Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization.

Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genome-wide association study (GWAS), the searching for sex-biased genetic variants showing differential association signals between sexes with COVID-19 hospitalization was severely hindered. We hypothesized genetic variants would show potentially sex-biased genetic effects on COVID-19 hospitalization if they display significant differential association effect sizes between male and female COVID-19 patients. By integrating two COVID-19 GWASs, including hospitalized COVID-19 patients vs. general population separated into males (case = 1,917 and control = 221,174) and females (case = 1,343 and control = 262,886), we differentiated the association effect sizes of each common single nucleotide polymorphism (SNP) within the two GWASs. Twelve SNPs were suggested to show differential COVID-19 associations between sexes. Further investigation of genes (n = 58) close to these 12 SNPs resulted in the identification of 34 genes demonstrating sex-biased differential expression in at least one GTEx tissue. Finally, 5 SNPs are mapped to 8 genes, including rs1134004 (GADD45G), rs140657166 (TRIM29 and PVRL1), rs148143613 (KNDC1 and STK32C), rs2443615 (PGAP2 and TRIM21), and rs2924725 (CSMD1). The 8 genes display significantly differential gene expression in blood samples derived from COVID-19 patients compared to healthy controls. These genes are potential genetic factors contributing to sex differences in COVID-19 hospitalization and warranted for further functional studies.

Genome-wide screening of sex-biased genetic variants potentially associated with COVID-19 hospitalization

Sex-biased difference in coronavirus disease 2019 (COVID-19) hospitalization has been observed as that male patients tend to be more likely to be hospitalized than female patients. However, due to the insufficient sample size and existed studies that more prioritized to sex-stratified COVID-19 genome-wide association study (GWAS), the searching for sex-biased genetic variants showing differential association signals between sexes with COVID-19 hospitalization was severely hindered. We hypothesized genetic variants would show potentially sex-biased genetic effects on COVID-19 hospitalization if they display significant differential association effect sizes between male and female COVID-19 patients. By integrating two COVID-19 GWASs, including hospitalized COVID-19 patients vs. general population separated into males (case = 1,917 and control = 221,174) and females (case = 1,343 and control = 262,886), we differentiated the association effect sizes of each common single nucleotide polymorphism (SNP) within the two GWASs. Twelve SNPs were suggested to show differential COVID-19 associations between sexes. Further investigation of genes (n = 58) close to these 12 SNPs resulted in the identification of 34 genes demonstrating sex-biased differential expression in at least one GTEx tissue. Finally, 5 SNPs are mapped to 8 genes, including rs1134004 (GADD45G), rs140657166 (TRIM29 and PVRL1), rs148143613 (KNDC1 and STK32C), rs2443615 (PGAP2 and TRIM21), and rs2924725 (CSMD1). The 8 genes display significantly differential gene expression in blood samples derived from COVID-19 patients compared to healthy controls. These genes are potential genetic factors contributing to sex differences in COVID-19 hospitalization and warranted for further functional studies.

Research progress of CRISPR-based biosensors and bioassays for molecular diagnosis.

CRISPR/Cas technology originated from the immune mechanism of archaea and bacteria and was awarded the Nobel Prize in Chemistry in 2020 for its success in gene editing. Molecular diagnostics is highly valued globally for its development as a new generation of diagnostic technology. An increasing number of studies have shown that CRISPR/Cas technology can be integrated with biosensors and bioassays for molecular diagnostics. CRISPR-based detection has attracted much attention as highly specific and sensitive sensors with easily programmable and device-independent capabilities. The nucleic acid-based detection approach is one of the most sensitive and specific diagnostic methods. With further research, it holds promise for detecting other biomarkers such as small molecules and proteins. Therefore, it is worthwhile to explore the prospects of CRISPR technology in biosensing and summarize its application strategies in molecular diagnostics. This review provides a synopsis of CRISPR biosensing strategies and recent advances from nucleic acids to other non-nucleic small molecules or analytes such as proteins and presents the challenges and perspectives of CRISPR biosensors and bioassays.

Stigmatizing Attitudes Toward COVID-19 Among Patients, Their Relatives and Healthy Residents in Zhangjiajie.

