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The global pandemic presents a critical threat to humanity, with no effective rapid-response solutions for early-stage virus dissemination. This study aims to create an AI-driven entry-blocker design system (AIEB) to fabricate inhalable virus-like nanocatchers (VLNCs) fused with entry-blocking peptides (EBPs) to counter pandemic viruses and explore therapeutic applications. This work focuses on developing angiotensin-converting enzyme 2 (ACE2)-mimic domain-fused VLNCs (ACE2@VLNCs) using AIEB and analyzing their interaction with the SARS-CoV-2 receptor binding domain (RBD), demonstrating their potential to hinder SARS-CoV-2 infection. Aerosol-based tests show ACE2@VLNCs persist over 70 min in the air and neutralize pseudoviruses within 30 min, indicating their utility in reducing airborne virus transmission. In vivo results reveal ACE2@VLNCs mitigate over 67% of SARS-CoV-2 infections. Biosafety studies confirm their safety, causing no damage to eyes, skin, lungs, or trachea, and not eliciting significant immune responses. These findings offer crucial insights into pandemic virus prevention and treatment, highlighting the potential of the ACE2@VLNCs system as a promising strategy against future pandemics., (© 2023 Wiley-VCH GmbH.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). COVID-19 is now recognized as a multiorgan disease with a broad spectrum of manifestations. A substantial proportion of individuals who have recovered from COVID-19 are experiencing persistent, prolonged, and often incapacitating sequelae, collectively referred to as long COVID. To date, definitive diagnostic criteria for long COVID diagnosis remain elusive. An emerging public health threat is neuropsychiatric long COVID, encompassing a broad range of manifestations, such as sleep disturbance, anxiety, depression, brain fog, and fatigue. Although the precise mechanisms underlying the neuropsychiatric complications of long COVID are presently not fully elucidated, neural cytolytic effects, neuroinflammation, cerebral microvascular compromise, breakdown of the blood-brain barrier (BBB), thrombosis, hypoxia, neurotransmitter dysregulation, and provoked neurodegeneration are pathophysiologically linked to long-term neuropsychiatric consequences, in addition to systemic hyperinflammation and maladaptation of the renin-angiotensin-aldosterone system. Vitamin D, a fat-soluble secosteroid, is a potent immunomodulatory hormone with potential beneficial effects on anti-inflammatory responses, neuroprotection, monoamine neurotransmission, BBB integrity, vasculometabolic functions, gut microbiota, and telomere stability in different phases of SARS-CoV-2 infection, acting through both genomic and nongenomic pathways. Here, we provide an up-to-date review of the potential mechanisms and pathophysiology of neuropsychiatric long COVID syndrome and the plausible neurological contributions of vitamin D in mitigating the effects of long COVID.

Background: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults., Methods: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses., Results: The COVID-19 pandemic was associated with increased depressive symptoms in older adults [ b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18-5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic., Conclusions: The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

Background: Basic life support (BLS) education is essential for improving bystander cardiopulmonary resuscitation (CPR) rates, but the imparting of such education faces obstacles during the outbreak of emerging infectious diseases, such as COVID-19. When face-to-face teaching is limited, distance learning-blended learning (BL) or an online-only model-is encouraged. However, evidence regarding the effect of online-only CPR training is scarce, and comparative studies on classroom-based BL (CBL) are lacking. While other strategies have recommended self-directed learning and deliberate practice to enhance CPR education, no previous studies have incorporated all of these instructional methods into a BLS course., Objective: This study aimed to demonstrate a novel BLS training model-remote practice BL (RBL)-and compare its educational outcomes with those of the conventional CBL model., Methods: A static-group comparison study was conducted. It included RBL and CBL courses that shared the same paradigm, comprising online lectures, a deliberate practice session with Little Anne quality CPR (QCPR) manikin feedback, and a final assessment session. In the main intervention, the RBL group was required to perform distant self-directed deliberate practice and complete the final assessment via an online video conference. Manikin-rated CPR scores were measured as the primary outcome; the number of retakes of the final examination was the secondary outcome., Results: A total of 52 and 104 participants from the RBL and CBL groups, respectively, were eligible for data analysis. A comparison of the 2 groups revealed that there were more women in the RBL group than the CBL group (36/52, 69.2% vs 51/104, 49%, respectively; P=.02). After adjustment, there were no significant differences in scores for QCPR release (96.9 vs 96.4, respectively; P=.61), QCPR depth (99.2 vs 99.5, respectively; P=.27), or QCPR rate (94.9 vs 95.5, respectively; P=.83). The RBL group spent more days practicing before the final assessment (12.4 vs 8.9 days, respectively; P<.001) and also had a higher number of retakes (1.4 vs 1.1 times, respectively; P<.001)., Conclusions: We developed a remote practice BL-based method for online-only distant BLS CPR training. In terms of CPR performance, using remote self-directed deliberate practice was not inferior to the conventional classroom-based instructor-led method, although it tended to take more time to achieve the same effect., Trial Registration: Not applicable., (©Kah Meng Chong, Hsiang-Wen Yang, Hsien-Chin He, Wan-Ching Lien, Mei-Fen Yang, Chien-Yu Chi, Yen-Pin Chen, Chien-Hua Huang, Patrick Chow-In Ko. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.04.2023.)

