Thymidine Phosphorylase Mediates SARS-CoV-2 Spike Protein Enhanced Thrombosis in K18-hACE2TG Mice (preprint)

COVID-19, caused by SARS-CoV-2, is associated with arterial and venous thrombosis, thereby increasing mortality. SARS-CoV-2 spike protein (SP), a viral envelope structural protein, is implicated in COVID-19-associated thrombosis. However, the underlying mechanisms remain unknown. Thymidine phosphorylase (TYMP), a newly identified prothrombotic protein, is upregulated in the plasma, platelets, and lungs of patients with COVID-19 but its role in COVID-19-associated thrombosis is not defined. In this study, we found that wild-type SARS-CoV-2 SP significantly promoted arterial thrombosis in K18-hACE2TG mice. SP-accelerated thrombosis was attenuated by inhibition or genetic ablation of TYMP. SP increased the expression of TYMP, resulting in the activation of signal transducer and activator of transcription 3 (STAT3) in BEAS-2B cells, a human bronchial epithelial cell line. A siRNA-mediated knockdown of TYMP inhibited SP-enhanced activation of STAT3. Platelets derived from SP-treated K18-hACE2TG mice also showed increased STAT3 activation, which was reduced by TYMP deficiency. Activated STAT3 is known to potentiate glycoprotein VI signaling in platelets. While SP did not influence ADP- or collagen-induced platelet aggregation, it significantly shortened activated partial thromboplastin time and this change was reversed by TYMP knockout. Additionally, platelet factor 4 (PF4) interacts with SP, which also complexes with TYMP. TYMP enhanced the formation of the SP/PF4 complex, which may potentially augment the prothrombotic and procoagulant effects of PF4. We conclude that SP upregulates TYMP expression, and TYMP inhibition or knockout mitigates SP-enhanced thrombosis. These findings indicate that inhibition of TYMP may be a novel therapeutic strategy for COVID-19-associated thrombosis.

Psychological Distress Reported by Patients with Atrial Fibrillation in China During COVID-19 (preprint)

Background: The COVID-19 pandemic significantly impacted routine cardiovascular health assessments and services. The objective of this study was to explore the factors associated with self-reported psychological distress among a sample of patients with atrial fibrillation (AF) in China in relation to COVID-19. Methods: An online survey was administered to 288 patients with AF at several hospitals in China. The survey consisted of three sections: demographic characteristics, questions related to COVID-19, and the General Health Questionnaire-12 (GHQ-12). Results: A total of 177 patients with AF completed the baseline survey; 177 (61.46%) were male and 133 (46.18%) were older than 65 years. High levels of psychological distress (GHQ-12 ≥3) were observed in 27 (9.4%) participants of the sample. These high levels were found to be associated with older age, radiofrequency ablation, drinking, and combined basic diseases (p values < .05). Logistic regression analysis showed that psychological distress in patients with AF was associated with radiofrequency ablation (OR = 0.316, 95% CI = 0.147–0.666), drinking (OR = 4.761, 95% CI = 2.076–10.916), and concerns regarding infection (OR = 1.244, 95% CI = 1.052–1.472). Conclusions: COVID-19 has resulted in high levels of psychological distress in approximately 9.4% of patients with AF in China. Factors associated with high levels of psychological distress in AF patients include older age, radiofrequency ablation, drinking, and combined comorbidities. These findings highlight the importance of enhancing psychological health throughout the course of infectious pandemics.

An approach combining deep learning and molecule docking for drug discovery of cathepsin L.

OBJECTIVES: Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders and COVID-19. However, there are still no clinically available CTSL inhibitors. Our objective is to develop an approach for the discovery of potential reversible covalent CTSL inhibitors. METHODS: The authors combined Chemprop, a deep learning-based strategy, and the Schrödinger CovDock algorithm to identify potential CTSL inhibitors. First, they used Chemprop to train a deep learning model capable of predicting whether a molecule would inhibit the activity of CTSL and performed predictions on ZINC20 in-stock librarie (~9.2 million molecules). Then, they selected the top-200 predicted molecules and performed the Schrödinger covalent docking algorithm to explore the binding patterns to CTSL (PDB: 5MQY). The authors then calculated the binding energies using Prime MM/GBSA and examined the stability between the best two molecules and CTSL using 100ns molecular dynamics simulations. RESULTS: The authors found five molecules that showed better docking results than the well-known cathepsin inhibitor odanacatib. Notably, two of these molecules, ZINC-35287427 and ZINC-1857528743, showed better docking results with CTSL compared to other cathepsins. CONCLUSION: Our approach enables drug discovery from large-scale databases with little computational consumption, which will save the cost and time required for drug discovery.