Introduction: In July 2021, Zhangjiajie City became the new epicenter of the COVID-19 outbreak. Aside from the physical manifestations of COVID-19, patients are also victims of severe social stigmatization. Stigma affects not only COVID-19 patients or survivors, but also individuals associated with them. This study aims to describe and assess the COVID-19-related stigma between patients, their relatives, and healthy local residents. Methods: The study included 43 COVID-19 patients, 68 relatives, and 75 healthy residents from Zhangjiajie. Demographic data was collected, including gender, age, marital status, and educational level. Stigma attitudes toward COVID-19 were measured using the Stigma Scale and Social Distance Scale. Frequencies and percentages were described for each item of the scales, and differences among the three groups were examined using the chi-square test. Results: With regards to personal and perceived stigma, most participants agreed that patients with COVID-19 "could snap out of the problem" and that "they were dangerous." For social distance, over 30% of participants from the three groups agreed with the item "unwillingness to marry into the family of someone with COVID-19." In all groups, there were significant statistical differences in the belief that "the problem is not a real medical illness" and the desire to "spend the evening socializing." Conclusion: Although the outbreak was well-contained in Zhangjiajie, stigmatizing attitudes toward COVID-19 and desire for social distance to such patients were common among patients, their relatives and healthy local residents. Our study's results suggest that public education, anti-stigma interventions, and policies are necessary for people living in Zhangjiajie in order to effectively curtail the spread of COVID-19 and provide a useful strategy for a tourist city like Zhangjiajie to recover sooner from economic decline.

The health and economic impact of constructing temporary field hospitals to meet the COVID-19 pandemic surge: Wuhan Leishenshan Hospital in China as a case study.

BACKGROUND: In response to the COVID-19 pandemic, two new temporary hospitals were constructed in record time in Wuhan, China, to help combat the fast-spreading virus in February 2020. Using the experience of one of the hospitals as a case study, we discuss the health and economic implications of this response strategy and its potential application in other countries. METHODS: This retrospective observational study analyzed health resource utilization and clinical outcomes data for 2011 inpatients diagnosed with COVID-19 and admitted to Leishenshan Hospital during its 67 days of operation from February 8th to April 14th, 2020. We used a top-down costing approach to estimate the total cost of treating patients at the Leishenshan Hospital, including capital cost for hospital construction, health personnel costs, and direct health care costs. We used a multivariate generalized linear model to examine risk factors associated with in-hospital deaths. RESULTS: During the 67 days of hospital operation, 19 medical teams comprising of 933 doctors and 2312 nurses were gradually transferred to Leishenshan Hospital from across China. Of the 2011 admissions, 4.5% used intensive care and 2.0% used ventilators. Overall median length of stay was 19 days, and 21 days for patients in the intensive care unit (ICU). The case fatality rate (CFR) was 2.3% overall, 41.8% in the ICU, and 0.4% in general ward (GW). CFRs were 55% and 50% among patients using non-invasive and invasive ventilators, respectively. The mean total cost and direct health care cost were CNY806 997 (US$114 793) and CNY16 087 (US$2288), respectively. Patients admitted to the ICU had much higher direct health care costs, on average, compared to those in the GW (CNY150 415 vs CNY9720, or US$21 396 vs US$1383). The mean direct health care cost per patient with severe or critical diseases was more than five times higher than those with mild or moderate diseases (CNY45 191 vs CNY8838, or US$6428 vs US$1257). Older age, having comorbidities, and critical disease were associated with higher risks of death from COVID-19. Lower health worker to patient ratio (<2.6) was not associated with in-hospital death. CONCLUSION: An adequate health workforce were mobilized and deployed to a new temporary hospital. The Leishenshan Hospital increased access to care during the surge in COVID-19 infections, facilitated timely treatment, and transferred COVID-19 patients between GWs and ICUs within the hospital, all of which are potential contributors to lowering the CFR. Patients in the ICU experienced a much higher CFR and a greater burden of health care cost than those in GW. Our results have important implications for other countries interested in constructing temporary emergency hospitals, such as the need for adequate infrastructure capacities and financial support, centralized strategies to mobilize health workforce and to provide respiratory protective devices, and improvement in access to health care.

Substance and Internet use during the COVID-19 pandemic in China.

The coronavirus disease 2019 (COVID-19) has adversely influenced human physical and mental health, including emotional disorders and addictions. This study examined substance and Internet use behavior and their associations with anxiety and depression during the COVID-19 pandemic. An online self-report questionnaire was administered to 2196 Chinese adults between February 17 and 29, 2020. The questionnaire contained the seven-item Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9), questions on demographic information, and items about substance and Internet use characteristics. Our results revealed that males consumed less alcohol (p < 0.001) and areca-nut (p = 0.012) during the pandemic than before the pandemic. Age, gender, education status, and occupation significantly differed among increased substance users, regular substance users, and nonsubstance users. Time spent on the Internet was significantly longer during the pandemic (p < 0.001) and 72% of participants reported increased dependence on the Internet. Compared to regular Internet users, increased users were more likely to be younger and female. Multiple logistic regression analysis revealed that age <33 years (OR = 2.034, p < 0.001), increased substance use (OR = 3.439, p < 0.001), and increased Internet use (OR = 1.914, p < 0.001) were significantly associated with depression. Moreover, anxiety was significantly related to female gender (OR = 2.065, p < 0.001), "unmarried" status (OR = 1.480, p = 0.017), nonstudents (OR = 1.946-3.030, p = 0.001), and increased substance use (OR = 4.291, p < 0.001). Although there was a significant decrease in social substance use during the pandemic, more attention should be paid to increased Internet use. Increased Internet use was significantly associated with both anxiety and depression, and increased substance use was related to depression. Professional support should be provided to vulnerable individuals to prevent addiction.

