Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19

SUMMARY We demonstrate that integrative analysis of CRISPR screening datasets enables network-based prioritization of prescription drugs modulating viral entry in SARS-CoV-2, by developing a network-based approach called Rapid proXimity Guidance for Repurposing Investigational Drugs (RxGRID). We use our results to guide a propensity-score-matched, retrospective cohort study of 64,349 COVID-19 patients, showing that a top candidate drug, spironolactone, is associated with improved clinical prognosis, measured by ICU admission and mechanical ventilation rates. Finally, we show that spironolactone exerts a dose-dependent inhibitory effect on viral entry in human lung epithelial cells. Our RxGRID method presents a computational framework, implemented as an open-source software package, enabling genomics researchers to identify drugs likely to modulate a molecular phenotype of interest based on high-throughput screening data. Our results, derived from this method and supported by experimental and clinical analysis, add additional supporting evidence for a potential protective role of the potassium-sparing diuretic spironolactone in severe COVID-19.

Covid-19 vaccination uptake by Hapu Mama - How are we progressing?

The Covid-19 vaccine has been recommended for pregnant people (hapu mama) in Aotearoa New Zealand since June 2021. We surveyed people birthing in a tertiary hospital regarding their vaccination status and reasons for this. There were 74% (142/191) of pregnant people who were fully vaccinated. Motivators for vaccination included protection against Covid-19 and antibody transfer to the baby (pepe). Unvaccinated participants worried about vaccine safety. Concerns were raised about the change in official advice without well-communicated reasons for the change. Future vaccine and booster rollouts must be delivered equitably and hapu mama must be a priority group.Copyright © 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists. © 2022 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Correction to: COVID-19: self-reported reductions in physical activity and increases in sedentary behaviour during the first national lockdown in the United Kingdom.

[This corrects the article DOI: 10.1007/s11332-022-01012-0.].

Future lines of research on phase angle: Strengths and limitations.

Bioelectrical impedance analysis (BIA) is the most widely used technique in body composition analysis. When we focus the use of phase sensitive BIA on its raw parameters Resistance (R), Reactance (Xc) and Phase Angle (PhA), we eliminate the bias of using predictive equations based on reference models. In particular PhA, have demonstrated their prognostic utility in multiple aspects of health and disease. In recent years, as a strong association between prognostic and diagnostic factors has been observed, scientific interest in the utility of PhA has increased. In the different fields of knowledge in biomedical research, there are different ways of assessing the impact of a scientific-technical aspect such as PhA. Single frequency with phase detection bioimpedance analysis (SF-BIA) using a 50 kHz single frequency device and tetrapolar wrist-ankle electrode placement is the most widely used bioimpedance approach for characterization of whole-body composition. However, the incorporation of vector representation of raw bioelectrical parameters and direct mathematical calculations without the need for regression equations for the analysis of body compartments has been one of the most important aspects for the development of research in this area. These results provide new evidence for the validity of phase-sensitive bioelectrical measurements as biomarkers of fluid and nutritional status. To enable the development of clinical research that provides consistent results, it is essential to establish appropriate standardization of PhA measurement techniques. Standardization of test protocols will facilitate the diagnosis and assessment of the risk associated with reduced PhA and the evaluation of changes in response to therapeutic interventions. In this paper, we describe and overview the value of PhA in biomedical research, technical and instrumental aspects of PhA research, analysis of Areas of clinical research (cancer patients, digestive and liver diseases, critical and surgical patients, Respiratory, infectious, and COVID-19, obesity and metabolic diseases, Heart and kidney failure, Malnutrition and sarcopenia), characterisation of the different research outcomes, Morphofunctional assessment in disease-related malnutrition and other metabolic disorders: validation of PhA with reference clinical practice techniques, strengths and limitations. Based on the detailed study of the measurement technique, some of the key issues to be considered in future PhA research. On the other hand, it is important to assess the clinical conditions and the phenotype of the patients, as well as to establish a disease-specific clinical profile. The appropriate selection of the most critical outcomes is another fundamental aspect of research.

