Modeling pH and Temperature Effects as Climatic Hazards in Vibrio Vulnificus and Vibrio Parahaemolyticus Planktonic Growth and Biofilm Formation.

Climate-induced stressors, such as changes in temperature, salinity, and pH, contribute to the emergence of infectious diseases. These changes alter geographical constraint, resulting in increased Vibrio spread, exposure, and infection rates, thus facilitating greater Vibrio-human interactions. Multiple efforts have been developed to predict Vibrio exposure and raise awareness of health risks, but most models only use temperature and salinity as prediction factors. This study aimed to better understand the potential effects of temperature and pH on V. vulnificus and V. parahaemolyticus planktonic and biofilm growth. Vibrio strains were grown in triplicate at 25°, 30°, and 37°C in 96 well plates containing Modified Seawater Yeast Extract modified with CaCl2 at pH's ranging from 5 to 9.6. AMiGA software was used to model growth curves using Gaussian process regression. The effects of temperature and pH were evaluated using randomized complete block analysis of variance, and the growth rates of V. parahaemolyticus and V. vulnificus were modeled using the interpolation fit on the MatLab Curve Fitting Toolbox. Different optimal conditions involving temperature and pH were observed for planktonic and biofilm Vibrio growth within- and between-species. This study showed that temperature and pH factors significantly affect Vibrio planktonic growth rates and V. parahaemolyticus biofilm formation. Therefore, pH effects must be added to the Vibrio growth modeling efforts to better predict Vibrio risk in estuarine and coastal zones that can potentially experience the cooccurrence of Vibrio and harmful algal bloom outbreak events.

"Building Back Better": Seeking an Equitable Return to Sport for Development in the Wake of COVID-19

The COVID-19 pandemic affected sport programming by restricting in-person activities. Concurrently, global outcry for racial justice for Black and racialized communities promoted calls to action to assess equitable practices in sport, including sport for development (SFD). This study critically examined SFD "return to play" programming to include perspectives from racialized persons' lived experiences. We present findings based on data collected from Maple Leaf Sports and Entertainment Foundation's Change the Game campaign, which explored questions of sport inequity to "build back better." Outcomes further SFD discourses challenging (potentially) harmful structures affecting participants, including underreported effects of racialization. The study used both quantitative and qualitative analyses of survey data on youth experiences, enablers, and barriers in sport and analyzed these results within an antiracist, antioppressive, and decolonial conceptual framework.

Simulating Changes in Aircraft Noise at Heathrow Airport during the 2020 Covid-19 Lockdown

Global restrictions on domestic and international travel introduced in March 2020 as a result of the Covid-19 pandemic resulted in a significant reduction in air traffic movements around the world. This paper presents the findings of research carried out at London Heathrow Airport exploring the day-by-day changes in aircraft noise exposure and event levels over the period March 2020 to June 2020. The research was carried out using validated modelling of aircraft procedures and noise profiles alongside radar data obtained from the airport. This allowed trends in metrics such as LAeq, N65, and overflight to be considered in the form of contours, and at community locations. This was facilitated using geospatial databases and interactive dynamic reporting toolkits. The research has allowed estimates to be made of the point where aircraft noise at Heathrow Airport reached a minimum. It also provides some helpful insight as to the potential of generating daily noise exposure data and the advantages, and disadvantages of modelling using radar data. © 2022 Internoise 2022 - 51st International Congress and Exposition on Noise Control Engineering. All rights reserved.

No transport? No worries! Cardiac telerehabilitation is a feasible and effective alternative to centre-based programs.

Given the under-utilisation of cardiac rehabilitation despite its benefits, there has been a shift towards alternative delivery models. The recent coronavirus disease 2019 (COVID-19) pandemic has accelerated this shift, leading to a growing interest in home-based cardiac rehabilitation including telerehabilitation. There is increasing evidence to support cardiac telerehabilitation, with studies generally demonstrating comparable outcomes and potential cost-benefits. This review aims to provide a synopsis of the current evidence on home-based cardiac rehabilitation with a focus on telerehabilitation and practical considerations.

