Efficacy of Host Cell Serine Protease Inhibitor MM3122 against SARS-CoV-2 for Treatment and Prevention of COVID-19 (preprint)

We have developed a novel class of peptidomimetic inhibitors targeting several host cell human serine proteases including TMPRSS2, matriptase and hepsin. TMPRSS2 is a membrane associated protease which is highly expressed in the upper and lower respiratory tract and is utilized by SARS-CoV-2 and other viruses to proteolytically process their glycoproteins, enabling host cell receptor binding, entry, replication, and dissemination of new virion particles. We have previously shown that compound MM3122 exhibited subnanomolar potency against all three proteases and displayed potent antiviral effects against SARS-CoV-2 in a cell-viability assay. Herein, we demonstrate that MM3122 potently inhibits viral replication in human lung epithelial cells and is effective against the XBB.1.5 and EG.5.1 variant of SARS-CoV-2. Further, we have evaluated MM3122 in a mouse model of COVID-19 and have demonstrated that MM3122 administered intraperitoneally (IP) before (prophylactic) or after (therapeutic) SARS-CoV-2 infection had significant protective effects against weight loss and lung congestion, and reduced pathology. Amelioration of COVID-19 disease was associated with a reduction in pro-inflammatory cytokines and chemokines production after SARS-CoV-2 infection. Prophylactic, but not therapeutic, administration of MM3122 also reduced virus titers in the lungs of SARS-CoV-2 infected mice. Therefore, MM3122 is a promising lead candidate small molecule drug for the treatment and prevention of infections caused by SARS-CoV-2 and other coronaviruses.

A comparison of methods for forecasting value at risk and expected shortfall of cryptocurrencies

Several procedures to forecast daily risk measures in cryptocurrency markets have been recently implemented in the literature. Among them, long‐memory processes, procedures taking into account the presence of extreme observations, procedures that include more than a single regime, and quantile regression‐based models have performed substantially better than standard methods in terms of forecasting risk measures. Those procedures are revisited in this paper, and their value at risk and expected shortfall forecasting performance are evaluated using recent Bitcoin and Ethereum data that include periods of turbulence due to the COVID‐19 pandemic, the third halving of Bitcoin, and the Lexia class action. Additionally, in order to mitigate the influence of model misspecification and enhance the forecasting performance obtained by individual models, we evaluate the use of several forecast combining strategies. Our results, based on a comprehensive backtesting exercise, reveal that, for Bitcoin, there is no single procedure outperforming all other models, but for Ethereum, there is evidence showing that the GAS model is a suitable alternative for forecasting both risk measures. We found that the combining methods were not able to outperform the better of the individual models.

Donald Trump, dominating masculine necropolitics, and COVID-19

This article discusses US president, Donald J. Trump and what the author labels his "dominating masculine necropolitics". Dominating masculinity involves commanding and controlling specific interactions, and exercising power and control over people and events-"calling the shots" and "running the show". Differing from hegemonic masculinities, dominating masculinities do not necessarily legitimate a hierarchical relationship between men and women, masculinity and femininity, and among masculinities. In that sense, then, dominating masculinities are often, but not always, analytically distinct from hegemonic masculinities. Trump's specific form of dominating masculinity involved commanding and controlling specific interactions, and exercising power and control over people and events;he called the shots and ran the show, demanded strict obedience to his authority, and displayed a lack of concern for the opinions of others. Throughout Trump's presidency, this dominating masculinity centered on several critical features, which were emphasized or de-emphasized depending upon the context. The arrival and spread of Covid-19 around the world provided a new and dangerous context within which Trump's dominating masculinity has been increasingly constructed through novel necropolitical practices. Although Trump's medical experts continued to advocate for mitigation in order to minimize the spread of the virus, Trump unwaveringly stayed on message by continually downplaying the danger of the virus. Trump's dominating masculine necropolitics especially involved flouting guidelines for mask wearing. The culprit for the staggering spread of Covid-19 and premature death within the United States is Trump and his dominating masculine necropolitical discourse and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

COVID-19 in Patients with a Primary Refugee-Associated Language in a Kentucky Emergency Department During 2020.