Exploring Nursing Staff's Experiences and Perspectives of COVID-19 Lockdown in a Residential Aged Care Setting in Australia.

An exploratory qualitative study was performed to evaluate the experiences of nursing staff (N = 10) working in a residential aged care facility (RACF) during the coronavirus disease 2019 (COVID-19) pandemic lockdown. Semi-structured, in-person interviews were performed, and thematic analysis was used to analyze the data. Care staff had little or no knowledge of how to cope with a lockdown necessitated by a pandemic. However, management developed proactive plans as they aligned with the changing care circumstances and ongoing government directives. Five major themes were identified: Prolonged Use and Shortage of Personal Protective Equipment; "Blind Leading the Blind"; Communication and Teamwork; Lack of Education; and Resident Response. RACF staff described working under stressful conditions during the initial COVID-19 pandemic lockdown; yet with experience, care staff and the management team adapted to pandemic requirements to meet the needs of residents in their care. RACFs should be prepared for the impact of pandemics on staff and ensure care resources and support are available for the continuity of safe and quality care of residents. [Journal of Gerontological Nursing, 49(3), 34-39.].

Definition of Post-COVID-19 Condition Among Published Research Studies.

This cross-sectional study examines the differing definitions of a post­COVID-19 condition among published studies.

Airborne antibiotic resistome and human health risk in railway stations during COVID-19 pandemic.

Antimicrobial resistance is recognized as one of the greatest public health concerns. It is becoming an increasingly threat during the COVID-19 pandemic due to increasing usage of antimicrobials, such as antibiotics and disinfectants, in healthcare facilities or public spaces. To explore the characteristics of airborne antibiotic resistome in public transport systems, we assessed distribution and health risks of airborne antibiotic resistome and microbiome in railway stations before and after the pandemic outbreak by culture-independent and culture-dependent metagenomic analysis. Results showed that the diversity of airborne antibiotic resistance genes (ARGs) decreased following the pandemic, while the relative abundance of core ARGs increased. A total of 159 horizontally acquired ARGs, predominantly confering resistance to macrolides and aminoglycosides, were identified in the airborne bacteria and dust samples. Meanwhile, the abundance of horizontally acquired ARGs hosted by pathogens increased during the pandemic. A bloom of clinically important antibiotic (tigecycline and meropenem) resistant bacteria was found following the pandemic outbreak. 251 high-quality metagenome-assembled genomes (MAGs) were recovered from 27 metagenomes, and 86 genera and 125 species were classified. Relative abundance of ARG-carrying MAGs, taxonomically assigned to genus of Bacillus, Pseudomonas, Acinetobacter, and Staphylococcus, was found increased during the pandemic. Bayesian source tracking estimated that human skin and anthropogenic activities were presumptive resistome sources for the public transit air. Moreover, risk assessment based on resistome and microbiome data revealed elevated airborne health risks during the pandemic.

Brief Report: Supporting Access to HIV Care for Children and Youth During the COVID-19 Pandemic With Telemedicine and Rideshare.

BACKGROUND: In response to the COVID-19 pandemic, we scaled up telemedicine and rideshare services for clinic and laboratory visits for pediatric and adolescent patients with HIV. SETTING: HIV subspecialty program for patients aged 0-24 years at Children's National Hospital, Washington, DC. METHODS: Using the χ2 and Wilcoxon rank sum tests, we compared demographics, visit and laboratory data, and rideshare usage among patients who scheduled telemedicine at least once (telemedicine) versus those who never scheduled telemedicine (no-telemedicine) during the pandemic (April-September 2020). We compared the number and proportion of scheduled and completed clinic visits before the pandemic (April-September 2019) with those during the pandemic. RESULTS: We analyzed 178 pediatric and adolescent patients with HIV (median age 17.9 years, 89.3% Black, 48.9% male patients, 78.7% perinatally infected), of whom 70.2% and 28.6% used telemedicine and rideshare, respectively. Telemedicine patients scheduled more visits (236 vs 179, P < 0.0001) and completed a similar proportion of visits (81.8% vs 86.0%, P = 0.3805) compared with no-telemedicine patients. Laboratory testing rates (81.3% versus 98.5%, P = 0.0005) were lower in telemedicine patients compared with no-telemedicine patients. Rideshare usage (12.4% versus 26.5%, P = 0.0068) was lower in telemedicine versus no-telemedicine patients. During the pandemic, most of the patients (81.0%) had HIV RNA <200 copies/mL. The total number of completed visits and the proportion of visits completed were similar before and during the pandemic. CONCLUSION: Most of the pediatric and adolescent patients with HIV used telemedicine and maintained HIV RNA <200 copies/mL during the pandemic. Despite rideshare usage, laboratory testing rates were lower with telemedicine compared with in-person visits.

