Depression, Perceived Risk of COVID-19, Loneliness, and Perceived Social Support from Friends Among University Students in Poland, UK, and India.

Background: The study examines the prevalence of depression among university students in Poland, the UK and India in the face of the second pandemic wave of COVID-19. The paper also examines the protective role of perceived social support, the hypothesis being that social support from friends would reduce depression. Methods: The data from university students (N=732) in Poland (N=335), UK (N= 198), and India (N=199) were collected online during of the fall/winter 2021. Participants completed measures of depression (CES-D), COVID-19 risk perception index, loneliness (DJGLS), and perceived social support (MSPSS). Results: Almost 52% of all participants (58.5% in Poland, 62.6% in the UK, and 29.1% in India) met the criteria for major depression. The higher levels of depression symptoms were associated with a higher perceived risk of COVID-19, greater loneliness, female gender, younger students' age, and the lower levels of perceived social support. The greater family support predicted lower levels of depression symptoms in the Polish and Indian samples. Structural equation analyses (SEM) revealed the indirect effect of perceived social support from friends on the association between social loneliness and depression and between age and depression. This result shows that the support from friends significantly reduced depression, regardless of age, the level of social loneliness, and the perceived risk of COVID-19. Conclusion: Our conclusions link to university specialists' enhancement of psychological help for students with depression. We also recommend information campaigns on depression and treatment options.

Application of neighborhood-scale wastewater-based epidemiology in low COVID-19 incidence situations.

Wastewater-based epidemiology (WBE), an emerging approach for community-wide COVID-19 surveillance, was primarily characterized at large sewersheds such as wastewater treatment plants serving a large population. Although informed public health measures can be better implemented for a small population, WBE for neighborhood-scale sewersheds is less studied and not fully understood. This study applied WBE to seven neighborhood-scale sewersheds (average population of 1471) from January to November 2021. Community testing data showed an average of 0.004 % incidence rate in these sewersheds (97 % of monitoring periods reported two or fewer daily infections). In 92 % of sewage samples, SARS-CoV-2 N gene fragments were below the limit of quantification. We statistically determined 10-2.6 as the threshold of the SARS-CoV-2 N gene concentration normalized to pepper mild mottle virus (N/PMMOV) to alert high COVID-19 incidence rate in the studied sewershed. This threshold of N/PMMOV identified neighborhood-scale outbreaks (COVID-19 incidence rate higher than 0.2 %) with 82 % sensitivity and 51 % specificity. Importantly, neighborhood-scale WBE can discern local outbreaks that would not otherwise be identified by city-scale WBE. Our findings suggest that neighborhood-scale WBE is an effective community-wide disease surveillance tool when COVID-19 incidence is maintained at a low level.

Gain-of-Signal Assays for Probing Inhibition of SARS-CoV-2 Mpro/3CLpro in Living Cells.

The main protease, Mpro, of SARS-CoV-2 is required to cleave the viral polyprotein into precise functional units for virus replication and pathogenesis. Here, we report quantitative reporters for Mpro function in living cells in which protease inhibition by genetic or chemical methods results in robust signal readouts by fluorescence (enhanced green fluorescent protein [eGFP]) or bioluminescence (firefly luciferase). These gain-of-signal systems are scalable to high-throughput platforms for quantitative discrimination between Mpro mutants and/or inhibitor potencies as evidenced by validation of several reported inhibitors. Additional utility is shown by single Mpro amino acid variants and structural information combining to demonstrate that both inhibitor conformational dynamics and amino acid differences are able to influence inhibitor potency. We further show that a recent variant of concern (Omicron) has an unchanged response to a clinically approved drug, nirmatrelvir, whereas proteases from divergent coronavirus species show differential susceptibility. Together, we demonstrate that these gain-of-signal systems serve as robust, facile, and scalable assays for live cell quantification of Mpro inhibition, which will help expedite the development of next-generation antivirals and enable the rapid testing of emerging variants. IMPORTANCE The main protease, Mpro, of SARS-CoV-2 is an essential viral protein required for the earliest steps of infection. It is therefore an attractive target for antiviral drug development. Here, we report the development and implementation of two complementary cell-based systems for quantification of Mpro inhibition by genetic or chemical approaches. The first is fluorescence based (eGFP), and the second is luminescence based (firefly luciferase). Importantly, both systems rely upon gain-of-signal readouts such that stronger inhibitors yield higher fluorescent or luminescent signal. The high versatility and utility of these systems are demonstrated by characterizing Mpro mutants and natural variants, including Omicron, as well as a panel of existing inhibitors. These systems rapidly, safely, and sensitively identify Mpro variants with altered susceptibilities to inhibition, triage-nonspecific, or off-target molecules and validate bona fide inhibitors, with the most potent thus far being the first-in-class drug nirmatrelvir.

