Exploring the effects of ventilation and air-conditioned environments, on droplet and airborne transmission of SARS-COV-2

To assess the implications of air conditioning and ventilation on droplet and airborne transmission of SARS-COV-2, several scientific research databases were searched and cross-referenced. Then, an analysis was conducted on the findings pertinent to interaction between several environmental variables affected by HVAC systems and their effect on Virus transmission. The results suggest that airflow velocity may interfere with the trajectories of large respiratory droplets and aerosols. Lower relative humidity provided suitable conditions for virus survival whereas higher temperatures increased aerosol formation, but were detrimental to virus survival. Suboptimal temperatures and humidity can compromise pathogen filtration functions in the nose, while proper use of HVAC functions can help preserve them. Transmission of SARS-COV-2 is not affected solely by the virus's internal properties. Ambient conditions, whether natural or modified by HVAC systems can have a significant effect on the transmissibility and virulence of both the virus and virus-related sickness. The current infection prevention measures, such as social distancing, need to be revised in certain scenarios where natural ventilation or HVAC systems are involved. This will offer, hopefully, higher protection from infections with SARS-COV-2 and similar pathogens. © 2023 by the authors.

SARS-CoV-2 E-PROTEIN VIROPORIN INHIBITOR BIT225 ACTIVE IN hACE2 TRANSGENIC MICE

Background: The CoV-2 envelope (E) protein plays an important role in virus assembly, budding, immunopathogenesis and disease severity. E protein has ion channel activity, is located in Golgi and ER membranes of infected cells and is associated with inflammasome activation and immune dysregulation. Here we report that BIT225, an investigational HIV clinical compound, inhibits E ion channel activity and prevents body weight loss and mortality and reduces inflammation in lethally infected K18-hACE2 transgenic mice. BIT225 efficacy was observed when dosing was initiated before or 24 h or 48 h after infection. Method(s): SARS-CoV-2 E protein ion channel activity and Xenopus TMEM16A were measured in Xenopus oocytes. K18-hACE2 transgenic mice were infected intranasally with 104 pfu SARS CoV 2 (US-WA1/2020) and dosed orally twice daily with BIT225 for up to 12 Days. Dosing was initiated 12 h pre-infection or 24 h or 48 h post-infection. Disease parameters measured were survival, body weight, viral RNA by qPCR and infectious virus titre (plaque assay) in lung tissue homogenates and serum. In addition, levels of pro-inflammatory cytokines (IL-6, IL-1alpha, IL-1beta, TNFalpha & TGFbeta, MCP-1) were measured in lung and serum samples. Result(s): BIT225 inhibited ion channel activity of E-protein, but not that of TMEM16A in Xenopus oocytes. BIT225 dosed at 300mg/kg BID for 12 days starting 12 h pre-infection completely prevented body weight loss and mortality in SARS-CoV-2 infected K18 mice (n=12), while all vehicle-dosed animals reached a mortality endpoint by day 9 across two studies (n=12). Figure 1 shows results from a time of addition study: When treatment with BIT225 started at 24 h post-infection, body weight loss and mortality was also prevented (100% survival, n=5). In the group of mice where treatment started at 48 h after infection, body weight loss and mortality were prevented in 4 of 5 mice. Treatment efficacy was associated with significant reduction in lung viral load (3.5 log10), virus titer (4000 pfu/ml) and lung and serum cytokine levels. Conclusion(s): BIT225 is an inhibitor of SARS-CoV-2 E-protein viroporin activity. In the K18 model BIT225 protected mice from weight loss and death, inhibited virus replication and reduced inflammation. These effects were noted when treatment with BIT225 was initiated before or 24-48 hours after infection and validate viroporin E as a viable antiviral target and support the clinical study of BIT225 in treatment of SARS-CoV-2.