Asymptomatic COVID-19 Patients Can Contaminate Their Surroundings: an Environment Sampling Study.

The contamination of patients' surroundings by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains understudied. We sampled the surroundings and the air of six negative-pressure non-intensive care unit (non-ICU) rooms in a designated isolation ward in Chengdu, China, that were occupied by 13 laboratory-confirmed coronavirus disease 2019 (COVID-19) patients who had returned from overseas travel, including 2 asymptomatic patients. A total of 44 of 112 (39.3%) surface samples were positive for SARS-CoV-2 as detected by real-time PCR, suggesting extensive contamination, although all of the air samples were negative. In particular, in a single room occupied by an asymptomatic patient, four sites were SARS-CoV-2 positive, highlighting that asymptomatic COVID-19 patients do contaminate their surroundings and impose risks for others with close contact. Placement of COVID-19 patients in rooms with negative pressure may bring a false feeling of safety, and the importance of rigorous environment cleaning should be emphasized.IMPORTANCE Although it has been well recognized that the virus SARS-CoV-2, the causative agent of COVID-19, can be acquired by exposure to fomites, surprisingly, the contamination of patients' surroundings by SARS-CoV-2 is largely unknown, as there have been few studies. We performed an environmental sampling study for 13 laboratory-confirmed COVID-19 patients and found extensive contamination of patients' surroundings. In particular, we found that asymptomatic COVID-19 patients contaminated their surroundings and therefore imposed risks for other people. Environment cleaning should be emphasized in negative-pressure rooms. The findings may be useful to guide infection control practice to protect health care workers.

Effective Responses to Public Emergencies at the Urban Community Level: A Perspective of COVID-19 Prevention and Control

Community is directly responsible for implementing the policy measures against public emergencies such as extreme weather, earthquake, flash flood and pandemic diseases. Summarizing the experience at the urban community level can help promote the global emergency management. This paper, from the perspective of COVID-19 prevention and control, selects three communities with different features to explore an effective response system for public emergency management at the urban community level. It demonstrates that based on a centralized leadership, the multi-level governance (MLG) network combined with information technology has mobilized their participation in combating COVID-19 and ensured the effective and timely response to the public emergencies, which blocked the spread of epidemic to the greatest extent, proving worthy of being promoted as one of the Chinese approaches and Chinese wisdom. [ FROM AUTHOR]

Strictinin, a Major Ingredient in Yunnan Kucha Tea Possessing Inhibitory Activity on the Infection of Mouse Hepatitis Virus to Mouse L Cells.

Theacrine and strictinin of Yunnan Kucha tea prepared from a mutant variety of wild Pu'er tea plants were two major ingredients responsible for the anti-influenza activity. As the COVID-19 outbreak is still lurking, developing safe and cost-effective therapeutics is an urgent need. This study aimed to evaluate the effects of these tea compounds on the infection of mouse hepatitis virus (MHV), a ß-coronavirus serving as a surrogate for SARS-CoV. Treatment with strictinin (100 µM), but not theacrine, completely eliminated MHV infection, as indicated by a pronounced reduction in plaque formation, nucleocapsid protein expression, and progeny production of MHV. Subsequently, a time-of-drug addition protocol, including pre-, co-, or post-treatment, was exploited to further evaluate the possible mechanism of antiviral activity mediated by strictinin, and remdesivir, a potential drug for the treatment of SARS-CoV-2, was used as a positive control against MHV infection. The results showed that all three treatments of remdesivir (20 µM) completely blocked MHV infection. In contrast, no significant effect on MHV infection was observed when cells were pre-treated with strictinin (100 µM) prior to infection, while significant inhibition of MHV infection was observed when strictinin was introduced upon viral adsorption (co-treatment) and after viral entry (post-treatment). Of note, as compared with the co-treatment group, the inhibitory effect of strictinin was more striking in the post-treatment group. These results indicate that strictinin suppresses MHV infection by multiple mechanisms; it possibly interferes with viral entry and also critical step(s) of viral infection. Evidently, strictinin significantly inhibited MHV infection and might be a suitable ingredient for protection against coronavirus infection.

Impact of human capital and social capital on employability of Chinese college students under COVID-19 epidemic-Joint moderating effects of perception reduction of employment opportunities and future career clarity.

This research constructed a relationship model between human capital, social capital, and the employability of college students. With two moderating variables introduced, the perception reduction of employment opportunities under the COVID-19 epidemic and future career clarity, this research studied the direct impact of human capital and social capital on the employability of college students and boundary conditions. Research data from 810 employed Chinese college graduates shows that both human capital and social capital have a positive and significant impact on the employability; the perception reduction of employment opportunities under the COVID-19 epidemic negatively regulates the relationship between human capital and the employability of college students; the future career clarity positively regulates the relationship between human capital and the employability of college students; the perception reduction of employment opportunities under COVID-19 epidemic and the future career clarity jointly regulate the relationship between human capital, social capital and the employability of college students. These conclusions enrich the relevant theoretical and practical research on the employability of college students under the COVID-19 epidemic.

