Cardiovascular outcomes after tixagevimab and cilgavimab use for pre-exposure prophylaxis against COVID-19: a population-based propensity-matched cohort study.

Tixagevimab and cilgavimab treatment was associated with higher rates of cardiovascular events in a post-hoc analysis of a phase 3 trial. In this large population-based propensity-matched study, we found no increased risk of cardiovascular events up to 90 days after tixagevimab and cilgavimab administration, including in patients with pre-existing cardiovascular disease.

Reverse adoption of information and communication technology among organisers of academic conferences.

This study examines the formats offered for academic conferences in the mature stages of the COVID-19 pandemic. Two out of three organisers discontinue their usage of online video tools and focus on in-person conferences. Only one out of five conferences offers hybrid solutions and even fewer a virtual alternative (13%). Data for the analysis originate from 547 calls for proposals announced in Spring 2022 for conferences to be held during the period August 2022 to July 2023. Estimates using a multinomial logit model show that the planning time is significantly related to the choice of format offered. The longer the lead time, the more likely it is to offer an in-person conference. International travel restrictions and bans on gatherings for the location of the venue at the time of planning are significantly related to the choice of virtual, but not hybrid formats. There are also large differences in the choice across disciplines, with conferences in arts and humanities as well as natural sciences showing the lowest preference for the virtual format.

In Times of Restricted Mobility: Cancel, Change Date, Or Change Format of Tourism Conferences

The aim of this article is to examine how tourism conference organizers react to the restricted mobility incurred by the spread of the COVID-19 virus. Do they cancel, change format, or change date for the event? This study contributes to an initial analysis of how organizers of international academic conferences in the tourism and hospitality industry deal with whole groups of participants who are no longer mobile and therefore cannot actively network personally. This uniquely compiled data covers a large representative number of conferences in this field. A Multinomial Logit model is used to estimate the options available. Data are based on unique information on almost 100 conferences, meetings, and congresses in the tourism and hospitality sector, including related fields such as leisure and recreation, planned to be held during the period of March to November 2020. Descriptive evidence shows that approximately one out of five conferences changes to a virtual format, somewhat more than half moves the date (mainly to the year 2021), and the remaining 25% cancel the event without alternative offers. Estimation results reveal that the decision to change to an online format increases nonlinearly over time in the form of an inverse U-shaped curve. This indicates a certain resistance to virtual conferences, although with more time for planning, a gradual adaptation to the actual situation appears to be possible. Longer conferences are less likely to change format. The probability of cancellations is lower for association conferences, which are held regularly.

Plasma Interleukin-6 Predicts Clinical Decline After Completion of Dexamethasone Therapy in Severe COVID-19.

To identify and characterize clinical decline after completion of dexamethasone in severe COVID-19 and determine whether interleukin (IL)-6 and other inflammatory biomarkers predict the occurrence of clinical decline. DESIGN: Prospective observational cohort. SETTING: ICUs in three University of Washington affiliated hospitals between July 2020 and April 2021. PATIENTS: Patients admitted to an ICU with COVID-19 who completed a course of dexamethasone. MEASUREMENTS AND MAIN RESULTS: We identified 65 adult patients with severe COVID-19 who completed a 10-day course of dexamethasone, of whom 60 had plasma samples collected within 3 days of dexamethasone completion. We measured IL-6 with a clinical-grade electrochemiluminescent assay and a larger panel of inflammatory biomarkers (IL-8, Monocyte Chemoattractant Protein-1, Monocyte Inflammatory Protein-1 alpha, interferon gamma, C-X-C Motif Chemokine Ligand 10, WBC, bicarbonate) with a research immunoassay. We defined clinical decline by the occurrence of incident severe kidney injury, incident or escalating shock or fever, worsening hypoxemia, or death within 5 days of completion of dexamethasone. We estimated risk for clinical decline by standardized log2 transformed biomarker concentration using multivariable logistic regression. Clinical decline post-dexamethasone was common, occurring in 49% of patients (n = 32). Among all biomarkers, IL-6 levels were most strongly associated with clinical decline. After adjustment for age, sex, and study site, the odds of post-dexamethasone clinical decline were 7.33 times higher per one sd increase in log2 transformed IL-6 concentrations (adjusted odds ratio, 7.33; CI, 2.62-20.47; p < 0.001). The discriminatory power of IL-6 for clinical decline was high (cross-validated mean area under the receiver operating characteristic curve, 0.90; 95% CI, 0.79-0.95). CONCLUSIONS: Clinical decline after completion of dexamethasone for severe COVID-19 is common. IL-6 concentrations obtained prior to completion of dexamethasone may have utility in identifying those at highest risk for subsequent worsening. If validated, future work might test whether plasma IL-6 could be used as a tool for a personalized approach to duration of dexamethasone treatment in severe COVID-19.

