DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function.

BACKGROUND: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm. METHODS: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety. FINDINGS: Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals. INTERPRETATION: DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04382053.

An approach for prevention planning based on the prevalence and comorbidity of neurodevelopmental disorders in 6-year-old children receiving primary care consultations on the island of Menorca.

BACKGROUND: Few studies have estimated the real prevalence of neurodevelopmental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) in Spain and worldwide. However, there are disparate prevalence figures. We consider research in this field essential to improve early detection, secondary prevention, and health planning. METHODS: The Minikid ADHD and TICS-Mini International Neuropsychiatric Interview for Children and Adolescents, the Autism Spectrum Quotient (Children's version, AQ- Child) and a protocol of general medical questions were administered for screening purposes. The PROLEXIA battery for children aged from 4 to 6 years was used for direct assessments. Parents provided information on emotional, medical, and school aspects. The final population evaluated using these tools consisted of 291 6-year-old subjects. RESULTS: The overall risk of presenting with a neurodevelopmental disorder was 55.4%. A 23.4% risk of presenting with attention-deficit/hyperactivity disorder (ADHD) in any modality (inattentive, hyperactive-impulsive and combined), a 2.8% risk of developing autism spectrum disorder (ASD), a 30.6% risk of presenting with a learning disorder with reading difficulties, a 5.5% risk of tics and a 22.5% risk of language problems (incomprehensible language or minor language problems) were detected in the sample. The most common combination of disorders was learning and language difficulties, accounting for 6.9% of the sample. The second most frequent combination was the presence of learning and language difficulties and ADHD, accounting for 4.5% of the sample. CONCLUSIONS: The prevalence of risks detected in our sample seems to be consistent with national and international studies. A significant proportion of our sample had never been previously diagnosed (85%), so early detection programs are recommended.

Lung ultrasound score severity cut-off points in COVID-19 pneumonia. A systematic review and validating cohort.

OBJECTIVES: Our purpose was to establish different cut-off points based on the lung ultrasound score (LUS) to classify COVID-19 pneumonia severity. METHODS: Initially, we conducted a systematic review among previously proposed LUS cut-off points. Then, these results were validated by a single-centre prospective cohort study of adult patients with confirmed SARS-CoV-2 infection. Studied variables were poor outcome (ventilation support, intensive care unit admission or 28-days mortality) and 28-days mortality. RESULTS: From 510 articles, 11 articles were included. Among the cut-off points proposed in the articles included, only the LUS>15 cut-off point could be validated for its original endpoint, demonstrating also the strongest relation with poor outcome (odds ratio [OR]=3.636, confidence interval [CI] 1.411-9.374). Regarding our cohort, 127 patients were admitted. In these patients, LUS was statistically associated with poor outcome (OR=1.303, CI 1.137-1.493), and with 28-days mortality (OR=1.024, CI 1.006-1.042). LUS>15 showed the best diagnostic performance when choosing a single cut-off point in our cohort (area under the curve 0.650). LUS≤7 showed high sensitivity to rule out poor outcome (0.89, CI 0.695-0.955), while LUS>20 revealed high specificity to predict poor outcome (0.86, CI 0.776-0.917). CONCLUSIONS: LUS is a good predictor of poor outcome and 28-days mortality in COVID-19. LUS≤7 cut-off point is associated with mild pneumonia, LUS 8-20 with moderate pneumonia and ≥20 with severe pneumonia. If a single cut-off point were used, LUS>15 would be the point which better discriminates mild from severe disease.

Lack of SARS-CoV-2 RNA evidence in the lungs from wild European polecats (Mustela putorius) from Spain.

Data on SARS-CoV-2 infection in wildlife species is limited. The high prevalences found in mustelid species such as free-ranging American minks (Neovison vison) and domestic ferrets (Mustela putorius furo) justify the study of this virus in the closely related autochthonous free-ranging European polecat (Mustela putorius). We analysed lung samples from 48 roadkilled polecats collected when the human infection reached its highest levels in Spain (2020-2021). We did not detect infections by SARS-CoV-2; however, surveillance in wild carnivores and particularly in mustelids is still warranted, due to their susceptibility to this virus.

Managing university e-learning environments and academic achievement in the United Arab Emirates: An instructor and student perspective.