Health workforce perceptions on telehealth augmentation opportunities.

BACKGROUND: The availability and use of telehealth to support health care access from a distance has expanded in response to the COVID-19 pandemic. Telehealth services have supported regional and remote health care access for many years and could be augmented to improve health care accessibility, acceptability and overall experiences for both consumers and clinicians. This study aimed to explore health workforce representatives' needs and expectations to move beyond existing telehealth models and plan for the future of virtual care. METHODS: To inform recommendations for augmentation, semi-structured focus group discussions were held (November-December 2021). Health workforce representatives with experience in health care delivery via telehealth across country Western Australia were approached and invited to join a discussion. RESULTS: Focus group participants included 53 health workforce representatives, with between two and eight participants per discussion. In total, 12 focus groups were conducted: seven were specific to regions, three with staff in centralised roles, and two with a mixture of participants from regional and central roles. Findings identified four key areas for telehealth augmentation: improvements required to existing service practice and processes; equity and access considerations; health workforce-focussed opportunities; and consumer-focussed opportunities. CONCLUSIONS: Following the onset of the COVID-19 pandemic and the rapid increase in health services delivered via telehealth modalities, it is timely to explore opportunities to augment pre-existing models of care. Workforce representatives consulted in this study suggested modifications to existing process and practice that would improve the current models of care, and recommendations on ways to improve clinician and consumer experiences with telehealth. Improving experiences with virtual delivery of health care is likely to support continued use and acceptance of this modality in health care delivery.

Assessing health-related quality-of-life in Australian Multiple Sclerosis Longitudinal Study participants using six multi-attribute utility instruments: implications for healthcare decision-making

Background: Despite important discoveries/advances in treating multiple sclerosis (MS), people with MS (pwMS) can experience delays in accessing new treatments if decision-makers lack robust health economic evidence including health-related quality-of-life (HRQoL) benefits of the intervention. Health state utilities (HSU) are a HRQoL input for cost-utility analysis. Objective(s): Several multi-attribute utility instruments (MAUIs) are available from which HSUs can be derived, but the most appropriate MAUI for use in MS has not been identified. We aimed to determine the preferentially sensitive MAUI(s) that capture the full impact of MS on HRQoL. Method(s): Participants in this study came from a comprehensive HRQoL survey (mid-2020) of the Australian MS Longitudinal Study. The survey included six MAUIs (EQ-5D-5L/ EQ-5D5LPsychosocial, SF-6D versions 1 and 2, AQoL-8D and PropR), and sociodemographic, Covid19-related and subjective wellbeing data. HSUs were generated from Australian value sets. Ceiling and floor effects were investigated. Bland-Altman plots and Shannon's Indices were examined. Minimal important differences and population norms were sourced from the literature. Result(s): N=1,683 pwMS completed the survey (67% response). HSUs were derived for >97% of respondents. Mean age 58.6 years, 80% female, 19% reported severe disease and 63% had relapsing-remitting MS. Mean (SD) HSUs ranged from 0.45+/-0.29 (SF-6Dv1) to 0.63+/-0.22 (AQoL-8D). EQ-5D-5L revealed the highest ceiling (HSU=1.0;n=157,10%) and floor (HSU<=0;n=113,7%) effects. PwMS with EQ-5D-5L HSU<=0/HSU=1 reported mean HSUs of 0.37/0.91, 0.35/0.90, and 0.08/0.85 for the AQoL-8D, EQ-5D5LPsychosocial and SF-6D, respectively. Conclusion(s): While the EQ-5D is the most commonly cited MAUI (in 85% of health technology assessment guidelines), our preliminary comparison results suggest the EQ-5D-5L is not preferentially sensitive in assessing the complex HRQoL domains for pwMS.

