CRISPR-Cas12a Coupled with DNA Nanosheet-Amplified Fluorescence Anisotropy for Sensitive Detection of Biomolecules.

DNA nanosheets (DNSs) have been utilized effectively as a fluorescence anisotropy (FA) amplifier for biosensing. But, their sensitivity needs to be further improved. Herein, CRISPR-Cas12a with strong trans-cleavage activity was utilized to enhance the FA amplification ability of DNSs for the sensitive detection of miRNA-155 (miR-155) as a proof-of-principle target. In this method, the hybrid of the recognition probe of miR-155 (T1) and a blocker sequence (T2) was immobilized on the surface of magnetic beads (MBs). In the presence of miR-155, T2 was released by a strand displacement reaction, which activated the trans-cleavage activity of CRISPR-Cas12a. The single-stranded DNA (ssDNA) probe modified with a carboxytetramethylrhodamine (TAMRA) fluorophore was cleaved in large quantities and could not bind to the handle chain on DNSs, inducing a low FA value. In contrast, in the absence of miR-155, T2 could not be released and the trans-cleavage activity of CRISPR-Cas12a could not be activated. The TAMRA-modified ssDNA probe remained intact and was complementary to the handle chain on the DNSs, and a high FA value was obtained. Thus, miR-155 was detected through the obviously decreased FA value with a low limit of detection (LOD) of 40 pM. Impressively, the sensitivity of this method was greatly improved about 322 times by CRISPR-Cas12a, confirming the amazing signal amplification ability of CRISPR-Cas12a. At the same time, the SARS-CoV-2 nucleocapsid protein was detected by the strategy successfully, indicating that this method was general. Moreover, this method has been applied in the analysis of miR-155 in human serum and the lysates of cells, which provides a new avenue for the sensitive determination of biomarkers in biochemical research and disease diagnosis.

COVID-19 Vaccine-Related Information on the WeChat Public Platform: Topic Modeling and Content Analysis.

BACKGROUND: The COVID-19 vaccine is an effective tool in the fight against the COVID-19 outbreak. As the main channel of information dissemination in the context of the epidemic, social media influences public trust and acceptance of the vaccine. The rational application of health behavior theory is a guarantee of effective public health information dissemination. However, little is known about the application of health behavior theory in web-based COVID-19 vaccine messages, especially from Chinese social media posts. OBJECTIVE: This study aimed to understand the main topics and communication characteristics of hot papers related to COVID-19 vaccine on the WeChat platform and assess the health behavior theory application with the aid of health belief model (HBM). METHODS: A systematic search was conducted on the Chinese social media platform WeChat to identify COVID-19 vaccine-related papers. A coding scheme was established based on the HBM, and the sample was managed and coded using NVivo 12 (QSR International) to assess the application of health behavior theory. The main topics of the papers were extracted through the Latent Dirichlet Allocation algorithm. Finally, temporal analysis was used to explore trends in the evolution of themes and health belief structures in the papers. RESULTS: A total of 757 papers were analyzed. Almost all (671/757, 89%) of the papers did not have an original logo. By topic modeling, 5 topics were identified, which were vaccine development and effectiveness (267/757, 35%), disease infection and protection (197/757, 26%), vaccine safety and adverse reactions (52/757, 7%), vaccine access (136/757, 18%), and vaccination science popularization (105/757, 14%). All papers identified at least one structure in the extended HBM, but only 29 papers included all of the structures. Descriptions of solutions to obstacles (585/757, 77%) and benefit (468/757, 62%) were the most emphasized components in all samples. Relatively few elements of susceptibility (208/757, 27%) and the least were descriptions of severity (135/757, 18%). Heat map visualization revealed the change in health belief structure before and after vaccine entry into the market. CONCLUSIONS: To the best of our knowledge, this is the first study to assess the structural expression of health beliefs in information related to the COVID-19 vaccine on the WeChat public platform based on an HBM. The study also identified topics and communication characteristics before and after the market entry of vaccines. Our findings can inform customized education and communication strategies to promote vaccination not only in this pandemic but also in future pandemics.