Online onboarding program to strengthen the commitment and retention of employees of a private company in the city of Chimbote

The present research determines the effect of telepsychology on the affective-emotional states represented by depression, anxiety and stress, in the Covid-19 pandemic, in students of a private university Áncash, 2021. The research was quasi-experimental with a quantitative approach and an explanatory scope, the instrument used was the DASS-21 applied to 108 undergraduate students. In this sense, the program was designed to be implemented synchronously online through the Zoom application and the use of other digital tools such as mentimeter, kahoot, wordwall, among others. In conclusion, a decrease in the score from 6 to 3.27 is shown which, for a value T = -46.746 and p = 0.000 less than 5% which shows that this difference is highly significant, therefore, it is concluded that the application of telepsychology has a highly significant effect on the decrease in levels of depression, anxiety and stress of the students who were the subject of this study. © 2022 Latin American and Caribbean Consortium of Engineering Institutions. All rights reserved.

Lessons for screen production pedagogy from pandemic-era experiences of teaching online

Screen production educators throughout Australasia pivoted to online and remote teaching as the Covid-19 pandemic restricted face-to-face teaching. Teachers' experiences in 2020–2021 are instructive for the lessons we can learn about effective online teaching for this typically hands-on and collaborative field. This article presents an analysis of semi-structured interviews conducted with nine screen production educators working across nine universities and film schools in Australia and New Zealand. The insights gathered through these interviews point to the challenges specific to teaching screen production online, particularly related to students acquiring skills in operating professional equipment and collaborating as a crew with their peers. Interviewees found some surprising value and possibilities during their adaptation to this mode under pandemic conditions but generally experienced it as unsuitable for the discipline and for students' successful acquisition of the suite of core skills. The swiftly adapted teaching practices undertaken in this period have helped to elucidate the possibilities and significant limitations of online teaching, as well as the needs and satisfaction levels of both staff and students when teaching and learning in this mode. © 2023 Informa UK Limited, trading as Taylor & Francis Group.

Mechanism of a rabbit monoclonal antibody broadly neutralizing SARS-CoV-2 variants.

Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.

"An increase in COVID-19 patients would be overwhelming": A qualitative description of healthcare workers' experiences during the first wave of COVID-19 (March 2020 to October 2020) at Malawi's largest referral hospital.

Background  COVID-19 is currently a global health threat. Healthcare workers are on the front-line of the COVID-19 outbreak response and therefore at heightened risk of infection. There is a dearth of evidence from Sub-Saharan Africa about healthcare worker experiences in managing COVID-19.  We have reported on healthcare worker responses, experiences, and perspectives on epidemic response strategies at Queen Elizabeth Central Hospital, Malawi's largest referral hospital.   Methods  We conducted 39 face-to-face in-depth interviews with a purposively selected sample of healthcare workers during the first wave of COVID-19 in Malawi (March 2020 to October 2020). The study included healthcare workers who provided direct and indirect patient care.   Results  During the early phase of the first wave (March to May 2020), healthcare workers expressed concerns with inadequate working space, unconducive infrastructure, delayed and rushed training on the management of COVID-19, and lack of incentives. Additionally, the hospital had staff shortages and limited essential resources such as piped oxygen and personal protective equipment. This increased healthcare worker fears of contracting COVID-19 and they were less willing to volunteer at COVID-19 isolation units. Resource constraints and limited preparedness compromised the care pathway particularly with increased numbers of COVID-19 patients. By the peak of the first wave (June to August 2020) many of these issues had been resolved. The hospital provided refresher training courses, personal protective equipment became available, incentives were offered to healthcare workers working in COVID-19 units and piped oxygen was installed. Staff morale was boosted, and more staff were willing to work at the COVID-19 isolation centres.   Conclusion  Experiences of healthcare workers during the first wave of COVID-19 are critical for improving care in future COVID-19 waves. Response strategies in resource-constrained areas should prioritise timely training of staff, creation of adequate isolation areas, provision of adequate medical supplies and strengthening leadership.

Coronavirus Disease 2019 and the Yale Response: A Semistructured Interview Study on Plastic Surgery Resident Education and Departmental Adaptation to the Lockdown.