SARS-CoV-2 concentration in wastewater consistently predicts trends in COVID-19 case counts by at least two days across multiple WWTP scales.

Wastewater surveillance of SARS-CoV-2 has proven instrumental in mitigating the spread of COVID-19 by providing an economical and equitable approach to disease surveillance. Here, we analyze the correlation of SARS-CoV-2 RNA in influents of seven wastewater plants (WWTPs) across the state of South Carolina with corresponding daily case counts to determine whether underlying characteristics of WWTPs and sewershed populations predict stronger correlations. The populations served by these WWTPs have varying social vulnerability and represent 24% of the South Carolina population. The study spanned 15 months from April 19, 2020, to July 1, 2021, which includes the administration of the first COVID-19 vaccines. SARS-CoV-2 RNA concentrations were measured by either reverse transcription quantitative PCR (RT-qPCR) or droplet digital PCR (RT-ddPCR). Although populations served and average flow rate varied across WWTPs, the strongest correlation was identified for six of the seven WWTPs when daily case counts were lagged two days after the measured SARS-CoV-2 RNA concentration in wastewater. The weakest correlation was found for WWTP 6, which had the lowest ratio of population served to average flow rate, indicating that the SARS-CoV-2 signal was too dilute for a robust correlation. Smoothing daily case counts by a 7-day moving average improved correlation strength between case counts and SARS-CoV-2 RNA concentration in wastewater while dampening the effect of lag-time optimization. Correlation strength between cases and SARS-CoV-2 RNA was compared for cases determined at the ZIP-code and sewershed levels. The strength of correlations using ZIP-code-level versus sewershed-level cases were not statistically different across WWTPs. Results indicate that wastewater surveillance, even without normalization to fecal indicators, is a strong predictor of clinical cases by at least two days, especially when SARS-CoV-2 RNA is measured using RT-ddPCR. Furthermore, the ratio of population served to flow rate may be a useful metric to assess whether a WWTP is suitable for a surveillance program.

Quantitative Reverse Transcription PCR Surveillance of SARS-CoV-2 Variants of Concern in Wastewater of Two Counties in Texas, United States

After its emergence in late November/December 2019, the severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) rapidly spread globally. Recognizing that this virus is shed in feces of individuals and that viral RNA is detectable in wastewater, testing for SARS-CoV-2 in sewage collections systems has allowed for the monitoring of a community's viral burden. Over a 9 month period, the influents of two regional wastewater treatment facilities were concurrently examined for wild-type SARS-CoV-2 along with variants B.1.1.7 and B.1.617.2 incorporated as they emerged. Epidemiological data including new confirmed COVID-19 cases and associated hospitalizations and fatalities were tabulated within each location. RNA from SARS-CoV-2 was detectable in 100% of the wastewater samples, while variant detection was more variable. Quantitative reverse transcription PCR (RTqPCR) results align with clinical trends for COVID-19 cases, and increases in COVID-19 cases were positively related with increases in SARS-CoV-2 RNA load in wastewater, although the strength of this relationship was location specific. Our observations demonstrate that clinical and wastewater surveillance of SARS-CoV-2 wild type and constantly emerging variants of concern can be combined using RT-qPCR to characterize population infection dynamics. This may provide an early warning for at-risk communities and increases in COVID-19 related hospitalizations.

COVID-19 Pandemic as a Transitional Event: From the Perspective of the Transition Theory

Definition: The COVID-19 pandemic has affected every aspect of people's lives across the globe. It is also unique in the way it changed their lives. In this entry, a framework, the Transition Theory, is outlined, which is used to interpret the transitional properties of this pandemic, the ways it differs from other transitional events, and how it impacts the lives and well-being of the individuals. The prediction is that people might consider the pandemic as an important life transition event only if there is a little similarity between their pre-pandemic and post-pandemic lives. Individual differences also need to be considered as those whose lives have been directly affected by the pandemic experience a greater COVID-related change (e.g., job loss vs. no job loss). Lastly, the transitional impact of the pandemic might have a strong link with people's mental outcomes. These notions call for a longitudinal approach to get an accurate understanding of the pandemic experience while this world-changing event unfolds rather than in retrospect. [ FROM AUTHOR] Copyright of Encyclopedia is the property of MDPI 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.)