The COVID-19 pandemic has evolved to immune escape and threatened small children and the elderly with a higher severity and fatality of non-pulmonary diseases. These life-threatening non-pulmonary COVID-19 diseases such as acute necrotizing encephalopathies (ANE) and multisystem inflammatory syndrome in children (MIS-C) are more prevalent in children. However, the mortality of multisystem inflammatory syndrome in adults (MIS-A) is much higher than that of MIS-C although the incidence of MIS-A is lower. Clarification of immunopathogenesis and genetic susceptibility of inflammatory non-pulmonary COVID-19 diseases would provide an appropriate guide for the crisis management and prevention of morbidity and fatality in the ongoing pandemic. This review article described three inflammatory non-pulmonary COVID-19 diseases including (1) meningoencephalitis (ME), (2) acute necrotizing encephalopathies (ANE), and (3) post-infectious multisystem inflammatory syndrome in children (MIS-C) and in adults (MIS-A). To prevent these life-threatening non-pulmonary COVID-19 diseases, hosts carrying susceptible genetic variants should receive prophylactic vaccines, avoid febrile respiratory tract infection, and institute immunomodulators and mitochondrial cocktails as early as possible.

Chronic kidney disease (CKD) is the most neglected chronic disease affecting over 750 million persons in the world. Currently, many patients with cancers or other chronic diseases (i.e., CKD) struggle to receive clinical treatment or examination due to hospitals cancelling or delaying in the COVID-19 pandemic, which may increase the risk of death. Cystatin C (Cys C) has been proposed as a potential glomerular filtration rate (GFR) marker for the early detection of acute kidney injury and CKD. However, most traditional methods for Cys C detection are immunoassays using serum as a sample and are tedious to perform and economically burdensome. To diagnose the disease in the early stage and carry out daily management during the current pandemic, we developed an integration of hydrogel microneedle patch (HMNP) and lateral flow cassette (LFC) to rapidly detect Cys C in skin interstitial fluid (ISF) in 25 min for blood-free CKD management anytime and anywhere by the naked eye that can reduce the impact of an individual's quality of life and life expectancy. Conceivably, this strategy presents a wide scope in the application of numerous other diseases if corresponding analytes are available in skin ISF., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Reusing treated wastewater can effectively alleviate water shortages and water contamination problems but depends on ensuring the safety of the reclaimed water that is produced. The operating and management conditions for water reclamation plants in China have been changed since the outbreak of the COVID-19 epidemic in China at the end of 2019 to prevent emerging viruses being spread through wastewater treatment processes and the reclaimed water that is produced. Removal of pathogens and trace organic compounds (e.g., pharmaceuticals and personal care products and endocrine disrupting chemicals) in a real water reclamation plant after the start of COVID-19 epidemic was studied. Disinfection byproduct formation caused by chlorine being added to meet disinfection requirements was also assessed. The pathogenic microorganism concentrations in effluent were <2 (most probable number)/L, and the removal rates for most trace organic compounds were >80% when advanced treatments were performed using ozone, ultraviolet light, and chlorine doses of 2 mg/L, 20.5 mJ/cm 2 , and 2-3 mg/L, respectively. The main disinfection byproduct produced at a chlorine dose of 2 mg/L and a residence time of 1 h was chloroform (at concentrations <15 μg/L). The results indicated that the water reclamation processes with modified conditions gave high pathogen and trace organic compound removal rates and reasonably well-controlled disinfection byproduct concentrations., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This study estimated tourists' willingness to pay (WTP) for tourist sites or facilities in the prolonged COVID-19 pandemic by applying the dichotomous choice-contingent valuation method to two different tourism destination types. A survey was conducted among domestic tourists in South Korea who had visited destinations within the last six months. We conducted a logistic regression with 1283 effective samples. The results showed differences in tourists' WTP, depending on type, and the factors affecting WTP differed. Tourists with higher tourism attitude and knowledge of tourism risk exhibited a higher WTP. Tourists with higher perceived risk of infectious disease exhibited less WTP.