The present research evaluates how E-learning environment, E-learning adoption, Digital readiness, and Students attitudes towards E-learning, affect Academic achievement. The study focuses on a much-neglected cultural context, Gulf Cooperation Council countries (GCC), since Student's readiness as well as institutions and professors' endowments greatly varied within countries and among universities. The study further incorporates Instructors attitudes and evaluates the mediation effect of Academic engagement on Academic achievement. The methodology relies on Partial Least Squares structural equation modelling (PLS-SEM). The research findings emphasize the role of E-learning environment, Digital readiness, Academic engagement, students as well as instructors E-learning attitude as the decisive factors that determine students' Academic achievement. This implies that institutions who adapt to a changing environment by aligning students and instructors' goals to develop a positive and supportive E-learning environment, will foment Academic engagement and promote students' Academic achievement.

A study of viral pathogens in bat species in the Iberian Peninsula: identification of new coronavirus genetic variants.

Bats have long been associated with multiple pathogens, including viruses affecting humans such as henipaviruses, filoviruses, bunyaviruses and coronaviruses. The alpha and beta coronaviruses genera can infect most mammalian species. Among them, betacoronavirus SARS-CoV, MERS-CoV and SARS-CoV-2, which have caused the three major pandemics in the last two decades, have been proposed to originate in bats. In this study, 194 oral swabs from 22 bats species sampled in 19 locations of the Iberian Peninsula were analysed and characterized by three different PCR tests (coronavirus generic real-time RT-PCR, multiplex conventional PCR, and SARS-CoV-2 specific real-time RT-PCR) to detect bat coronaviruses. Screening with coronavirus generic PCR showed 102 positives out of 194 oral swabs analysed. Then, metabarcoding with multiplex PCR amplified 15 positive samples. Most of the coronaviruses detected in this study belong to alphacoronavirus (α-CoV) genus, with multiple alphacoronaviruses identified by up to five different genetic variants coexisting in the same bat. One of the positive samples identified in a Miniopterus schreibersii bat positive for the generic coronavirus PCR and the specific SARS-CoV-2 PCR was classified as betacoronavirus (-CoV) through phylogenetic analysis. These results support the rapid evolution of coronaviruses to generate new genomic potentially pathogenic variants likely through co-infection and recombination.

Bagaza virus and Plasmodium spp. coinfection in red-legged partridges (Alectoris rufa), in Southern Spain 2019.

Flaviviruses such as West Nile (WNV), Usutu (USUV) and Bagaza (BAGV) virus and avian malaria parasites are vector borne pathogens that circulate naturally between avian and mosquito hosts. WNV and USUV and potentially also BAGV constitute zoonoses. Temporal and spatial cocirculation and coinfection with Plasmodium spp., and West Nile virus has been documented in birds and mosquito vectors, and fatally USUV-infected passerines coinfected with Plasmodium spp. had more severe lesions. Also, WNV, USUV and BAGV have been found to cocirculate. Yet little is known about the interaction of BAGV and malaria parasites during consecutive or coinfections of avian hosts. Here we report mortality of free-living red-legged partridges in a hunting estate in Southern Spain that were coinfected with BAGV and Plasmodium spp. The outbreak occurred in the area where BAGV first emerged in Europe in 2010 and where cocirculation of BAGV, USUV and WNV was confirmed in 2011 and 2013. Partridges were found dead in early October 2019. Birds had mottled locally pale pectoral muscles, enlarged, congestive greenish-black tinged livers and enlarged kidneys. Microscopically congestion and predominantly mononuclear inflammatory infiltrates were evident and Plasmodium phanerozoites were present in the liver, spleen, kidneys, muscle and skin. Molecular testing and sequencing detected Plasmodium spp. and BAGV in different tissues of the partridges, and immunohistochemistry confirmed the presence and colocalization of both pathogens in the liver and spleen. Due to the importance of the red-legged partridge in the ecosystem of the Iberian Peninsula and as driver of regional economy such mortalities are of concern. Such outbreaks may reflect climate change related shifts in host, vector and pathogen ecology and interactions that could emerge similarly for other pathogens.

HEPA filters of portable air cleaners as a tool for the surveillance of SARS-CoV-2.