The association of typical and atypical symptoms with in-hospital mortality in older adults with COVID-19: a multicentre cohort study

Atypical disease presentations are common in older adults with COVID-19. The objective of this study was to determine the prevalence of atypical and typical symptoms in older adults with COVID-19 through progressive pandemic waves and the association of these symptoms with in -hospital mortality. This retrospective cohort study included consecutive adults aged over 65 years with confirmed COVID-19 infection who were admitted to seven hospitals in Toronto, Canada, from 1 March 2020 to 30 June 2021. The median age for the 1786 patients was 78.0 years and 847 (47.5%) were female. Atypical symptoms (as defined by geriatric syndromes) occurred in 1187 patients (66.5%), but rarely occurred in the absence of other symptoms (n = 106;6.2%). The most common atypical symptoms were anorexia (n = 598;33.5%), weakness (n = 519;2 3.9%), and delirium (n = 449;25.1%). Dyspnea (adjusted odds ratio [aOR] 2.05;95% confidence interval [CI] 1.62-2.62), tachycardia (aOR 1.87;95% CI 1.14-3.04), and delirium (aOR 1.52;95% CI 1.18-1.96) were inde-pendently associated with in-hospital mortality. In a cohort of older adults hospitalized with COVID-19 infection, atypical presentations frequently overlapped with typical symptoms. Further research should be directed at understanding the cause and clinical significance of atypical presenta-tions in older adults.

Building-level wastewater surveillance of SARS-CoV-2 is associated with transmission and variant trends in a university setting.

The University of South Carolina (UofSC) was among the first universities to include building-level wastewater surveillance of SARS-CoV-2 to complement clinical testing during its reopening in the Fall 2020 semester. In the Spring 2021 semester, 24h composite wastewater samples were collected twice per week from 10 residence halls and the on-campus student isolation and quarantine building. The isolation and quarantine building served as a positive control site. The wastewater was analyzed using RT-ddPCR for the quantification of nucleocapsid genes (N1 and N2) to identify viral transmission trends within residence halls. Log10 SARS-CoV-2 RNA concentrations were compared to both new clinical cases identified in the days following wastewater collection and recovered cases returning to sites during the days preceding sample collection to test temporal and spatial associations. There was a statistically significant positive relationship between the number of cases reported from the sites during the seven-day period following wastewater sampling and the log10 viral RNA copies/L (overall IRR 1.08 (1.02, 1.16) p-value 0.0126). Additionally, a statistically significant positive relationship was identified between the number of cases returning to the residence halls after completing isolation during the seven-day period preceding wastewater sampling and the log10 viral RNA copies/L (overall 1.09 (1.01, 1.17) p-value 0.0222). The statistical significance of both identified cases and recovered return cases on log10 viral RNA copies/L in wastewater indicates the importance of including both types of clinical data in wastewater-based epidemiology (WBE) research. Genetic mutations associated with variants of concern (VOCs) were also monitored. The emergence of the Alpha variant on campus was identified, which contributed to the second wave of COVID-19 cases at UofSC. The study was able to identify sub-community transmission hotspots for targeted intervention in real-time, making WBE cost-effective and creating less of a burden on the general public compared to repeated individual testing methods.