RISK AND PROTECTIVE FACTORS ASSOCIATED WITH MENTAL HEALTH DIFFICULTIES FOR CHILDREN WITH ADHD OVER THE COVID-19 PANDEMIC: A LONGITUDINAL STUDY

Background: A growing number of studies have reported both positive and negative outcomes associated with COVID-19 in children with attention-deficit/hyperactivity disorder (ADHD) and their families. However, very few longitudinal studies have examined outcomes over multiple time points over the pandemic. Objectives: To examine COVID-19-related mental health (MH) impacts for children with ADHD and their families over a 12-month period over the pandemic. Methods: The parents of 213 Australian children (5-17 years) with ADHD were recruited in May 2020 when COVID-19 restrictions were in place. Parents completed surveys at repeated time points assessing MH (CoRonavIruS Health Impact Survey [CRISIS] - mood states subscale) and predictors. Latent profile analyses were used to examine the patterns of MH difficulties over the pandemic using the first four waves of data collected from May to August 2020, and the fifth wave of data collected in May-July 2021. Numerous baseline predictors of MH patterns were examined. Findings: Using the first four waves of data, three groups were identified comprising: (1) children with unchanging (36%), (2) increasing resolved (30%) and (3) increasing persistent (34%) MH difficulties. The most robust predictor of increasing persistent MH difficulties was stress related to COVID-19 (e.g. stress associated with restrictions related to COVID-19). Analyses are being updated to include our fifth wave of data collection (May-July 2021) (70% retention rate). Conclusion: A subgroup of children with ADHD appears to be struggling with MH, which is related to the stress associated with COVID-19 restrictions.

Teaching during the Covid-19 Pandemic - Online Programming Education

Teaching programming skills is an essential part of the first-semester computer science curriculum. During the Covid-19, it became particularly challenging as, in particular, the essential exercise lessons had to be implemented virtually. Before the pandemic, we implemented didactic concepts like objects-first and gamification with the hamster simulator. They had to be transferred to the virtual setting as good as possible. In this paper, we report on the implementation of our virtual course programming and software development. In particular, we report on the lessons we learnt from our course implementation, which, overall, was relatively successful. © 2022 Gesellschaft fur Informatik (GI). All rights reserved.

IT-REX - A Vision for a Gamified e-Learning Platform for the First Semesters of Computer Science Courses

Digital learning is becoming increasingly important, especially in situations when students cannot attend presence lectures as we experienced during the Covid-19 pandemic. However, while there are platforms that support generic learning concepts such as multiple-choice questions, we believe that the first semesters of computer science courses can benefit from tailored learning platforms that support IT-specific learning. For example, programming tasks that are automatically checked for correctness. Moreover, in times when students cannot meet each other, self-organization and motivation quickly become severe problems. Therefore, this paper presents a vision for a gamified e-Learning platform specialized for the first semesters of computer science courses. © 2022 Gesellschaft fur Informatik (GI). All rights reserved.

Selinexor in Combination with R-GDP for Patients with Relapsed/Refractory B-Cell Lymphoma: Results of the Selinda Phase Ib Lysa Study

