Use of Monoclonal Antibodies in Immunocompromised Patients Hospitalized with Severe COVID-19: A Retrospective Multicenter Cohort.

OBJECTIVE: We aim to describe the safety and efficacy of sotrovimab in severe cases of COVID-19 in immunocompromised hosts. METHODS: We used a retrospective multicenter cohort including immunocompromised hospitalized patients with severe COVID-19 treated with sotrovimab between October 2021 and December 2021. RESULTS: We included 32 patients. The main immunocompromising conditions were solid organ transplantation (46.9%) and hematological malignancy (37.5%). Seven patients (21.9%) had respiratory progression: 12.5% died and 9.4% required mechanical ventilation. Patients treated within the first 14 days of their symptoms had a lower progression rate: 12.0% vs. 57.1%, p = 0.029. No adverse event was attributed to sotrovimab. CONCLUSIONS: Sotrovimab was safe and may be effective in its use for immunocompromised patients with severe COVID-19. More studies are needed to confirm these preliminary data.

Evaluation of the clinical evolution and transmission of SARS-CoV-2 infection in cats by simulating natural routes of infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic disease denominated as Coronavirus Disease 2019 (COVID-19). Several studies suggest that the original source of this virus was a spillover from an animal reservoir and its subsequent adaptation to humans. Of all the different animals affected, cats are one of the most susceptible species. Moreover, several cases of natural infection in domestic and stray cats have been reported in the last few months. Although experimental infection assays have demonstrated that cats are successfully infected and can transmit the virus to other cats by aerosol, the conditions used for these experiments have not been specified in terms of ventilation. We have, therefore, evaluated the susceptibility of cats using routes of infection similar to those expected under natural conditions (exposure to a sneeze, cough, or contaminated environment) by aerosol and oral infection. We have also evaluated the transmission capacity among infected and naïve cats using different air exchange levels. Despite being infected using natural routes and shed virus for a long period, the cats did not transmit the virus to contact cats when air renovation features were employed. The infected animals also developed gross and histological lesions in several organs. These outcomes confirm that cats are at risk of infection when exposed to infected people, but do not transmit the virus to other cats with high rates of air renovation.

An Upgrade on the Surveillance System of SARS-CoV-2: Deployment of New Methods for Genetic Inspection.

SARS-CoV-2 variants surveillance is a worldwide task that has been approached with techniques such as Next Generation Sequencing (NGS); however, this technology is not widely available in developing countries because of the lack of equipment and limited funding in science. An option is to deploy a RT-qPCR screening test which aids in the analysis of a higher number of samples, in a shorter time and at a lower cost. In this study, variants present in samples positive for SARS-CoV-2 were identified with a RT-qPCR mutation screening kit and were later confirmed by NGS. A sample with an abnormal result was found with the screening test, suggesting the simultaneous presence of two viral populations with different mutations. The DRAGEN Lineage analysis identified the Delta variant, but there was no information about the other three mutations previously detected. When the sequenced data was deeply analyzed, there were reads with differential mutation patterns, that could be identified and classified in terms of relative abundance, whereas only the dominant population was reported by DRAGEN software. Since most of the software developed to analyze SARS-CoV-2 sequences was aimed at obtaining the consensus sequence quickly, the information about viral populations within a sample is scarce. Here, we present a faster and deeper SARS-CoV-2 surveillance method, from RT-qPCR screening to NGS analysis.

Large-scale study on virological and serological prevalence of SARS-CoV-2 in cats and dogs in Spain.

The disease produced by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is currently one of the primary concerns worldwide. Knowing the zoonotic origin of the disease and that several animal species, including dogs and cats, are susceptible to viral infection, it is critical to assess the relevance of pets in this pandemic. Here, we performed a large-scale study on SARS-CoV-2 serological and viral prevalence in cats and dogs in Spain in order to elucidate their role and susceptibility. Samples from animals in contact with COVID-19 positive people and/or compatible symptoms (n = 492), as well as from random animals (n = 1024), were taken. Despite the large number of animals analyzed, only 12 animals (eight dogs and four cats), which represents 0.79% of the total analyzed animals (n = 1516), were positive for viral SARS-CoV-2 RNA detection by reverse transcription quantitative PCR (RT-qPCR) in which viral isolation was possible in four animals. We detected neutralizing antibodies in 34 animals, four of them were also positive for PCR. This study evidences that pets are susceptible to SARS-CoV-2 infection in natural conditions but at a low level, as evidenced by the low percentage of positive animals detected, being infected humans the main source of infection. However, the inclusion of animals in the surveillance of COVID-19 is still recommended.

