Mb specific CD4 and CD8 T-cells. More specifically, compared to NTCs, SOT recipients had increased proportions of IFN-γ, or IL-2 producing CD4+ T-cells, as well as polyfunctional CD4+ T-cells reactive to S peptides. SOT recipients also had increased proportions of IFN-γ, IL-2 or TNF-α producing CD4+ T-cells, and CD4+ polyfunctional T-cells reactive to NP peptides. NTCs were also characterized by lower proportions of IL-2 producing CD8+ T-cells reactive to S peptides. Hospitalization of SOT recipients (severe illness) was associated with higher proportions of total PD-1+ CD4 T-cells (22.2% vs 13.3% of CD4 T-cells, p=0.02) and low frequencies of CD8+ polyfunctional T-cells reactive to NP peptides (5.80 vs. 49.9 per 106 polyfunctional CD8 T-cells, p=0.014). Conclusions: Despite immune suppression, SOT recipients mount SARS-CoV-2 reactive T-cells at magnitudes often exceeding non-transplant controls. However, perturbations in global T-cell proportions, and increased expression of T-cell exhaustion markers, such as PD-1, may compromise the SARS-CoV-2-specific immune response.

ALTERNATIVES TO THE NEW FISCAL REGIME IN THE FACE OF THE COVID-19 PANDEMIC

The objective of the research is to verify which mechanisms may be used to raise and reallocate resources to cope with the demands of the health and economic crises, caused by the pandemic of COVID-19. To this end, the deductive method was used, starting from the studies of the New Fiscal Regime, developing the research through bibliographic and documental research, and having observed studies about the allocation of resources, through the Tax on Great Wealth, Untying of Union Revenues, Partisan Fund and Contingency. The results indicate that the maintenance of a fiscal austerity policy, without the adoption of alternatives to expand the collection and reallocation of resources to stabilize health and the Brazilian economy, may cause implications for a plausible and imminent resolution by the Public Power of the indicated health and economic crises experienced.

Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center

Health care workers (HCWs) are at higher risk for SARS-CoV-2 infection and may play a role in transmitting the infection to vulnerable patients and members of the community. This is particularly worrisome in the context of asymptomatic infection. We performed a cross-sectional study looking at asymptomatic SARS-CoV-2 infection in HCWs. We screened asymptomatic HCWs for SARS-CoV-2 via PCR. Complementary viral genome sequencing was performed on positive swab specimens. A seroprevalence analysis was also performed using multiple assays. Asymptomatic health care worker cohorts had a combined swab positivity rate of 29/5776 (0.50%, 95%CI 0.32-0.75) relative to a comparative cohort of symptomatic HCWs, where 54/1597 (3.4%) tested positive for SARS-CoV-2 (ratio of symptomatic to asymptomatic 6.8:1). SARS-CoV-2 seroprevalence among 996 asymptomatic HCWs with no prior known exposure to SARS-CoV-2 was 1.4-3.4%, depending on assay. A novel in-house Coronavirus protein microarray showed differing SARS-CoV-2 protein reactivities and helped define likely true positives vs. suspected false positives. Our study demonstrates the utility of routine screening of asymptomatic HCWs, which may help to identify a significant proportion of infections.

HUISGEN AND HIS ADVENTURES IN A PLAYGROUND OF MECHANISMS AND NOVEL REACTIONS

The death of professor Rolf Huisgen (1920-2020) was announced on March 26th 2020, in the midst of the COVID-19 pandemic. Professor Huisgen was professor emeritus at the University of Munich in Germany, and studied in detail the mechanism of the 1,3-dipolar cycloaddition reaction, significantly expanding its scope. Even though he did not discover this reaction, it was through his studies that it became important in organic synthesis. Indeed, in honor of his work, the reaction became known as Huisgen's cycloaddition and it has been consolidated as a useful method for the preparation of five-membered heterocyclic compounds. Considering these facts, in this review we provide an overview on the applications of 1,3-dipolar cycloaddition reactions, starting with the seminal examples in the field and further discussing the most recent applications.

Contributions of Chemistry to Low Contact Economy at the Time of COVID-19

The SARS-CoV-2 virus, also known as Corona, has infected millions of people worldwide and part of them developed COVID-19 and cured themselves. But unfortunately, another part of those infected died. In Brazil, tens of thousands of deaths have already been accounted in 2020. The speed and global spread of the coronavirus has caused a major change in people's behavior and is leading the world towards a type of low contact economy, or contactless economy (auto-isolation), in which the flow of people and business between the producer and the consumer is carried out remotely in order to restrict and prevent personal interactions that can promote the transmission of the virus. Chemistry is playing a very important role in easing or avoiding contact between people with the development of products and materials that could slow the progress of SARS-CoV-2.

Lemierre's Syndrome: Case Report Of 'The Forgotten Disease' In Current Covid-19 Pandemic

Introduction Lemierre's syndrome (LS) refers to infectious thrombophlebitis of the internal jugular vein (IJV) developed as a complication of an oropharyngeal infection. It is a serious condition which may lead to septicemia and septic embolization. LS is most frequently caused by the anaerobic Fusobacterium necrophorum. In the current post-antibiotic era, it is rare (annual incidence of 0.8 cases/million). Many clinicians are unaware of LS, leading it to be termed "the forgotten disease." Signs and symptoms include odynophagia, fever and easy fatigue simulating, among others, infection by COVID-19. Broad spectrum antibiotherapy should be started promptly. If a deep abscess is present, drainage is indicated. In cases of persistent sepsis or embolization, surgical ligation/excision of the IJV may be considered. Currently, the most controversial role in LS management is anticoagulation. Compared with pre-antibiotic era mortality has much improved (0-18%). Since 2004 there are only four cases of LS reported in Portugal (Medline).

Technologies of information and communication in the "Lives Generating in a Covid-19 context".

The Covid-19 pandemic stimulates the production of innovative Technologies that are viable for the national reality and are expressed by the need to reorganize care services. The management teleconsulting, an interdisciplinary, interprofessional and transversal support network, developed a set of interventions to support municipalities.The objective of this manuscript was to share a reflective critical analysis, based on a teachingextension-service and community experience, in the context of the Covid-19 pandemic. This is an experience report of a multi-territorial study, of theoreticalpractical construction of an experience in the field of Extension, Teaching and Research. It is concluded that the elements of management teleconsultation should be incorporated into the daily practice of health and management professionals. Copyright © 2022, Fundacao UNI Botucatu/UNESP. All rights reserved.