DNA-scaffolded multivalent vaccine against SARS-CoV-2.

Short peptides are poor immunogens. One way to increase their immune responses is by arraying immunogens in multivalency. Simple and efficient scaffolds for spatial controlling the inter-antigen distance and enhancing immune activation are required. Here, we report a molecular vaccine design principle that maximally drives potent SARS-CoV-2 RBD subunit vaccine on DNA duplex to induce robust and efficacious immune responses in vivo. We expect that the DNA-peptide epitope platform represents a facile and generalizable strategy to enhance the immune response. STATEMENT OF SIGNIFICANCE: DNA scaffolds offer a biocompatible and convenient platform for arraying immunogens in multivalency antigenic peptides, and spatially control the inter-antigen distance. This can effectively enhance immune response. Peptide (instead of entire protein) vaccines are highly attractive. However, short peptides are poor immunogens. Our DNA scaffolded multivalent peptide immunogen system induced robust and efficacious immune response in vivo as demonstrated by the antigenic peptide against SARS-CoV-2. The present strategy could be readily generalized and adapted to prepare multivalent vaccines against other viruses or disease. Particularly, the different antigens could be integrated into one single vaccine and lead to super-vaccines that can protect the host from multiple different viruses or multiple variants of the same virus.

Modeling particulate nitrate in China: Current findings and future directions.

Particulate nitrate (pNO3) is now becoming the principal component of PM2.5 during severe winter haze episodes in many cities of China. To gain a comprehensive understanding of the key factors controlling pNO3 formation and driving its trends, we reviewed the recent pNO3 modeling studies which mainly focused on the formation mechanism and recent trends of pNO3 as well as its responses to emission controls in China. The results indicate that although recent chemical transport models (CTMs) can reasonably capture the spatial-temporal variations of pNO3, model-observation biases still exist due to large uncertainties in the parameterization of dinitrogen pentoxide (N2O5) uptake and ammonia (NH3) emissions, insufficient heterogeneous reaction mechanism, and the predicted low sulfate concentrations in current CTMs. The heterogeneous hydrolysis of N2O5 dominates nocturnal pNO3 formation, however, the contribution to total pNO3 varies among studies, ranging from 21.0% to 51.6%. Moreover, the continuously increasing PM2.5 pNO3 fraction in recent years is mainly due to the decreased sulfur dioxide emissions, the enhanced atmospheric oxidation capacity (AOC), and the weakened nitrate deposition. Reducing NH3 emissions is found to be the most effective control strategy for mitigating pNO3 pollution in China. This review suggests that more field measurements are needed to constrain the parameterization of heterogeneous N2O5 and nitrogen dioxide (NO2) uptake. Future studies are also needed to quantify the relationships of pNO3 to AOC, O3, NOx, and volatile organic compounds (VOCs) in different regions of China under different meteorological conditions. Research on multiple-pollutant control strategies involving NH3, NOX, and VOCs is required to mitigate pNO3 pollution, especially during severe winter haze events.

Ovatodiolide inhibits SARS-CoV-2 replication and ameliorates pulmonary fibrosis through suppression of the TGF-ß/TßRs signaling pathway.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to pose threats to public health. The clinical manifestations of lung pathology in COVID-19 patients include sustained inflammation and pulmonary fibrosis. The macrocyclic diterpenoid ovatodiolide (OVA) has been reported to have anti-inflammatory, anti-cancer, anti-allergic, and analgesic activities. Here, we investigated the pharmacological mechanism of OVA in suppressing SARS-CoV-2 infection and pulmonary fibrosis in vitro and in vivo. Our results revealed that OVA was an effective SARS-CoV-2 3CLpro inhibitor and showed remarkable inhibitory activity against SARS-CoV-2 infection. On the other hand, OVA ameliorated pulmonary fibrosis in bleomycin (BLM)-induced mice, reducing inflammatory cell infiltration and collagen deposition in the lung. OVA decreased the levels of pulmonary hydroxyproline and myeloperoxidase, as well as lung and serum TNF-ɑ, IL-1ß, IL-6, and TGF-ß in BLM-induced pulmonary fibrotic mice. Meanwhile, OVA reduced the migration and fibroblast-to-myofibroblast conversion of TGF-ß1-induced fibrotic human lung fibroblasts. Consistently, OVA downregulated TGF-ß/TßRs signaling. In computational analysis, OVA resembles the chemical structures of the kinase inhibitors TßRI and TßRII and was shown to interact with the key pharmacophores and putative ATP-binding domains of TßRI and TßRII, showing the potential of OVA as an inhibitor of TßRI and TßRII kinase. In conclusion, the dual function of OVA highlights its potential for not only fighting SARS-CoV-2 infection but also managing injury-induced pulmonary fibrosis.

