Insufficient epitope-specific T cell clones are responsible for impaired cellular immunity to inactivated SARS-CoV-2 vaccine in older adults.

Aging is a critical risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine efficacy. The immune responses to inactivated vaccine for older adults, and the underlying mechanisms of potential differences to young adults, are still unclear. Here we show that neutralizing antibody production by older adults took a longer time to reach similar levels in young adults after inactivated SARS-CoV-2 vaccination. We screened SARS-CoV-2 variant strains for epitopes that stimulate specific CD8 T cell response, and older adults exhibited weaker CD8 T-cell-mediated responses to these epitopes. Comparison of lymphocyte transcriptomes from pre-vaccinated and post-vaccinated donors suggested that the older adults had impaired antigen processing and presentation capability. Single-cell sequencing revealed that older adults had less T cell clone expansion specific to SARS-CoV-2, likely due to inadequate immune receptor repertoire size and diversity. Our study provides mechanistic insights for weaker response to inactivated vaccine by older adults and suggests the need for further vaccination optimization for the old population.

Perceptions towards online learning among medical students during the COVID-19 pandemic.

Social distancing has been essential during the COVID-19 pandemic to slow the spread of the disease. Online learning ensures students can participate in learning activities while also maintaining a physical distance from other students. Although online learning was used to prevent the spread of COVID-19, the development of online learning has also been promoted. Here, we sought to explore the perceptions and responses of students to online learning during the pandemic using a cross-sectional study. Electronic questionnaire was used for data collection. Statistical analyses were performed for 1614 valid questionnaires and P < 0.05 was considered statistically significant. Overall, COVID-19 had more effect on female students, such as fear of COVID-19 (2.4 times higher than the number of male students) and length of time spent learning (H = 42.449, P < 0.05). However, the higher the students' grades were, the less the impact of COVID-19. For the style of lessons, all students would prefer shorter lessons (P < 0.05). Female and fifth-grade students were more prefer combined online and face-to-face learning, and male and freshmen students were more likely to prefer face-to-face learning after the pandemic. More than 50% of students thought the main advantage of online learning was convenience, with low efficiency being a disadvantage. The main factors negatively influencing online learning were eyestrain, poor network connections, and poor learning environments at home. In conclusion, synchronous online and face-to-face learning may become more common in future curricula, however the efficiency of online learning and the female students more attentions.

Gross Pathology in COVID-19

The global infectious disease COVID-19 is caused by SARS-CoV-2, a new member of the Coronaviridae family. Though presented as a novel disease that primarily affects the respiratory system, multi-organ involvement has been well-noticed and documented since the beginning of the pandemic. When performed properly with adequate safety measures, autopsy provides the most valuable information to decipher the pathogenesis of this novel disease, therefore providing a basis for clinical management. In addition to reviewing the macroscopic changes in organs and tissues involved in COVID-19, the relevant microscopic alterations and possible pathogenesis are also discussed.

Child transmission of SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Understanding of the role of children in COVID-19 transmission has significant implications for school and childcare policies, as well as appropriate targeting of vaccine campaigns. The objective of this systematic review was to identify the role of children in SARS-CoV-2 transmission to other children and adults. METHODS: MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and Web of Science were electronically searched for articles published before March 31, 2021. Studies of child-to-child and child-to-adult transmission and quantified the incidence of index and resulting secondary attack rates of children and adults in schools, households, and other congregate pediatric settings were identified. All articles describing confirmed transmission of SARS-CoV-2 from a child were included. PRISMA guidelines for data abstraction were followed, with each step conducted by two reviewers. RESULTS: 40 of 6110 articles identified met inclusion criteria. Overall, there were 0.8 secondary cases per primary index case, with a secondary attack rate of 8.4% among known contacts. The secondary attack rate was 26.4% among adult contacts versus 5.7% amongst child contacts. The pooled estimate of a contact of a pediatric index case being infected as secondary case was 0.10 (95% CI 0.03-0.25). CONCLUSIONS: Children transmit COVID-19 at a lower rate to children than to adults. Household adults are at highest risk of transmission from an infected child, more so than adults or children in other settings.