COVID-19 has heavily impacted the refugee population in the United States due to exposure risks, living and working conditions, and healthcare access, but little is known about outcomes. We reviewed emergency department visits to a Kentucky hospital among 2163 patients from March-December 2020, studying incidence of COVID-19 diagnosis for patients with a primary refugee-associated language compared to English speakers, and outcomes after diagnosis including hospitalization, length of stay, and in-hospital mortality. Patients in the population of interest had higher odds of COVID-19 diagnosis in the hospital (OR = 12.31, 95% CI 7.80-19.40), but, among those with COVID-19, lower odds of hospital admission (OR = 0.58, 95% CI 0.37-0.90) and shorter median length of stay (4.1 vs. 10.5 days) compared to English speakers. The study corroborates reports of comparatively higher COVID-19 incidence in patients speaking a primary refugee-associated language, but implies milder illness severity, possibly reflecting this population's baseline health.

Mpox in Nigeria: Perceptions and knowledge of the disease among critical stakeholders-Global public health consequences.

BACKGROUND: The mpox (monkeypox) disease is a re-emerging viral zoonosis of international concern that is endemic in parts of Africa. The mpox virus (MPXV), which was hitherto largely limited to some Central and West African countries, was declared a public health emergency of international concern by the WHO on July 23, 2022 following the rapid spread of the virus to non-endemic countries. Globally, as of March 16, 2023, the WHO had reported 86,496 laboratory-confirmed cases of mpox and 111 deaths in 110 countries. Of the 1,420 cases of mpox reported in Africa as of March 16, 2023, Nigeria alone recorded 57.1% (812) of the confirmed cases and eight fatalities recorded in the continent. To help improve on the understanding of the current situation in Nigeria, the present study assessed the perception and knowledge of mpox among Nigerian healthcare workers, academics and tertiary students. The study also sought to highlight the global public health significance of the MPXV, and recommend a One Health approach to limit exporting of the virus beyond the borders of Nigeria. METHODS: A web-based cross-sectional survey was conducted between 24 July 2022 and 12 August 2022 to evaluate the perception and knowledge of mpox among 1544 Nigerians, consisted of healthcare workers (n = 832), academics (n = 306) and tertiary students (n = 462). Data on the respondents' socio demographics and their information sources on mpox were also collected. Each correct response was allotted one point while an incorrect response was scored zero. The scores for perception and knowledge were dichotomized into positive (>5.5) and negative (≤5.5) and adequate (>5.8) and inadequate (≤5.8), respectively; using the average scores for perception and knowledge. The average score for perception and knowledge were summarised and presented as the mean and standard deviation (SD). Chi-square tests of association and binary logistic regression were carried out to determine factors associated with the outcome variables. RESULTS: Of the 1452 respondents that had heard of mpox, 878 (60.5%) and 419 (28.9%) had adequate knowledge and positive perception concerning MPXV infection respectively. Average perception score was 5.5. Mean perception and knowledge scores were 4.5(SD: 2.0) and 5.8 (SD: 1.9), respectively. Factors that were significantly associated with knowledge level were age (p = 0.020) educational qualification attained (p = 0.004), occupation (p<0.001), and geopolitical zone of residency (p = 0.001). There was a positive correlation between perception and knowledge scores (r = 0.4, p<0.001). Positive perceptions were likely among respondents who had tertiary education, and residing in North-west Nigeria. Likewise, adequate knowledge scores were likely among respondents under 30 years of age, with tertiary education or reside in North-west Nigeria. Sources of information were significantly associated with perception (p = 0.004) and knowledge (p<0.001) of the respondents. CONCLUSION: The findings of this study show that there is disparity in the knowledge and perception of mpox in the study population, and as a result, there is a need to intensify awareness about MPXV infection to enhance positive perception among the respondents. This has potential to safeguard public health and contain the disease thus preventing it from spreading to the global community. A One Health approach involving animal and human health workers is imperative for improved knowledge and a good perception towards the disease among respondents, and enhanced active surveillance and early detection of MPXV in reservoir hosts (rodents and non-human primates); to prevent reverse zoonotic transmission of the virus at the human-animal interface.