COVID-19 CT ground-glass opacity segmentation based on attention mechanism threshold.

The ground glass opacity (GGO) of the lung is one of the essential features of COVID-19. The GGO in computed tomography (CT) images has various features and low-intensity contrast between the GGO and edge structures. These problems pose significant challenges for segmenting the GGO. To tackle these problems, we propose a new threshold method for accurate segmentation of GGO. Specifically, we offer a framework for adjusting the threshold parameters according to the image contrast. Three functions include Attention mechanism threshold, Contour equalization, and Lung segmentation (ACL). The lung is divided into three areas using the attention mechanism threshold. Further, the segmentation parameters of the attention mechanism thresholds of the three parts are adaptively adjusted according to the image contrast. Only the segmentation regions restricted by the lung segmentation results are retained. Extensive experiments on four COVID datasets show that ACL can segment GGO images at low contrast well. Compared with the state-of-the-art methods, the similarity Dice of the ACL segmentation results is improved by 8.9%, the average symmetry surface distance ASD is reduced by 23%, and the required computational power F L O P s are only 0.09% of those of deep learning models. For GGO segmentation, ACL is more lightweight, and the accuracy is higher. Code will be released at https://github.com/Lqs-github/ACL.

An Exploration of Sedentary Behavior, Physical Activity, and Quality of Life During the COVID-19 Outbreak.

Objectives: Staying physically active is a cost-efficient strategy for disease prevention during a pandemic. The purposes of this study were to explore precautionary behaviors, psychological factors associated with physical activity and sedentary behavior, and impacts of active and sedentary lifestyles on the quality of life in the early stage of the coronavirus disease 2019 (COVID-19) outbreak. Methods: Participants were community-dwelling adults aged over 20 years who had not been infected with COVID-19 and who lived in the United States. A study with a cross-sectional design was conducted between July and October 2020. Quantitative data were collected by a self-reported questionnaire. Results: In total, 467 valid responses were obtained. Participants who engaged in an active lifestyle had significantly higher scores on all domains of quality of life compared to those who engaged in an inactive lifestyle. Participants with a non-sedentary lifestyle had significantly higher scores of psychological and social domains of quality of life than those with a sedentary lifestyle. Conclusion: Engaging in an active lifestyle and avoiding a sedentary lifestyle are recommended when facing future, unpredictable pandemics similar to COVID-19.

Autoimmune blistering skin diseases triggered by COVID-19 vaccinations: An Australian case series.

Autoimmune blistering skin diseases (AIBD) can be induced or flared by a multitude of sources, however, there have been some reports suggesting that this occurrence is due to COVID-19 vaccinations. At a single academic blistering disease centre in Sydney, Australia, a retrospective review was conducted, identifying 59 patients with AIBD seen between February 2021 and November 2022. Secondary to recent COVID-19 vaccination, four patients had induction of bullous pemphigoid, three patients had a flare of pre-existing bullous pemphigoid, one patient had induction of pemphigus, and two patients had a flare of pre-existing pemphigus vulgaris. This adds to our understanding of the role of vaccinations in the activity of AIBD.

