A 17-month longitudinal environmental sampling study carried out on public transport vehicles operating in England during the COVID-19 pandemic identified low levels of SARS-CoV-2 RNA contamination (preprint)

AimsTo monitor severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) RNA contamination in vehicles operating in England during the pandemic, to better understand transmission risk of SARS-CoV-2 on public transport. Methods and ResultsWe collected 1,314 surface samples between December 2020 and April 2022 on trains and buses managed by five different transport operators. The presence of SARS-CoV-2 RNA was investigated through reverse transcription polymerase chain reaction (RT-PCR). SARS-CoV-2 RNA was found on 197 (15%) of the 1,314 surfaces sampled, including seat head rests, handholds, and air extract grilles, but the levels of RNA recovered on those samples (median value of 23.4, inter-quartile range: 14.3-35.4, N gene copies per extraction) made the presence of infectious virus at the time of sampling extremely unlikely. However, detection rates varied over time with peaks broadly coinciding with times of high community transmission, suggesting that people infected with SARS-CoV-2 when travelling on public transport could create opportunities for transmission. ConclusionDuring the pandemic, and as in other public spaces, low levels of SARS-CoV-2 RNA were found on surfaces associated with public transport. Impact statementThe results of this study will inform modelling approaches and the implementation of mitigation strategies to minimise the risk of transmission of respiratory viruses in public transport.

Persistance des anticorps neutralisants induits par le vaccin à protéine recombinante souche B1.531 contre les variants Omicron du SARS-COV-2

Introduction Nous avons précédemment montré que le vaccin monovalent (souche B1.351) à protéine recombinante avec adjuvant AS03 (MVB.1.351, Sanofi/GSK), administré en 1ère dose de rappel chez des adultes préalablement vaccinés par 2 doses du vaccin BNT162b2 (Pfizer-BioNTech), induit une meilleure réponse immunitaire qu'une 3ème dose de vaccin BNT162b2 à 15 jours du rappel, tant sur la souche sauvage que sur les 3 variants testés (Delta, Beta et Omicron BA.1). Nous montrons ici la persistance d'anticorps neutralisants contre Omicron BA.5, jusqu'à 6 mois post vaccination. Matériels et méthodes Dans le cadre d'un essai multicentrique, randomisé en simple aveugle selon le ratio 1.1.1, les participants ont reçu l'un des trois vaccins suivants en 1ère dose de rappel: les vaccins à protéine recombinante MV B.1.351 ou MVD614 (Sanofi/ GSK) ou le vaccin BNT162b2. La persistance des anticorps neutralisants contre la souche sauvage et divers variants du SARS-CoV2, y compris Omicron BA.1 et BA.5, jusqu'à 6 mois après le rappel, a été évaluée à l'aide d'un test de microneutralisation. L'analyse de la population per-protocole inclut les participants sans infection par le SRAS CoV-2 (sérologie anti-nucléocapside négative ou test de confirmation pour le SRAS CoV-2) entre le 28e jour et le 6e mois (M6) après le rappel. Résultats Parmi les 247 participants randomisés, 99 participants ont été inclus dans l'analyse per protocole à M6 (32 dans le groupe MVD614, 35 dans le groupe MVB.1.351 et 32 dans le groupe BNT162b2) Pour l'ensemble de la population étudiée, le vaccin MVB.1.351 a induit des titres d'anticorps neutralisants plus élevés contre la souche sauvage et les variants testés y compris Omicron BA.1 et BA.5 jusqu'à 6 mois après la dose de rappel comparés aux vaccins MVD614 et BNT162b2. À 6 mois post vaccination, la moyenne géométrique des titres (MGT) d'anticorps neutralisants contre la souche sauvage, Beta, Delta, Omicron BA.1 et Omicron BA.5 était respectivement de: 599.7 (CI 95%: 398.7 – 902.1), 221.4 (CI 95%: 133.8 – 366.4), 515.4 (CI 95%: 328.3 – 808.9), 48.6 (CI 95%: 30.5 – 77.6) et 37.5 (CI 95%: 26.3 – 53.5) pour MVD614;764.9 (CI 95%: 505.7 – 1156.9), 475.5 (CI 95%: 328.1 – 689.2), 706.6 (CI 95%: 497.0 – 1004.7), 97.5 (CI 95%: 64.7 –147.0) et 71.0 (CI95%: 49.9 – 101.2) pour MVB.1.531;252.2 (CI95%: 174.5 – 364.3);113.1 (CI95%: 77.7 – 164.7), 221.4 (CI95%: 149.7 – 327.4), 24.8 (CI95%: 17.9 – 34.4) et 23.3 (CI95%: 17.1 -31.7) pour BNT162b2 Conclusion Les titres d'anticorps neutralisants induits par le vaccin MVB.1.531 (Sanofi/GSK), administré en 1ère dose de rappel après 2 doses du vaccin BNT162b2, restent plus élevés et durables contre la souche sauvage et les variants du SRAS-COV-2 incluant Omicron BA.1 et BA.5, jusqu'à 6 mois post vaccination par rapport à une 3ème dose du vaccin BNT162b2. Ceci pourrait constituer une option intéressante pour un schéma de vaccination hétérologue. Liens d'intérêts déclarés O.L. Recherches/essais cliniques: en qualité d'investigateur principal, coodonnateur, MSD, Sanofi Pasteur, Janssen, Pfizer • Advisory Boards/DSMB: Sanofi Pasteur, Janssen, Pfizer • Cours, formations: Pfizer, MSD, Sanofi Pasteur

