Timeline of changes in spike conformational dynamics in emergent SARS-CoV-2 variants reveal progressive stabilization of trimer stalk with altered NTD dynamics.

SARS-CoV-2 emergent variants are characterized by increased viral fitness and each shows multiple mutations predominantly localized to the spike (S) protein. Here, amide hydrogen/deuterium exchange mass spectrometry has been applied to track changes in S dynamics from multiple SARS-CoV-2 variants. Our results highlight large differences across variants at two loci with impacts on S dynamics and stability. A significant enhancement in stabilization first occurred with the emergence of D614G S followed by smaller, progressive stabilization in subsequent variants. Stabilization preceded altered dynamics in the N-terminal domain, wherein Omicron BA.1 S showed the largest magnitude increases relative to other preceding variants. Changes in stabilization and dynamics resulting from S mutations detail the evolutionary trajectory of S in emerging variants. These carry major implications for SARS-CoV-2 viral fitness and offer new insights into variant-specific therapeutic development.

Changes in dispensing of anti-osteoporotic drugs during COVID-19 pandemic

Care of osteoporosis patients during COVID-19 pandemic is challenging. Due to lockdowns and restrictions, the management of osteoporosis has changed. Diagnosis of osteoporosis decreased and the influence of COVID-19 on drug prescriptions and dispensing is currently unclear. Therefore, the aim of the study was to assess the dispensing of anti-osteoporotic drugs during the Covid19 pandemic. Methods This study was a nationwide retrospective register-based observational study which included all patients in Austria aged >= 50 who received at least one prescription for anti-osteoporotic drug between January 2016 and November 2020. Pseudonymized individual-level patients' data were obtained from social insurance authorities and the Federal Ministry of Labour, Social Affairs, Health and Consumer Protection in Austria. Anti-osteoporotic agents were divided into: (i) oral bisphosphonates, (ii) intravenous bisphosphonates, (iii) selective estrogen receptor modulators (SERMs), (iv) teriparatide (TPTD) and (v) Denosumab (DMAB). We used interrupted time series analysis with autoregressive integrated moving average models (ARIMA) for the prediction of drug dispensing. Results There were 2,884,627 dispensing of anti-osteoporotic drugs by 318,573 patients between 2016-2020. The mean monthly prescriptions for oral bisphosphonates (-14.5 %) and SERMs (-12.9 %) decreased during COVID-19 pandemic, compared to the non-COVID-19 period. The dispensing for intravenous bisphosphonates (1.7 %) and teriparatide (9.5 %) increased during COVID- 19. The prescriptions for DMAB decreased during the first lock-down in March and April 2020 (24 %), however increased by 29.1 % for the total observation time. The ARIMA model for alendronate showed, that the estimated step change was minus 1443 dispensing (95 % CI - 2870 to - 17), while the estimated change in slope was minus 29 dispensing per month (95 % CI - 327 to 270). Thus, there were 1472 (1443 + 29) fewer dispensing in March 2020 than predicted had the lockdown not occurred. Discussion The total number of prescriptions dispensed to patients treated with anti-osteoporotic medications declined rapidly during the first COVID-19 lockdown. The largest drops in absolute terms were observed for ibandronate, followed by alendronate, denosumab, zolendronic acid and risendronate. The observed decrease of DMAB during the first lockdown, was compensated in the following months. Current evidence suggests no need for discontinuation of anti-osteoporotic drugs during COVID-19 pandemic, nor because of vaccination. Taking into account the massive treatment gap for osteoporosis, and the related fracture risk, clinicians should continue treatment, even in times of pandemics.

Training LEADers to Accelerate Global Mental Health Disparities Research (LEAD) Program: A Research Training Program Protocol.