Acute pulmonary emboli following rebound phenomenon after Nirmatrelvir/Ritonavir treatment for COVID-19.

The return of COVID-19 symptoms after Nirmatrelvir/Ritonavir (Nm/R) treatment is being increasingly reported. Limited evidence suggests most cases of rebound symptoms are mild and do not require further intervention. Here we present a male veteran reporting rebound symptoms who was found to be hypoxic with pulmonary emboli. Our case highlights the need to evaluate known complications of SARS-CoV-2 including venous thromboembolism in patients reporting recurring symptoms. Further, cases of severe rebound phenomenon should continue to be reported by clinicians to better appreciate the use of the Nm/R during the Omicron wave and among vaccinated persons.

Teclistamab in Relapsed or Refractory Multiple Myeloma.

BACKGROUND: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better). RESULTS: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2). CONCLUSIONS: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).

Antibody and T-cell responses by ultra-deep T-cell receptor immunosequencing after COVID-19 vaccination in patients with plasma cell dyscrasias.

We investigated antibody and coronavirus disease 2019 (COVID-19)-specific T-cell mediated responses via ultra-deep immunosequencing of the T-cell receptor (TCR) repertoire in patients with plasma cell dyscrasias (PCD). We identified 364 patients with PCD who underwent spike antibody testing using commercially available spike-receptor binding domain immunoglobulin G antibodies ≥2 weeks after completion of the initial two doses of mRNA vaccines or one dose of JNJ-78436735. A total of 56 patients underwent TCR immunosequencing after vaccination. Overall, 86% tested within 6 months of vaccination had detectable spike antibodies. Increasing age, use of anti-CD38 or anti-B-cell maturation antigen therapy, and receipt of BNT162b2 (vs. mRNA-1273) were associated with lower antibody titres. We observed an increased proportion of TCRs associated with surface glycoprotein regions of the COVID-19 genome after vaccination, consistent with spike-specific T-cell responses. The median spike-specific T-cell breadth was 3.11 × 10^-5 , comparable to those in healthy populations after vaccination. Although spike-specific T-cell breadth correlated with antibody titres, patients without antibody responses also demonstrated spike-specific T-cell responses. Patients receiving mRNA-1273 had higher median spike-specific T-cell breadth than those receiving BNT162b2 (p = 0.01). Although patients with PCD are often immunocompromised due to underlying disease and treatments, COVID-19 vaccination can still elicit humoral and T-cell responses and remain an important intervention in this patient population.

Safety and Feasibility of Ultra-Restrictive Transfusion Protocol as a Blood-Preservation Strategy During Shortage Crises.

BACKGROUND: We hypothesized that implementation of new ultra-restrictive transfusion protocol in adult surgical intensive care units (SICU) was safe and feasible during pandemic-associated shortage crises. METHODS: Retrospective analysis two months pre- and post-implementation of ultra-restrictive transfusion protocol in March 2020 with hemoglobin cutoff of 6 g/dL (6.5 g/dL if ≥ 65 years old) for patients without COVID, active bleeding, or myocardial ischemia. RESULTS: We identified 16/93 and 27/168 patients PRE and POST meeting standard transfusion threshold (7 g/dL); within POST, 12 patients met ultra-restrictive cutoffs. There was no significant difference between PRE and POST in the rate of mortality, ischemic complications, or the number of transfusions per patient, however, the overall incidence of transfusion was lower in the POST group (7.1 vs 17.2%, p = 0.02). Patients received a mean (SD) of 4(3.8) and 2.4(1.5) PRBC transfusions pre- and post-implementation. Odds ratio of mortality in POST group was 0.62 (95%CI: 0.08-5.12) adjusted for age, sex, and SOFA score. CONCLUSIONS: Implementation of an ultra-restrictive transfusion protocol was feasible and effective as a blood- preservation strategy.

