COVID-19 related antiviral drugs are less adsorbable on sediment under alkaline and high cation conditions

The COVID-19 pandemic resulted in unprecedented usage and elevated environmental concentrations of antiviral drugs. However, very limited studies have reported their sorption characteristics on environmental matrices. This study investigated the sorption of six COVID-19 related antivirals on Taihu Lake sediment with varied aqueous chemistry. Results showed that the sorption isotherms for arbidol (ABD), oseltamivir (OTV), and ritonavir (RTV) were linear, while the Freundlich model was the best-fit for ribavirin (RBV) and the Langmuir model for favipiravir (FPV) and remdesivir (RDV). Their distribution coefficient, Kd, varied between 5.051 L/kg to 248.6 L/kg with the sorption capacities ranked as FPV > RDV > ABD > RTV > OTV > RBV. Alkaline conditions (pH 9) and elevated cation strength (0.05 M to 0.1 M) decreased the sorption capacities of the sediment for these drugs. Thermodynamic analysis revealed that the spontaneous sorption of RDV, ABD, and RTV was between physisorption and chemisorption while FPV, RBV, and OTV were mainly physisorption. Functional groups related to hydrogen bonds, π – π interaction, and surface complexation were implicated in the sorption processes. These findings enhance our understanding about the environmental fate of COVID-19 related antivirals and provide basic data for predicting their distribution and risk in the environment. Graphical Unlabelled Image

Association between negative psychology and sleep quality in dialysis patients during the COVID-19 pandemic.

AIMS AND OBJECTIVES: The aim of this study was to assess the sleep quality in dialysis patients during the COVID-19 epidemic and explore the association between negative psychology (including depression, anxiety, and stress) and sleep quality in this population. DESIGN: A cross-sectional study including three centres. METHODS (PATIENTS OR PUBLIC CONTRIBUTION): This cross-sectional study included 378 dialysis patients from April to May 2022 in three dialysis centres in Shanghai. METHODS: Depression, anxiety, stress, and sleep quality were measured by the Hospital Anxiety and Depression Scale (HADS), Perceived Stress Scale-14 (PSS-14), and Pittsburgh sleep quality index (PSQI), respectively. With a threshold of 5 to classify participants into good and poor sleep quality, with HADS/PSS-14 scores as independent variables (per standard deviation (SD) increment), respectively and binary Logistic regression model was constructed to explore the association between the three negative psychological aspects of depression, anxiety, and stress and sleep quality. RESULTS: The median PSQI score was 11.0 (mean ± SD: 11.8 ± 4.8). Among them, poor sleep quality (i.e., PSQI >5) was reported by 90.2% of participants. After adjusting for sociodemographic and disease-related information, HADS-depression was associated with a significant 49% (odds ratio (OR): 1.49; 95% CI 1.02-2.18) increase in the risk of poor sleep quality for each additional SD (2.4). Correspondingly, for each SD (7.1) increase in PSS-14, the risk of poor sleep quality was significantly increased by 95% (OR: 1.95; 95% CI 1.35-2.82). CONCLUSION: During the COVID-19 pandemic, there was a significant negative association between negative psychology, such as depression and stress, and sleep quality in dialysis patients, and this relationship was independent of the dialysis modality. RELEVANCE TO CLINICAL PRACTICE: In the context of the rampant COVID-19, the vast majority of dialysis-dependent chronic kidney disease presents with severe sleep quality problems, and negative psychology is a potential influencing factor.

Formation mechanism and governance strategies of stigma in public health emergencies: Based on event system theory.

