Whole genome sequencing of a German cohort to understand host genetics in COVID-19

Background/Objectives: The disease course upon SARS-CoV-2 infection is highly variable and comprises a range from asymptomatic infection to severe (and even lethal) COVID-19. Genetic factors substantially contribute to this variability, as evidenced by epidemiological studies and recent results from genome-wide association studies (GWAS) as well as sequencing-based approaches. The host genetics group of the German COVID-19 OMICs Initiative (DeCOI) has been founded with the aim to identify additional genetic variants that influence COVID-19 severity through whole genome sequencing (WGS) analyses. Method(s): Until January 2022, WGS has been performed on approximately 1200 individuals affected by COVID-19. Result(s): The most recent data freeze comprised 952 individuals. In this dataset, no carrier of a deleterious protein-altering variant has been detected in TLR7, which is the only conclusive risk gene for severe COVID-19. Applying a gene-based association test of rare variants to the subcohort of European individuals (n = 752, mean age: 56 years, females: 44%), including 199 severely affected individuals, we did not observe any significant association after correction for multiple testing. Exome-wide association analysis of common variants in this subcohort replicated the GWAS-locus on chromosome 3. Conclusion(s): With this ongoing work, we are contributing to international efforts to elucidate the host genetics of COVID-19, also by sharing our summary statistics for meta-analyses. Currently, we are sequencing additional severely affected individuals and we are refining analytical strategies, which will also include the joint analysis of common and rare variants at genomewide scale.

Blood derivative therapy

There are three main components manufactured from whole blood: red blood cells (RBCs), plasma, and platelets. Plasma contains a multitude of different proteins, peptides, and biologic substances. Approximately 53 million liters of plasma was collected in the United States in 2019. Following collection, plasma is frozen and manufactured into plasma-derived medicinal products (PDMPs). During the manufacture process, several thousand plasma units are pooled for Cohn fractionation, which is based upon cold ethanol precipitation of proteins. The PDMPs are further prepared using ion exchange or affinity chromatography and additional steps to inactivate and remove infectious diseases such as viruses. Almost 20 different therapeutic plasma proteins are purified from plasma via these multi-step manufacturing processes. Interestingly, the demand for pharmaceutical plasma products, particularly intravenous immunoglobulin (IVIG) products, has been increasing. The manufacture and therapeutic role of blood derivatives particularly immunoglobulin therapy, Rh immunoglobulin (RhIG), COVID-19 convalescent plasma (CCP) and hyperimmune globulins, albumin, clotting factors, fibrin sealants, and platelet rich plasma will be described.Copyright © 2022 AME Publishing Company. All Rights Reserved.

EFFECT OF THE COVID-19 ON THE REPRODUCTIVE HEALTH INDICATORS OF CADETS

The study investigated the influence of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 on the reproductive health indicators of cadets of military educational organizations. In the Department of Assisted Reproductive Technologies at the Clinic of Obstetrics and Gynecology of the Kirov Military Medical Academy, 183 male cadets aged 21–27 years were divided into two groups and examined. The first group consisted of 132 cadets who had mild and moderate COVID-19, and the second group included 51 cadets without COVID-19 in the anamnesis. COVID-19 was found negatively affect the reproductive health of cadets. Individuals who previously had COVID-19 were found to have a significant decrease in the level of total testosterone and decreased concentration and mobility of sperm in the ejaculate. Moreover, in cadets without COVID-19 who were vaccinated with the combined vector vaccine "Gam-COVID-Vac,” the indicators of the hormonal profile and spermograms were within the reference values. The results indicate the need for further investigation of the effect of various negative factors, including severe acute respiratory syndrome coronavirus 2, on the reproductive health of cadets of military educational organizations. Moreover, the development of preventive, therapeutic, and rehabilitation measures will reduce the risk of infertility and reproductive losses, which is consistent with the interests of national projects on healthcare and demography. The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

Digi-cultural mindset

With this chapter, we want to provide a reading experience on how digitalization not only evokes a technical transformation but is also strongly related to a company's culture. Talking about digital transformation, there is more to consider than alignment between IT and business functions. We want to arouse interest in the reader to discover their organization's value system and provide triggers toward the development of a digi-cultural mindset. We will dive deeper into the stages of change and provide a target vision with ideas on how to master a transformation journey. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2021.