No Transfer Without Validation: A Data Sharing Framework Use Case.

Availability and accessibility are important preconditions for using real-world patient data across organizations. To facilitate and enable the analysis of data collected at a large number of independent healthcare providers, syntactic- and semantic uniformity need to be achieved and verified. With this paper, we present a data transfer process implemented using the Data Sharing Framework to ensure only valid and pseudonymized data is transferred to a central research repository and feedback on success or failure is provided. Our implementation is used within the CODEX project of the German Network University Medicine to validate COVID-19 datasets at patient enrolling organizations and securely transfer them as FHIR resources to a central repository.

Predictive value of coagulation variables and glycocalyx shedding in hospitalized COVID-19 patients - a prospective observational study.

OBJECTIVES: Covid-19 disease causes an immense burden on the healthcare system. It has not yet been finally clarified which patients will suffer from a severe course and which will not. Coagulation disorders can be detected in many of these patients. The aim of the present study was therefore to identify variables of the coagulation system including standard and viscoelastometric tests as well as components of glycocalyx damage that predict admission to the intensive care unit. METHODS: Adult patients were included within 24 h of admission. Blood samples were analyzed at hospital admission and at ICU admission if applicable. We analyzed group differences and furthermore performed receiver operator characteristics (ROC). RESULTS: This study included 60 adult COVID-19 patients. During their hospital stay, 14 patients required ICU treatment. Comparing ICU and non-ICU patients at time of hospital admission, D-dimer (1450 µg/ml (675/2850) vs. 600 µg/ml (500/900); p = 0.0022; cut-off 1050 µg/ml, sensitivity 71%, specificity 89%) and IL-6 (47.6 pg/ml (24.9/85.4 l) vs. 16.1 pg/ml (5.5/34.4); p = 0.0003; cut-off 21.25 pg/ml, sensitivity 86%, specificity 65%) as well as c-reactive protein (92 mg/dl (66.8/131.5) vs. 43.5 mg/dl (26.8/83.3); p = 0.0029; cutoff 54.5 mg/dl, sensitivity 86%, specificity 65%) were higher in patients who required ICU admission. Thromboelastometric variables and markers of glycocalyx damage (heparan sulfate, hyaluronic acid, syndecan-1) at the time of hospital admission did not differ between groups. CONCLUSION: General inflammatory variables continue to be the most robust predictors of a severe course of a COVID-19 infection. Viscoelastometric variables and markers of glycocalyx damage are significantly increased upon admission to the ICU without being predictors of ICU admission.