Seeking Equity, Agility, and Sustainability in the Provision of Emergency Remote Teaching during the COVID-19 Pandemic: A Center for Teaching and Learning Takes an Expanded Role

Objectives: The purpose of the study was to illuminate and assess the experiences and feelings of the staff of a center for teaching and learning at one South African university during the early months (April--June 2020) of the COVID-19 pandemic lockdowns when it switched from face-to-face teaching to emergency remote teaching (ERT). It explores the practical, operational, ethical, cultural, and emotional questions that the staff of this center dealt with as they supported the university in ERT provision. Method: This paper draws on in-depth interviews with 23 staff members of the Centre for Innovation in Learning and Teaching (CILT) who revealed not only the logistical, technical, and administrative challenges faced during the ERT rollout period but the efforts they made to ensure that their efforts promoted equity (for students), agility (for the university), and psychological sustainability (for themselves). Findings: Using cultural historical activity theory as a lens to assess CILT staff activities, findings indicate that a number of contradictions and tensions emerged during this period--concerning exacerbated inequities, pedagogical compromises, cultural anxieties, and psychological pressures--that could not be fully resolved but only managed. Implications for Research: CILT staff are interested not only in providing logistical, technical, and practical support to a university but also in dealing effectively with the ethical, cultural, and emotional concerns that arise in times of crisis and transition, such as the current one. Understanding what happened during COVID-19 may offer insights into how other centers for teaching and learning can adjust to what will likely remain an unstable future in higher education. Conclusion: The pandemic ruptured the previously organic change and growth that characterized CILT development, transforming it as the staff responded to this South African university's need to provide support to academics and students engaging with ERT.

Coming out of the pandemic: What have we learned and what should we learn?

In this editorial, we reviewed the articles collected in the special issue "Economics of Pandemic Disease” along with other relevant literature. We found that the pandemic has had a devastating impact on the economy as a whole and on small and medium-sized enterprises (SMEs) and private firms in particular, which may have deepened the economic inequality and impeded poverty reduction in China. The pandemic also resulted in substantial damage to the mental health and well-being of the Chinese population, with a disproportionate impact on minorities, including the female and the illiterate. We also examined the available evidence regarding the effectiveness of China's policy response to the COVID pandemic, which suggested that China's zero-Covid policy succeeded in stabilizing its economy and maintaining a safe environment in earlier phases of the pandemic, but hardly achieved a balance between disease control and economic growth in the later stage when less fatal but more transmissive coronavirus variants emerged. Lastly, we discussed policy options that China may take to protect the health of its people and avoid a potentially substantial loss of lives during the transition toward the post-pandemic new normal, which include prioritizing the timely administration of effective vaccines among the elderly and vulnerable populations, improving public communications regarding when and how to seek medical help, and strengthening the surge capacity of the healthcare systems, especially in less developed regions.

Autoimmune blistering skin diseases triggered by COVID-19 vaccinations: An Australian case series

Autoimmune blistering skin diseases (AIBD) can be induced or flared by a multitude of sources, however, there have been some reports suggesting that this occurrence is due to COVID-19 vaccinations. At a single academic blistering disease centre in Sydney, Australia, a retrospective review was conducted, identifying 59 patients with AIBD seen between February 2021 and November 2022. Secondary to recent COVID-19 vaccination, four patients had induction of bullous pemphigoid, three patients had a flare of pre-existing bullous pemphigoid, one patient had induction of pemphigus, and two patients had a flare of pre-existing pemphigus vulgaris. This adds to our understanding of the role of vaccinations in the activity of AIBD.

COVID-19 CT ground-glass opacity segmentation based on attention mechanism threshold

The ground glass opacity (GGO) of the lung is one of the essential features of COVID-19. The GGO in computed tomography (CT) images has various features and low-intensity contrast between the GGO and edge structures. These problems pose significant challenges for segmenting the GGO. To tackle these problems, we propose a new threshold method for accurate segmentation of GGO. Specifically, we offer a framework for adjusting the threshold parameters according to the image contrast. Three functions include Attention mechanism threshold, Contour equalization, and Lung segmentation (ACL). The lung is divided into three areas using the attention mechanism threshold. Further, the segmentation parameters of the attention mechanism thresholds of the three parts are adaptively adjusted according to the image contrast. Only the segmentation regions restricted by the lung segmentation results are retained. Extensive experiments on four COVID datasets show that ACL can segment GGO images at low contrast well. Compared with the state-of-the-art methods, the similarity Dice of the ACL segmentation results is improved by 8.9%, the average symmetry surface distance ASD is reduced by 23%, and the required computational power

Understanding the adoption of the mask-supply information platforms during the COVID-19.