Key Drivers of COVID-19 Vaccine Hesitancy: A Perspective of Collectivism.

Vaccination against the COVID-19 pandemic remains a major part of global immunization policy. The aim of this study was to explore young people's willingness to continue to receive vaccination against COVID-19 in a collectivist culture. In this study, an online questionnaire was used to measure willingness to continue vaccination, the tendency towards collectivism, the degree of disease anxiety, vaccine brand loyalty, and perceived infectability in 2022. The results showed that women were more willing to be vaccinated than men (70.1% vs. 29.9%). Young people who were willing to receive continuous vaccination had a relatively higher tendency towards collectivism (p < 0.001), a relatively higher degree of disease anxiety (p < 0.001), and lower vaccine brand loyalty (p = 0.034). The COVID-19 pandemic is still ongoing and, since young people are the most active in group activities, policy-makers should weigh the factors influencing vaccination among the young to create effective policy measures.

Oral Azvudine (FNC) Tablets in Patients infected with SARS-CoV-2 Omicron Variant: A Retrospective Cohort Study (preprint)

BackgroundThere is a lack of data on the efficacy of oral Azvudine in Coronavirus Disease treatment. This study aimed to assess the association between Azvudine treatment and clinical outcomes in a cohort of patients infected with the SARS-CoV-2 Omicron variant. MethodsThis is a retrospective study conducted in two mobile cabin hospitals. All consecutive patients with a diagnosis of COVID-19 admitted from August to October 2022 were included in the study. Linear regression models and Cox proportional hazards models were used to assess the association between Azvudine treatment and time to obtain the first negative nucleic acid test results. ResultsA total of 207 patients were analyzed, of whom 166 patients (80.2%) received Azvudine treatment after hospitalization, and the rest did not. Linear regression models showed that Azvudine treatment was associated with reduced time to obtain the first negative nucleic acid test results after adjusting for age and gender [mean difference = -1.658; 95% CI: -2.772 to -0.544, P = 0.0039]. The multivariable Cox analysis conforms to the results from the linear regression model (hazard ratio = 1.461; 95% CI: 1.01 to 2.11, P = 0.044). ConclusionAzvudine treatment was associated with reduced virus shedding time. Further studies are needed to confirm our findings.

Cancer Evaluations During the COVID-19 Pandemic: An Observational Study Using National Veterans Affairs Data.

INTRODUCTION: Fewer cancer diagnoses have been made during the COVID-19 pandemic. Pandemic-related delays in cancer diagnosis could occur from limited access to care or patient evaluation delays (e.g., delayed testing after abnormal results). Follow-up of abnormal test results warranting evaluation for cancer was examined before and during the pandemic. METHODS: Electronic trigger algorithms were applied to the Department of Veterans Affairs electronic health record data to assess follow-up of abnormal test results before (March 10, 2019-March 7, 2020) and during (March 8, 2020-March 6, 2021) the pandemic. RESULTS: Electronic triggers were applied to 8,021,406 veterans' electronic health records to identify follow-up delays for abnormal results warranting evaluation for 5 cancers: bladder (urinalysis with high-grade hematuria), breast (abnormal mammograms), colorectal (positive fecal occult blood tests/fecal immunochemical tests or results consistent with iron deficiency anemia), liver (elevated alpha-fetoprotein), and lung (chest imaging suggestive of malignancy) cancers. Between prepandemic and pandemic periods, test quantities decreased by 12.6%-27.8%, and proportions of abnormal results lacking follow-up decreased for urinalyses (-0.8%), increased for fecal occult blood tests/fecal immunochemical test (+2.3%) and chest imaging (+1.8%), and remained constant for others. Follow-up times decreased for most tests; however, control charts suggested increased delays at 2 stages: early (pandemic beginning) for urinalyses, mammograms, fecal occult blood tests/fecal immunochemical test, iron deficiency anemia, and chest imaging and late (30-45 weeks into pandemic) for mammograms, fecal occult blood tests/fecal immunochemical test, and iron deficiency anemia. CONCLUSIONS: Although early pandemic delays in follow-up may have led to reduced cancer rates, the significant decrease in tests performed is likely a large driver of these reductions. Future emergency preparedness efforts should bolster essential follow-up and testing procedures to facilitate timely cancer diagnosis.

Management of Emerging Health Conditions to Improve Resilience and Mental Health.

Good health is when a person is in a complete, optimal physical, mental, and social condition [...].