Comparative Analysis of RNA-Extraction Approaches and Associated Influences on RT-qPCR of the SARS-CoV-2 RNA in a University Residence Hall and Quarantine Location

Wastewater-based epidemiology (WBE) provides an early warning and trend analysis approach for determining the presence of COVID-19 in a community and complements clinical testing in assessing the population level, even as viral loads fluctuate. Here, we evaluate combinations of two wastewater concentration methods (i.e., ultrafiltration and composite supernatant-solid), four pre-RNA extraction modifications, and three nucleic acid extraction kits using two different wastewater sampling locations. These consisted of a quarantine facility containing clinically confirmed COVID-19-positive inhabitants and a university residence hall. Of the combinations examined, composite supernatant-solid with pre-RNA extraction consisting of water concentration and RNA/DNA shield performed the best in terms of speed and sensitivity. Further, of the three nucleic acid extraction kits examined, the most variability was associated with the Qiagen kit. Focusing on the quarantine facility, viral concentrations measured in wastewater were generally significantly related to positive clinical cases, with the relationship dependent on method, modification, kit, target, and normalization, although results were variable-dependent on individual time points (Kendall's Tau-b (tau) = 0.17 to 0.6) or cumulatively (Kendall's Tau-b (tau) = -0.048 to 1). These observations can support laboratories establishing protocols to perform wastewater surveillance and monitoring efforts for COVID-19.

Development of an aerosol intervention for COVID-19 disease: Tolerability of soluble ACE2 (APN01) administered via nebulizer.

As ACE2 is the critical SARS-CoV-2 receptor, we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung, and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here, after demonstrating in vitro neutralization of SARS-CoV-2 by APN01, and after obtaining preliminary evidence of its tolerability and preventive efficacy in a mouse model, we pursued development of an aerosol formulation. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers has now been initiated (NCT05065645), with subsequent Phase II testing planned for individuals with SARS-CoV-2 infection.

Dispersion of SARS-CoV-2 RNA across a wastewater treatment plant and its workers.

Within urban and suburban sewersheds, SARS-CoV-2 released through faeces is transported through sewage systems into municipal wastewater treatment plants (WWTPs). Studies have shown that viral RNA is detectable in untreated wastewater but not in WWTP effluent. In this study, we investigated treatment steps between the influent and final treated effluent to identify the point at which viral RNA is below detection. Additionally, we examined air surrounding high turbulence treatment steps to test for the presence of SARS-CoV-2 RNA in WWTP-generated bioaerosols. To examine potential worker exposure to SARS-CoV-2, WWTP workers were tested for the presence of viral RNA. The data show that despite high viral RNA concentration in the influent, SARS-CoV-2 RNA concentration decreased significantly (p < 0.02) in the main treatment steps and was below detection in the effluent. Additionally, SARS-CoV-2 RNA was below detection in air samples (n = 42), and the worker rate of infection was not significantly different (p = 0.99) from the rate of infection in the surrounding community. These results suggest that WWTP workers may have minimal exposure to SARS-CoV-2 during routine outdoor work procedures and that the WWTP successfully reduces the amount of viral RNA entering effluent receiving waters, providing a vital public health service to communities.

Wastewater surveillance of SARS-CoV-2 mutational profiles at a university and its surrounding community reveals a 20G outbreak on campus.

Wastewater surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been leveraged during the Coronavirus Disease 2019 (COVID-19) pandemic as a public health tool at the community and building level. In this study, we compare the sequence diversity of SARS-CoV-2 amplified from wastewater influent to the Columbia, South Carolina, metropolitan wastewater treatment plant (WWTP) and the University of South Carolina campus during September 2020, which represents the peak of COVID-19 cases at the university during 2020. A total of 92 unique mutations were detected across all WWTP influent and campus samples, with the highest frequency mutations corresponding to the SARS-CoV-2 20C and 20G clades. Signature mutations for the 20G clade dominated SARS-CoV-2 sequences amplified from localized wastewater samples collected at the University of South Carolina, suggesting that the peak in COVID-19 cases during early September 2020 was caused by an outbreak of the 20G lineage. Thirteen mutations were shared between the university building-level wastewater samples and the WWTP influent collected in September 2020, 62% of which were nonsynonymous substitutions. Co-occurrence of mutations was used as a similarity metric to compare wastewater samples. Three pairs of mutations co-occurred in university wastewater and WWTP influent during September 2020. Thirty percent of the detected mutations, including 12 pairs of concurrent mutations, were only detected in university samples. This report affirms the close relationship between the prevalent SARS-CoV-2 genotypes of the student population at a university campus and those of the surrounding community. However, this study also suggests that wastewater surveillance at the building-level at a university offers important insight by capturing sequence diversity that was not apparent in the WWTP influent, thus offering a balance between the community-level wastewater and clinical sequencing.