Since late 2019, coronavirus disease 2019 (COVID-19) has led to a significant increase in the demand for medical resources. To publish data on face mask supplies, the Taiwanese government collaborated with program developers to construct a mask-supply information transitional platform (MITP). To comprehend the adoption of MITP, the study proposes a research model that integrates the health behavior model (HBM) and IS/IT continuance model for examining the factors affecting intention to use an MITP. Survey data collected from 524 respondents indicated that (1) intention to use an MITP is directly influenced by perceived threat of COVID-19 and beliefs toward using the MITP; (2) cues to action directly influence the perceived threat of COVID-19; and (3) perceived ease of use of MITP is a significant determinant of perceived usefulness of MITP. These results provide practical guidelines for health authorities and government to develop health information systems and strategies to control pandemics.

Association of delayed chemoradiotherapy with elevated Epstein-Barr virus DNA load and adverse clinical outcome in nasopharyngeal carcinoma treatment during the COVID-19 pandemic: a retrospective study.

BACKGROUND: To summarize the impact of radiotherapy (RT) and chemotherapy delays on patients with nasopharyngeal carcinoma (NPC) during the COVID-19 pandemic. METHODS: We retrospectively included 233 patients with stage II-IVa NPC treated with RT and chemotherapy between December 11, 2019 and March 11, 2020. The outcomes were elevation in the EBV DNA load between two adjacent cycles of chemotherapy or during RT, and 1-year disease-free survival (DFS). RESULTS: RT delay occurred in 117 (50%) patients, and chemotherapy delay occurred in 220 (94%) patients. RT delay of ≥ 6 days was associated with a higher EBV DNA elevation rate (20.4% vs. 3.6%, odds ratio [OR] = 6.93 [95% CI = 2.49-19.32], P < 0.001), and worse 1-year DFS (91.2% vs. 97.8%, HR = 3.61 [95% CI = 1.37-9.50], P = 0.006), compared with on-schedule RT or delay of < 6 days. Chemotherapy delay of ≥ 10 days was not associated with a higher EBV DNA elevation rate (12.5% vs. 6.8%, OR = 1.94 [95% CI = 0.70-5.40], P = 0.20), or worse 1-year DFS (93.8% vs. 97.1%, HR = 3.73 [95% CI = 0.86-16.14], P = 0.059), compared with delay of < 10 days. Multivariable analyses showed RT delay of ≥ 6 days remained an independent adverse factor for both EBV DNA elevation and DFS. CONCLUSION: To ensure treatment efficacy for patients with nonmetastatic NPC, initiation of RT should not be delayed by more than 6 days; the effect of chemotherapy delay requires further investigation.

Hourly organic tracers-based source apportionment of PM2.5 before and during the Covid-19 lockdown in suburban Shanghai, China: Insights into regional transport influences and response to urban emission reductions.