Rossi's principles of transfusion medicine

ROSSI'S PRINCIPLES OF TRANSFUSION MEDICINE: Transfusion Medicine impacts patients with hematologic, oncologic, and surgical conditions as well as all areas of critical care medicine and multiple areas of chronic care. This book aims to be the single best source for information related to any aspect or application of Transfusion Medicine. Contributors for the sixth edition have once again been drawn from various scientific, medical, and surgical disciplines. Thus, this book ranges from encouraging and managing donors, to collecting and preserving the blood, to matching it to the appropriate recipient, all the way to its clinical uses. It also extends these concepts to implantable tissue and regenerative medicine. Other sample topics covered within the work include: Contemporary issues in donation and transfusion: patient blood management, clinical and technical aspects of blood administration, and donor and patient Hemovigilance. Blood components and derivatives: red blood cell metabolism, preservation and oxygen delivery, blood groups, and composition of plasma. Apheresis, transplantation, and new therapies: hematopoietic growth factors, therapeutic phlebotomy and cellular apheresis, HLA antigens, alleles, and antibodies. How Transfusion Medicine has been affected by the coronavirus pandemic, the role of pathogen reduction and other modern trends. This book serves as a complete and comprehensive resource on Transfusion Medicine for clinicians who prescribe blood, students who expect to enter clinical practice, and for the scientists, physicians, nurses, technologists, and others who assure the quality and availability of blood services. © 2022 John Wiley & Sons Ltd. All rights reserved.

Episodic future thinking and compassion reduce non-compliance urges regarding public health guidelines: a randomised controlled trial.

BACKGROUND: People often feel urges to engage in activities that violate pandemic public health guidelines. Research on these urges has been reliant on measures of typical behaviour, which fail to capture these urges as they unfold. Guideline adherence could be improved through interventions, but few methods allow for ecologically valid observation of the range of behaviours that pandemic guidelines prescribe. METHODS: In this preregistered parallel randomised trial, 95 participants aged 18-65 from the UK were assigned to three groups using blinded block randomisation, and engaged in episodic future thinking (n = 33), compassion exercises (n = 31), or a control procedure (n = 31). Following an ecological momentary assessment procedure, participants report on the intensity of their occurrent urges (min. 1, max. 10) and their ability to control them. The study further investigates whether, and through which mechanism, state impulsivity and vaccine attitudes affect guideline adherence. RESULTS: Episodic future thinking (b = -1.80) and compassion exercises (b = -1.45) reduced the intensity of urges. State impulsivity is associated with stronger urges, but we found no evidence that vaccine hesitancy predicts lesser self-control. CONCLUSIONS: We conclude that episodic future thinking exercises and compassion training may be used to decrease non-compliance urges of individuals who are an acute public health risk for the community, such as those in voluntary isolation.

Hyperoncotic human albumin solutions for intravenous fluid therapy: Effectiveness of pathogen safety and purification methods, and clinical safety

Albumin solutions derived from human plasma have demonstrated clinical benefits as intravenous fluid therapy in clinical settings such as liver disease, sepsis, intensive care, and surgery. For all plasma-derived medicinal products, there is a potential risk from pathogens, including relevant blood-borne viruses, emerging viruses, and prion proteins. To minimize the risk of transmissible infections, the production of human albumin solutions includes rigorous donor selection and plasma testing, and effective pathogen removal and inactivation methods such as fractionation and pasteurization. Compliance with international pharmacopeial standards for purity and prekallikrein activator and aluminum content is crucial, as is post-marketing pharmacovigilance for the continuous monitoring of adverse events. This review focuses on the effectiveness of manufacturing methods in the production of plasma-derived albumin, to ensure the safety of hyperoncotic solutions for volume expansion. We evaluated evidence identified through online database (PubMed) searches and from unpublished sources, on the manufacturing and pathogen safety of plasma-derived albumin solutions. The results confirmed the already established and evolving pathogen reduction capacity of the reviewed manufacturing methods. Up-to-date post-marketing pharmacovigilance data and log10 reduction factors for known and emerging pathogens during albumin production are included. Towards the goal of ever-increasing clinical safety, potential areas of improvement, such as compliance rates for the completion of donor health questionnaires, are also discussed. Taken together, the current manufacturing and pathogen reduction steps result in albumin products of greater purity than previous-generation products, with a high margin of pathogen safety against known and emerging pathogens, such as severe acute respiratory syndrome-associated coronavirus 2. © 2022 Chinese Medical Association Publishing House

Successful aging after elective surgery II: Study design and methods.