Lessons learned from academic medical centers' response to the COVID-19 pandemic in partnership with the Navajo Nation.

INTRODUCTION: Structural forces that drive health inequalities are magnified in crises. This was especially true during the COVID-19 pandemic, and minority communities were particularly affected. The University of California San Francisco and Health, Equity, Action, Leadership Initiative jointly sent volunteer teams of nurses and doctors to work in the Navajo Nation during the COVID-19 pandemic. This presented an opportunity to explore how academic medical centers (AMCs) could effectively partner with vulnerable communities to provide support during healthcare crises. Therefore, the aims of this study were to describe volunteers' perspectives of academic-community partnerships by exploring their personal, professional and societal insights and lessons learned based on their time in the Navajo Nation during COVID-19. METHODS: We recruited key informants using purposeful sampling of physicians and nurses who volunteered to go to the Navajo Nation during the spring 2020 COVID-19 surge, as well as hospital administrators and leaders involved in organizing the COVID-19 efforts. We used in-depth qualitative interviews to explore key informants' experiences pre-departure, during their stay, and after their return, as well as perspectives of the partnership between an AMC and the Navajo Nation. We used thematic analysis to systematically identify, analyze and report patterns (themes) within the data. RESULTS: In total, 37 clinicians and hospital administrators were interviewed including 14 physicians, 16 nurses, and 7 health system leaders. Overall, we found 4 main themes each with several subthemes that defined the partnership between the AMC and the Navajo Nation. Mission and values incorporated civic duty, community engagement, leadership commitment and employee dedication. Solidarity, trust and humility encompassed pre-existing trust, workforce sustainability, humility and erasure of 'savior narratives.' Coordination included logistical coordination, flexibility, selectivity of who and what traveled to the response and coordination around media response. Workforce preparation and support encompassed understanding of historical context and providing healthcare in limited settings, dangers of inadequate preparation and the need for emotional support. CONCLUSION: This study provides guidelines which AMCs might use to develop and improve partnerships they have or would like to develop with vulnerable communities. These guidelines may even be broadly applied to partnerships outside of a pandemic response. Importantly, such partnerships need to be built with trust and with an eye towards sustainability and long-term relationships as opposed to 'medical missions'.

The Military Treatment Facility COVID-19 Response in an Isolated Rural Environment: Challenges and Lessons Learned.

The coronavirus disease-2019 (COVID-19) pandemic remains an extraordinary event that continues to strain healthcare systems worldwide. Unlike the military treatment facilities (MTFs) in the USA, which have ready access to tertiary care facilities, those MTFs in foreign countries confront a host of challenges in meeting mission requirements. In this article, we discuss the MTFs' COVID-19 response in the rural environment of Bavaria, Germany. Relevant factors including regional and clinic response, force health protection, and contingency planning, which influenced the MTFs response, are identified. These factors are further analyzed from a "lessons learned" perspective, and recommendations to shape the future response to a pandemic are provided. This current crisis portends a future where pandemics may remain an omnipresent threat.

COVID 19: An unprecedented opportunity for nurse practitioners to reform healthcare and advocate for permanent full practice authority.