Scalable mRNA Machine for Regulatory Approval of Variable Scale between 1000 Clinical Doses to 10 Million Manufacturing Scale Doses

The production of messenger ribonucleic acid (mRNA) and other biologics is performed primarily in batch mode. This results in larger equipment, cleaning/sterilization volumes, and dead times compared to any continuous approach. Consequently, production throughput is lower and capital costs are relatively high. Switching to continuous production thus reduces the production footprint and also lowers the cost of goods (COG). During process development, from the provision of clinical trial samples to the production plant, different plant sizes are usually required, operating at different operating parameters. To speed up this step, it would be optimal if only one plant with the same equipment and piping could be used for all sizes. In this study, an efficient solution to this old challenge in biologics manufacturing is demonstrated, namely the qualification and validation of a plant setup for clinical trial doses of about 1000 doses and a production scale-up of about 10 million doses. Using the current example of the Comirnaty BNT162b2 mRNA vaccine, the cost-intensive in vitro transcription was first optimized in batch so that a yield of 12 g/L mRNA was achieved, and then successfully transferred to continuous production in the segmented plug flow reactor with subsequent purification using ultra- and diafiltration, which enables the recycling of costly reactants. To realize automated process control as well as real-time product release, the use of appropriate process analytical technology is essential. This will also be used to efficiently capture the product slug so that no product loss occurs and contamination from the fill-up phase is <1%. Further work will focus on real-time release testing during a continuous operating campaign under autonomous operational control. Such efforts will enable direct industrialization in collaboration with appropriate industry partners, their regulatory affairs, and quality assurance. A production scale-operation could be directly supported and managed by data-driven decisions. © 2023 by the authors.

Sensitivity of the reward system in post-COVID-fatigue

Background: The health consequences of the SARS-CoV-2 pandemic are dominating the international healthcare systems. More than 15% of patients with supposedly mild SARS-CoV-II disease develop persisting symptoms (Sudre et al., 2021). In addition to known internal limitations, such as respiratory distress or tachycardia, severe neurological deficits are prominent. For example, fatigue persisting for months, cognitive impairment, and a marked increase in daytime sleepiness, sometimes accompanied by an inability to work, are described (Taquet et al., 2021). Previous research indicates that hospitalized patients suffering from COVID-19 often develop fatigue or muscle weakness (63%), difficulties in sleep (26%) and psychiatric disorders, such as anxiety and depression (23%) (Taquet et al., 2021). This constellation of symptoms can lead to severe limitations in the everyday lives of the people concerned. The pathophysiology of this multifaceted neurological and dysautonomic symptom complex is not yet understood but now becoming the focus of interdisciplinary research in the context of the global pandemic. A similar disease is chronic fatigue syndrome (CFS). Affected patients suffer from very comparable limitations, especially persistent fatigue. Evidence suggests an alteration of the specific cerebral reward system in CFS, an important modulator of learning processes involved in various homeostatic regulatory processes (Wylie and Flashman, 2017). Objective(s): Based on the similarity of symptoms in CFS and Post-COVID fatigue this study aims to investigate whether a reduced sensitivity of the reward system in the context of postviral fatigue syndrome is present. We hypothesize that the sensitivity of the reward system in patients with Post-COVID syndrome is reduced compared to healthy adults. Method(s): 24 subjects with a diagnosed Post-COVID syndrome and 20 healthy individuals between the age of 18-55 without relevant neurological or psychiatric disorders in the medical record participated in the study. Magnetoencephalography and electroencephalography were used for the characterization of the reward system during the monetary incentive delay task, a classic paradigm used in existing publications (Frank et al., 2004;Opitz et al., 2022). In addition, standardized questionnaires were used to obtain further information about the included individuals' living conditions and the severity of symptoms. Result(s) and Conclusion(s): Results of the study will help to better characterize reward network changes in the context of fatigue symptoms to open up therapeutic options for medication or psychotherapeutic interventions. Data analysis will be completed by the start of the conference.Copyright © 2023

Is the Star of Modern Monetary Theory Burning Out?