Methodological Perspective for Assessing European Consumers’ Awareness of Cybersecurity and Sustainability in E-Commerce

The increasing European consumer awareness of cybersecurity and sustainability issues in e-commerce is raising key methodological concerns. In a field like this, still unexplored by scholars, it is crucial to identify reliable data as well as to choose the modalities of combining primary and secondary data. As the robustness of the outcome of a study on a complex issue is highly sensitive to the quality of the data used, this paper is a communication that aims to complement and support previously published empirical research. This communication describes the methodological path to collect, integrate, and process data from different sources to interpret European consumers’ attitudes towards cybersecurity and sustainability during e-commerce. In fact, COVID-19 has driven many users to shop online, raising concerns especially about the security of digital transactions. Scientific studies analyzing these effects are still lacking in the literature and therefore this paper aims to fill this gap. The limits of a rigid dataset such as Eurostat’s are overcome by integrating the results of European citizens’ behavior during online purchases, with a survey that involved some experts appropriately selected by the research team. The combination of primary and secondary sources of data and the application of a hybrid methodological approach using MCDA (multi-criteria decision analysis) and a Likert scale allowed new information that fills some gaps in the literature to be extracted from the data. How European citizens correlate e-commerce with cybersecurity and sustainability emerged, thus providing important insights for decision-makers.

Factors shaping the COVID-19 epidemic curve: a multi-country analysis.

BACKGROUND: Lockdown measures are the backbone of containment measures for the COVID-19 pandemic both in high-income countries (HICs) and low- and middle-income countries (LMICs). However, in view of the inevitably-occurring second and third global covid-19 wave, assessing the success and impact of containment measures on the epidemic curve of COVID-19 and people's compliance with such measures is crucial for more effective policies. To determine the containment measures influencing the COVID-19 epidemic curve in nine targeted countries across high-, middle-, and low-income nations. METHODS: Four HICs (Germany, Sweden, Italy, and South Korea) and five LMICs (Mexico, Colombia, India, Nigeria, and Nepal) were selected to assess the association using interrupted time series analysis of daily case numbers and deaths of COVID-19 considering the following factors: The "stringency index (SI)" indicating how tight the containment measures were implemented in each country; and the level of compliance with the prescribed measures using human mobility data. Additionally, a scoping review was conducted to contextualize the findings. RESULTS: Most countries implemented quite rigorous lockdown measures, particularly the LMICs (India, Nepal, and Colombia) following the model of HICs (Germany and Italy). Exceptions were Sweden and South Korea, which opted for different strategies. The compliance with the restrictions-measured as mobility related to home office, restraining from leisure activities, non-use of local transport and others-was generally good, except in Sweden and South Korea where the restrictions were limited. The endemic curves and time-series analysis showed that the containment measures were successful in HICs but not in LMICs. CONCLUSION: The imposed lockdown measures are alarming, particularly in resource-constrained settings where such measures are independent of the population segment, which drives the virus transmission. Methods for examining people's movements or hardships that are caused by covid- no work, no food situation are inequitable. Novel and context-adapted approach of dealing with the COVID-19 crisis are therefore crucial.

Flexibility and Resilience in Corporate Decision Making: A New Sustainability-Based Risk Management System in Uncertain Times

Risk management plays a key role in uncertain times, preventing corporations from acting rashly and incorrectly, allowing them to become flexible and resilient. A global turbulence such as the COVID-19 pandemic has had a strong impact on individual companies and entire economic sectors, raising the question of whether a paradigm shift is necessary, in order to enable a new cycle of development that is much environmentally, socially and economically sustainable. This environmental and socio-economic context of profound uncertainty forces organizations to consider more carefully the risk factors affecting their business continuity, as well as how these factors relate to sustainability issues. However, there is a gap in knowledge about how risk management systems relate to sustainability management systems, and how both of them exert influence on business performance, especially from a theoretical point of view. The aim of this study is to address this gap, by developing a new interpretative framework for the analysis of risk management strategies in organizations. This approach has been identified in economic hermeneutics as an innovative methodological tool to improve the knowledge of risk and design the most appropriate management strategies. The paper provides two main results: the first one is the construction of a theoretical model that relates risk management to sustainability management;the second one is an operational framework of multidimensional risk assessment useful for analysis at different levels (business, competitive scenario and system). Finally, the model also makes it possible to carry out a sustainability assessment through risk evaluation in the perspective of the sustainable development goals.

