The Environmental Stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on the Surfaces of Widely Used Transport Packaging Materials.

The increased transmissibility of SARS-CoV-2 variants of concern (VOCs) has raised questions regarding the environmental stability of these viruses. Although a prolonged survival time has been reported for SARS-CoV-2, how long new variants can persist on contaminated surfaces and how environmental factors affect the persistence time are not fully characterized. The present study provides a comprehensive assessment of the stability of Omicron variants BA.1 and BA.5, which are currently circulating strains, on the surfaces of widely used transport packaging materials. By monitoring viable virus detection over a 7-day period under different environmental conditions, it was found that the environmental stability of SARS-CoV-2 Omicron variants depended heavily on the surface type, temperature, and virus concentration. In addition, virus nucleic acid exhibited high stability on the material surface independent of whether viable virus was detected. These findings provide useful information for logistics practitioners and the general public to appropriately deal with transport items under different conditions to minimize the risk of epidemic transmission. IMPORTANCE This study shows the environmental stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on surfaces of widely used transport packaging materials. The findings demonstrate that the environmental stability of the SARS-CoV-2 Omicron variants varies based on material type. The viability of SARS-CoV-2 on material surfaces depends heavily on temperature and viral titer. Low temperatures and high viral titers promote virus survival. Moreover, in contrast to virus viability, virus nucleic acid exhibits high stability on the surfaces of widely used materials, making the detection of virus nucleic acid unsuitable for evaluating the risk of epidemic transmission.

Serosurvey for SARS-CoV-2 among blood donors in Wuhan, China from September to December 2019.

The emerging of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 pandemic. The first case of COVID-19 was reported at early December in 2019 in Wuhan City, China. To examine specific antibodies against SARS-CoV-2 in biological samples before December 2019 would give clues when the epidemic of SARS-CoV-2 might start to circulate in populations. We obtained all 88,517 plasmas from 76,844 blood donors in Wuhan between 1 September and 31 December 2019. We first evaluated the pan-immunoglobin (pan-Ig) against SARS-CoV-2 in 43,850 samples from 32,484 blood donors with suitable sample quality and enough volume. Two hundred and sixty-four samples from 213 donors were pan-Ig reactive, then further tested IgG and IgM, and validated by neutralizing antibodies against SARS-CoV-2. Two hundred and thirteen samples (from 175 donors) were only pan-Ig reactive, 8 (from 4 donors) were pan-Ig and IgG reactive, and 43 (from 34 donors) were pan-Ig and IgM reactive. Microneutralization assay showed all negative results. In addition, 213 screened reactive donors were analyzed and did not show obviously temporal or regional tendency, but the distribution of age showed a difference compared with all tested donors. Then we reviewed SARS-CoV-2 antibody results from these donors who donated several times from September 2019 to June 2020, partly tested in a previous published study, no one was found a significant increase in S/CO of antibodies against SARS-CoV-2. Our findings showed no SARS-CoV-2-specific antibodies existing among blood donors in Wuhan, China before 2020, indicating no evidence of transmission of COVID-19 before December 2019 in Wuhan, China.

Global research trends in the COVID-19 and digestive disease: A review of visualization and bibliometric study

Background: The rapid spread of coronavirus disease 2019 (COVID-19) has attracted worldwide attention. There were also reported gastrointestinal symptoms in patients with COVID-19. This work aims to analyze the global research trends in COVID-19 and digestive disease. Methods: The related papers on COVID-19 and digestive disease were identified with Pubmed and web of science core collection on September 3, 2021. Bibliometric visualization was conducted through VOSviewer and CiteSpace. Results: The analytic research was based on original articles and reviews. There were 997 articles found, with citations ranging from 0 to 878. These articles were distributed among 86 countries and 355 journals. The USA mainly contributed (288 articles), where 3 of the top 10 institutions were located. Followed by China (215 articles) and Italy (160 articles). The highest level of scientific collaboration has been formed between the USA to China. The World Journal of Gastroenterology (39 papers) published the most significant number of articles. Concerning the research topic, the colon/small bowel had the largest number of articles, followed by the liver and pancreaticobiliary. "Liver injury,” "inflammatory bowel disease,” "management,” and "endoscopy” were the hotspot keywords. The largest cluster of liver transplantation had offered hints regarding research frontiers. Conclusion: The analytic results showed that the liver, especially liver transplantation, and inflammatory bowel disease were the 2 most influential research topics in COVID-19 and digestive disease.

Utility of Epstein-Barr Virus DNA in Nasopharynx Swabs as a Reflex Test to Triage Seropositive Individuals in Nasopharyngeal Carcinoma Screening Programs.