Network pharmacology and bioinformatics analysis identified essential genes of Jingulian in the treatment of rheumatoid arthritis and COVID-19.

Background: Patients with rheumatoid arthritis (RA) may be more susceptible to infection by coronavirus disease-19 (COVID-19) due to immune system dysfunction. However, there are still insufficient treatment strategies for patients with RA and COVID-19. Since Jingulian is a traditional Chinese medicine (TCM) with anti-viral and immune regulatory functions, our study aims to explore the detailed mechanisms of Jingulian in treating patients with RA and COVID-19. Methods: All the components of Jingulian were retrieved from pharmacology databases. Then, a series of network pharmacology-based analyses and molecular docking were used to understand the molecular functions, core targets, related pathways, and potential therapeutic targets of Jingulian in patients with RA/COVID-19. Results: A total of 93 genes were identified according to the disease-compound-target network. We investigated that the main targets, signaling pathways, and biological functions of Jingulian in RA and COVID-19. Our results indicated that Jingulian may treat patients with RA/COVID-19 through immune processes and viral processes. Moreover, the results of molecular docking revealed that tormentic acid was one of the top compounds of Jingulian, which had high affinity with Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and epidermal growth factor receptor (EGFR) in patients with RA/COVID-19. Furthermore, 5 core targets of Jingulian were also identified, including JAK1, Janus kinase 2 (JAK2), STAT3, lymphocyte specific protein tyrosine kinase (LCK), and EGFR. Conclusions: Tormentic acid in Jingulian may regulate JAK1, STAT3, and EGFR, and might play a critical role in RA/COVID-19.

Exploring potential mechanisms of Suhexiang Pill against COVID-19 based on network pharmacology and molecular docking.

BACKGROUND: The traditional Chinese medicine prescription Suhexiang Pill (SHXP), a classic prescription for the treatment of plague, has been recommended in the 2019 Guideline for coronavirus disease 2019 (COVID-19) diagnosis and treatment of a severe type of COVID-19. However, the bioactive compounds and underlying mechanisms of SHXP for COVID-19 prevention and treatment have not yet been elucidated. This study investigates the mechanisms of SHXP in the treatment of COVID-19 based on network pharmacology and molecular docking. METHODS: First, the bioactive ingredients and corresponding target genes of the SHXP were screened from the traditional Chinese medicine systems pharmacology database and analysis platform database. Then, we compiled COVID-19 disease targets from the GeneCards gene database and literature search. Subsequently, we constructed the core compound-target network, the protein-protein interaction network of the intersection of compound targets and disease targets, the drug-core compound-hub gene-pathway network, module analysis, and hub gene search by the Cytoscape software. The Metascape database and R language software were applied to analyze gene ontology biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Finally, AutoDock software was used for molecular docking of hub genes and core compounds. RESULTS: A total of 326 compounds, 2450 target genes of SHXP, and 251 genes related to COVID-19 were collected, among which there were 6 hub genes of SHXP associated with the treatment of COVID-19, namely interleukin 6, interleukin 10, vascular endothelial growth factor A, signal transducer and activator of transcription 3 (STAT3), tumor necrosis factor (TNF), and epidermal growth factor. Functional enrichment analysis suggested that the effect of SHXP against COVID-19 is mediated by synergistic regulation of several biological signaling pathways, including Janus kinase/ STAT3, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), T cell receptor, TNF, Nuclear factor kappa-B, Toll-like receptor, interleukin 17, Chemokine, and hypoxia-inducible factor 1 signaling pathways. SHXP may play a vital role in the treatment of COVID-19 by suppressing the inflammatory storm, regulating immune function, and resisting viral invasion. Furthermore, the molecular docking results showed an excellent binding affinity between the core compounds and the hub genes. CONCLUSION: This study preliminarily predicted the potential therapeutic targets, signaling pathways, and molecular mechanisms of SHXP in the treatment of severe COVID-19, which include the moderate immune system, relieves the "cytokine storm," and anti-viral entry into cells.