The State of Health, Burnout, Healthy Behaviors, Workplace Wellness Support and Concerns of Medication Errors in Pharmacists During the COVID-19 Pandemic.

OBJECTIVE: To describe the well-being and lifestyle behaviors of health-system pharmacists during the COVID-19 pandemic and to determine the relationships among well-being, perceptions of workplace wellness support, and self-reported concern of having made a medication error. METHODS: Pharmacist (N = 10,445) were randomly sampled for a health and well-being survey. Multiple logistic regression assessed associations with wellness support and concerns of medication error. RESULTS: The response rate was 6.4% (N = 665). Pharmacists whose workplaces very much supported wellness were 3x more likely to have no depression, anxiety, and stress; 10x more likely to have no burnout; and 15x more likely to have a higher professional quality of life. Those with burnout had double the concern of having made a medication error in the last three months. CONCLUSION: Healthcare leadership must fix system issues that cause burnout and actualize wellness cultures to improve pharmacist well-being.

Angular Combining of Forecasts of Probability Distributions (preprint)

When multiple forecasts are available for a probability distribution, forecast combining enables a pragmatic synthesis of the available information to extract the wisdom of the crowd. A linear opinion pool has been widely used, whereby the combining is applied to the probability predictions of the distributional forecasts. However, it has been argued that this will tend to deliver overdispersed distributional forecasts, prompting the combination to be applied, instead, to the quantile predictions of the distributional forecasts. Results from different applications are mixed, leaving it as an empirical question whether to combine probabilities or quantiles. In this paper, we present an alternative approach. Looking at the distributional forecasts, combining the probability forecasts can be viewed as vertical combining, with quantile forecast combining seen as horizontal combining. Our alternative approach is to allow combining to take place on an angle between the extreme cases of vertical and horizontal combining. We term this angular combining. The angle is a parameter that can be optimized using a proper scoring rule. We show that, as with vertical and horizontal averaging, angular averaging results in a distribution with mean equal to the average of the means of the distributions that are being combined. We also show that angular averaging produces a distribution with lower variance than vertical averaging, and, under certain assumptions, greater variance than horizontal averaging. We provide empirical support for angular combining using weekly distributional forecasts of COVID-19 mortality at the national and state level in the U.S.

Cyproheptadine Treatment of COVID-19-Induced Enteritis: Implications for Hyperinflammatory Phase Management

A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

General population reference values for the Functional Assessment of Cancer Therapy-Lung and PROMIS-29.

BACKGROUND: Therapeutic advances in lung cancer have turned attention toward patient-reported outcome measures (PROMs) as important clinical outcomes. The Functional Assessment of Cancer Therapy-Lung (FACT-L) is a common endpoint in lung cancer trials. This study calculated FACT-L reference values for the United States (US) general population. METHODS: Adults from the US general population (N = 2001) were surveyed between September 2020 and November 2020. Surveys contained 126 questions, including the FACT-L [36 items; FACT-G and four subscales (Physical Well-Being [PWB], Social Well-Being [SWB], Emotional Well-Being [EWB], and Functional Well-Being [FWB]) and the Lung Cancer Subscale (LCS), and a Trial Outcome Index (TOI)]. Reference values for each FACT-L scale were calculated with means for the total sample and separately for participants with: no comorbidities, COVID-19 as only comorbidity, no COVID-19. RESULTS: In the total sample, the reference scores were as follows: PWB = 23.1; SWB = 16.8; EWB = 18.5; FWB = 17.6; FACT-G = 76.0; LCS = 23.0, TOI = 63.7, and FACT-L Total = 99.0. Scores were lower for those reporting a prior diagnosis of COVID-19, especially for SWB (15.7) and FWB (15.3). SWB scores were lower than previous references values. CONCLUSIONS: These data provide US general adult population reference value set for FACT-L. While some of the subscale results were lower than those found in the reference data for other PROMs, these data were obtained in a more contemporaneous time frame juxtaposed with the COVID-19 pandemic and may represent a new peri-pandemic norm. Thus, these reference values will be useful for future clinical research.