Background: Salvage chemotherapy followed by high-dose therapy (HDT) and autologous stem-cell transplantation (ASCT) is the standard treatment of young patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). A complete remission before ASCT is the most important prognosis factor for a better outcome. Selinexor is a first-in-class, oral selective inhibitor of nuclear export compound, an exportin 1 [XPO1] inhibitor, which, through XPO1 blockade, causes nuclear accumulation and activation of tumor suppressor proteins, reduction in oncoproteins and cancer cell apoptosis. Selinexor has been approved by the US Food and Drug Administration for the treatment of R/R DLBCL, de novo or transformed from follicular lymphoma (FL) pts after ≥2 therapies. The phase Ib SELINDA (EUDRACT 2015-005612-15) study assessed safety and efficacy of selinexor, in combination with R-GDP for pts with R/R B-cell lymphoma. Patients & methods: Eligible pts < 70 years with R/R B-cell lymphoma after first or second treatment failure received every 21 days (d) 3 cycles of rituximab 375 mg/m² on d1, dexamethasone 40 mg on d1 to 4, cisplatin 75 mg/m² d1 and gemcitabine 1 gr/m² on d1 and 8 (R-GDP) in combination with escalating doses of selinexor. The starting dose (dose level 1, DL1) 40 mg was given on days 1, 3, 8, 10 (Cohort A), and from December 2017 on days 1, 8 and 15 (Cohort B). The dose-variation scheme followed a traditional “3+3” design (DL1: 40 mg;DL2: 60 mg). The primary endpoint of SELINDA was the determination of the recommended phase 2 dose of selinexor in combination with R-GDP. Secondary and exploratory endpoints were safety, efficacy, and feasibility of ASCT after selinexor-R-GDP. Results: The R2PD for selinexor in combination with R-GDP was established as 40 mg on days 1, 8, and 15 (Maerevoet, IMCL 2021#176). Between January 2017 and January 2021, 32 pts received selinexor-R-GDP. We focused on the 18 pts who received the R2PD: 15 had DLBCL, 2 FL, 1 marginal zone lymphoma. In this cohort, median age was 61 years (range 44-69);14 pts (78%) has stage III/IV. Thirteen pts received 1 previous line before inclusion, 5 pts received 2 previous lines. At inclusion, 6 pts had refractory disease and 12 relapsed. Four pts prematurely discontinued treatment: 2 for thrombocytopenia, 1 for COVID, 1 for progression. Major adverse events (AEs) in >10% of pts were reversible neutropenia (50%), thrombocytopenia (39%), and nausea (22%). No AEs leading to death were observed. Seven pts (39%) achieved a complete metabolic response (CMR), 5 pts (28%) partial metabolic response (PMR). Overall response rate (CMR+PMR) assessed at the end of treatment according to Lugano classification was 67% (12 of 18). Nine of the 15 pts (60 %) with DLBCL had metabolic response (CMR:4, PMR:5). Per protocol, peripheral stem cell collection and ASCT were optional, 4 pts of this RP2D cohort proceeded to high dose therapy (BEAM) and ASCT. Conclusion: This study established the safety profile of weekly 40mg of Selinexor in combination with R-GDP for R/R B cell lymphoma with an ORR of 67%. Reversible AEs are expected for platinum-based regimen. An ongoing randomized phase 2 study comparing R-GDP and R-GDP plus selinexor in pts with R/R DLBCL will now establish the safety and efficacy of the combination. Disclosures: Casasnovas: Janssen: Consultancy;BMS: Consultancy;Gilead/Kite: Consultancy, Research Funding;TAKEDA: Consultancy, Research Funding;ROCHE: Consultancy, Research Funding;Amgen: Consultancy. Morschhauser: Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees;F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Consultancy, Speakers Bureau;AstraZenenca: Membership on an entity's Board of Directors or advisory committees;BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees;Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria;Genen ech, Inc.: Consultancy;Chugai: Honoraria;Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees;Incyte: Membership on an entity's Board of Directors or advisory committees;Celgene: Membership on an entity's Board of Directors or advisory committees;AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees;Servier: Consultancy;Genmab: Membership on an entity's Board of Directors or advisory committees. Thieblemont: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding;Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Hospira: Research Funding;Bayer: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Feugier: Amgen: Honoraria;Janssen: Consultancy, Honoraria;Gilead: Consultancy, Honoraria;Abbvie: Consultancy, Honoraria;Astrazeneca: Consultancy, Honoraria.

COVID-19-Impfungen: Replizierend oder Nichtreplizierend?

Innovative and effective vaccination strategies are the most important lever to address the global SARS-COV2 pandemic. Within months scientists all over the world have developed promising new vaccines, many of which use adenoviral vectors to incorporate immunogenic molecules of SARS-coronavirus in order to elicit effective immune responses. The Gamaleya institute developed the COVID-19 vaccine named Sputnik (Gam-COVID-Vac) using adenoviral vectors ad 26 and ad5 to incorporate a full SARS-Spike Protein for vaccination. Two differing vectors enable so called prime-boost, thus avoiding neutralizing effects against the vector itself, ensuring proper immunogenicity against the vaccine. Current available published evidence has raised controversy among small sample sizes in phase II and early endpoints in phase III studies with Sputnik and scientific community took notice that full study protocols and clinical data haven't been made available yet. Patient subgroups and vaccination efficacy in healthy vaccinated may be at risk in case of partial viral replication of Ad5 vectors or when batch to batch reproducibility is not warranted, as concerns from authorities in Brazil and Slovakia have recently been raised. Final approval by governing health authorities (e. g. EMA) should therefore be awaited.