E-Commerce Calls for Cyber-Security and Sustainability: How European Citizens Look for a Trusted Online Environment

The pandemic has changed the citizens’ behavior, inducing them to avoid any real contact. This has given an incredible impulse to e-commerce;however, the complexity of the topic has not yet been adequately explored in the literature. To fill this gap, this study has a twofold purpose: (1) to investigate how European countries comparatively perform in e-commerce, and (2) to describe what are the most important challenges for the further expansion of e-commerce. To this end, we adopted a hybrid methodology based on multi-criteria decision analysis (MCDA) and a Likert scale survey. The first method allows to us rank the e-commerce performance of different European countries, while the second one looks at the problems and barriers that characterize online shopping. The results of the study show that European countries have different sensitivities to the issue of cyber-security, and among them it is possible to identify three groups with different levels of attention to the critical issues of e-commerce. The Netherlands, Sweden and Denmark belong to the group of countries most responsive to e-commerce. This request is part of a broader framework of transition toward sustainable development, i.e., a reliable digital environment where citizens and businesses can exercise their rights and freedoms in complete security. Finally, from a theoretical perspective, this paper adds a new baseline to the literature on the state of the art of e-commerce in Europe that addresses the effects of the pandemic. From a managerial point of view, decision makers can find in the results of this analysis a support for the setting of business strategies for the expansion of firms in certain markets and guidance for public authorities when defining regulatory policies for e-commerce.

RT-qPCR Assays for Rapid Detection of the N501Y, 69-70del, K417N, and E484K SARS-CoV-2 Mutations: A Screening Strategy to Identify Variants With Clinical Impact.

Background: Several variants of the SARS-CoV-2 have been documented globally during the current COVID-19 pandemic. The N501Y, 69-70del, K417N, and E484K SARS-CoV-2 mutations have been documented among the most relevant due to their potential pathogenic biological effects. This study aimed to design, validate, and propose a fast real-time RT-qPCR assay to detect SARS-CoV-2 mutations with possible clinical and epidemiological relevance in the Mexican population. Methods: Targeting spike (S) gene mutations of SARS-CoV-2 (N501Y, 69-70del, K417N, and E484K), specific primers, and probes for three specific quantitative reverse transcription PCR (RT-qPCR) assays were designed, and validated using Sanger sequencing. These assays were applied in clinical samples of 1060 COVID-19 patients from Jalisco Mexico. Results: In silico analyzes showed high specificity of the three assays. Amplicons of samples were confirmed through sequencing. The screening of samples of COVID-19 patients allowed the identification of the E484K mutation in nine individuals and the identification of P.2 Brazilian variant in Mexico. Conclusion: This work provides low-cost RT-qPCR assays for rapid screening and molecular surveillance of mutations with potential clinical impact. This strategy allowed the detection of E484K mutation and P.2 variant for the first time in samples from the Mexican population.

The Covid-19 pandemic in low- and middle-income countries, who carries the burden? Review of mass media and publications from six countries.

During the Covid-19 pandemic, rich countries employed lockdown and physical distancing policies for transmission control. However, the question still remains whether these measures are also suitable in countries with a fragile economy, which rests mainly on the informal sector. The impacts of lockdown measures in disadvantaged population strata in six low- and middle-income countries (LMICs) were reviewed using i) 93 media reports and ii) 17 published scientific papers. This review showed that those who suffered the most from the lockdown were migrants, workers in the large informal sector, small businesses, slum dwellers, women and elderly, revealing the social, cultural and economic inequalities of societies. Financial and food support for the poor was inadequate and sometimes mismanaged. In the better organized societies, the resilience was stronger (South Korea, Kerala/India) but here also the poor had to suffer the most. It is strongly recommended that outbreak response strategies should particularly focus on the poor and vulnerable population.

Infodemic and Fake News in Spain during the COVID-19 Pandemic.