Ebselen, a multi-target compound: its effects on biological processes and diseases

Ebselen is a well-known synthetic compound mimicking glutathione peroxidase (GPx), which catalyses some vital reactions that protect against oxidative damage. Based on a large number of in vivo and in vitro studies, various mechanisms have been proposed to explain its actions on multiple targets. It targets thiol-related compounds, including cysteine, glutathione, and thiol proteins (e.g., thioredoxin and thioredoxin reductase). Owing to this, ebselen is a unique multifunctional agent with important effects on inflammation, apoptosis, oxidative stress, cell differentiation, immune regulation and neurodegenerative disease, with anti-microbial, detoxifying and anti-tumour activity. This review summarises the current understanding of the multiple biological processes and molecules targeted by ebselen, and its pharmacological applications.

Patient Use of Low-cost Digital Videoscopes and Smartphones for Remote Ear and Oropharyngeal Examinations.

Importance: During the novel coronavirus disease 2019 pandemic, telehealth has become a vital component of health care delivery. For otolaryngology evaluations, examination of the ear and oropharynx is important but difficult to achieve remotely. Objective: To assess the feasibility of patient use of low-cost digital videoscopes and smartphones for examination of the ear and oropharynx. Design, Setting, and Participants: A prospective quality improvement study was conducted in an academic adult otolaryngology clinic including 23 patients who presented for an in-person appointment and owned a smartphone device. The study was conducted from July 1 to 15, 2020. Interventions: Participants were asked to capture pictures and videos of their ear canals and oropharynx with digital videoscopes and their smartphones under real-time guidance over a telehealth platform. They were then surveyed about their experience. Main Outcomes and Measures: The primary outcomes were ratings by health care clinicians and a blinded otolaryngologist reviewer of image acceptability. Secondary outcomes included participant time to image acquisition and willingness to purchase digital videoscopes for telehealth use. Results: Of the 23 participants included, 14 were women (61%); mean age was 50 years (range, 21 to 80 years). Of the images obtained using the digital otoscope ear examination, 95% were considered acceptable by the health care clinicians and 91% were considered acceptable by the blinded reviewer; 16 participants (70%) reported that the otoscope was easy to use. The mean time to acquire images for both ears was 114 seconds (95% CI, 84-145 seconds). Twenty-one participants (91%) were willing to pay for a digital otoscope for telehealth use. For the oropharyngeal examination, a greater proportion of smartphone video examinations were considered acceptable by clinicians (63% acceptability) and the blinded reviewer (55%) compared with the digital endoscope (clinicians, 40%; blinded reviewer, 14%). The mean time required for the oropharyngeal examination smartphone video capture was shorter at 35 seconds compared with both the digital endoscope (difference, -27 seconds; 95% CI, -7 to -47 seconds) and smartphone photo capture (difference, -53 seconds; 95% CI, -20 to -87 seconds). Conclusions and Relevance: Digital otoscopes and smartphones apparently can facilitate remote head and neck physical examination in telehealth. Digital otoscopes were useful for ear examinations, and smartphone videos appeared to be the most useful for oropharyngeal examinations. Further studies are required to determine specific diagnostic capabilities in various telehealth practice settings.

Evolving Otolaryngology Resident Roles and Concerns at the Peak of the US COVID-19 Pandemic.

BACKGROUND: The roles of US otolaryngology residents have changed in response to the coronavirus disease 2019 (COVID-19) pandemic. As the pandemic peaked in the United States, we characterized resident activities and concerns. METHODS: A cross-sectional study of US otolaryngology residents between April 20, 2020 and May 2, 2020. RESULTS: A total of 219 residents at 65/118 (55%) institutions responded. Thirty (14%) residents had been redeployed. Residents reported greatest concerns regarding education (P < .00001). Assuming adequate protective equipment, 55% desired active participation in high-risk procedures on COVID-19-positive patients. Redeployed residents had greater concern for burnout and reduced in-hospital well-being (P < .05). Resident satisfaction correlated with comfort communicating concerns to their department (odds ratio [OR] = 4.9, 95% confidence interval [CI] 1.4-17.3, P = .01) and inversely correlated with low perceived meaning in work (OR = 3.1, CI 1.1-9.1, P = .03). CONCLUSION: Otolaryngology resident concerns have evolved as the pandemic progressed. Residency programs should prioritize resident education, well-being in redeployed residents, and open communication as they transition toward recovery.

Evaluations of the serological test in the diagnosis of 2019 novel coronavirus (SARS-CoV-2) infections during the COVID-19 outbreak.