BACKGROUND: The Successful Aging after Elective Surgery (SAGES) II study was designed to increase knowledge of the pathophysiology and linkages between delirium and dementia. We examine novel biomarkers potentially associated with delirium, including inflammation, Alzheimer's disease (AD) pathology and neurodegeneration, neuroimaging markers, and neurophysiologic markers. The goal of this paper is to describe the study design and methods for the SAGES II study. METHODS: The SAGES II study is a 5-year prospective observational study of 400-420 community dwelling persons, aged 65 years and older, assessed prior to scheduled surgery and followed daily throughout hospitalization to observe for development of delirium and other clinical outcomes. Delirium is measured with the Confusion Assessment Method (CAM), long form, after cognitive testing. Cognitive function is measured with a detailed neuropsychologic test battery, summarized as a weighted composite, the General Cognitive Performance (GCP) score. Other key measures include magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS)/electroencephalography (EEG), and Amyloid positron emission tomography (PET) imaging. We describe the eligibility criteria, enrollment flow, timing of assessments, and variables collected at baseline and during repeated assessments at 1, 2, 6, 12, and 18 months. RESULTS: This study describes the hospital and surgery-related variables, delirium, long-term cognitive decline, clinical outcomes, and novel biomarkers. In inter-rater reliability assessments, the CAM ratings (weighted kappa = 0.91, 95% confidence interval, CI = 0.74-1.0) in 50 paired assessments and GCP ratings (weighted kappa = 0.99, 95% CI 0.94-1.0) in 25 paired assessments. We describe procedures for data quality assurance and Covid-19 adaptations. CONCLUSIONS: This complex study presents an innovative effort to advance our understanding of the inter-relationship between delirium and dementia via novel biomarkers, collected in the context of major surgery in older adults. Strengths include the integration of MRI, TMS/EEG, PET modalities, and high-quality longitudinal data.

Immunogenicity against SARS CoV-2 ancestral strain and variants of two new COVID-19 recombinant adjuvanted vaccines compared to BNT162b2 as a third dose following two doses of BNT162b2: a single-blinded multicenter randomized controlled trial

Background. New adjuvanted recombinant protein vaccines against coronavirus disease 2019 (COVID-19) as heterologous boosters could maximize the benefits of vaccination against SARS CoV-2. Methods. In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3-7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a >= 10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between D0 and D15. Results. The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor >= 10 between Day 0 and Day 15 was 55.3% (95% CI 43.4-66.7) in MV(D614) group (n=76), 76.1% (64.5-85.4) in MV(Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV(Beta) vaccine compared to the other vaccines. Comparable reactogenicity profile was observed the three vaccines. Conclusion. All three vaccines boosted antibodies and neutralizing response after BNT162b2 initial course. Heterologous boosting with the Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein vaccine B.1.351 (Beta formulation) provided higher neutralizing antibodies response rates against variants, including Omicron BA.1, compared with the mRNA BNT162b2 vaccine.

Corimmuno19-BEVA : essai ouvert controle randomise evaluant l'efficacite et l'innocuite du bevacizumab (BEV) (Zirabev) en addition du traitement standard (STD) chez les patients atteints de pneumonie COVID-19 hypoxemique severe (ClinicalTrials.gov, NCT04822818)

Declaration de liens d'interets: Les auteurs declarent ne pas avoir de liens d'interets. Copyright © 2022

Modeling the effect of temperature and relative humidity on exposure to SARS-CoV-2 in a mechanically ventilated room.