Domestic tourism demand in the North and the South of Europe in the Covid-19 summer of 2020.

This study investigates empirically changes in domestic summer tourism demand following the Covid-19 pandemic in 305 regions across six European countries (Denmark, Finland, France, Italy, Spain and Sweden) based on official data. Five different groups of NUTS 3 regions are identified in accordance with a typology suggested by the OECD where density and connectivity are aspects of importance. Dynamic panel data estimations show that large metropolitan regions experience strong decreases in demand (approximately 30 per cent) both in July and August 2020. There are, however, clear differences between the Northern and Southern European countries. In the North, the remote regions encounter an increased demand that is partially offsetting losses in the large metropolitan regions. This pattern cannot be found in the South. The decline in domestic tourism flows to the major metropolitan areas is also more pronounced in the South of Europe, approximately 50 per cent per summer month compared with 20 per cent (July 2020) and stagnation (August 2020) in the North regions.

School Reopening Simulations with COVID-19 Agent-based Model for the Philippine Regions (preprint)

Background: Schools have been closed in the Philippines since March 2020 due to the COVID-19 pandemic. In September 2021, the government already allowed a pilot run of limited in-person classes in low-risk areas around the country, in the face of the continuing threat of the virus. Objective: We aim to assess which regions in the Philippines can already reopen their schools. Methods: In this study, we simulate school reopening scenarios with our modified COVID-19 agent-based model for the seventeen regions of the country. We tested different vaccination coverages and calculated the coverage at which deaths and infections would begin to show a downtick. The School Reopening Viability (SRV) of a region is then determined by getting the difference between the current vaccination coverage (as of 13 February 2022) and the downtick in infection or death. Results: The recent data on the COVID-19 Omicron variant transmission shows that all regions except Regions 7, 9, and BARMM can reopen. Comparing the SRV of a region to its vaccination progress, we see that those with high vaccination rates are the ones most viable for school reopening, as in the case of regions in Luzon. On the other hand, those with low vaccination rates are the ones that would need to ramp up their vaccination efforts before reopening their schools. Conclusions: We recommend that with the current vaccination coverages for the regions, all regions except Regions 7, 9, and BARMM may undergo school reopening. Alongside efforts to reopen schools, vaccination efforts should still be continued and ramped up, especially in the regions of interest. Policymakers may take insights from this study

Clinical Characteristics, Risk Factors for Severity and Pharmacotherapy in Hospitalized COVID-19 Patients in the United Arab Emirates.

Data on the clinical characteristics, severity and management of COVID-19 from the Middle East region, especially the United Arab Emirates (UAE), is very limited. We studied the clinical characteristics, laboratory biomarkers, risk factors for severity and pharmacotherapy of hospitalized COVID-19 patients in this single-center, analytical cross-sectional study conducted in a secondary care hospital of the UAE. A total of 585 patients were included in the study (median age, 49 years (IQR, 39-59); 66% male). Age > 45 years (OR = 2.07, 95% CI: 1.04-4.14, p = 0.040), male gender (OR = 3.15, 95% CI: 1.52-6.51, p = 0.002), presentation symptoms such as fever (OR = 3.68, 95% CI:1.34-10.11, p = 0.011) and shortness of breath/dyspnea (OR = 5.36, 95% CI: 2.69-10.67, p < 0.001), Hb < 13 g/dL (OR = 3.17, 95% CI: 1.51-6.65, p = 0.002), neutrophils > 7 × 103/mcL (OR = 4.89, 95% CI: 1.66-14.37, p=0.004), lymphocytes < 1 × 103/mcL (OR = 7.78, 95% CI: 1.01-60.19, p = 0.049), sodium < 135 mmol/L (OR = 5.42, 95% CI: 1.05-27.95, p = 0.044), potassium < 3.6 mmol/L (OR = 3.36, 95% CI: 1.03-11.01, p = 0.045), urea > 6.5 mmol/L (OR = 3.37, 95% CI: 1.69-6.73, p = 0.001) and LDH > 227 IU/L (OR = 6.26, 95% CI: 1.61-24.32, p = 0.008) were independent predictors of the severity of COVID-19. Antivirals (524, 89.6%) and corticosteroids (358, 61.2%) were prescribed for the management of COVID-19. In conclusion, older age, male gender, presentation symptoms such as fever and dyspnea, low hemoglobin, neutrophilia, lymphopenia, hyponatremia, hypokalemia, elevated levels of urea and lactate dehydrogenase were found to be independent risk factors for severe COVID-19. The pharmacotherapy of COVID-19 patients in our study was diverse, and the medications were prescribed based on the clinical condition of the patients.