BACKGROUND: Epstein-Barr virus (EBV) DNA detection in the nasopharynx is considered a biomarker for nasopharyngeal carcinoma (NPC). We evaluated its performance as a reflex test to triage EBV seropositives within an NPC screening program in China. METHODS: The study population was embedded within an ongoing NPC screening trial and included 1111 participants who screened positive for anti-EBV VCA (antibodies against EBV capsid antigens)/EBNA1 (EBV nuclear antigen1)-IgA antibodies (of 18 237 screened). Nasopharynx swabs were collected/tested for EBNA1 gene EBV DNA load. We evaluated performance of EBV DNA in the nasopharynx swab as a reflex test to triage EBV serological high-risk (those referred to endoscopy/MRI) and medium-risk (those referred to accelerated screening) individuals. RESULTS: By the end of 2019, we detected 20 NPC cases from 317 serological high-risk individuals and 4 NPC cases from 794 medium-risk individuals. When used to triage serological high-risk individuals, nasopharynx swab EBV DNA was detected in 19/20 cases (positivity rate among cases: 95.0%; 95% CI, 75.1%-99.9%), with a referral rate of 63.4% (201/317, 95% CI, 57.8%-68.7%) and NPC detection rate among positives of 9.5% (19/201, 95% CI, 5.8%-14.4%). The performance of an algorithm that combined serology with triage of serology high-risk individuals using EBV DNA testing yielded a sensitivity of 72.4% (95% CI, 3.0%-81.4%) and specificity of 97.6% (95% CI, 97.2%-97.9%). When used to triage EBV serological medium-risk individuals, the positivity rate among cases was 75.0% (95% CI, 19.4%-99.4%), with a referral rate of 61.8% (95% CI, 58.4%-65.2%) and NPC detection rate among positives of 0.6% (95% CI, 0.1%-1.8%). CONCLUSIONS: Nasopharynx swab EBV DNA showed promise as a reflex test to triage serology high-risk individuals, reducing referral by ca. 40% with little reduction in sensitivity compared to a serology-only screening program.

ZBP1-Mediated Necroptosis: Mechanisms and Therapeutic Implications.

Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. Recently, ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. Recent studies have also reported that ZBP1 induces necroptosis in non-viral infections and mediates necrotic signal transduction by a unique mechanism. This review highlights the discovery of ZBP1 and its novel findings in necroptosis and provides an insight into its critical role in the crosstalk between different types of cell death, which may represent a new therapeutic option.

Chlorine poisoning caused by improper mixing of household disinfectants during the COVID-19 pandemic: Case series.

BACKGROUND: Misuse of disinfectants during the coronavirus disease 2019 pandemic has led to several poisoning incidents. However, there are few clinical case reports on poisoning caused by improper mixing of household disinfectants. AIM: To summarize the clinical characteristics and treatment effects of chlorine poisoning caused by improper mixing of hypochlorite bleach with acidic cleaning agents.METHODSWe retrospectively analyzed baseline and clinical data, clinical symptoms, and treatment methods of seven patients with chlorine poisoning who were admitted to the National Army Poisoning Treatment Center. RESULTS: Among the seven patients, the average poisoning time (exposure to admission) was 57 h (4-240 h). All patients were involved in cleaning bathrooms. Chest computed tomography scans revealed bilateral lung effusions or inflammatory changes in five patients. The partial pressure of oxygen decreased in six patients, and respiratory failure occurred in one. Five patients had different degrees of increase in white blood cell count. Humidified oxygen therapy, non-invasive mechanical ventilation, anti-inflammatory corticosteroids, antioxidants, and antibiotics were administered for treatment. The average length of hospital stay was 7 d (4-9 d). All seven patients recovered and were discharged. CONCLUSION: Improper mixing of household disinfectants may cause damage to the respiratory system due to chlorine poisoning. Corticosteroids may improve lung exudation in severe cases, and symptomatic supportive treatment should be performed early.

SARS-CoV-2-specific antibody and T-cell responses 1 year after infection in people recovered from COVID-19: a longitudinal cohort study.