Computational fluid dynamics models have been developed to predict airborne exposure to the SARS-CoV-2 virus from a coughing person in a mechanically ventilated room. The models were run with three typical indoor air temperatures and relative humidities (RH). Quantile regression was used to indicate whether these have a statistically significant effect on the airborne exposure. Results suggest that evaporation is an important effect. Evaporation leads to respiratory particles, particularly those with initial diameters between 20 and 100 µm, remaining airborne for longer, traveling extended distances and carrying more viruses than expected from their final diameter. In a mechanically ventilated room, with all of the associated complex air movement and turbulence, increasing the RH may result in reduced airborne exposure. However, this effect may be so small that other factors, such as a small change in proximity to the infected person, could rapidly counter the effect. The effect of temperature on the exposure was more complex, with both positive and negative correlations. Therefore, within the range of conditions studied here, there is no clear guidance on how the temperature should be controlled to reduce exposure. The results highlight the importance of ventilation, face coverings and maintaining social distancing for reducing exposure.

Early antithrombotic post-discharge therapy using prophylactic DOAC or dipyridamole improves long-term survival and cardiovascular outcomes in hospitalized COVID-19 survivors.

Introduction: Cardiovascular events are common in COVID-19. While the use of anticoagulation during hospitalization has been established in current guidelines, recommendations regarding antithrombotic therapy in the post-discharge period are conflicting. Methods: To investigate this issue, we conducted a retrospective follow-up (393 ± 87 days) of 1,746 consecutive patients, hospitalized with and surviving COVID-19 pneumonia at a single tertiary medical center between April and December 2020. Survivors received either 30-day post-discharge antithrombotic treatment regime using prophylactic direct oral anticoagulation (DOAC; n = 1,002) or dipyridamole (n = 304), or, no post-discharge antithrombotic treatment (Ctrl; n = 440). All-cause mortality, as well as cardiovascular mortality (CVM) and further cardiovascular outcomes (CVO) resulting in hospitalization due to pulmonary embolism (PE), myocardial infarction (MI) and stroke were investigated during the follow-up period. Results: While no major bleeding events occured during follow-up in the treatment groups, Ctrl showed a high but evenly distributed rate all-cause mortality. All-cause mortality (CVM) was attenuated by prophylactic DOAC (0.6%, P < 0.001) and dipyridamole (0.7%, P < 0.001). This effect was also evident for both therapies after propensity score analyses using weighted binary logistic regression [DOAC: B = -3.33 (0.60), P < 0.001 and dipyridamole: B = -3.04 (0.76), P < 0.001]. While both treatment groups displayed a reduced rate of CVM [DOAC: B = -2.69 (0.74), P < 0.001 and dipyridamole: B = -17.95 (0.37), P < 0.001], the effect in the DOAC group was driven by reduction of both PE [B-3.12 (1.42), P = 0.012] and stroke [B = -3.08 (1.23), P = 0.028]. Dipyridamole significantly reduced rates of PE alone [B = -17.05 (1.01), P < 0.001]. Conclusion: Late cardiovascular events and all-cause mortality were high in the year following hospitalization for COVID-19. Application of prophylactic DOAC or dipyridamole in the early post-discharge period improved mid- and long-term CVO and all-cause mortality in COVID-19 survivors.

Prevalence of sleep disorders symptoms in health professionals attending patients with suspicion or confirmation of COVID-19

Introduction: In November 2019, in China, an outbreak of a disease caused by the new coronavirus (SARS-CoV-2) has begun. The spread of Coronavirus Disease 2019 (COVID-19) to hundreds of countries, causing respiratory illness and death, especially in risk groups, led the World Health Organization to declare a pandemic in March 2020. For patient's management, an extensive network of multidisciplinary care is necessary, exposing them to a greater contamination risk. Objective: This study aims to describe the prevalence of sleep disorders on health professionals who care for patients with suspicion/ confirmation of COVID-19. Methods: This is a crosssectional study, carried out using an online form sent to health professionals, with higher education, of both genders, aged 18 years or more, from any city in Brazil. Data collection took place from August to December 2020 (epidemiological weeks 32 to 53). The participants were asked about the frequency of several sleep disorders, sociodemographic, health and lifestyle characteristics. Subsequently, descriptive statistics were performed. The study protocol was approved by the National Research Ethics Committee (CONEP) under opinion 4.073.427. Results: The sample consisted of 184 health professionals with an average age of 37 (±9,3) years, predominantly female (69,9%), physicians (48,4%), living in Rio Grande do Sul (77,7%), graduated in the last 10 years (53,3%), working in the morning (83,1%), afternoon (82,6%) and night (32,1%), who have non-transferable chronic diseases (25,5%), consume alcoholic beverages (54,9%) and practice physical activities (57,6%). Regarding sleep disorders, participants presented tiredness on waking up (88,6%), waking up at night (82,1%), excessive daytime sleepiness (73,4%), nightmares (69,6%), difficulty in starting sleep (69%), waking up too early and not being able to go back to sleep (63,6%), grinding or clenching teeth during sleep (59,2%), snoring (58,7%), sleep apnea (13%) and sleepwalking (8,7%). 74,5% of participants had 5 or more symptoms simultaneously. Conclusion: The results demonstrate a high number of symptoms of sleep disorders in the sample, especially tiredness on waking up and night awaking, as well as a high number of health professionals with 5 or more associated symptoms. The data are of concern, as they affect the performance of these professionals, which may expose them and the patients to greater risks.