Infection Diseases Following Natural Disaster in Children: Health Prevention and Assessment

[17] Diseases with a long incubation period (leishmaniasis and leptospirosis) and vector-borne diseases such as malaria and dengue should be considered as possible infections during the recovery phase (> 4 weeks) of natural disasters. [20] Outbreaks of group A streptococcus infection in camps could have devastating consequences, not just as a cause of respiratory infection, but also of wound infections. [10] In the post-earthquake period, the first wave of infectious diseases is caused by food-borne and/or water-borne infections, and/or by infections transmitted by respiratory droplets. [Extracted from the article] Copyright of Journal of Pediatric Infectious Diseases is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Whither compassionate leadership? A systematic review

Recent disastrous events, such as the COVID-19 pandemic, has amplified the appeal for compassionate leadership in organizations and is viewed as the need of the hour. While compassion is a timeless concept, there appears to be a lack of clarity around the idea of compassionate leadership, and the current understanding appears limited, fragmented, and scattered across the literature. This integrative systematic review of 41 articles during the last 20 years (2002–2021) conceptualizes six critical dimensions of compassionate leadership, namely: empathy;openness and communication;physical, mental health and well-being;inclusiveness;integrity;respect and dignity. These findings enhance our understanding of how organizational leaders can effectively incorporate the dimensions to become compassionate leaders. The review examines how compassionate leadership is defined and understood in the literature, and a contribution in the form of a definition for compassionate leadership is offered. Finally, gaps in the literature are highlighted, offering avenues for future research, along with implications for research, theory, and practice. © 2023, The Author(s).

Predictors of Mental Health Service Utilization among Frontline Healthcare Workers during the COVID-19 Pandemic.

(1) Background: This study examined the prevalence and correlates of factors associated with self-reported mental health service use in a longitudinal cohort of frontline health care workers (FHCWs) providing care to patients with COVID-19 throughout 2020. (2) Methods: The study comprised a two-wave survey (n = 780) administered in April-May 2020 (T1) and November 2020-January 2021 (T2) to faculty, staff, and trainees in a large urban medical center. Factors associated with initiation, cessation, or continuation of mental health care over time were examined. (3) Results: A total of 19.1% of FHCWs endorsed currently utilizing mental health services, with 11.4% continuing, 4.2% initiating, and 3.5% ceasing services between T1 and T2. Predisposing and need-related factors, most notably a history of a mental health diagnosis and distress related to systemic racism, predicted service initiation and continuation. Among FHCWs with a prior mental health history, those with greater perceived resilience were less likely to initiate treatment at T2. Descriptive data highlighted the importance of services around basic and safety needs (e.g., reliable access to personal protective equipment) relative to mental health support in the acute phase of the pandemic. (4) Conclusions: Results may be helpful in identifying FHCWs who may benefit from mental health services.

Does the threat of COVID-19 modulate automatic imitation?

The tendency to involuntarily imitate the actions of others (automatic imitation) can be modulated by social affiliative cues. Here, we explored whether the disruption to our social lives caused by the COVID-19 pandemic may subsequently influence automatic imitation. Three groups were initially presented a sentence comprehension task that featured either neutral (control), safe or unsafe primes to COVID-19 infection. They then completed an automatic imitation task, where a numeric cue was presented alongside apparent motion of an index or middle finger, which was either compatible or incompatible with the required response. Reaction times were longer for the incompatible compared to compatible trials, and thus demonstrated automatic imitation. However, there was no influence of the primes indicating that automatic imitation was unaffected by the risk of COVID-19. The potential theoretical explanations and practical implications of pathogen avoidance and social bonding incentives are discussed with reference to pandemic events.