Research Progress in Anti-Inflammatory Bioactive Substances Derived from Marine Microorganisms, Sponges, Algae, and Corals.

Inflammation is the body's defense reaction in response to stimulations and is the basis of various physiological and pathological processes. However, chronic inflammation is undesirable and closely related to the occurrence and development of diseases. The ocean gives birth to unique and diverse bioactive substances, which have gained special attention and been a focus for anti-inflammatory drug development. So far, numerous promising bioactive substances have been obtained from various marine organisms such as marine bacteria and fungi, sponges, algae, and coral. This review covers 71 bioactive substances described during 2015-2020, including the structures (65 of which), species sources, evaluation models and anti-inflammatory activities of these substances. This review aims to provide some reference for the research progress of marine-organism-derived anti-inflammatory metabolites and give more research impetus for their conversion to novel anti-inflammatory drugs.

Heterogeneity Analysis of Chest CT Predict Individual Prognosis of COVID-19 Patients.

BACKGROUND: Ground-glass Opacity (GGO) and Consolidation Opacity (CLO) are the common CT lung opacities, and their heterogeneity may have potential for prognosis ofcoronavirus disease-19 (COVID-19) patients. OBJECTIVE: This study aimed to estimate clinical outcomes in individual COVID-19 patients using histogram heterogeneity analysis based on CT opacities. METHODS: 71 COVID-19 cases' medical records were retrospectively reviewed from a designated hospital in Wuhan, China, from January 24th to February 28th at the early stage of the pandemic. Two characteristic lung abnormity opacities, GGO and CLO, were drawn on CT images to identify the heterogeneity using quantitative histogram analysis. The parameters (mean, mode, kurtosis, and skewness) were derived from histograms to evaluate the accuracy of clinical classification and outcome prediction. Nomograms were built to predict the risk of death and median length of hospital stays (LOS), respectively. RESULTS: A total of 57 COVID-19 cases were eligible for the study cohort after excluding 14 cases. The highest lung abnormalities were GGO mixed with CLO in both the survival populations (26 in 42, 61.9%) and died population (10 in 15, 66.7%). The best performance heterogeneity parameters to discriminate severe type from mild/moderate counterparts were as follows: GGO_skewness: specificity= 66.67%, sensitivity=78.12%, AUC=0.706; CLO_mean: specificity=70.00%, sensitivity= 76.92%, and AUC=0.746. Nomogram based on histogram parameters can predict the individual risk of death and the prolonged median LOS of COVID-19 patients. C-indexes were 0.763 and 0.888 for risk of death and prolonged median LOS, respectively. CONCLUSION: Histogram analysis method based on GGO and CLO has the ability for individual risk prediction in COVID-19 patients.

SARS-CoV-2 NSP12 Protein Is Not an Interferon-ß Antagonist.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is bringing an unprecedented health crisis to the world. To date, our understanding of the interaction between SARS-CoV-2 and host innate immunity is still limited. Previous studies reported that SARS-CoV-2 nonstructural protein 12 (NSP12) was able to suppress interferon-ß (IFN-ß) activation in IFN-ß promoter luciferase reporter assays, which provided insights into the pathogenesis of COVID-19. In this study, we demonstrated that IFN-ß promoter-mediated luciferase activity was reduced during coexpression of NSP12. However, we could show NSP12 did not affect IRF3 or NF-κB activation. Moreover, IFN-ß production induced by Sendai virus (SeV) infection or other stimulus was not affected by NSP12 at mRNA or protein level. Additionally, the type I IFN signaling pathway was not affected by NSP12, as demonstrated by the expression of interferon-stimulated genes (ISGs). Further experiments revealed that different experiment systems, including protein tags and plasmid backbones, could affect the readouts of IFN-ß promoter luciferase assays. In conclusion, unlike as previously reported, our study showed SARS-CoV-2 NSP12 protein is not an IFN-ß antagonist. It also rings the alarm on the general usage of luciferase reporter assays in studying SARS-CoV-2. IMPORTANCE Previous studies investigated the interaction between SARS-CoV-2 viral proteins and interferon signaling and proposed that several SARS-CoV-2 viral proteins, including NSP12, could suppress IFN-ß activation. However, most of these results were generated from IFN-ß promoter luciferase reporter assay and have not been validated functionally. In our study, we found that, although NSP12 could suppress IFN-ß promoter luciferase activity, it showed no inhibitory effect on IFN-ß production or its downstream signaling. Further study revealed that contradictory results could be generated from different experiment systems. On one hand, we demonstrated that SARS-CoV-2 NSP12 could not suppress IFN-ß signaling. On the other hand, our study suggests that caution needs to be taken with the interpretation of SARS-CoV-2-related luciferase assays.