Relationship between the application of sleep hygiene measures and the perception of sleep by parents of children and adolescents during the COVID-19 pandemic

Introduction: Sleep is the result of reversible changes in the behavioral and physiological spheres, associated with the modification of brain activities, being an important mechanism for physical restoration, memory consolidation and learning, mood regulation and modulation of the immune system. Sleep habits are affected by stimuli and interferences of daily life, especially in a COVID-19 pandemic situation, so it is essential to apply sleep hygiene measures to improve sleep patterns, including having a regular time to sleep and wake up, dim lighting in the periods before bedtime, manage stress and use relaxation techniques. Objective: To assess the relationship between the application of sleep hygiene measures and the perception of sleep quality by parents of children and adolescents during the COVID-19 pandemic. Methods: This is a cross-sectional study, carried out using an online form sent to parents/guardians (over 18 years old) of children and adolescents of both sexes, aged between 4 and 17 years old, by convenience, in the period from October 28, 2020 to December 7, 2020. The analysis of the application of sleep hygiene measures took into account the application of 8 or more sleep hygiene measures by parents/guardians, among the 14 described in the online questionnaire. For the questioning about the perception of parents/guardians regarding the quality of sleep of children, a scale of 0 to 10 was adopted, considering from 0 to 5 for perception of poor sleep quality, and from 6 to 10 for perception of regular or good sleep. The distribution of the dependent variable according to the independent ones was verified using the Chi-square test, considering 95% CI. Results: The sample was composed of 532 children and adolescents of both sexes, mean age 9.7 (± 3.8 years), with a predominance of female sex (51.9%), residing in Rio Grande do Sul (63.7%), aged between 6 and 13 years (60.2%). It was observed that 83.3% of the parents/ guardians evaluated perceived the sleep of children and adolescents as regular or good. Of these, 87.1% applied 8 or more sleep hygiene measures, proving the positive relationship between the application of sleep hygiene measures and the perception of sleep quality (p 0.001). Conclusion: The study data allowed us to analyze how the application of sleep hygiene measures in children and adolescents caused positive outcomes in the sleep pattern, thus demonstrating the benefits that these actions have on the physiological development of children.

Inhibitors of dihydroorotate dehydrogenase cooperate with molnupiravir and N4-hydroxycytidine to suppress SARS-CoV-2 replication.

The nucleoside analog N4-hydroxycytidine (NHC) is the active metabolite of the prodrug molnupiravir, which has been approved for the treatment of COVID-19. SARS-CoV-2 incorporates NHC into its RNA, resulting in defective virus genomes. Likewise, inhibitors of dihydroorotate dehydrogenase (DHODH) reduce virus yield upon infection, by suppressing the cellular synthesis of pyrimidines. Here, we show that NHC and DHODH inhibitors strongly synergize in the inhibition of SARS-CoV-2 replication in vitro. We propose that the lack of available pyrimidine nucleotides upon DHODH inhibition increases the incorporation of NHC into nascent viral RNA. This concept is supported by the rescue of virus replication upon addition of pyrimidine nucleosides to the media. DHODH inhibitors increased the antiviral efficiency of molnupiravir not only in organoids of human lung, but also in Syrian Gold hamsters and in K18-hACE2 mice. Combining molnupiravir with DHODH inhibitors may thus improve available therapy options for COVID-19.