Background: There is a critical need to address mental health needs across the globe, especially in low and middle-income countries where mental health disparities are pervasive, including among children. The global mental health disparities suggest an imperative for culturally and contextually-congruent mental health services models that expand upon the existing services and interventions for these groups. Rigorous research is a key tool in providing the scientific evidence to inform public policy and practice efforts to effectively address these needs. Yet, there is a limited number of researchers, especially those from diverse backgrounds, who study these issues. In this paper, we describe the "TrainingLEADers to Accelerate Global Mental Health Disparities Research" (LEAD) program, a research training program funded by the National Institute on Minority Health and Health Disparities and focused on global mental health disparities research for early career researchers from under-represented minority groups. Methods: The LEAD program is designed as a two-phase training program for advanced pre-doctoral students, postdoctoral fellows, and junior faculty from diverse backgrounds in the U.S., including groups underrepresented in biomedical, behavioral, clinical and social sciences research, interested in global mental health disparities research. Trainees are matched with mentors and participate in an intensive 12-week program. Discussion: The LEAD program seeks to provide a robust platform for the development, implementation and expansion of evidence-based culturally and contextually-congruent interventions and services models addressing global mental health disparities across the life cycle, especially in low-resource communities in the global context. By producing a sustainable network of well-trained investigators from underrepresented backgrounds, LEAD will potentially contribute to the shared lessons and efforts relevant to addressing global mental health disparities and improving care for vulnerable populations in low-resource settings.

Fear, distress, and perceived risk shape stigma toward Ebola survivors: a prospective longitudinal study.

BACKGROUND: During the 2014-15 Ebola Virus Disease (EVD) epidemic, thousands of people in Sierra Leone were infected with the devastating virus and survived. Years after the epidemic was declared over, stigma toward EVD survivors and others affected by the virus is still a major concern, but little is known about the factors that influence stigma toward survivors. This study examines how key personal and ecological factors predicted EVD-related stigma at the height of the 2014-2015 epidemic in Sierra Leone, and the personal and ecological factors that shaped changes in stigma over time. METHODS: Using three waves of survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines factors associated with self-reported personal stigma toward Ebola survivors (11 items, α = 0.77) among 1008 adults (74.6% retention rate) from 63 census enumeration areas of the Western Rural and Western Urban districts of Sierra Leone. Participants were randomly sampled at the height of the EVD epidemic and followed up as the epidemic was waning and once the epidemic had been declared over by the WHO. Three-level mixed effects models were fit using Stata 16 SE to examine cross-sectional associations as well as predictors of longitudinal changes in stigma toward EVD survivors. RESULTS: At the height of the EVD epidemic, female sex, household wealth, post-traumatic stress, EVD-related fear and perceived infection risk are a few of the factors which predicted higher levels of stigma toward survivors. On average, stigma toward EVD survivors decreased significantly as the epidemic declined in Sierra Leone, but female sex, EVD fear, and risk perceptions predicted a slower rate of change. CONCLUSION: This study identified key individual and psychosocial characteristics which may predict higher levels of stigma toward infectious disease survivors. Future studies should pursue a better understanding of how personal characteristics and perceptions, including psychosocial distress, fear, and perceived infection risk serve as pathways for stigma in communities affected by infectious disease.

Visible blue light inhibits infection and replication of SARS-CoV-2 at doses that are well-tolerated by human respiratory tissue.