Internet, new technologies and social networks have changed the consumption and dissemination of information. The world is witnessing the proliferation of so-called false news, especially since the beginning of 2020, when COVID-19 became the main issue on the global agenda. Alleged government actions, remedies, advice, etc., are the cause of a multitude of messages that are often false. Through surveys (1115 responses were obtained) and a review of the literature, we explore how the proliferation of COVID-19's false news affects and impacts public opinion in Spain. We also examine how citizens are being informed about the pandemic, identify the main channels of communication used and discover the impact of misinformation. The main conclusions are that, in Spain, citizens are interested in information related to the coronavirus, but there is a lack of media credibility and reliability; the social networks and instant messaging are considered the channels that transmit the greatest amount of false news.

Double-blind, randomized, controlled, trial to assess the efficacy of allogenic mesenchymal stromal cells in patients with acute respiratory distress syndrome due to COVID-19 (COVID-AT): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: 1. To assess the efficacy of Mesenchymal Stromal Cells (MSC) versus a control arm as described in the primary endpoint. 2. To evaluate the effects of MSC on the secondary efficacy endpoints. 3. To evaluate the safety and tolerability profiles of MSC. 4. To study soluble and cellular biomarkers that might be involved in the course of the disease and the response to the investigational product. TRIAL DESIGN: A double-blind, randomized, controlled, trial to evaluate the efficacy and safety of MSC intravenous administration in patients with COVID-induced Acute Respiratory Distress Syndrome (ARDS) compared to a control arm. PARTICIPANTS: The trial is being conducted at a third level hospital, Hospital Universitario Puerta de Hierro, in Majadahonda, Madrid (Spain). Inclusion criteria 1. Informed consent prior to performing study procedures (witnessed oral consent with written consent by representatives will be accepted to avoid paper handling). Written consent by patient or representatives will be obtained whenever possible. 2. Adult patients ≥18 years of age at the time of enrolment. 3. Laboratory-confirmed SARS-CoV-2 infection as determined by Polymerase Chain Reaction (PCR), in oropharyngeal swabs or any other relevant specimen obtained during the course of the disease. Alternative tests (e.g., rapid antigen tests) are also acceptable as laboratory confirmation if their specificity has been accepted by the Sponsor. 4. Moderate to severe ARDS (PaO2/FiO2 ratio equal or less than 200 mmHg) for less than 96 hours at the time of randomization. 5. Patients requiring invasive ventilation are eligible within 72 hours from intubation. 6. Eligible for ICU admission, according to the clinical team. Exclusion criteria 1. Imminent and unavoidable progression to death within 24 hours, irrespective of the provision of treatments (in the opinion of the clinical team). 2. "Do Not Attempt Resuscitation" order in place. 3. Any end-stage organ disease or condition, which in the investigator's opinion, makes the patient an unsuitable candidate for treatment. 4. History of a moderate/severe lung disorder requiring home-based oxygen therapy. 5. Patient requiring Extracorporeal Membrane Oxygenation (ECMO), haemodialysis or hemofiltration at the time of treatment administration. 6. Current diagnosis of pulmonary embolism. 7. Active neoplasm, except carcinoma in situ or basalioma. 8. Known allergy to the products involved in the allogeneic MSC production process. 9. Current pregnancy or lactation (women with childbearing potential should have a negative pregnancy test result at the time of study enrolment). 10. Current participation in a clinical trial with an experimental treatment for COVID-19 (the use of any off-label medicine according to local treatment protocols is not an exclusion criteria). 11. Any circumstances that in the investigator's opinion compromises the patient's ability to participate in the clinical trial. INTERVENTION AND COMPARATOR: - Experimental treatment arm: Allogeneic MSC (approximately 1 x 106 cells/kg). - Control arm: placebo solution (same composition as the experimental treatment, without the MSC). One single intravenous dose of the assigned treatment will be administered on Day 0 of the study. All trial participants will receive standard of care (SOC). In the context of the current worldwide pandemic, SOC can include medicines that are being used in clinical practice (e.g. lopinavir/ritonavir; hydroxy/chloroquine, tocilizumab, etc.), as well as those authorised for COVID (e.g., remdesivir). MAIN OUTCOMES: Primary endpoint: Change in the PaO2/FiO2 ratio from baseline to day 7 of treatment administration, or to the last available PaO2/FiO2 ratio if death occurs before day 7. Secondary endpoints: - All-cause mortality on days 7, 14, and 28 after treatment. - PaO2/FiO2 ratio at baseline and days 2, 4, 7, 14 and 28 after treatment. - Oxygen saturation (by standardized measurement) at baseline, daily until day 14, and on day 28 after treatment. - Time to PaO2/FiO2 ratio greater than 200 mmHg. - Subjects' clinical status on the WHO 7-point ordinal scale at baseline, daily until day 14, and on day 28 after treatment. - Time to an improvement of one category from admission on the WHO 7-point ordinal scale. - Percentage of patients that worsen at least one category on the WHO 7-point ordinal scale. - Percentage of patients that improve at least one category (maintained 48h) on the WHO 7-point ordinal scale. - Sequential Organ Failure Assessment (SOFA) scale at baseline and days 2, 4, 7, 14 and 28 after treatment. - Duration of hospitalization (days). - Duration of ICU stay (days). - Oxygen therapy-free days in the first 28 days after treatment. - Duration of supplemental oxygen. - Incidence of and duration of non-invasive and invasive mechanical ventilation in the first 28 days after treatment. - Mechanical ventilation-free days in the first 28 days after treatment. - Ventilation parameters. - Incidence of new onset pulmonary fibrosis at 3 and 12 months after treatment, based on CT scan and pulmonary function tests. - Survival at 3 and 12 months. - Cumulative incidence of Serious Adverse events (SAEs) and Grade 3 and 4 Adverse Events (AEs). - Cumulative incidence of Adverse Drug Reactions (ADR) in the experimental treatment arm. - Cumulative incidence of AEs of special interest. - Levels of analytical markers (C-Reactive Protein, lymphocyte and neutrophil counts, lymphocyte subpopulations, LDH, ferritin, D-dimer, coagulation tests and cytokines...) at baseline and days 2, 4, 7, 14 and 28 after treatment. - Other soluble and cellular biomarkers that might be involved in the course of the disease and the response to MSC. RANDOMISATION: The assignment to treatment will be carried out randomly and blinded, with a 1:1 allocation. Randomization will be done through a centralized system embedded in the electronic Case Report Form (CRF). BLINDING (MASKING): To ensure blinding, treatments will be prepared for administration at the Cell Production Unit and the administration of the treatment will be masked, not allowing the identification of the Investigational Medicinal Product (IMP). NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 participants are planned to be randomized, 10 to each treatment group. TRIAL STATUS: Protocol version: 1.2, dated October 14th, 2020 Start of recruitment: 01/10/2020 End of recruitment (estimated): December 2020. TRIAL REGISTRATION: EudraCT Number: 2020-002193-27 , registered on July 14th, 2020. NCT number: NCT04615429 , registered on November 4th, 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Psychological Impact of COVID-19 on ICU Caregivers.