Studies about the identification of SARS-CoV-2 in indoor aerosols have been conducted in hospital patient rooms and to a lesser extent in nonhealthcare environments. In these studies, people were already infected with SARS-CoV-2. However, in the present study, we investigated the presence of SARS-CoV-2 in HEPA filters housed in portable air cleaners (PACs) located in places with apparently healthy people to prevent possible outbreaks. A method for detecting the presence of SARS-CoV-2 RNA in HEPA filters was developed and validated. The study was conducted for 13 weeks in three indoor environments: school, nursery, and a household of a social health center, all in Ciudad Real, Spain. The environmental monitoring of the presence of SARS-CoV-2 was conducted in HEPA filters and other surfaces of these indoor spaces for a selective screening in asymptomatic population groups. The objective was to limit outbreaks at an early stage. One HEPA filter tested positive in the social health center. After analysis by RT-PCR of SARS-CoV-2 in residents and healthcare workers, one worker tested positive. Therefore, this study provides direct evidence of virus-containing aerosols trapped in HEPA filters and the possibility of using these PACs for environmental monitoring of SARS-CoV-2 while they remove airborne aerosols and trap the virus.

A machine learning COVID-19 mass screening based on symptoms and a simple olfactory test.

The early detection of symptoms and rapid testing are the basis of an efficient screening strategy to control COVID-19 transmission. The olfactory dysfunction is one of the most prevalent symptom and in many cases is the first symptom. This study aims to develop a machine learning COVID-19 predictive tool based on symptoms and a simple olfactory test, which consists of identifying the smell of an aromatized hydroalcoholic gel. A multi-centre population-based prospective study was carried out in the city of Reus (Catalonia, Spain). The study included consecutive patients undergoing a reverse transcriptase polymerase chain reaction test for presenting symptoms suggestive of COVID-19 or for being close contacts of a confirmed COVID-19 case. A total of 519 patients were included, 386 (74.4%) had at least one symptom and 133 (25.6%) were asymptomatic. A classification tree model including sex, age, relevant symptoms and the olfactory test results obtained a sensitivity of 0.97 (95% CI 0.91-0.99), a specificity of 0.39 (95% CI 0.34-0.44) and an AUC of 0.87 (95% CI 0.83-0.92). This shows that this machine learning predictive model is a promising mass screening for COVID-19.

Pembrolizumab in combination with tocilizumab in high-risk hospitalized patients with COVID-19 (COPERNICO): A randomized proof-of-concept phase II study.

OBJECTIVES: Severe COVID-19 is associated with immune dysregulation and hyperinflammation (lymphocyte exhaustion and elevated interleukin 6. Pembrolizumab (P; immune-activating anti-programmed cell death-1 antibody) plus tocilizumab (TCZ; anti- interleukin 6 receptor antibody) might interrupt the hyperinflammation and restore cellular immunocompetence. We assessed the efficacy and safety of P + TCZ + standard of care (SOC) in high-risk, hospitalized patients with COVID-19 pneumonia without mechanical ventilation. METHODS: Randomized, controlled, open-label, phase II trial in patients with severe SARS-CoV-2 infection to assess the hospitalization period to discharge. RESULTS: A total of 12 patients were randomized (P + TCZ + SOC, n = 7; SOC, n = 5). Nine (75%) were males, with a median age of 68 (41-79) years. The median time to discharge for P + TCZ + SOC and SOC was 10 and 47.5 days (P = 0.03), with zero (n = 1 patient had P-related grade 5 myositis) and two COVID-19-related deaths, respectively. CONCLUSION: The addition of P and TCZ to SOC reduced the hospitalization period, with higher and faster discharges without sequelae than SOC alone.

Hematological- and Immunological-Related Biomarkers to Characterize Patients with COVID-19 from Other Viral Respiratory Diseases.

COVID-19 has overloaded health system worldwide; thus, it demanded a triage method for an efficient and early discrimination of patients with COVID-19. The objective of this research was to perform a model based on commonly requested hematological variables for an early featuring of patients with COVID-19 form other viral pneumonia. This investigation enrolled 951 patients (mean of age 68 and 56% of male) who underwent a PCR test for respiratory viruses between January 2019 and January 2020, and those who underwent a PCR test for detection of SARS-CoV-2 between February 2020 and October 2020. A comparative analysis of the population according to PCR tests and logistic regression model was performed. A total of 10 variables were found for the characterization of COVID-19: age, sex, anemia, immunosuppression, C-reactive protein, chronic obstructive pulmonary disease, cardiorespiratory disease, metastasis, leukocytes and monocytes. The ROC curve revealed a sensitivity and specificity of 75%. A deep analysis showed low levels of leukocytes in COVID-19-positive patients, which could be used as a primary outcome of COVID-19 detection. In conclusion, this investigation found that commonly requested laboratory variables are able to help physicians to distinguish COVID-19 and perform a quick stratification of patients into different prognostic categories.