The delivery of safe, visible wavelengths of light can be an effective, pathogen-agnostic, countermeasure that would expand the current portfolio of SARS-CoV-2 intervention strategies beyond the conventional approaches of vaccine, antibody, and antiviral therapeutics. Employing custom biological light units, that incorporate optically engineered light-emitting diode (LED) arrays, we harnessed monochromatic wavelengths of light for uniform delivery across biological surfaces. We demonstrated that primary 3D human tracheal/bronchial-derived epithelial tissues tolerated high doses of a narrow spectral band of visible light centered at a peak wavelength of 425 nm. We extended these studies to Vero E6 cells to understand how light may influence the viability of a mammalian cell line conventionally used for assaying SARS-CoV-2. The exposure of single-cell monolayers of Vero E6 cells to similar doses of 425 nm blue light resulted in viabilities that were dependent on dose and cell density. Doses of 425 nm blue light that are well-tolerated by Vero E6 cells also inhibited infection and replication of cell-associated SARS-CoV-2 by > 99% 24 h post-infection after a single five-minute light exposure. Moreover, the 425 nm blue light inactivated cell-free betacoronaviruses including SARS-CoV-1, MERS-CoV, and SARS-CoV-2 up to 99.99% in a dose-dependent manner. Importantly, clinically applicable doses of 425 nm blue light dramatically inhibited SARS-CoV-2 infection and replication in primary human 3D tracheal/bronchial tissue. Safe doses of visible light should be considered part of the strategic portfolio for the development of SARS-CoV-2 therapeutic countermeasures to mitigate coronavirus disease 2019 (COVID-19).

Outbreaks of Covid-19 Variants in Prisons: A Mathematical Modeling Analysis of Vaccination and Re-Opening Policies (preprint)

Background: Residents of correctional facilities have experienced disproportionately higher rates of SARS-CoV-2 infection and Covid-19-related mortality. To protect against outbreaks, many prisons and jails imposed heavy restrictions on in-person activities, which are now beginning to lift. Uncertainty surrounds the safety of these moves. Methods and Findings: We obtained system-wide resident-day level data for the California state prison system, the nation's third largest. We used the data to develop a transmission-dynamic stochastic microsimulation model that projects the impact of various policy scenarios on risks of SARS-CoV-2 infections and related hospitalization among residents after an initial infection is introduced to a prison. The policy scenarios vary according to levels of vaccine coverage, baseline immunity, resumption of activities, and use of non-pharmaceutical interventions (e.g., masking, physical distancing). The analyses were conducted across 5 types of prisons that differed in their residential layouts, security levels, and resident demographics. If a viral variant is introduced into a prison that has resumed pre-2020 contact levels, has moderate vaccine coverage, and has no baseline immunity, 23-74% of residents are expected to be infected over 200 days. High vaccination coverage coupled with use of non-pharmaceutical measures reduces cumulative infections to 2-54% of residents. In prisons consisting mostly of dormitory housing, even with high vaccine coverage and non-pharmaceutical interventions, resumption of in-person activities is associated with substantial risk, unless there is high baseline immunity (e.g., [≥]50%) from prior outbreaks. In prisons consisting mostly of cell housing, <10% of residents are expected to become infected, even with no baseline immunity. However, hospitalization risks are substantial in prisons that house medically vulnerable populations, even for prisons consisting mostly of cells. Risks of large outbreaks are substantially higher if there is continued introduction of infections into a prison. Some findings may not be transportable to other carceral settings, and our assumptions regarding viral variants will not be accurate for all variants. Conclusions: Balancing the benefits of resuming normal in-person activities against the risks of Covid-19 outbreaks is a difficult challenge for correctional systems. The policy choices are not strictly binary. To protect against viral variants, prisons should focus on achieving both high vaccine coverage and maintaining widespread use of non-pharmaceutical interventions. With both in place, some prisons, especially those with lower room occupancy that have already had large outbreaks, could safely resume in-person activities, while continuing testing and measures to protect the medically-vulnerable.

Impact of mobile health and medical applications on clinical practice in gastroenterology.

Mobile health apps (MHAs) and medical apps (MAs) are becoming increasingly popular as digital interventions in a wide range of health-related applications in almost all sectors of healthcare. The surge in demand for digital medical solutions has been accelerated by the need for new diagnostic and therapeutic methods in the current coronavirus disease 2019 pandemic. This also applies to clinical practice in gastroenterology, which has, in many respects, undergone a recent digital transformation with numerous consequences that will impact patients and health care professionals in the near future. MHAs and MAs are considered to have great potential, especially for chronic diseases, as they can support the self-management of patients in many ways. Despite the great potential associated with the application of MHAs and MAs in gastroenterology and health care in general, there are numerous challenges to be met in the future, including both the ethical and legal aspects of applying this technology. The aim of this article is to provide an overview of the current status of MHA and MA use in the field of gastroenterology, describe the future perspectives in this field and point out some of the challenges that need to be addressed.