Introduction: With the new coronavirus (COVID-19) pandemic across the world, it is critical to propose effective strategies for stigma governance in public health emergencies in order to reduce negative effects caused by stigma. However, no known research has focused on the essential role of events in understanding stigma phenomenon from the perspective of external dynamic changes. Methods: Based on the event system theory, this paper analyzes the evolution mode and characteristics of specific events in the process of stigmatization from strength, space and time aspects, and taking COVID-19 event as an example, 1202 questionnaires and empirical analysis were conducted. Results and discussion: Our results reveal that event strength directly affects the results of stigmatization, and such impact appears to be more prominent with a novel, disruptive and critical event. In addition, spatial and temporal attributes represent the dynamic development of an event, and they can interact with event strength to regulate the relationship between event strength and outcomes. Finally, stigma governance strategies under public health emergencies from three aspects of event strength, space, and time were put forward.

Force-tuned avidity of spike variant-ACE2 interactions viewed on the single-molecule level.

Recent waves of COVID-19 correlate with the emergence of the Delta and the Omicron variant. We report that the Spike trimer acts as a highly dynamic molecular caliper, thereby forming up to three tight bonds through its RBDs with ACE2 expressed on the cell surface. The Spike of both Delta and Omicron (B.1.1.529) Variant enhance and markedly prolong viral attachment to the host cell receptor ACE2, as opposed to the early Wuhan-1 isolate. Delta Spike shows rapid binding of all three Spike RBDs to three different ACE2 molecules with considerably increased bond lifetime when compared to the reference strain, thereby significantly amplifying avidity. Intriguingly, Omicron (B.1.1.529) Spike displays less multivalent bindings to ACE2 molecules, yet with a ten time longer bond lifetime than Delta. Delta and Omicron (B.1.1.529) Spike variants enhance and prolong viral attachment to the host, which likely not only increases the rate of viral uptake, but also enhances the resistance of the variants against host-cell detachment by shear forces such as airflow, mucus or blood flow. We uncover distinct binding mechanisms and strategies at single-molecule resolution, employed by circulating SARS-CoV-2 variants to enhance infectivity and viral transmission.

Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants.

It is urgent to develop more effective mRNA vaccines against the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants owing to the immune escape. Here, we constructed a novel mRNA delivery system [IC8/Mn lipid nanoparticles (IC8/Mn LNPs)]with high immunogenicity, via introducing a stimulator of interferon genes (STING) agonist [manganese (Mn)] based on a newly synthesized ionizable lipid (IC8). It was found that Mn can not only promote maturation of antigen-presenting cells via activating STING pathway but also improve mRNA expression by facilitating lysosomal escape for the first time. Subsequently, IC8/Mn LNPs loaded with mRNA encoding the Spike protein of SARS-CoV-2 Delta or Omicron variant (IC8/Mn@D or IC8/Mn@O) were prepared. Both mRNA vaccines induced substantial specific immunoglobulin G responses against Delta or Omicron. IC8/Mn@D displayed strong pseudovirus neutralization ability, T helper 1-biased immune responses, and good safety. It can be concluded that IC8/Mn LNPs have great potential for developing Mn-coordinated mRNA vaccines with robust immunogenicity and good safety.

A molecularly engineered, broad-spectrum anti-coronavirus lectin inhibits SARS-CoV-2 and MERS-CoV infection in vivo.

"Pan-coronavirus" antivirals targeting conserved viral components can be designed. Here, we show that the rationally engineered H84T-banana lectin (H84T-BanLec), which specifically recognizes high mannose found on viral proteins but seldom on healthy human cells, potently inhibits Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (including Omicron), and other human-pathogenic coronaviruses at nanomolar concentrations. H84T-BanLec protects against MERS-CoV and SARS-CoV-2 infection in vivo. Importantly, intranasally and intraperitoneally administered H84T-BanLec are comparably effective. Mechanistic assays show that H84T-BanLec targets virus entry. High-speed atomic force microscopy depicts real-time multimolecular associations of H84T-BanLec dimers with the SARS-CoV-2 spike trimer. Single-molecule force spectroscopy demonstrates binding of H84T-BanLec to multiple SARS-CoV-2 spike mannose sites with high affinity and that H84T-BanLec competes with SARS-CoV-2 spike for binding to cellular ACE2. Modeling experiments identify distinct high-mannose glycans in spike recognized by H84T-BanLec. The multiple H84T-BanLec binding sites on spike likely account for the drug compound's broad-spectrum antiviral activity and the lack of resistant mutants.