The paper provides a critical analysis of Modern Monetary Theory (MMT). Facing the current macroeconomic problems of supply shocks caused by the Corona pandemic and the war in the Ukraine and its consequences on inflation, the authors ask whether the MMT could seriously influence macroeconomic policymaking. Based on a brief analysis of the historical roots of MMT, the authors show substantial economic problems with this theory. Especially the non-consideration of inflation issues, the inadequacy of tax policy, the problems of open economies, and the neglected problems of the New Political Economy increase the doubts about the suitability of the MMT for overcoming the current economic challenges. © Der/die Autor:in 2023.

Revisiting old and opening new spaces for feminist organizing in Austria

Before the onset of COVID-19, the political mood in Europe shifted to the right. This is indicated, for example, by efforts to close the borders to migrants, an undermining of legislative and executive democratic structures as well as restrictions on free speech. Such anti-democratic developments have also impacted gender equality - at the level of policy and in daily life. Our paper aims to examine the policies on gender equality of the center-right Austrian government from 2017 to 2019 and their influence on feminist organizing. Applying a participatory, action-based research approach in the context of a neoliberal conservative nation state, the data shows a clear backtrack from a pluralist perspective of gender equality policies and regression towards heteronormativity, complemented by a focus on the gender binary that discounts the social construction of gender. These trends clearly influence feminist organizing.

Meaningful Movement towards Campus-Based Outdoor Learning: Characterizing Pre-Scenery with Stakeholder Perspective

This study seeks to characterize what matters to stakeholders as a school moves towards campus-based outdoor learning. Results from a survey (n=87) demonstrate stakeholder alignment in relation to a longstanding outdoor education movement and emerging movements responding to COVID-19. Discussion considers the polylogic of local communities that work to inspire, enable, and sustain commitments to campus-based outdoor learning. © ISLS.

A Canadian Perspective on Patient Experience using Virtual Care During COVID-19

The COVID-19 pandemic has necessitated a rapid change in the delivery of healthcare around the world. Many facilities have transitioned suitable services to virtual care to reduce the risk of viral transmission and preserve healthcare resources for spikes in COVID-19 cases. Since institutions have rapidly expanded the usage of virtual care beyond its previous confines, investigations are required to ensure that the adapted system is working for patients. While important, clinical and patient-reported outcome data do not provide complete insight into the specific impacts of pandemic-time changes from the patient's perspective. Therefore, to get a complete picture of these changes, it is also necessary to look at patient experience, which evidence suggests, could be impacted by virtual care in positive ways, but only in specific cases. Thus, it is vital to record pandemic-time patient experiences and analyse how the implementation of virtual visits impacts the delivery of person-centred care. This data should be used to determine how virtual care can be optimally implemented into the Canadian healthcare system after the resolution of the COVID-19 pandemic. Although it is currently unclear how virtual care will be integrated into the post-pandemic landscape, the approach offers benefits to both patients and providers. Canada-wide, longitudinal studies investigating patient experience using virtual care during the COVID-19 pandemic are required in order to ascertain exactly how this novel approach can be leveraged to benefit patients.