Protocol for a prospective double-blind, randomised, placebo-controlled feasibility trial of octreotide infusion during liver transplantation.

INTRODUCTION: Liver transplantation is a complex operation that can provide significant improvements in quality of life and survival to the recipients. However, serious complications are common and include major haemorrhage, hypotension and renal failure. Blood transfusion and the development of acute kidney injury lead to both short-term and long-term poor patient outcomes, including an increased risk of death, graft failure, length of stay and reduced quality of life. Octreotide may reduce the incidence of renal dysfunction, perioperative haemorrhage and enhance intraoperative blood pressure. However, octreotide does have risks, including resistant bradycardia, hyperglycaemia and hypoglycaemia and QT prolongation. Hence, a randomised controlled trial of octreotide during liver transplantation is needed to determine the cost-efficacy and safety of its use; this study represents a feasibility study prior to this trial. METHODS AND ANALYSIS: We describe a multicentre, double-blind, randomised, placebo-controlled feasibility study of continuous infusion of octreotide during liver transplantation surgery. We will recruit 30 adult patients at two liver transplant centres. A blinded infusion during surgery will be administered in a 2:1 ratio of octreotide:placebo. The primary outcomes will determine the feasibility of this study design. These include the recruitment ratio, correct administration of blinded study intervention, adverse event rates, patient and clinician enrolment refusal and completion of data collection. Secondary outcome measures of efficacy and safety will help shape future trials by assessing potential primary outcome measures and monitoring safety end points. No formal statistical tests are planned. This manuscript represents study protocol number 1.3, dated 2 June 2021. ETHICS AND DISSEMINATION: This study has received Research Ethics Committee approval. The main study outcomes will be submitted to an open-access journal. TRIAL SPONSOR: The Joint Research Office, University College London, UK.Neither the sponsor nor the funder have any role in study design, collection, management, analysis and interpretation of data, writing of the study report or the decision to submit the report for publication. TRIAL REGISTRATION: The study is registered with ClinicalTrials.gov (NCT04941911) with recruitment due to start in August 2021 with anticipated completion in July 2022. CLINICAL TRIALS UNIT: Surgical and Interventional Group, Division of Surgery & Interventional Science, University College London.

Home-based and remote functional exercise testing in cardiac conditions, during the covid-19 pandemic and beyond: a systematic review.

BACKGROUND: With the change in healthcare to one that adopts a greater reliance on remote delivery, guidance regarding functional exercise testing, either in-person in the home or performed remotely, is urgently needed for people with cardiac conditions. OBJECTIVES: To identify functional exercise tests that have been conducted in the home or remotely in patients with cardiac conditions. DATA SOURCES: A search was undertaken across four electronic databases and grey literature for English language publications without time restrictions. STUDY ELIGIBILITY CRITERIA: Studies of any designs were selected if they reported an exercise test conducted at home or remotely in patients with cardiac conditions. STUDY APPRAISAL AND SYNTHESIS: Studies were independently screened and graded by two reviewers according to the Downs and Black checklist. A narrative synthesis of the included studies was undertaken. RESULTS: Five studies (six articles) were included, with a total of 438 patients with cardiac conditions. Tests used at home or remotely were the 6-minute walk test (6MWT, five studies) and the timed up and go test (one study). No studies reported the use of step tests in the home or remotely. The 6MWTs were administered via a smartphone application, rope, videoconferencing and accelerometer and proved to be feasible, valid and reliable. CONCLUSIONS: Despite a marked demand for home-based exercise programs, the 6MWT remains the most commonly administered functional exercise test for people with cardiac conditions. Surprisingly few studies have explored alternative tests for this patient population that may be more suitable for home or remote performance. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO: CRD42020219512.