BACKGROUND: Sooner-than-expected progression to statewide lockdown at the height of the coronavirus disease 2019 pandemic left minimal time for medical specialty boards, including The American Board of Plastic Surgery, to issue guidance for their respective programs. As a result, programs were tasked with developing creative alternatives to their standard resident curricula and department schedules. OBJECTIVE: To capture attending and resident experience of the coronavirus disease 2019 lockdown in narrative form and to understand what specific changes enacted to maintain adequate education should be considered for continuation after the pandemic's conclusion. METHODS: Qualitative, semistructured interviews of residents, fellows, and faculty of the Section of Plastic and Reconstructive Surgery during 2019 to 2020 academic year were conducted on the following topics: (1) general reflection on lockdown, (2) resident maintenance of daily logs, (3) multi-institutional collaborative lectures, (4) modified didactic curriculum, (5) virtual 3-dimensional craniofacial planning sessions, (6) maintenance of department camaraderie, and (7) effect on preparation to become a surgeon. RESULTS: Twenty interviews (response rate 77%) were conducted between October 2020 and February 2021. Of residents, 100% felt observing the craniofacial planning sessions was beneficial, with many explicitly noting it provided a unique perspective into the surgeon's thought process behind planned manipulations, to which they usually are not privy. Of residents, 100% felt confident at the time of the interview that the lockdown would have no lasting effects on their preparation to become a surgeon. CONCLUSIONS: Rapid changes enacted at Yale enabled resident training to advance, and documentation of the success of these changes can inform future curriculum design.

The Value of a Negative Pleural Fluid Cytology and Biopsy in Diagnosing Malignant Pulmonary Lesions.

Over 2 million patients developed lung cancer in 2018, and lung malignancy is responsible for an estimated 1.8 million deaths worldwide. Lung cancer diagnosis usually occurs after suspicious symptoms or incidental radiologic findings on chest imaging when the cancer is probably in an advanced stage. Therefore, initial evaluation, diagnosis, staging, and prompt treatment of lung cancer are required to improve pulmonary malignancies' morbidity and mortality rate. Unfortunately, the size of the tumor, the time of imaging, the quality and quantity of pleural fluid, and pleural biopsy all contribute to diagnostic difficulties in evaluating a lung lesion, leaving even the most astute clinician occasionally perplexed. We discuss a case of a female with lung cancer whose diagnosis was challenging because of a negative pleural biopsy, despite initial radiographic imaging suggesting a lung lesion.

Longitudinal Chest X-ray Scores and their Relations with Clinical Variables and Outcomes in COVID-19 Patients.

Background: This study evaluated the temporal characteristics of lung chest X-ray (CXR) scores in COVID-19 patients during hospitalization and how they relate to other clinical variables and outcomes (alive or dead). Methods: This is a retrospective study of COVID-19 patients. CXR scores of disease severity were analyzed for: (i) survivors (N = 224) versus non-survivors (N = 28) in the general floor group, and (ii) survivors (N = 92) versus non-survivors (N = 56) in the invasive mechanical ventilation (IMV) group. Unpaired t-tests were used to compare survivors and non-survivors and between time points. Comparison across multiple time points used repeated measures ANOVA and corrected for multiple comparisons. Results: For general-floor patients, non-survivor CXR scores were significantly worse at admission compared to those of survivors (p < 0.05), and non-survivor CXR scores deteriorated at outcome (p < 0.05) whereas survivor CXR scores did not (p > 0.05). For IMV patients, survivor and non-survivor CXR scores were similar at intubation (p > 0.05), and both improved at outcome (p < 0.05), with survivor scores showing greater improvement (p < 0.05). Hospitalization and IMV duration were not different between groups (p > 0.05). CXR scores were significantly correlated with lactate dehydrogenase, respiratory rate, D-dimer, C-reactive protein, procalcitonin, ferritin, SpO2, and lymphocyte count (p < 0.05). Conclusions: Longitudinal CXR scores have the potential to provide prognosis, guide treatment, and monitor disease progression.

COVID-19: self-reported reductions in physical activity and increases in sedentary behaviour during the first national lockdown in the United Kingdom.