Impact of COVID-19 on hospitalisation for diverse conditions in European countries : Andrea Schmidt

Background The COVID-19 pandemic has had an unprecedented impact on Europe. Health systems came under strain, with non-urgent treatments postponed and resources reserved for treatment of COVID-19 patients. Delayed care seeking has been reported, for fear of infection with SARS-CoV2. Yet, the scale of this impact remains under researched. This study aims to compare indirect effects of the pandemic in a European cross-country study aiming to highlight the potential of Population Health Information Research Infrastructures (www.phiri.eu). Methods Focusing on (i) major vascular events (MVE) and (ii) elective surgery for joint replacements (ESJR) as well as (iii) serious trauma this study analyses individual level hospital data in a standardised harmonised data model. We compared pre-pandemic incidence rates (2018-2019) with rates for 2020 and 2021. Analyses are systematically contrasted with SARS CoV2 incidence rates, and policy measures taken based on the OxCGRT index. Results A drop in hospital discharge rates was observed during the pandemic in all countries but differing by condition and month. Socio-economic differences also varied by condition. Our evidence suggests that periods of more severe policy measures also correlated with more dramatic drops in regular hospital activities. Conclusions Our findings provide new insights on the dramatic level of de-prioritisation of essential services faced by non-COVID-19 patients in Europe. From a public health perspective, hospital escalation plans should be developed early on to avoid negative mid and long-term health and financial consequences of indirect effects. The study demonstrates the tremendous potential in exploiting health information systems in a systematic way across countries and the value of the PHIRI system. Further research should investigate policy trade-offs involved in severe lockdown measures during a pandemic and variations in health service resilience for future pandemic preparedness.

View from the Nursing Frontline - COVID-19 and the Acute Care of Older Adults

This article unveils stories from a "lived experience"by frontline medical-surgical nurses caring for SARS-CoV-2 (COVID-19) using a compilation of written and verbal examples. The article intends to enrich the readers' perspective regarding nurses' thoughts, emotions, and actions as they care for patients diagnosed and hospitalized with COVID-19. A culmination of lessons learned via the "lived"knowledge exchange completes the article. © 2022 American Society on Aging.

HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: Results from a prospective observational study in Germany.

Aims: Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. Methods: The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). Results: During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the 2nd quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in 1st quarter of 2020, to 7 partners in 4th quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. Conclusion: The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis.

An update on the overall epidemiology, clinical characteristics, and outcomes from the COVID-19 and Cancer Consortium (CCC19)

Background: Despite mitigation and treatment strategies, COVID-19 continues to negatively impact patients (pts) with cancer. Identifying factors that remain consistently associated with morbidity and mortality is critical for risk identification and care delivery. Methods: Using CCC19 registry data through 12/31/2021 we report clinical outcomes (30-day case fatality rate [CFR], mechanical ventilation use (MV), intensive care unit admission (ICU), and hospitalization) in adult pts with cancer and laboratory confirmed SARS-CoV-2, stratified by patient, cancer, and treatment-related factors. Results: In this cohort of 11,417 pts (with 4% reported vaccination prior to COVID-19), 55% required hospitalization, 15% ICU, 9% MV, and 12% died. Overall outcome rates remained similar for 2020 and 2021 (Table). Hydroxychloroquine was utilized in 11% and other anti-COVID-19 drugs (remdesivir, tocilizumab, convalescent plasma, and/or steroids) in 30%. Higher CFRs were observed in older age, males, Black race, smoking (14%), comorbidities (pulmonary [17%], diabetes mellitus [16%], cardiovascular [19%], renal [21%]), ECOG performance status 2+ (31%), co-infection (25%), especially fungal (35%), and initial presentation with severe COVID-19 (48%). Pts with hematologic malignancy, active/ progressing cancer status, or receiving systemic anti-cancer therapy within 1-3 months prior to COVID-19 also had worse CFRs. CFRs were similar across anti-cancer modalities. Other outcomes (ICU, MV, hospitalization) followed similar distributions by pt characteristics. Conclusions: Unfavorable outcome rates continue to remain high over 2 years, despite fewer case reports in 2021 owing to multiple factors (e.g., pandemic dynamics, respondent fatigue, overwhelmed healthcare systems). Pts with specific socio-demographics, performance status, comorbidities, type and status of cancer, immunosuppressive therapies, and COVID-19 severity at presentation experienced worse COVID-19 severity;and these factors should be further examined through multivariable modeling. Understanding epidemiological features, patient and cancer-related factors, and impact of anti-COVID-19 interventions can help inform risk stratification and interpretation of results from clinical trials.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.