Impact of asynchronous virtual learning on student well-being and success.

INTRODUCTION: As the world has rapidly changed during the COVID-19 pandemic, doctor of pharmacy (PharmD) students' overall well-being has been prioritized. This study aimed to evaluate PharmD students' well-being and perceived academic engagement when moved involuntarily to a majority asynchronous and virtual curriculum during the 2020-2021 academic year in response to the COVID-19 pandemic. Additionally, this study aimed to assess demographic predictors relating student well-being and academic engagement. METHODS: A survey administered via Qualtrics (SAP) was sent to three cohorts of professional students (Classes of 2022 to 2024) enrolled in the PharmD program at The Ohio State University College of Pharmacy. These cohorts were engaged in a primarily asynchronous and virtual curriculum due to COVID-19. RESULTS: Although students displayed mixed results on how asynchronous learning affected their well-being, students replied that they would want to continue learning via a hybrid model (53.3%) or completely asynchronous (24%), while 17.3% wanted primarily synchronous and 5.3% did not reply. CONCLUSIONS: Our results indicated that aspects of the majority asynchronous and virtual learning environment were favored by students. Through student responses, our faculty and staff can take into consideration students' opinions when making future changes to the curriculum. We provided this data for others to consider when evaluating well-being and engagement with a virtual and asynchronous curriculum.

Improving wastewater-based epidemiology performance through streamlined automation

Wastewater-based epidemiology (WBE) has enabled us to describe Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in populations. However, implementation of wastewater monitoring of SARS-CoV-2 is limited due to the need for expert staff, expensive equipment, and prolonged processing times. As WBE increases in scope (beyond SARS-CoV-2) and scale (beyond developed regions), there is a need to make WBE processes simpler, cheaper, and faster. We developed an automated workflow based on a simplified method termed exclusion-based sample preparation (ESP). Our automated workflow takes 40 minutes from raw wastewater to purified RNA, which is several times faster than conventional WBE methods. The total assay cost per sample/replicate is $6.50 which includes consumables and reagents for concentration, extraction, and RT-qPCR quantification. The assay complexity is reduced significantly, as extraction and concentration steps are integrated and automated. The high recovery efficiency of the automated assay (84.5±25.4%) yielded an improved Limit of Detection (LoDAutomated=40 copies/mL) compared to the manual process (LoDManual=206 copies/mL), increasing analytical sensitivity. We validated the performance of the automated workflow by comparing it with the manual method using wastewater samples from several locations. The results from the two methods correlated strongly (r=0.953), while the automated method was shown to be more precise. In 83% of the samples, the automated method showed lower variation between replicates, which is likely due to higher technical errors in the manual process e.g., pipetting. Our automated wastewater workflow can support the expansion of WBE in the fight against Coronavirus Disease of 2019 (COVID-19) and other epidemics. Graphical

Racial disparities in air pollution burden and COVID-19 deaths in Louisiana, USA, in the context of long-term changes in fine particulate pollution. (Special Issue: Disparities during times of a pandemic and epidemic.)