A Prospective Study Evaluating Cumulative Incidence and a Specific Prediction Rule in Pulmonary Embolism in COVID-19.

Rationale: Abnormal values of hypercoagulability biomarkers, such as D-dimer, have been described in Coronavirus Disease 2019 (COVID-19), which has also been associated with disease severity and in-hospital mortality. COVID-19 patients with pneumonia are at greater risk of pulmonary embolism (PE). However, the real incidence of PE is not yet clear, since studies have been limited in size, mostly retrospective, and PE diagnostic procedures were only performed when PE was clinically suspected. Objectives: (1) To determine the incidence, clinical, radiological, and biological characteristics, and clinical outcomes of PE among patients hospitalized for COVID-19 pneumonia with D-dimer > 1,000 ng/mL. (2) To develop a prognostic model to predict PE in these patients. Methods: Single-center prospective cohort study. Consecutive confirmed cases of COVID-19 pneumonia with D-dimer > 1,000 ng/mL underwent computed tomography pulmonary angiography (CTPA). Demographic and laboratory data, comorbidities, CTPA scores, treatments administered, and clinical outcomes were analyzed and compared between patients with and without PE. A risk score was constructed from all these variables. Results: Between 6 April 2020 and 2 February 2021, 179 consecutive patients were included. The overall incidence of PE was 39.7% (71 patients) (CI 95%, 32-47%). In patients with PE, emboli were located mainly in segmental/subsegmental arteries (67%). Patients with PE did not differ from the non-PE group in sex, age, or risk factors for thromboembolic disease. Higher urea, D-Dimer, D-dimer-to-ferritin and D-dimer-to-lactate dehydrogenase (LDH) ratios, platelet distribution width (PDW), and neutrophil-to-lymphocyte ratio (NLR) values were found in patients with PE when compared to patients with non-PE. Besides, lymphocyte counts turned out to be lower in patients with PE. A score for PE prediction was constructed with excellent overall performance [area under the ROC curve-receiver operating characteristic (AUC-ROC) 0.81 (95% CI: 0.73-0.89)]. The PATCOM score stands for Pulmonary Artery Thrombosis in COVID-19 Mallorca and includes platelet count, PDW, urea concentration, and D-dimer-to-ferritin ratio. Conclusion: COVID-19 patients with pneumonia and D-dimer values > 1,000 ng/mL were presented with a very high incidence of PE, regardless of clinical suspicion. Significant differences in urea, D-dimer, PDW, NLR, and lymphocyte count were found between patients with PE and non-PE. The PATCOM score is presented in this study as a promising PE prediction rule, although validation in further studies is required.

Intraoperative pulmonary embolism in shoulder arthroscopy in a patient with previous SARS-CoV-2 infection: a case report.

The objective of this article is to describe intraoperative pulmonary embolism during shoulder arthroscopy in a patient with previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Further, we describe how the pandemic has influenced the population by increasing the rate of embolisms. Awareness of such cases will help to increase knowledge regarding SARS-Cov-2 and to determine if such patients should receive routine antithrombotic prophylaxis.

Exploring the role of human resource development functions on crisis management: The case of Dubai-UAE during Covid-19 crisis.

Employee welfare represents a critical element of success for companies to remain competitive. Human resources increasingly encompass the management of critical situations that affect the employees' wellbeing. This research analyzes the effect of Human Resource Development (HRD), functions on the effectiveness of crisis management. It is an attempt to include HRD in the theory of Crisis management. Using Structural Equation Models-Partial Least Squares (SEM-PLS) analysis, the study analyzes how training, leadership, organizational strategy, and organizational culture directly positively impact the efficiency of Crisis management (CM) during the Covid-19 crisis in the public entities of Dubai-UAE. In particular, training showed to be the best predictor, followed by the Organizational culture. Organizational structure, Values and uniqueness show no impact on CM within the context of public entities of Dubai-UAE.

Ultrasound findings of lung ultrasonography in COVID-19: A systematic review.