SUBJECT AND PURPOSE: Just as every pandemic, COVID-19 could lead to emotional and psychological disturbances among caregivers, especially in the Intensive Care Unit (ICU), where significant stress related to the influx of patients, exposure to the virus and the lack of documentation on this new SARS occurred. The present study aimed at assessing the psychological impact of COVID-19 on the caregivers at the peak of the "crisis period". MATERIALS AND METHODS: A survey using the Hospital Anxiety and Depression Scale (HADS) and Impact of Event Scale - Revised (IES-R) was proposed to the persons working in 5 ICUs of a French teaching hospital (8th of April to the 21st of April 2020). Logistic regression was performed to find independent risk factors for anxiety and post-traumatic stress disorder (PTSD). A value of p < 0.05 was considered significant. RESULTS: The incidence of anxiety and depression were 48% and 16%, respectively. PTSD symptoms were present in 27% of respondents. The independent risk factors for developing anxiety syndrome were being assigned in COVID-19 + ICU (OR = 2.081 [95% confident interval (CI), 1.035-4.184)], and not be trained in intensive care medicine, OR = 2.570 [95% CI, 1.344-4.901]. The independent risk factors for PTSD are having a history of burn-out (OR = 4.591 [95% CI, 1.464-14.397] and not being trained in ICU, (OR = 2.155 [95% CI, 1.047-4.440]). CONCLUSION: COVID-19 could have a strong impact on ICU workers. These findings should lead to prevention procedures (ICU training sessions) in persons at risk.