Black Americans in Louisiana are disproportionately dying from COVID-19, and environmental disparities may be contributing to this injustice. While Black communities in Louisiana's industrialized regions (e.g., Cancer Alley, Calcasieu Parish) have been overburdened with pollution for decades, this disparity has not been evaluated by using recent data. Here, we explore statewide relationships among air pollution burden, race, COVID-19 death rates, and other health/socioeconomic factors. Measures of pollution burden included satellite-derived particulate matter (PM2.5) concentrations and health risks from toxic air pollution (i.e., respiratory hazard [RH] and immunological hazard [IH], estimated by the Environmental Protection Agency). In addition, we evaluate changes in emissions and ambient concentrations of fine PM2.5 in Louisiana over the past few decades. Our overall goal was to better understand Louisiana's burden of air pollution in the context of COVID-19. By all measures, a higher burden of air pollution was associated with larger percentages of Black residents and increased unemployment across Louisiana census tracts. Across parishes, higher COVID-19 death rates were associated with increased RH and IH and larger percentages of Black residents. These associations were not driven by diabetes, obesity, smoking, age, or poverty. Industrial sources comprised more of Louisiana's PM2.5 in 2017 versus 1990, as vehicle contributions declined 75% whereas industrial emissions remained about the same overall (despite variation in the interim). Ambient concentrations of PM2.5 decreased statewide from 2000 to 2015, but subsequently increased in south Louisiana, concurrent with an upward trend in industrial emissions. Our findings highlight the critical need to address Louisiana's pollution disparities and to recognize air pollution exposure as a risk factor for COVID-19.

Using Interteaching to Promote Online Learning Outcomes.

Due to the COVID-19 pandemic, educators have been forced to rapidly transition away from in-person learning environments to completely online formats. Many of these educators have had little or no training and experience teaching online, contributing to stress and anxiety. To compound this problem even further, there are a multitude of online learning technologies from which to choose that can be relatively costly and require an intensive production process. In an effort to provide immediate relief to those dealing with this problem, we detail how interteaching, an empirically supported behavioral teaching technique, can be used to cultivate an interactive online learning environment in either an asynchronous or synchronous format. Specifically, we describe some best practices and provide some examples on how to generate active student responding (ASR) as well as provide pinpointed performance-based feedback. We specifically reference the relatively easy-to-use online software Kaltura, but it is hoped that our suggestions inspire others to develop and use these strategies across a variety of platforms in effort to provide evidence-based quality education during this crisis.

The mediating effect of health literacy on COVID-19 vaccine confidence among a diverse sample of urban adults in Boston and Chicago

Background A high rate of COVID-19 vaccination is critical to reduce morbidity and mortality related to infection and to control the COVID-19 pandemic. Understanding the factors that influence vaccine confidence can inform policies and programs aimed at vaccine promotion. We examined the impact of health literacy on COVID-19 vaccine confidence among a diverse sample of adults living in two major metropolitan areas. Methods Questionnaire data from adults participating in an observational study conducted in Boston and Chicago from September 2018 through March 2021 were examined using path analyses to determine whether health literacy mediates the relationship between demographic variables and vaccine confidence, as measured by an adapted Vaccine Confidence Index (aVCI). Results Participants (N = 273) were on average 49 years old, 63% female, 4% non-Hispanic Asian, 25% Hispanic, 30% non-Hispanic white, and 40% non-Hispanic Black. Using non-Hispanic white and other race as the reference category, Black race and Hispanic ethnicity were associated with lower aVCI (-0.76, 95% CI -1.00 to -0.50;-0.52, 95% CI -0.80 to -0.27, total effects from a model excluding other covariates). Lower education was also associated with lower aVCI (using college or more as the reference, -0.73 for 12th grade or less, 95% CI -0.93 to -0.47;-0.73 for some college/associate's/technical degree, 95% CI -1.05 to -0.39). Health literacy partially mediated these effects for Black and Hispanic participants and those with lower education (indirect effects -0.19 and -0.19 for Black race and Hispanic ethnicity;0.27 for 12th grade or less;-0.15 for some college/associate's/technical degree). Conclusions Lower levels of education, Black race, and Hispanic ethnicity were associated with lower scores on health literacy, which in turn were associated with lower vaccine confidence. Our findings suggest that efforts to improve health literacy may improve vaccine confidence, which in turn may improve vaccination rates and vaccine equity. Clinical Trials Number: NCT03584490