During the Covid-19 outbreak, strict lockdown measures led to notable reductions in transportation-related emissions and significantly altered atmospheric pollution characteristics in urban and suburban areas. In this work, we compare comprehensive online measurements of PM2.5 major components and organic molecular markers in a suburban location in Shanghai, China before lockdown (Dec. 28, 2019 to Jan. 23, 2020) and during lockdown (Jan. 24 to Feb. 9, 2020). The NOx levels declined sharply by 59% from 44 to 18 ppb during the lockdown, while O3 rose two times higher to 42 ppb. The PM2.5 level dropped from 64 to 49 µg m-3 (-24%). The major components all showed reductions, with the reduction of nitrate most prominent at -58%, followed by organics at -19%, and sulfate at -17%. Positive matrix factorization analysis identifies fourteen source factors, including nine primary sources and five secondary sources. The secondary sources consist of sulfate-rich factor, nitrate-rich factor, and three secondary organic aerosol (SOA) factors, with SOA_I being anthropogenic SOA, SOA_II associated with later generation products of organic oxidation, and SOA_III being biogenic SOA. The combined secondary sources contributed to 69% and 63% (40 and 22 µg m-3) of PM2.5 before and during lockdown, respectively, among which the reductions in the nitrate-rich (-55%) factor was the most prominent. Among primary sources, large reductions (>80%) were observed in contributions from industrial, cooking, and vehicle emissions. Unlike some studies reporting that the restriction during the Covid-19 resulted in enhanced secondary sulfate and SOA formation, we observed decreases in both secondary inorganic and SOA formation despite the overall elevated oxidizing capacity in the suburban site. Our results indicate that the formation change in secondary inorganic and organic compounds in response to substantial reductions in urban primary precursors are different for urban and suburban environments.

Disease-Specific Factors Associated with Readmissions or Mortality After Hospital Discharge in COVID-19 Patients: a Retrospective Cohort Study.

BACKGROUND: Understanding the implications of disease-specific factors beyond baseline patient characteristics for coronavirus disease 2019 (COVID-19) may allow for identification of indicators for safe hospital discharge. OBJECTIVE: Assess whether disease-specific factors are associated with adverse events post-discharge using a data-driven approach. DESIGN: Retrospective cohort study. SETTING: Fifteen medical centers within Kaiser Permanente Southern California. PARTICIPANTS: Adult patients (n=3508) discharged alive following hospitalization for COVID-19 between 05/01/2020 and 09/30/2020. INTERVENTIONS: None. MAIN MEASURES: Adverse events defined as all-cause readmission or mortality within 14 days of discharge. Least absolute shrinkage and selection operator (LASSO) was used for variable selection and logistic regression was performed to estimate odds ratio (OR) and 95% confidence interval (CI). KEY RESULTS: Four variables including age, Elixhauser index, treatment with remdesivir, and symptom duration at discharge were selected by LASSO. Treatment with remdesivir was inversely associated with adverse events (OR: 0.46 [95%CI: 0.36-0.61]), while symptom duration ≤ 10 days was associated with adverse events (OR: 2.27 [95%CI: 1.79-2.87]) in addition to age (OR: 1.02 [95%CI: 1.01-1.03]) and Elixhauser index (OR: 1.15 [95%CI: 1.11-1.20]). A significant interaction between remdesivir and symptom duration was further observed (p=0.01). The association of remdesivir was stronger among those with symptom duration ≤10 days vs >10 days at discharge (OR: 0.30 [95%CI: 0.19-0.47] vs 0.62 [95%CI: 0.44-0.87]), while the association of symptom duration ≤ 10 days at discharge was weaker among those treated with remdesivir vs those not treated (OR: 1.31 [95%CI: 0.79-2.17] vs 2.71 [95%CI 2.05-3.59]). CONCLUSIONS: Disease-specific factors including treatment with remdesivir, symptom duration, and their interplay may help guide clinical decision making at time of discharge.

Preparation of the RIPK3 Polyclonal Antibody and Its Application in Immunoassays of Nephropathogenic Infectious Bronchitis Virus-Infected Chickens.