Background: The memory immune response is crucial for preventing reinfection or reducing disease severity. However, the robustness and functionality of the humoral and T-cell response to SARS-CoV-2 remains unknown 12 months after initial infection. The aim of this study is to investigate the durability and functionality of the humoral and T-cell response to the original SARS-CoV-2 strain and variants in recovered patients 12 months after infection. Methods: In this longitudinal cohort study, we recruited participants who had recovered from COVID-19 and who were discharged from the Wuhan Research Center for Communicable Disease Diagnosis and Treatment at the Chinese Academy of Medical Sciences, Wuhan, China, between Jan 7 and May 29, 2020. Patients received a follow-up visit between Dec 16, 2020, and Jan 27, 2021. We evaluated the presence of IgM, IgA, and IgG antibodies against the SARS-CoV-2 nucleoprotein, Spike protein, and the receptor-binding domain 12 months after initial infection, using ELISA. Neutralising antibodies against the original SARS-CoV-2 strain, and the D614G, beta (B.1.351), and delta (B.1.617.2) variants were analysed using a microneutralisation assay in a subset of plasma samples. We analysed the magnitude and breadth of the SARS-CoV-2-specific memory T-cell responses using the interferon γ (IFNγ) enzyme-linked immune absorbent spot (ELISpot) assay and intracellular cytokine staining (ICS) assay. The antibody response and T-cell response (ie, IFN-γ, interleukin-2 [IL-2], and tumour necrosis factor α [TNFα]) were analysed by age and disease severity. Antibody titres were also analysed according to sequelae symptoms. Findings: We enrolled 1096 patients, including 289 (26·4%) patients with moderate initial disease, 734 (67·0%) with severe initial disease, and 73 (6·7%) with critical initial disease. Paired plasma samples were collected from 141 patients during the follow-up visits for the microneutralisation assay. PBMCs were collected from 92 of 141 individuals at the 12-month follow-up visit, of which 80 were analysed by ELISpot and 92 by ICS assay to detect the SARS-CoV-2-specific memory T-cell responses. N-IgG (899 [82·0%]), S-IgG (1043 [95·2%]), RBD-IgG (1032 [94·2%]), and neutralising (115 [81·6%] of 141) antibodies were detectable 12 months after initial infection in most individuals. Neutralising antibodies remained stable 6 and 12 months after initial infection in most individuals younger than 60 years. Multifunctional T-cell responses were detected for all SARS-CoV-2 viral proteins tested. There was no difference in the magnitude of T-cell responses or cytokine profiles in individuals with different symptom severity. Moreover, we evaluated both antibody and T-cell responses to the D614G, beta, and delta viral strains. The degree of reduced in-vitro neutralising antibody responses to the D614G and delta variants, but not to the beta variant, was associated with the neutralising antibody titres after SARS-CoV-2 infection. We also found poor neutralising antibody responses to the beta variant; 83 (72·2%) of 115 patients showed no response at all. Moreover, the neutralising antibody titre reduction of the recovered patient plasma against the delta variant was similar to that of the D614G variant and lower than that of the beta variant. By contrast, T-cell responses were cross-reactive to the beta variant in most individuals. Importantly, T-cell responses could be detected in all individuals who had lost the neutralising antibody response to SARS-CoV-2 12 months after the initial infection. Interpretation: SARS-CoV-2-specific neutralising antibody and T-cell responses were retained 12 months after initial infection. Neutralising antibodies to the D614G, beta, and delta viral strains were reduced compared with those for the original strain, and were diminished in general. Memory T-cell responses to the original strain were not disrupted by new variants. This study suggests that cross-reactive SARS-CoV-2-specific T-cell responses could be particularly important in the protection against severe disease caused by variants of concern whereas neutralising antibody responses seem to reduce over time. Funding: Chinese Academy of Medical Sciences, National Natural Science Foundation, and UK Medical Research Council.

Innovative Application of SERS in Food Quality and Safety: A Brief Review of Recent Trends.

Innovative application of surface-enhanced Raman scattering (SERS) for rapid and nondestructive analyses has been gaining increasing attention for food safety and quality. SERS is based on inelastic scattering enhancement from molecules located near nanostructured metallic surfaces and has many advantages, including ultrasensitive detection and simple protocols. Current SERS-based quality analysis contains composition and structural information that can be used to establish an electronic file of the food samples for subsequent reference and traceability. SERS is a promising technique for the detection of chemical, biological, and harmful metal contaminants, as well as for food poisoning, and allergen identification using label-free or label-based methods, based on metals and semiconductors as substrates. Recognition elements, including immunosensors, aptasensors, or molecularly imprinted polymers, can be linked to SERS tags to specifically identify targeted contaminants and perform authenticity analysis. Herein, we highlight recent studies on SERS-based quality and safety analysis for different foods categories spanning the whole food chain, 'from farm to table' and processing, genetically modified food, and novel foods. Moreover, SERS detection is a potential tool that ensures food safety in an easy, rapid, reliable, and nondestructive manner during the COVID-19 pandemic.