Exploring People's Reaction and Perceived Issues of the COVID-19 Pandemic at Its Onset.

The experience of the COVID-19 Pandemic has varied considerably from individual-to-individual. Little is known about the changes in the level of experience general people went through during the first few months after the coronavirus (COVID-19) was declared as a Pandemic. This longitudinal qualitative study explores the general public's reports of their experience with the COVID-19 Pandemic during its early stage. An online survey was conducted using a convenience/snowball sampling technique in March and again in May 2020, where North American adults with at least a college-degree, and female majority, shared their experiences with the COVID-19 Pandemic in response to an open-ended question, apart from completing questionnaires assessing transitional impact and psychological well-being. Open responses were first content analyzed to identify themes most commonly reported, and then, the quantitative analysis examined the reliability of the changes of themes between the two-time points. Text-analysis of the open-responses from the two waves identified seven themes, namely emotional response, social contact, virus-infected, financial impact, impact on plans, disease, and non-disease related concern, as well as social-distance. These themes indicated that, (a) people were distressed and having negative affective thoughts; (b) they spoke more about their plans-and-goals that were affected by the Pandemic than their financial condition; (c) people mostly used digital platforms to maintain contact with their social network, although they preferred face-to-face interactions; (d) they spoke more about the infection experienced by people in general than infection experienced by themselves and individuals they know. Surprisingly, (e) people mentioned more about the way the Pandemic had disrupted their day-to-day activities than the disease-related health concern. Finally, (f) most of the respondents approved of the practice of social distancing while some expressed its negative or neutral effect on their social lives. The quantitative measure determined that as time passed, people's experience with the Pandemic became quite different as people talked more about getting infected, and their affected goals-and-plans. We concluded with a remark that this Pandemic would most likely leave an impression on people's lives and that these online comment-style responses might provide us with insights into people's perspectives as the Pandemic unfolds, helping us in understanding the uniqueness of the Pandemic experience of individuals for an effective tailored intervention to protect their well-being during a health-crisis.

Development of a novel, pan-variant aerosol intervention for COVID-19 (preprint)

To develop a universal strategy to block SARS-CoV-2 cellular entry and infection represents a central aim for effective COVID-19 therapy. The growing impact of emerging variants of concern increases the urgency for development of effective interventions. Since ACE2 is the critical SARS-CoV-2 receptor and all tested variants bind to ACE2, some even at much increased affinity (see accompanying paper), we hypothesized that aerosol administration of clinical grade soluble human recombinant ACE2 (APN01) will neutralize SARS-CoV-2 in the airways, limit spread of infection in the lung and mitigate lung damage caused by deregulated signaling in the renin-angiotensin (RAS) and Kinin pathways. Here we show that intranasal administration of APN01 in a mouse model of SARS-CoV-2 infection dramatically reduced weight loss and prevented animal death. As a prerequisite to a clinical trial, we evaluated both virus binding activity and enzymatic activity for cleavage of Ang II following aerosolization. We report successful aerosolization for APN01, retaining viral binding as well as catalytic RAS activity. Dose range-finding and IND-enabling repeat-dose aerosol toxicology testing were conducted in dogs. Twice daily aerosol administration for two weeks at the maximum feasible concentration revealed no notable toxicities. Based on these results, a Phase I clinical trial in healthy volunteers can now be initiated, with subsequent Phase II testing in individuals with SARS-CoV-2 infection. This strategy could be used to develop a viable and rapidly actionable therapy to prevent and treat COVID-19, against all current and future SARS-CoV-2 variants. One Sentence SummaryPreclinical development and evaluation of aerosolized soluble recombinant human ACE2 (APN01) administered as a COVID-19 intervention is reported.