PURPOSE: To identify the defining lung ultrasound (LUS) findings of COVID-19, and establish its association to the initial severity of the disease and prognostic outcomes. METHOD: Systematic review was conducted according to the PRISMA guidelines. We queried PubMed, Embase, Web of Science, Cochrane Database and Scopus using the terms ((coronavirus) OR (covid-19) OR (sars AND cov AND 2) OR (2019-nCoV)) AND (("lung ultrasound") OR (LUS)), from 31st of December 2019 to 31st of January 2021. PCR-confirmed cases of SARS-CoV-2 infection, obtained from original studies with at least 10 participants 18 years old or older, were included. Risk of bias and applicability was evaluated with QUADAS-2. RESULTS: We found 1333 articles, from which 66 articles were included, with a pooled population of 4687 patients. The most examined findings were at least 3 B-lines, confluent B-lines, subpleural consolidation, pleural effusion and bilateral or unilateral distribution. B-lines, its confluent presentation and pleural abnormalities are the most frequent findings. LUS score was higher in intensive care unit (ICU) patients and emergency department (ED), and it was associated with a higher risk of developing unfavorable outcomes (death, ICU admission or need for mechanical ventilation). LUS findings and/or the LUS score had a good negative predictive value in the diagnosis of COVID-19 compared to RT-PCR. CONCLUSIONS: The most frequent ultrasound findings of COVID-19 are B-lines and pleural abnormalities. High LUS score is associated with developing unfavorable outcomes. The inclusion of pleural effusion in the LUS score and the standardisation of the imaging protocol in COVID-19 LUS remains to be defined.

Psychological Impact and Risk of Suicide in Hospitalized COVID-19 Patients, During the Initial Stage of the Pandemic: A Cross-Sectional Study.

OBJECTIVES: This study aimed to assess the psychological impact and risk of suicide in patients hospitalized for COVID-19. METHODS: A cross-sectional study was conducted on a representative sample of patients hospitalized for COVID-19 at the "San Cecilio" University Hospital (Granada, Spain) between March and May 2020. Sociodemographic and clinical variables were collected. All participants were evaluated using the Gijon's Social-Familial Evaluation Scale to assess social problems, the Impact of Event Scale-6 and the Hospital Anxiety-Depression Scale to assess psychological impact, the Columbia Suicide Severity and Beck Hopelessness scales to assess risk of suicide, and the List of Threatening Experiences questionnaire to control for confounding bias. RESULTS: Thirty-six COVID-19 patients were evaluated. Of them, 33.3% had a significant psychological impact; 13.9% showed symptoms of anxiety, 13.9% showed symptoms of depression, and 47.2% showed symptoms of anxiety-depression. Moderate and severe risk of suicide were found in 75% and 2.8% of the patients, respectively. Suicidal ideation was observed in 16.7% and suicide behaviors in 5.6% of the patients. Psychological impact was associated with previous psychological treatment, a greater degree of functional dependency, and increased social-familial risk. In addition, the risk of suicide was mainly associated with active treatment of a psychiatric illness and active smoking. No significant correlation was found between psychological impact and risk of suicide. CONCLUSIONS: Psychological impact and risk of suicide were significant in patients admitted for COVID-19. Although the risk of suicide was not associated with increased psychological impact, both should be assessed, especially in patients at higher risk based on significantly associated factors.

Lung Ultrasound, Clinical and Analytic Scoring Systems as Prognostic Tools in SARS-CoV-2 Pneumonia: A Validating Cohort.

At the moment, several COVID-19 scoring systems have been developed. It is necessary to determine which one better predicts a poor outcome of the disease. We conducted a single-center prospective cohort study to validate four COVID-19 prognosis scores in adult patients with confirmed infection at ward. These are National Early Warning Score (NEWS) 2, Lung Ultrasound Score (LUS), COVID-19 Worsening Score (COWS), and Spanish Society of Infectious Diseases and Clinical Microbiology score (SEIMC Score). Our outcomes were the combined variable "poor outcome" (non-invasive mechanical ventilation, intubation, intensive care unit admission, and death at 28 days) and death at 28 days. Scores were analysed using univariate logistic regression models, receiver operating characteristic curves, and areas under the curve. Eighty-one patients were included, from which 21 had a poor outcome, and 9 died. We found a statistically significant correlation between poor outcome and NEWS2, LUS > 15, and COWS. Death at 28 days was statistically correlated with NEWS2 and SEIMC Score although COWS also performs well. NEWS2, LUS, and COWS accurately predict poor outcome; and NEWS2, SEIMC Score, and COWS are useful for anticipating death at 28 days. Lung ultrasound is a diagnostic tool that should be included in COVID-19 patients evaluation.