We developed a chemiluminescence immunoassay method based on the recombinant nucleocapsid antigen and assessed its performance for the clinical diagnosis of severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections by detecting SARS-CoV-2-specific IgM and IgG antibodies in patients. Full-length recombinant nucleocapsid antigen and tosyl magnetic beads were used to develop the chemiluminescence immunoassay approach. Plasmas from 29 healthy cohorts, 51 tuberculosis patients, and 79 confirmed SARS-CoV-2 patients were employed to evaluate the chemiluminescence immunoassay method performance for the clinical diagnosis of SARS-CoV-2 infections. A commercial ELISA kit (Darui Biotech, China) using the same nucleocapsid antigen was used for the in-parallel comparison with our chemiluminescence immunoassay method. The IgM and IgG manner of testing in the chemiluminescence immunoassay method showed a sensitivity and specificity of 60.76% (95% CI 49.1 to 71.6) and 92.25% (95% CI 83.4 to 97.2) and 82.28% (95% CI 72.1 to 90.0) and 97.5% (95% CI 91.3 to 99.7), respectively. Higher sensitivity and specificity were observed in the chemiluminescence immunoassay method compared with the Darui Biotech ELISA kit. The developed high sensitivity and specificity chemiluminescence immunoassay IgG testing method combined with the RT-PCR approach can improve the clinical diagnosis for SARS-CoV-2 infections and thus contribute to the control of COVID-19 expansion.

Engaging the communities in Wuhan, China during the COVID-19 outbreak.

During the early stage of the COVID-19 outbreak in Wuhan, the lockdown of the densely-populated metropolis caused panic and disorderly behavior among its population. Community governance systems (CGSs) were mobilized to lead community engagement to address the challenges and issues brought about by the sudden quarantine measures, still unprecedented in any part of the world during that time. This commentary aims to describe and analyze the roles of the CGSs, its implementation of culturally-tailored strategies and the performance of new functions as called for by the outbreak. We will introduce the community governance structure which has two parallel administrative units of government including the branches of the Communist Party of China (CPC). The pandemic showed that the roles of the CGSs evolved and may continue to be improved in the future. It is important to engage the community and to have community-based approaches in addressing issues brought about by lockdowns. This community experience in Wuhan provides important lessons for the rest of the world.

Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19.

Aim: We aimed to explore the biomarkers for disease progression or the risk of nonsurvivors. Materials & methods: This study included 134 hospitalized patients with confirmed COVID-19 infection. The outcome of moderate versus severe versus critically ill patients and survivors versus nonsurvivors were compared. Results: An increase in the severity of COVID-19 pneumonia was positively associated with lower levels of platelets and albumin (all p < 0.05). In the critical group, the plasma levels of albumin continued to have a significant association for the risk of nonsurvivors (p < 0.05), even after adjusting for confounding factors. Conclusion: Albumin levels could be used as an independent predictor of the risk of nonsurvivors in critically ill patients with COVID-19.

Otolaryngology Resident Practices and Perceptions in the Initial Phase of the U.S. COVID-19 Pandemic.

OBJECTIVE: The coronavirus 2019 (COVID-19) pandemic has had widespread implications on clinical practice at U.S. hospitals. These changes are particularly relevant to otolaryngology-head and neck surgery (OHNS) residents because reports suggest an increased risk of contracting COVID-19 for otolaryngologists. The objectives of this study were to evaluate OHNS residency program practice changes and characterize resident perceptions during the initial phase of the pandemic. STUDY DESIGN: A cross-sectional survey of U.S. OHNS residents at 81 programs was conducted between March 23, 2020, and March 29, 2020. RESULTS: Eighty-two residents from 51 institutions (63% of invited programs) responded. At the time of survey, 98% of programs had enacted policy changes to minimize COVID-19 spread. These included filtered respirator use for aerosol-generating procedures even in COVID-19-negative patients (85%), decreased resident staffing of surgeries (70%), and reduced frequency of tracheotomy care (61%). The majority of residents (66%) perceived that residents were at higher risk of contracting COVID-19 compared to attendings. Residents were most concerned about protective equipment shortage (93%) and transmitting COVID-19 to patients (90%). The majority of residents (73%) were satisfied with their department's COVID-19 response. Resident satisfaction correlated with comfort level in discussing concerns with attendings (r = 0.72, P < .00001) and inversely correlated with perceptions of increased risk compared to attendings (r = -0.52, P < .00001). CONCLUSION: U.S. OHNS residency programs implemented policy changes quickly in response to the COVID-19 pandemic. Sources of resident anxieties demonstrate the importance of open communication and an integrated team approach to facilitate optimal patient and provider care during this unprecedented crisis. LEVEL OF EVIDENCE: 4. Laryngoscope, 130:2550-2557, 2020.