Application of HPC and Big Data in Post-Pandemic Times

We lay out the ramifications of the 2020 pandemic for all people in geosciences, especially the young, and argue for significant changes on training and career development. We focus primarily on its devastating impact in U.S.A. and compare with that in other countries especially China. We review the potential effect for the next four years or so on the aspirations of an academic career versus more realistic career goals. We urge people in mid-career about the need to reassess previous goals. We stress the need for students or researchers to acquire technical skills in high-performance computing (HPC), data analytics, artificial intelligence, and/or visualization along with a broad set of technical skills in applied computer science and mathematics. We give advice about hot prospects in several areas that have great potential for advancement in the coming decade, such as visualization, deep learning, quantum computing and information, and cloud computing, all of which lie within the aegis of HPC. Our forecast is that the pandemic will significantly reshape the job landscape and career paths for both young and established researchers and we discuss bluntly the dire situation facing junior people in geosciences in the aftermath of the pandemic around the world until 2024.

Rational use of drug and pharmaceutical care in patients with coronavirus disease 2019 combined with stroke

Coronavirus disease 2019 (COVID-19) patients are particularly critically ill, often accompanied by D-djurogen elevation, easy to induce or aggravate the occurrence of ischemic stroke. Both diseases have similar symptoms such as headache, vomiting, fever and shortness of breath in the early stages of their medical history, which can easily lead to misdiagnosis, missed diagnosis, and mutual influence, resulting in prolonged course of illness. For patients with COVID-19, anti-venom treatment should be actively taken as soon as possible, combined with stroke patients, the indicator change of D-diamer should be closely monitored, according to its indicators to give patients appropriate anti-thrombosis treatment, once the D-diamer rises, it is recommended to start anticoagulant immediately, while controlling the patient's blood pressure lipids and other high-risk factors. In this paper, combined with the research on stroke-related drug use, this paper discusses the rational drug use strategy and pharmacological care of high-risk groups such as COVID-19 combined with stroke, and provides reasonable drug use reference for such patients.

Engage in Exploration: Pathology Gross Laboratory in the COVID-Era.

The outbreak of Covid-19 has changed education, including the mechanism of delivery of gross pathology laboratories. Herein, we describe how we revised our preclinical gross pathology lab to a flipped model to fit with COVID-19 regulations. A series of short, session objective-driven videos are made available online. Students are expected to watch the videos before coming to the hands-on lab. Groups of 2 students enter the gross lab on a timed basis and rotate through a series of stations. At each station, students examine gross pathology specimens while answering questions designed to apply the clinical correlation of pathophysiology and heighten observational skills. One or 2 pathologists are available throughout the lab session to address the questions from the students. The design of this laboratory exercise maintains appropriate distancing and hygiene in the time of COVID-19. The laboratory rooms are mapped to set up an appropriate number of timed stations. Flow-through of the rooms is unidirectional. Comparing with the traditional show-and-tell of teaching gross pathology, the renovated flipped model is genuinely student-centered and focuses on active learning. Holding the specimen in their hands, students learn from discovery as they are completely engaged by exploring the specimen and deriving answers themselves. The flipped learning gross pathology method has been very well received and evaluated highly by both faculty and students.