SARS-CoV-2-Associated Deaths Among Persons Aged <21 Years - United States, February 12-July 31, 2020.

Since February 12, 2020, approximately 6.5 million cases of SARS-CoV-2 infection, the cause of coronavirus disease 2019 (COVID-19), and 190,000 SARS-CoV-2-associated deaths have been reported in the United States (1,2). Symptoms associated with SARS-CoV-2 infection are milder in children compared with adults (3). Persons aged <21 years constitute 26% of the U.S. population (4), and this report describes characteristics of U.S. persons in that population who died in association with SARS-CoV-2 infection, as reported by public health jurisdictions. Among 121 SARS-CoV-2-associated deaths reported to CDC among persons aged <21 years in the United States during February 12-July 31, 2020, 63% occurred in males, 10% of decedents were aged <1 year, 20% were aged 1-9 years, 70% were aged 10-20 years, 45% were Hispanic persons, 29% were non-Hispanic Black (Black) persons, and 4% were non-Hispanic American Indian or Alaska Native (AI/AN) persons. Among these 121 decedents, 91 (75%) had an underlying medical condition,* 79 (65%) died after admission to a hospital, and 39 (32%) died at home or in the emergency department (ED).† These data show that nearly three quarters of SARS-CoV-2-associated deaths among infants, children, adolescents, and young adults have occurred in persons aged 10-20 years, with a disproportionate percentage among young adults aged 18-20 years and among Hispanics, Blacks, AI/ANs, and persons with underlying medical conditions. Careful monitoring of SARS-CoV-2 infections, deaths, and other severe outcomes among persons aged <21 years remains particularly important as schools reopen in the United States. Ongoing evaluation of effectiveness of prevention and control strategies will also be important to inform public health guidance for schools and parents and other caregivers.

COVID-19 Among Workers in Meat and Poultry Processing Facilities - 19 States, April 2020.

Congregate work and residential locations are at increased risk for infectious disease transmission including respiratory illness outbreaks. SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is primarily spread person to person through respiratory droplets. Nationwide, the meat and poultry processing industry, an essential component of the U.S. food infrastructure, employs approximately 500,000 persons, many of whom work in proximity to other workers (1). Because of reports of initial cases of COVID-19, in some meat processing facilities, states were asked to provide aggregated data concerning the number of meat and poultry processing facilities affected by COVID-19 and the number of workers with COVID-19 in these facilities, including COVID-19-related deaths. Qualitative data gathered by CDC during on-site and remote assessments were analyzed and summarized. During April 9-27, aggregate data on COVID-19 cases among 115 meat or poultry processing facilities in 19 states were reported to CDC. Among these facilities, COVID-19 was diagnosed in 4,913 (approximately 3%) workers, and 20 COVID-19-related deaths were reported. Facility barriers to effective prevention and control of COVID-19 included difficulty distancing workers at least 6 feet (2 meters) from one another (2) and in implementing COVID-19-specific disinfection guidelines.* Among workers, socioeconomic challenges might contribute to working while feeling ill, particularly if there are management practices such as bonuses that incentivize attendance. Methods to decrease transmission within the facility include worker symptom screening programs, policies to discourage working while experiencing symptoms compatible with COVID-19, and social distancing by workers. Source control measures (e.g., the use of cloth face covers) as well as increased disinfection of high-touch surfaces are also important means of preventing SARS-CoV-2 exposure. Mitigation efforts to reduce transmission in the community should also be considered. Many of these measures might also reduce asymptomatic and presymptomatic transmission (3). Implementation of these public health strategies will help protect workers from COVID-19 in this industry and assist in preserving the critical meat and poultry production infrastructure (4).