Modeling and experimental study of dispersion and deposition of respiratory emissions with implications for disease transmission.

The ability to model the dispersion of pathogens in exhaled breath is important for characterizing transmission of the SARS-CoV-2 virus and other respiratory pathogens. A Computational Fluid Dynamics (CFD) model of droplet and aerosol emission during exhalations has been developed and for the first time compared directly with experimental data for the dispersion of respiratory and oral bacteria from ten subjects coughing, speaking, and singing in a small unventilated room. The modeled exhalations consist of a warm, humid, gaseous carrier flow and droplets represented by a discrete Lagrangian particle phase which incorporates saliva composition. The simulations and experiments both showed greater deposition of bacteria within 1 m of the subject, and the potential for a substantial number of bacteria to remain airborne, with no clear difference in airborne concentration of small bioaerosols (<10 µm diameter) between 1 and 2 m. The agreement between the model and the experimental data for bacterial deposition directly in front of the subjects was encouraging given the uncertainties in model input parameters and the inherent variability within and between subjects. The ability to predict airborne microbial dispersion and deposition gives confidence in the ability to model the consequences of an exhalation and hence the airborne transmission of respiratory pathogens such as SARS-CoV-2.

International Politics in a Time of Risk and Uncertainty: The Covid-19 Crisis and Beyond *

Climate change, environmental degradation and the continuing scourge of poverty are leading to unforeseen political, economic and security challenges. Speaking with Syrian and international NGOs and UN agencies working in north-west Syria brought home to me the sheer human misery that results from conflict, and how the Security Council's role is vital to ensure humanitarian access and an end to conflict. [...]there is the EU vaccine strategy, which demonstrates the benefits of EU collaboration and solidarity. [...]the EU's multiannual financial framework (MFF)/Recovery Fund package totalling €1.82 trillion is truly historic.

Modeling the factors that influence exposure to SARS-CoV-2 on a subway train carriage.

We propose the Transmission of Virus in Carriages (TVC) model, a computational model which simulates the potential exposure to SARS-CoV-2 for passengers traveling in a subway rail system train. This model considers exposure through three different routes: fomites via contact with contaminated surfaces; close-range exposure, which accounts for aerosol and droplet transmission within 2 m of the infectious source; and airborne exposure via small aerosols which does not rely on being within 2 m distance from the infectious source. Simulations are based on typical subway parameters and the aim of the study is to consider the relative effect of environmental and behavioral factors including prevalence of the virus in the population, number of people traveling, ventilation rate, and mask wearing as well as the effect of model assumptions such as emission rates. Results simulate generally low exposures in most of the scenarios considered, especially under low virus prevalence. Social distancing through reduced loading and high mask-wearing adherence is predicted to have a noticeable effect on reducing exposure through all routes. The highest predicted doses happen through close-range exposure, while the fomite route cannot be neglected; exposure through both routes relies on infrequent events involving relatively few individuals. Simulated exposure through the airborne route is more homogeneous across passengers, but is generally lower due to the typically short duration of the trips, mask wearing, and the high ventilation rate within the carriage. The infection risk resulting from exposure is challenging to estimate as it will be influenced by factors such as virus variant and vaccination rates.

Cory COVID-Bot: An Evidence-Based Behavior Change Chatbot for COVID-19.

Cory COVID-Bot is an artificial intelligence chatbot designed and built by a multisector collaboration to help people safely step towards COVID normal. Achieving COVID normal and avoiding unnecessary adverse health outcomes requires effective communication to the public regarding COVID safe behaviors, but reaching young, culturally and linguistically diverse members of the community is challenging for government. Cory COVID-Bot was developed to directly engage with difficult to reach populations in English and Vietnamese. In order to resolve public ambiguity and uncertainty about public health guidelines, and to stimulate safe behavior, Cory COVID-Bot provides updated recommendations and behavior change interventions, which emphasize the importance of COVID safe behaviors.