Practice in Information Technology Support for Fangcang Shelter Hospital during COVID-19 Epidemic in Wuhan, China.

In confronting the sudden epidemic of COVID-19, China and other countries have been under great deal of pressure to block virus transmission and reduce death cases. Fangcang shelter hospital, which is converted from large-scale public venue, is proposed and proven to be an effective way for administering medical care and social isolation. This paper presents the practice in information technology support for a Fangcang shelter hospital in Wuhan, China. The experiences include the deployment strategy of IT infrastructure, the redesign of function modules in the hospital information system (HIS), equipment maintenance and medical staff training. The deployment strategy and HIS modules have ensured smoothness and efficiency of clinical work. The team established a quick response mechanism and adhered to the principle of nosocomial infection control. Deployment of network and modification of HIS was finished in the 48 hours before patient admittance. A repair hotline and remote support for equipment and software were available whenever medical workers met with any questions. No engineer ever entered the contaminated areas and no one was infected by the coronavirus during the hospital operation. Up to now, Fangcang shelter hospital is adopted by many regions around the world facing the collapse of their medical systems. This valuable experience in informatization construction and service in Wuhan may help participators involving in Fangcang shelter hospital get better information technology support, and find more practical interventions to fight the epidemic.

Coagulopathy is associated with multiple organ damage and prognosis of COVID-19.

Mortality rate is high with COVID-19. Multiple organ damage is a common and lethal complication of the severe COVID-19 patients. Of 198 recruited participants, 65 patients (32.8 %) had coagulopathy. In this retrospective study, we analyzed the association of coagulopathy with organ dysfunction in hospitalized COVID-19 patients. The incidence of coagulopathy was associated with increased odds of acute liver injury, renal dysfunction and acute respiratory distress syndrome (ARDS) by multivariable regression. Overall mortality was 65 % for the patients with coagulopathy and 3.76 % for the patients without coagulopathy. History of hypertension, leukocytosis and elevated CRP concentrations were associated with higher odds of coagulopathy. Patients with coagulopathy had similar levels of hepatic and renal functional enzymes prior to the onset of coagulopathy as the patients without coagulopathy, suggesting that coagulopathy is an association of the progression of multi-organ dysfunction in COVID-19. Plasma IL-6 was higher in patients with coagulopathy than controls, but it's not a risk factor for organ dysfunction by logistic regression. The present study shows that coagulopathy, overt DIC and non-overt DIC, associates with organ dysfunction and higher mortality rate in COVID-19. Thus, anticoagulant therapy may prevent organ dysfunction and increase survival rate in COVID-19.

Isolation and characterization of a variant subgroup GII-a porcine epidemic diarrhea virus strain in China.

BACKGROUND: Highly virulent variants of porcine epidemic diarrhea virus (PEDV) have been closely associated with recent outbreaks of porcine epidemic diarrhea (PED) in China, which have resulted in severe economic losses to the pork industry. METHODS: In the current study, the variant PEDV strain HM2017 was isolated and purified and a viral growth curve was constructed according to the median tissue culture infective dose (TCID50). HM2017 were amplify with RT-PCR and analyzed by phylogeny analysis. Animal pathogenicity experiment was carried to evaluate the HM2017 clinical assessment. RESULTS: Genome-based phylogenetic analysis revealed that PEDV strain HM2017 was clustered into the variant subgroup GII-a that is currently circulating in pig populations in China. The highest median tissue culture infectious dose of strain HM2017 after 15 passages in Vero cells was 1.33 × 107 viral particles/mL. Strain HM2017 was highly virulent to suckling piglets, which exhibited clinical symptoms at 12 h post-infection (hpi) (i.e., weight loss at 12-84 hpi, increased body temperatures at 24-48 hpi, high viral loads in the jejunum and ileum, and 100% mortality by 84 hpi). CONCLUSION: The present study reports a variant subgroup GII-a PEDV HM2017 strain in China and characterize its pathogenicity. PEDV strain HM2017 of subgroup GII-a presents a promising vaccine candidate for the control of PED outbreaks in China.