The coronavirus disease 2019 (COVID-19) pandemic ushered in a new era for advanced practice registered nurses, as emergency regulatory and policy changes expanded the nurse practitioner (NP) scope of practice. The legislative changes enabled NPs to bolster the national pandemic response by working to the full extent of their education and training. The changes are only temporary, and many have contemplated the permanent impact of COVID-19 when healthcare transitions to a postpandemic normal. NPs now have a unique opportunity to educate others about the merit of their role and advocate for permanent legislative changes. In this creative controversy manuscript, we build a case that national NP full practice authority increases access to care and is vital for a sustainable and resilient healthcare system that can react to future pandemic crises.

Quantification of Aerosol Particle Concentrations During Endoscopic Sinonasal Surgery in the Operating Room.

BACKGROUND: Recent indirect evidence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) transmission during endoscopic endonasal procedures has highlighted the dearth of knowledge surrounding aerosol generation with these procedures. As we adapt to function in the era of Coronavirus Disease 2019 (COVID-19) a better understanding of how surgical techniques generate potentially infectious aerosolized particles will enhance the safety of operating room (OR) staff and learners. OBJECTIVE: To provide greater understanding of possible SARS-CoV-2 exposure risk during endonasal surgeries by quantifying increases in airborne particle concentrations during endoscopic sinonasal surgery. METHODS: Aerosol concentrations were measured during live-patient endoscopic endonasal surgeries in ORs with an optical particle sizer. Measurements were taken throughout the procedure at six time points: 1) before patient entered the OR, 2) before pre-incision timeout during OR setup, 3) during cold instrumentation with suction, 4) during microdebrider use, 5) during drill use and, 6) at the end of the case prior to extubation. Measurements were taken at three different OR position: surgeon, circulating nurse, and anesthesia provider. RESULTS: Significant increases in airborne particle concentration were measured at the surgeon position with both the microdebrider (p = 0.001) and drill (p = 0.001), but not for cold instrumentation with suction (p = 0.340). Particle concentration did not significantly increase at the anesthesia position or the circulator position with any form of instrumentation. Overall, the surgeon position had a mean increase in particle concentration of 2445 particles/ft3 (95% CI 881 to 3955; p = 0.001) during drill use and 1825 particles/ft3 (95% CI 641 to 3009; p = 0.001) during microdebrider use. CONCLUSION: Drilling and microdebrider use during endonasal surgery in a standard operating room is associated with a significant increase in airborne particle concentrations. Fortunately, this increase in aerosol concentration is localized to the area of the operating surgeon, with no detectable increase in aerosol particles at other OR positions.

Quantification of Aerosol Concentrations During Endonasal Instrumentation in the Clinic Setting.

OBJECTIVE: Recent anecdotal reports and cadaveric simulations have described aerosol generation during endonasal instrumentation, highlighting a possible risk for transmission of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) during endoscopic endonasal instrumentation. This study aims to provide a greater understanding of particle generation and exposure risk during endoscopic endonasal instrumentation. STUDY DESIGN: Prospective quantification of aerosol generation during office-based nasal endoscopy procedures. METHODS: Using an optical particle sizer, airborne particles concentrations 0.3 to 10 microns in diameter, were measured during 30 nasal endoscopies in the clinic setting. Measurements were taken at time points throughout diagnostic and debridement endoscopies and compared to preprocedure and empty room particle concentrations. RESULTS: No significant change in airborne particle concentrations was measured during diagnostic nasal endoscopies in patients without the need for debridement. However, significant increases in mean particle concentration compared to preprocedure levels were measured during cold instrumentation at 2,462 particles/foot3 (95% CI 837 to 4,088; P = .005) and during suction use at 2,973 particle/foot3 (95% CI 1,419 to 4,529; P = .001). In total, 99.2% of all measured particles were ≤1 µm in diameter. CONCLUSION: When measured with an optical particle sizer, diagnostic nasal endoscopy with a rigid endoscope is not associated with increased particle aerosolization in patient for whom sinonasal debridement is not needed. In patients needing sinonasal debridement, endonasal cold and suction instrumentation were associated with increased particle aerosolization, with a trend observed during endoscope use prior to tissue manipulation. Endonasal debridement may potentially pose a higher risk for aerosolization and SARS-CoV-2 transmission. Appropriate personal protective equipment use and patient screening are recommended for all office-based endonasal procedures. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E1415-E1421, 2021.