Purpose: The United Kingdom (UK) government imposed its first national lockdown in response to COVID-19 on the 23rd of March 2020. Physical activity and sedentary behaviour levels are likely to have changed during this period. Methods: An online survey was completed by n = 266 adults living within the UK. Differences in day-to-day and recreational physical activity (at moderate and vigorous intensities), travel via foot/cycle, and sedentary behaviour were compared before and during the initial COVID-19 lockdown. Results: The median level of total weekly physical activity significantly reduced (- 15%, p < 0.001) and daily sedentary time significantly increased (+ 33%, p < 0.001). The former was caused by a significant reduction in weekly day-to-day physical activity at moderate intensities (p < 0.001), recreational activities at vigorous (p = 0.016) and moderate (p = 0.030) intensities, and travel by foot/cycle (p = 0.031). Sub-group analyses revealed that some populations became disproportionally more physically inactive and/or sedentary than others, such as those that were: living in a city (versus village), single (versus a relationship), an athlete (versus non-athlete), or earning an average household income < £25,000 (versus > £25,000). Conclusions: Now that the UK is transitioning to a state of normal living, strategies that can help individuals gradually return to physical activities, in accordance with the 2020 WHO guidelines, are of paramount importance to reducing risks to health associated with physical inactivity and sedentary behaviour.

Retrospective Analysis of Outcomes in Qualified and Non-Qualified Medicare Admissions in a Long-Term Acute Care Hospital During Year One of the Pandemic Waiver Period (preprint)

Objective: To compare the characteristics and outcomes of Medicare insured patients admitted to the long-term acute care hospital (LTCH) setting, before and during the first year of the CARES Act, and to determine whether there is functional benefit or projected cost-savings associated with admitting non-qualified patients beyond the waiver period. Data Source and Study Setting: Using the LTRAX outcome and demographic reporting system, primary data was collected for all Medicare insured patients admitted March 2019 through February 2021. Study activities were conducted at an independent LTCH located in Connecticut, USA. Study Design: This was a single-site retrospective cohort study. For each cohort, demographics and CMS required assistance scores for metrics such as self-care, communication, and functional mobility were compared. A sub-analysis of the stroke population was also conducted. Data Collection/Extraction Methods: Collected data were separated by admission date [historic control cohort (March 2019 through February 2020) or COVID-19 cohort (March 2020 through February 2021)] and qualified status. Principle Findings: Analysis revealed that non-qualified and qualified Medicare patients admitted before and during the COVID-19 waiver period were characteristically similar, were functionally similar at admission, and received a similar significant rehabilitation benefit. The stroke sub-analysis again demonstrated functional similarities between cohorts. However, in this sub-population, the traditionally non-qualified population saw a significant increase in the proportion of patients discharged home and a significant reduction in acute care readmissions within 30-days post LTCH discharge. Conclusions: Despite not meeting the three-midnight qualification, the non-qualified population was functionally similar at admission and received a similar rehabilitation benefit as the qualified population, while discharging home more often. This data then makes a compelling case to eliminate the three-midnight stay qualifier for LTCH admission, which would ultimately improve the rehabilitation outcomes and decrease the lifetime cost of care and caregiver burden for the traditionally non-qualified Medicare population.

Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study (preprint)

Background: Spironolactone has been proposed as a potential modulator of SARS-CoV-2 cellular entry. We aimed to measure the effect of spironolactone use on the risk of adverse outcomes following COVID-19 hospitalization. Methods: We performed a retrospective cohort study of COVID-19 outcomes for patients with or without exposure to spironolactone, using population-scale claims data from the Komodo Healthcare Map. We identified all patients with a hospital admission for COVID-19 in the study window, defining treatment status based on spironolactone prescription orders. The primary outcomes were progression to respiratory ventilation or mortality during the hospitalization. Odds ratios (OR) were estimated following either 1:1 propensity score matching (PSM) or multivariable regression. Subgroup analysis was performed based on age, gender, body mass index (BMI), and dominant SARS-CoV-2 variant. Findings: Among 898,303 eligible patients with a COVID-19-related hospitalization, 16,324 patients (1.8%) had a spironolactone prescription prior to hospitalization. 59,937 patients (6.7%) met the ventilation endpoint, and 26,515 patients (3.0%) met the mortality endpoint. Spironolactone use was associated with a significant reduction in odds of both ventilation (OR 0.82; 95% CI: 0.75-0.88; p < 0.001) and mortality (OR 0.88; 95% CI: 0.78-0.99; p = 0.033) in the PSM analysis, supported by the regression analysis. Spironolactone use was associated with significantly reduced odds of ventilation for all age groups, men, women, and non-obese patients, with the greatest protective effects in younger patients, men, and non-obese patients. Interpretation: Spironolactone use was associated with a protective effect against ventilation and mortality following COVID-19 infection, amounting to up to 64% of the protective effect of vaccination against ventilation and consistent with an androgen-dependent mechanism. The findings warrant initiation of large-scale randomized controlled trials to establish a potential therapeutic role for spironolactone in COVID-19 patients.