COVID-19 compliance behaviors of older people: The role of cognitive and non-cognitive skills.

This paper examines the empirical relationship between individuals' cognitive and non-cognitive abilities and COVID-19 compliance behaviors using cross-country data from the Survey of Health, Ageing and Retirement in Europe (SHARE). We find that both cognitive and non-cognitive skills predict responsible health behaviors during the COVID-19 crisis. Episodic memory is the most important cognitive skill, while conscientiousness and neuroticism are the most significant personality traits. There is also some evidence of a role for an internal locus of control in compliance.

Comprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccines.

Large-scale COVID-19 vaccinations are currently underway in many countries in response to the COVID-19 pandemic. Here, we report, besides generation of neutralizing antibodies, consistent alterations in hemoglobin A1c, serum sodium and potassium levels, coagulation profiles, and renal functions in healthy volunteers after vaccination with an inactivated SARS-CoV-2 vaccine. Similar changes had also been reported in COVID-19 patients, suggesting that vaccination mimicked an infection. Single-cell mRNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) before and 28 days after the first inoculation also revealed consistent alterations in gene expression of many different immune cell types. Reduction of CD8+ T cells and increase in classic monocyte contents were exemplary. Moreover, scRNA-seq revealed increased NF-κB signaling and reduced type I interferon responses, which were confirmed by biological assays and also had been reported to occur after SARS-CoV-2 infection with aggravating symptoms. Altogether, our study recommends additional caution when vaccinating people with pre-existing clinical conditions, including diabetes, electrolyte imbalances, renal dysfunction, and coagulation disorders.

Identification of lectin receptors for conserved SARS-CoV-2 glycosylation sites.

New SARS-CoV-2 variants are continuously emerging with critical implications for therapies or vaccinations. The 22 N-glycan sites of Spike remain highly conserved among SARS-CoV-2 variants, opening an avenue for robust therapeutic intervention. Here we used a comprehensive library of mammalian carbohydrate-binding proteins (lectins) to probe critical sugar residues on the full-length trimeric Spike and the receptor binding domain (RBD) of SARS-CoV-2. Two lectins, Clec4g and CD209c, were identified to strongly bind to Spike. Clec4g and CD209c binding to Spike was dissected and visualized in real time and at single-molecule resolution using atomic force microscopy. 3D modelling showed that both lectins can bind to a glycan within the RBD-ACE2 interface and thus interferes with Spike binding to cell surfaces. Importantly, Clec4g and CD209c significantly reduced SARS-CoV-2 infections. These data report the first extensive map and 3D structural modelling of lectin-Spike interactions and uncovers candidate receptors involved in Spike binding and SARS-CoV-2 infections. The capacity of CLEC4G and mCD209c lectins to block SARS-CoV-2 viral entry holds promise for pan-variant therapeutic interventions.

Compensating for academic loss: Online learning and student performance during the COVID-19 pandemic.

The COVID-19 pandemic has led to widespread school shutdowns, with many continuing distance education via online-learning platforms. We here estimate the causal effects of online education on student exam performance using administrative data from Chinese Middle Schools. Taking a difference-in-differences approach, we find that receiving online education during the COVID-19 lockdown improved student academic results by 0.22 of a standard deviation, relative to pupils without learning support from their school. Not all online education was equal: students who were given recorded online lessons from external higher-quality teachers had higher exam scores than those whose lessons were recorded by teachers from their own school. The educational benefits of distance learning were the same for rural and urban students, but the exam performance of students who used a computer for online education was better than those who used a smartphone. Last, while everyone except the very-best students performed better with online learning, it was low achievers who benefited from teacher quality.