Advancing precision medicine for acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a heterogeneous clinical syndrome. Understanding of the complex pathways involved in lung injury pathogenesis, resolution, and repair has grown considerably in recent decades. Nevertheless, to date, only therapies targeting ventilation-induced lung injury have consistently proven beneficial, and despite these gains, ARDS morbidity and mortality remain high. Many candidate therapies with promise in preclinical studies have been ineffective in human trials, probably at least in part due to clinical and biological heterogeneity that modifies treatment responsiveness in human ARDS. A precision medicine approach to ARDS seeks to better account for this heterogeneity by matching therapies to subgroups of patients that are anticipated to be most likely to benefit, which initially might be identified in part by assessing for heterogeneity of treatment effect in clinical trials. In October 2019, the US National Heart, Lung, and Blood Institute convened a workshop of multidisciplinary experts to explore research opportunities and challenges for accelerating precision medicine in ARDS. Topics of discussion included the rationale and challenges for a precision medicine approach in ARDS, the roles of preclinical ARDS models in precision medicine, essential features of cohort studies to advance precision medicine, and novel approaches to clinical trials to support development and validation of a precision medicine strategy. In this Position Paper, we summarise workshop discussions, recommendations, and unresolved questions for advancing precision medicine in ARDS. Although the workshop took place before the COVID-19 pandemic began, the pandemic has highlighted the urgent need for precision therapies for ARDS as the global scientific community grapples with many of the key concepts, innovations, and challenges discussed at this workshop.

A Joint Action in Times of Pandemic: The German BioImaging Recommendations for Operating Imaging Core Facilities During the SARS-Cov-2 Emergency.

Operating shared resource laboratories (SRLs) in times of pandemic is a challenge for research institutions. In a multiuser, high-turnover working space, the transmission of infectious agents is difficult to control. To address this challenge, imaging core facility managers being members of German BioImaging discussed how shared microscopes could be operated with minimal risk of spreading SARS-CoV-2 between users and staff. Here, we describe the resulting guidelines and explain their rationale, with a focus on separating users in space and time, protective face masks, and keeping surfaces virus-free. These recommendations may prove useful for other types of SRLs. © 2020 The Authors. Cytometry Part A published by Wiley Periodicals LLC. on behalf of International Society for Advancement of Cytometry.

Case Report: Can Inhaled Adenosine Attenuate COVID-19?

This case report demonstrates a small repetition of the case series carried out in Italy wherein inhaled adenosine was administered to patients experiencing severe and worsening coronavirus disease-2019 (COVID-19). The two cases are important not only because they were the first of their type in the United States, but also because both patients were DNR/DNI and were therefore expected to die. Study repetition is vitally important in medicine. New work in pharmacology hypothesizes that adenosine-regulator proteins may play a role in the pathogenesis of COVID-19 infection. Furthermore, adenosine, by interacting with cell receptor sites, has pluripotent effects upon inflammatory cells, is anti-inflammatory, and is important in tissue hypoxia signaling. Inhaled adenosine is potentially safe; thousands have received it for asthmatic challenge testing. The effects of adenosine in these two cases were rapid, positive, and fit the pharmacologic hypotheses (as seen in prior work in this journal) and support its role as a therapeutic nucleoside.