Risk and protective factors for new-onset binge eating, low weight, and self-harm symptoms in >35,000 individuals in the UK during the COVID-19 pandemic.

OBJECTIVE: The disruption caused by the COVID-19 pandemic has been associated with poor mental health, including increases in eating disorders and self-harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. METHOD: Data were from the COVID-19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio-demographic characteristics, lifetime psychiatric disorder, and COVID-related variables, including SARS-CoV-2 infection/illness with COVID-19. We identified four subsamples of participants without pre-pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self-harm ideation (n = 18,040), and self-harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes. RESULTS: Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self-harm ideation, and 3.5% for self-harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS-CoV-2/illness with COVID-19 was linked to lower odds of binge eating, low weight, and suicidal and/or self-harm ideation. DISCUSSION: Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self-harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics. PUBLIC SIGNIFICANCE: In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self-harm ideation, and self-harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms.

Survey of Implemented Mitigation Strategies and Further Needs of the U.S. Food Industry to Control COVID-19 in the Work Environment in Early 2021

Our objective was to determine the needs of the U.S. food industry to control COVID-19 in the work environment and what mitigation strategies are being implemented. A Web-based needs assessment survey was distributed in early 2021, targeting professionals in management positions at food industry facilities and operations. Statistical analyses were conducted on the self-reported adoption of mitigation strategies against COVID-19 in the participants' facilities and operations and the perceived needs of the industry regarding COVID-19. A total of 79 usable responses were received (those with data on the participant's industry sector), including 38 (48%) from the dairy, 17 (22%) from the fresh produce, and 24 (30%) from a mixture of other food industry sectors. Two usable responses were from the beef and pork sector, but none were from the poultry sector. Analyses revealed widespread implementation of mitigation strategies in the participants' facilities and oper-ations. Participants perceived that collaboration between the food industry and government agencies, contingency plans and appropriate training, and new technologies are needed to control COVID-19 in the food industry. Subject to limitations associated with low participation, these findings will aid efforts in the represented U.S. food industry sectors to protect workers' health in the event of the emergence of a new SARS-CoV-2 variant or similar future disaster. © 2023, International Association for Food Protection.

Promoting preservice teachers' psychological and pedagogical competencies for online learning and teaching: The T.E.A.C.H. program

During the widespread COVID-19 pandemic, face-to-face teaching was not viable because many schools were forced to close as a preventive measure. Educators abruptly shifted to online classes without sufficient time and resources to prepare for such an enormous transition. Although shifting from traditional face-to-face format to modern e-learning approach ensured that students could be educated outside of the classroom, its impact on the quality of learning and teaching (L&T) can be mixed. This study aims to address the knowledge gap in conventional teacher training by developing a web-based program called T.E.A.C.H. to enhance preservice teachers' psychological and pedagogical competencies for conducting online L&T. The program consisted of five modules, each focused on one dimension of psychological competence (creativity, curiosity, love of learning, judgment, and perspective) and applied to the ‘three foci' for online L&T (attendance and participation, engagement, and assessment). Adopting a quasi-experimental design with matched sampling, a total of 314 preservice teachers were allocated into the intervention or control group. The intervention group was given access to the web-based program to receive training materials, learn about the content, and take part in the online L&T exercises. Program effectiveness was evaluated using pretest and posttest questionnaires, a teaching design task, short quizzes, and a program quality assessment. The results showed that the T.E.A.C.H. program was effective in promoting preservice teachers' psychological competencies, positive attitudes toward online L&T, self-efficacy to teach in an online format, intentions to use technology for L&T, and online pedagogical skills. The successful implementation of T.E.A.C.H. encourages school leaders, teachers, and teacher professional development providers to utilize this web-based program to enhance online teaching practices.