Time Series Based Data Explorer and Stream Analysis for Anomaly Prediction

All over the world, time series-based anomaly prediction plays a vital role in all walks of life such as medical monitoring in hospitals and climate and environment risks. In the present study, a survey on the methods and techniques for time series data mining and proposes is carried, in order to solve a brand-new problem, time series progressive anomaly prediction. In terms of contents, the first part sketches out the methods that have captured most of the interest of researchers, which include an overview of abnormal prediction problems, a summary of main characteristics of anomaly prediction, and an introduction of anomaly prediction methodology in literature. The second part focuses on the future research trends on the phase/staged abnormal prediction of time series, where a novel time series compression method and a corresponding similarity measure will be designed, which can be explored subsequently. Finally, the related challenges to take this trend are mentioned. It is hoped that this paper can provide a profound understanding of anomaly prediction for the time series-based data mining research field.

Circular RNA vaccines against SARS-CoV-2 and emerging variants.

As the emerging variants of SARS-CoV-2 continue to drive the worldwide pandemic, there is a constant demand for vaccines that offer more effective and broad-spectrum protection. Here, we report a circular RNA (circRNA) vaccine that elicited potent neutralizing antibodies and T cell responses by expressing the trimeric RBD of the spike protein, providing robust protection against SARS-CoV-2 in both mice and rhesus macaques. Notably, the circRNA vaccine enabled higher and more durable antigen production than the 1mΨ-modified mRNA vaccine and elicited a higher proportion of neutralizing antibodies and distinct Th1-skewed immune responses. Importantly, we found that the circRNARBD-Omicron vaccine induced effective neutralizing antibodies against the Omicron but not the Delta variant. In contrast, the circRNARBD-Delta vaccine protected against both Delta and Omicron or functioned as a booster after two doses of either native- or Delta-specific vaccination, making it a favorable choice against the current variants of concern (VOCs) of SARS-CoV-2.

Retrospective analysis of influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) has spread widely around the world with strong infectivity, rapid mutation and a high mortality rate. Mechanical ventilation has been included in the Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 8) as an important treatment for severe and critical COVID-19 patients, but its clinical efficacy in COVID-19 patients is various. Therefore, it is necessary to study the influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients. AIM: The aim of this study was to determine the influencing factors on the efficacy of mechanical ventilation in severe and critical COVID-19 patients. METHODS: A total of 27 severe and critical COVID-19 patients were enrolled in this study and treated with mechanical ventilation at the Optical Valley Campus of Hubei Maternal and Child Health Care Hospital (Wuhan, Hubei Province) from February 20, 2020 to April 5, 2020. According to the final treatment outcomes, the patients were divided into the "effective group" and "death group." The clinical data of the two groups, such as the treatment process and final outcome, were retrospectively analyzed in order to determine the specific curative effects on the two groups and the reasons for the differences in such curative effects, as well as to explore the factors related to death. RESULTS: This study enrolled 27 severe and critical COVID-19 patients, including 17 males (63.0%) and 10 females (37.0%). Their ages were 74.41 ± 11.73-years-old, and 19 patients (70.4%) were over 70-years-old. Severe COVID-19 patients over 70-years-old who were treated with mechanical ventilation died in 14 cases (82.4%); thus, this was the peak age. A total of 17 patients died of basic disease, 16 of whom had more than two basic diseases. The basic diseases were hypertension, diabetes, and cardiovascular and cerebrovascular diseases. At the same time, 13 patients (76.5%) died from an abnormal increase in blood glucose. Among them, eight had diabetes before contracting COVID-19 and five had a stress-induced increase in blood glucose after contracting COVID-19. Diabetic ketoacidosis occurred in one case. The use of tocilizumab may be a double-edged sword that carries a certain risk in clinical usage. Among the patients who died, 16 (94.1%) went into septic shock at the end. There were significant differences in the degree of infection, cardiac and renal function, and blood glucose between the death group and effective group. CONCLUSION: Age, blood glucose, cardiac and renal function, and inflammatory reaction are important indicators of poor prognosis for mechanical ventilation in severe and critical COVID-19 patients.

Sensing of cytoplasmic chromatin by cGAS activates innate immune response in SARS-CoV-2 infection.

The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2'3'-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells' self-nucleic acids can be employed as a "danger signal" to alarm the immune system.

An antibody-based proximity labeling map reveals mechanisms of SARS-CoV-2 inhibition of antiviral immunity.