Determinants of CO2 emissions generated by air travel vary across reasons for the trip.

This study estimates factors of importance for the carbon dioxide equivalent (CO2e) emissions generated by travellers flying for different reasons based on representative Austrian micro data for the period 2014-2016. The annual average number of flights taken by adults vary between 0.1 (visiting friends) and 0.8 (going on holiday), and the amount of CO2e emissions generated by each return flight is approximately 1100 kg. This leads to a total of 6 million tonnes CO2e emissions per year. Results of the Pseudo Poisson Maximum Likelihood estimations reveal that the amount of CO2e emissions created is related to socio-demographic, locational and seasonal factors, although mainly for the largest group of travellers: the holiday makers. In this group, individuals with university degrees, young persons (16-24 years) and capital city residents generate the largest amounts of emissions, as opposed to persons with children and large households. Residents of the capital region each quarter cause 64 kg more CO2e emissions than inhabitants of rural areas, persons with university degrees create 74 kg larger emissions than those without degrees and young adults instigate 90 kg more emissions than middle-aged persons. CO2e emissions of holiday flights are highest in the first quarter of the year. The importance of education is also pronounced for CO2e emissions related to business travel, as is gender.

Variation in COVID-19 Mortality Across 117 US Hospitals in High- and Low-Burden Settings.

Some hospitals have faced a surge of patients with COVID-19, while others have not. We assessed whether COVID-19 burden (number of patients with COVID-19 admitted during April 2020 divided by hospital certified bed count) was associated with mortality in a large sample of US hospitals. Our study population included 14,226 patients with COVID-19 (median age 66 years, 45.2% women) at 117 hospitals, of whom 20.9% had died at 5 weeks of follow-up. At the hospital level, the observed mortality ranged from 0% to 44.4%. After adjustment for age, sex, and comorbidities, the adjusted odds ratio for in-hospital death in the highest quintile of burden was 1.46 (95% CI, 1.07-2.00) compared to all other quintiles. Still, there was large variability in outcomes, even among hospitals with a similar level of COVID-19 burden and after adjusting for age, sex, and comorbidities.

Nordic stock market performance of the travel and leisure industry during the first wave of Covid-19 pandemic

This article investigates the performance of the stock market and its volatility in the travel and leisure industry for three Nordic countries using daily data from June 2018 to June 2020, a period that includes the first wave of Covid-19 pandemic. The methodology is based on the Markov regime switching model that allows unobservable regime shifts in the stock return relationship between the travel and leisure industry and the overall market in the period before the outbreak of Covid-19 crisis and during the recovery period at the end of the first wave. The results provide strong evidence of regime switching behaviour in the form of idiosyncratic risk as measured by volatility. The period before Covid-19 corresponds to a low/medium idiosyncratic risk, while the period of the pandemic is characterized by a regime with high idiosyncratic risk. Overall, the timing, likelihood and duration of this crisis regime depend on the composition of the travel and leisure firms. Those with a large proportion of online gambling firms perform better, while those consisting of international transportation firms, hotels and restaurants perform negatively. This study shows that the high-frequency data and the model chosen here can provide timely information on the impact of the pandemic on various tourism and leisure businesses that could be useful for policymaking.

When international academic conferences go virtual.

This study investigates the extent to which international academic conferences changes format to virtual when faced by sudden Covid-19 related immobility. Data on 587 conferences in the fields of business, economics, information technology, management and other social sciences that were planned to be held between March and August 2020 are retrieved from authorised conference listings. Approximately 28% of the conferences changed to virtual format during the period of time studied. Probit estimations reveal that the probability of changing format to virtual increases with the country of location (United States), planning horizon and the available quality of broadband infrastructure in the scheduled conference country. However, the role of planning horizon differs across fields and location of the conference. The probability of virtual conferences is highest in the United States and for academic conferences in the field of information technology.