Social Presence Despite Isolation - Insights into the Relation Between Psychological Distance and Sensory Synchronization in Computer-Mediated Communication

Whilst social distancing (e.g., during a pandemic), electronic communication allows users to keep in touch with social contacts, thereby fulfilling needs for human interaction. Accordingly, it is important to examine social closeness in the context of computer-mediated communication in more detail and to take a closer look at the relation between the feeling of presence to achieve the maximum potential for such communication. In this paper we introduce the concept of sensory synchronization as a predictor for perceived social presence. To this end, social activities conducted virtually during the Covid-19 pandemic were surveyed and analyzed to understand the connection between a feeling of presence and possible sensory synchronization of communication partners. Context of activities were collected in preliminary interviews and examined more closely in an online survey (N = 234). Most frequently reported activities included video calls, playing virtual games and virtual meals. The results showed that there is a significant positive correlation between sensory synchronization and social presence in all activity categories. The activity categories significantly explain different variances of the evaluated social presence and sensory synchronization. The results of this work motivate further research on the topic of sensory synchronization and social presence. New predictors in social presence research were identified and a questionnaire for the assessment of sensory synchronization and social presence was developed. © 2021, The Author(s), under exclusive license to Springer Nature Switzerland AG.

COVID-19 Vaccination of Allergic Patients in Conjunction with allergen immunotherapy (AIT) – A position paper of the Association of German Allergists (AeDA) and the German Society for Allergology and Clinical Immunology (DGAKI)

Background: Vaccinations against Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are intended to induce an immune response in the sense of protection against infection/disease. Allergen-specific immunotherapy (AIT) is also thought to induce a (different) immune response in the sense of tolerance to allergens. There is uncertainty among patients and physicians regarding the use of vaccination and AIT in temporal relation, which this position paper aims to clarify. The four vaccines currently approved in Germany for vaccination against SARS-CoV-2 are described and possible immunological interactions with AIT are highlighted, as well as practical recommendations for action. Methods: Based on the current internationally published literature, this position paper provides specific recommendations for action regarding the use of AIT in temporal relation to a SARS-CoV-2 vaccination. Results: The present recommendations for action relate to the following conditions for which AIT is used i) allergic rhinitis, ii) allergic bronchial asthma, iii) insect venom allergy, iiii) food allergy (peanut). Conclusions: If vaccination is imminent, initiation of subcutaneous (SCIT), sublingual (SLIT), or oral (OIT) AIT should be delayed until 1 week after the 2nd vaccination date. Thus, there should generally be an interval of approximately 1 week between SCIT and COVID-19 vaccination. For the continuation of an ongoing AIT, we recommend an interval of 1 week before and after vaccination for SCIT. For SLIT and OIT, we recommend taking them up to the day before vaccination and taking a break from SLIT and OIT for 2 – 7 days after vaccination.

Assessment of the impact of multiple mild-steam decontaminations on the protection performance of disposable KN95 filtering facepiece respirators.

The COVID-19 pandemic caused tremendous supply bottlenecks of single-use filtering facepiece respirators (FFRs) leading to a growing need for a potential reuse. This study assesses the impact of multiple mild-steam decontaminations with 121 °C/2000 mbar/20 min on the protection performance of disposable FFRs. It focuses on FFRs of type KN95 that is recently dominating the markets, but its decontamination is not covered in the literature. It was found that up to ten cycles, only minor degradation in the filter efficiency, breathing resistance and none in the material structure is apparent, suggesting a potential for multiple decontamination cycles at almost unchanged protective properties of KN95 FFRs.