The global epidemic caused by the coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in the infection of over 200 million people. To extend the knowledge of interactions between SARS-CoV-2 and humans, we systematically investigate the interactome of 29 viral proteins in human cells by using an antibody-based TurboID assay. In total, 1,388 high-confidence human proximal proteins with biotinylated sites are identified. Notably, we find that SARS-CoV-2 manipulates the antiviral and immune responses. We validate that the membrane protein ITGB1 associates angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 entry. Moreover, we reveal that SARS-CoV-2 proteins inhibit activation of the interferon pathway through the mitochondrial protein mitochondrial antiviral-signaling protein (MAVS) and the methyltransferase SET domain containing 2, histone lysine methyltransferase (SETD2). We propose 111 potential drugs for the clinical treatment of coronavirus disease 2019 (COVID-19) and identify three compounds that significantly inhibit the replication of SARS-CoV-2. The proximity labeling map of SARS-CoV-2 and humans provides a resource for elucidating the mechanisms of viral infection and developing drugs for COVID-19 treatment.

Targeting lysophospholipid acid receptor 1 and ROCK kinases promotes antiviral innate immunity.

Growing evidence indicates the vital role of lipid metabolites in innate immunity. The lipid lysophosphatidic acid (LPA) concentrations are enhanced in patients upon HCV or SARS-CoV-2 infection, but the function of LPA and its receptors in innate immunity is largely unknown. Here, we found that viral infection promoted the G protein­coupled receptor LPA1 expression, and LPA restrained type I/III interferon production through LPA1. Mechanistically, LPA1 signaling activated ROCK1/2, which phosphorylated IRF3 Ser97 to suppress IRF3 activation. Targeting LPA1 or ROCK in macrophages, fibroblasts, epithelial cells, and LPA1 conditional KO mice promoted interferon-induced clearance of multiple viruses. LPA1 was colocalized with the receptor ACE2 in lung and intestine. Together with previous findings that LPA1 and ROCK1/2 promoted vascular leaking or lung fibrosis, we propose that the current available preclinical drugs targeting the LPA1-ROCK module might protect from SARS-CoV-2 or various virus infections in the intestine or lung.

Challenges for Obstetricians and the Countermeasures of COVID-19 Epidemic.

Since the outbreak of the novel coronavirus in Wuhan, China, as obstetricians, we also face great challenges. We need to identify pregnant patients with 2019 coronavirus disease infection timely, and give them appropriate treatment in order to obtain a good maternal and infant prognosis. Here, we would like to share a case and provide some suggestions on how to screen, diagnose and treat pregnant women with 2019 coronavirus disease infection during the outbreak.

Genome-wide CRISPR activation screen identifies candidate receptors for SARS-CoV-2 entry.

The outbreak of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has created a global health crisis. SARS-CoV-2 infects varieties of tissues where the known receptor ACE2 is low or almost absent, suggesting the existence of alternative viral entry pathways. Here, we performed a genome-wide barcoded-CRISPRa screen to identify novel host factors that enable SARS-CoV-2 infection. Beyond known host proteins, i.e., ACE2, TMPRSS2, and NRP1, we identified multiple host components, among which LDLRAD3, TMEM30A, and CLEC4G were confirmed as functional receptors for SARS-CoV-2. All these membrane proteins bind directly to spike's N-terminal domain (NTD). Their essential and physiological roles have been confirmed in either neuron or liver cells. In particular, LDLRAD3 and CLEC4G mediate SARS-CoV-2 entry and infection in an ACE2-independent fashion. The identification of the novel receptors and entry mechanisms could advance our understanding of the multiorgan tropism of SARS-CoV-2, and may shed light on the development of COVID-19 countermeasures.

The architecture of the SARS-CoV-2 RNA genome inside virion.

SARS-CoV-2 carries the largest single-stranded RNA genome and is the causal pathogen of the ongoing COVID-19 pandemic. How the SARS-CoV-2 RNA genome is folded in the virion remains unknown. To fill the knowledge gap and facilitate structure-based drug development, we develop a virion RNA in situ conformation sequencing technology, named vRIC-seq, for probing viral RNA genome structure unbiasedly. Using vRIC-seq data, we reconstruct the tertiary structure of the SARS-CoV-2 genome and reveal a surprisingly "unentangled globule" conformation. We uncover many long-range duplexes and higher-order junctions, both of which are under purifying selections and contribute to the sequential package of the SARS-CoV-2 genome. Unexpectedly, the D614G and the other two accompanying mutations may remodel duplexes into more stable forms. Lastly, the structure-guided design of potent small interfering RNAs can obliterate the SARS-CoV-2 in Vero cells. Overall, our work provides a framework for studying the genome structure, function, and dynamics of emerging deadly RNA viruses.