Receptor interacting protein kinase 3 (RIPK3) is a vital serine/threonine kinase in regulating the programmed destruction of infected cells to defend against RNA viruses. Although the role of RIPK3 in viruses in mice is well characterized, it remains unclear where in nephropathogenic infectious bronchitis virus (NIBV) in chickens. Here, we use a self-prepared polyclonal antibody to clarify the abundance of RIPK3 in tissues and define the contributions of RIPK3 in tissue damage caused by NIBV infection in chickens. Western blot analyses showed that RIPK3 polyclonal antibody can specifically recognize RIPK3 in the vital tissues of Hy-Line brown chicks and RIPK3 protein is abundantly expressed in the liver and kidney. Moreover, NIBV significantly upregulated the expression levels of RIPK3 in the trachea and kidney of chicks in a time-dependent manner. In addition, the activation of necroptosis in response to NIBV infection was demonstrated by the coimmunoprecipitation (CoIP) experiments through RIPK3 in the necrosome, which phosphorylates its downstream mixed-spectrum kinase structural domain-like protein (MLKL). Our findings offered preliminary insights into the key role of RIPK3 protein in studying the underlying mechanism of organ failure caused by NIBV infection.

Comparison of safety and outcomes related to remdesivir treatment among dialysis patients hospitalized with COVID-19.

Background: Patients with end-stage kidney disease (ESKD) are highly susceptible to coronavirus disease 2019 (COVID-19) infection and its complications. Remdesivir has improved outcomes in COVID-19 patients but its use has been limited among ESKD patients due to insufficient data regarding safety outcomes. We sought to evaluate the safety of remdesivir among dialysis patients hospitalized with COVID-19. Methods: This retrospective cohort study was conducted among patients age ≥18 years on maintenance dialysis and hospitalized with COVID-19 between 1 May 2020 and 31 January 2021 within an integrated health system who were treated or not treated with remdesivir. The primary outcome was 30-day all-cause mortality. Secondary outcomes were intensive care unit (ICU) stay, and transaminitis (AST/ALT >5× normal). Pseudo-populations were created using inverse probability of treatment weights with propensity scoring to balance patient characteristics among the two groups. Multivariable Poisson regression with robust error was performed to estimate 30-day mortality risk ratio. Results: A total of 486 (407 hemodialysis and 79 peritoneal dialysis) patients were hospitalized with COVID-19, among which 112 patients (23%) were treated with remdesivir [median treatment four days (interquartile range 2-5)]. The 30-day mortality rate was 24.1% among remdesivir-treated and 27.8% among non-treated patients. The estimated 30-day mortality rate was 0.74 (95% confidence interval 0.52-1.05) among remdesivir treated compared with non-treated patients. Liver injury and ICU admission rates were 1.8% and 14.3% among remdesivir-treated patients compared with 2.4% and 16% among non-treated patients. Conclusion: Among dialysis patients hospitalized with COVID-19, remdesivir was not associated with higher rates of liver injury or ICU admissions, and demonstrated a trend toward lower 30-day mortality.

In situ structure and dynamics of an alphacoronavirus spike protein by cryo-ET and cryo-EM

Porcine epidemic diarrhea (PED) is a highly contagious swine disease caused by porcine epidemic diarrhea virus (PEDV). PED causes enteric disorders with an exceptionally high fatality in neonates, bringing substantial economic losses in the pork industry. The trimeric spike (S) glycoprotein of PEDV is responsible for virus-host recognition, membrane fusion, and is the main target for vaccine development and antigenic analysis. The atomic structures of the recombinant PEDV S proteins of two different strains have been reported, but they reveal distinct N-terminal domain 0 (D0) architectures that may correspond to different functional states. The existence of the D0 is a unique feature of alphacoronavirus. Here we combined cryo-electron tomography (cryo-ET) and cryo-electron microscopy (cryo-EM) to demonstrate in situ the asynchronous S protein D0 motions on intact viral particles of a highly virulent PEDV Pintung 52 strain. We further determined the cryo-EM structure of the recombinant S protein derived from a porcine cell line, which revealed additional domain motions likely associated with receptor binding. By integrating mass spectrometry and cryo-EM, we delineated the complex compositions and spatial distribution of the PEDV S protein N-glycans, and demonstrated the functional role of a key N-glycan in modulating the D0 conformation. Hsu and co-workers integrate cryo-electron tomography, cryo-electron microscopy and mass spectrometry to reveal the structural polymorphism of a pig coronavirus spike protein within intact viral particles, and how glycosylation modulates the conformational changes pertinent to host recognition.