We describe a mammalian cell-based assay to identify coronavirus 3CL protease (3CLpro) inhibitors. This assay is based on rescuing protease-mediated cytotoxicity and does not require live virus. By enabling the facile testing of compounds across a range of 15 distantly related coronavirus 3CLpro enzymes, we identified compounds with broad 3CLpro-inhibitory activity. We also adapted the assay for use in compound screening and in doing so uncovered additional severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3CLpro inhibitors. We observed strong concordance between data emerging from this assay and those obtained from live-virus testing. The reported approach democratizes the testing of 3CLpro inhibitors by developing a simplified method for identifying coronavirus 3CLpro inhibitors that can be used by the majority of laboratories, rather than the few with extensive biosafety infrastructure. We identified two lead compounds, GC376 and compound 4, with broad activity against all 3CL proteases tested, including 3CLpro enzymes from understudied zoonotic coronaviruses. IMPORTANCE Multiple coronavirus pandemics have occurred over the last 2 decades. This has highlighted a need to be proactive in the development of therapeutics that can be readily deployed in the case of future coronavirus pandemics. We developed and validated a simplified cell-based assay for the identification of chemical inhibitors of 3CL proteases encoded by a wide range of coronaviruses. This assay is reporter free, does not require specialized biocontainment, and is optimized for performance in high-throughput screening. By testing reported 3CL protease inhibitors against a large collection of 3CL proteases with variable sequence similarity, we identified compounds with broad activity against 3CL proteases and uncovered structural insights into features that contribute to their broad activity. Furthermore, we demonstrated that this assay is suitable for identifying chemical inhibitors of proteases from families other than 3CL proteases.

Background: Outbreaks of emerging infectious diseases, such as COVID-19, have negative impacts on bystander cardiopulmonary resuscitation (BCPR) for fear of transmission while breaking social distancing rules. The latest guidelines recommend hands-only cardiopulmonary resuscitation (CPR) and facemask use. However, public willingness in this setup remains unknown., Methods: A cross-sectional, unrestricted volunteer Internet survey was conducted to assess individuals' attitudes and behaviors toward performing BCPR, pre-existing CPR training, occupational identity, age group, and gender. The raking method for weights and a regression analysis for the predictors of willingness were performed., Results: Among 1,347 eligible respondents, 822 (61%) had negative attitudes toward performing BCPR. Healthcare providers (HCPs) and those with pre-existing CPR training had fewer negative attitudes (p < 0.001); HCPs and those with pre-existing CPR training and unchanged attitude showed more positive behaviors toward BCPR (p < 0.001). Further, 9.7% of the respondents would absolutely refuse to perform BCPR. In contrast, 16.9% would perform BCPR directly despite the outbreak. Approximately 9.9% would perform it if they were instructed, 23.5%, if they wore facemasks, and 40.1%, if they were to perform hands-only CPR. Interestingly, among the 822 respondents with negative attitudes, over 85% still tended to perform BCPR in the abovementioned situations. The weighted analysis showed similar results. The adjusted predictors for lower negative attitudes toward BCPR were younger age, being a man, and being an HCP; those for more positive behaviors were younger age and being an HCP., Conclusions: Outbreaks of emerging infectious diseases, such as COVID-19, have negative impacts on attitudes and behaviors toward BCPR. Younger individuals, men, HCPs, and those with pre-existing CPR training tended to show fewer negative attitudes and behaviors. Meanwhile, most individuals with negative attitudes still expressed positive behaviors under safer measures such as facemask protection, hands-only CPR, and available dispatch instructions., Competing Interests: The authors have declared that no competing interests exist.

This study aims to evaluate acceptance of COVID-19 vaccines and the impact of risk perception on vaccine acceptance and personal health protective behaviors in Taiwan. A nationwide cross-sectional study was conducted from 19 to 30 October 2020; 1020 participants were included in the final analysis; chi-square and logistic regression analyses were conducted. In total, 52.7% of participants were willing to receive COVID-19 vaccines, 63.5% perceived the severity of COVID-19 in Taiwan as "not serious", and nearly 40% were worried about COVID-19 infection. Participants with higher perceived severity of COVID-19 had significantly higher odds of refusing the vaccine (OR = 1.546), while those worried about infection had lower odds of poor health protective behaviors (OR = 0.685). Vaccine refusal reasons included "the EUA process is not strict enough" (48.7%) and "side effects" (30.3%). Those who had previously refused other vaccinations were 2.44 times more likely to refuse the COVID-19 vaccines. Participants' age had an influence on COVID-19 vaccine acceptance. In general, the Taiwanese public's acceptance of the vaccine was lower than that in other high-income countries. Elderly participants and those with college-level education and above who had previously refused vaccines had lower willingness to receive a COVID-19 vaccine. Risk perception was positively associated with personal health protective behaviors but negatively associated with COVID-19 vaccine acceptance.