Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo.

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

Cellular and Molecular Atlas of Peripheral Blood Mononuclear Cells from a Pregnant Woman after Recovery from COVID-19

Objective This study aimed to investigate the immune response of a pregnant woman who recovered from the coronavirus disease 2019 (COVID_RS) by using single-cell transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) and to analyze the properties of different immune cell subsets. Methods PBMCs were collected from the COVID_RS patient at 28 weeks of gestation, before a cesarean section. The PBMCs were then analyzed using single-cell RNA sequencing. The transcriptional profiles of myeloid, T, and natural killer (NK) cell subsets were systematically analyzed and compared with those of healthy pregnant controls from a published single-cell RNA sequencing data set. Results We identified major cell types such as T cells, B cells, NK cells, and myeloid cells in the PBMCs of our COVID_RS patient. The increase of myeloid and B cells and decrease of T cells and NK cells in the PBMCs in this patient were quite distinct compared with that in the control subjects. After reclustering and Augur analysis, we found that CD16 monocytes and mucosal-Associated invariant T (MAIT) cells were mostly affected within different myeloid, T, and NK cell subtypes in our COVID_RS patient. The proportion of CD16 monocytes in the total myeloid population was increased, and the frequency of MAIT cells in the total T and NK cells was significantly decreased in the COVID-RS patient. We also observed significant enrichment of gene sets related to antigen processing and presentation, T-cell activation, T-cell differentiation, and tumor necrosis factor superfamily cytokine production in CD16 monocytes, and enrichment of gene sets related to antigen processing and presentation, response to type II interferon, and response to virus in MAIT cells. Conclusion Our study provides a single-cell resolution atlas of the immune gene expression patterns in PBMCs from a COVID_RS patient. Our findings suggest that CD16-positive monocytes and MAIT cells likely play crucial roles in the maternal immune response against severe acute respiratory syndrome coronavirus 2 infection. These results contribute to a better understanding of the maternal immune response to severe acute respiratory syndrome coronavirus 2 infection and may have implications for the development of effective treatments and preventive strategies for the coronavirus disease 2019 in pregnant women.Copyright © Wolters Kluwer Health, Inc. All rights reserved.

Allergic reactions of COVID-19 vaccine based on mRNA-LNP and its pharmacokinetics in vivo

Vaccination has been proved to be the most effective strategy to prevent the Corona Virus Disease 2019 (COVID-19). The mRNA vaccine based on nano drug delivery system (NDDS) - lipid nanoparticles (LNP) has been widely used because of its high effectiveness and safety. Although there have been reports of severe allergic reactions caused by mRNA-LNP vaccines, the mechanism and components of anaphylaxis have not been completely clarified yet. This review focuses on two mRNA-LNP vaccines, BNT162b2 and mRNA-1273. After summarizing the structural characteristics, potential allergens, possible allergic reaction mechanism, and pharmacokinetics of mRNA and LNP in vivo, this article then reviews the evaluation methods for patients with allergic history, as well as the regulations of different countries and regions on people who should not be vaccinated, in order to promote more safe injection of vaccines. LNP has become a recognized highly customizable nucleic acid delivery vector, which not only shows its value in mRNA vaccines, but also has great potential in treating rare diseases, cancers and other broad fields in the future. At the moment when mRNA-LNP vaccines open a new era of nano medicine, it is expected to provide some inspiration for safety research in the process of research, development and evaluation of more nano delivery drugs, and promote more nano drugs successfully to market.Copyright © 2023, Chinese Pharmaceutical Association. All rights reserved.

TARGETING THE HOST-VIRUS INTERFACE TO BLOCK SARS-CoV-2 ASSEMBLY IN AIRWAY CELLS

Background: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many therapies illustrates the need for antiviral treatments with high genetic barriers to resistance. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly with minimal host toxicity. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low susceptibility to evolutionary escape. Here, we investigated the capacity of PAV-104 to inhibit SARS-CoV-2 replication in human airway epithelial cells (AECs). Method(s): Dose-dependent cytotoxicity of PAV-104 in Calu-3 cells was determined by MTT assay. Calu-3 cells were infected with SARS-CoV-2 isolate USA-WA1/2020 (MOI=0.01). Primary AECs were isolated from healthy donor lung transplant tissue, cultured at air liquid interface (ALI), and infected with SARS-CoV-2 Gamma, Delta, and Omicron variants (MOI=0.1). SARS-CoV-2 replication was assessed by RT-PCR quantitation of the N gene, immunofluorescence assay (IFA) of nucleocapsid (N) protein, and titration of supernatant (TCID50). Transient co-expression of four SARS-CoV-2 structural proteins (N, M, S, E) to produce virus-like particles (VLPs) was used to study the effect of PAV-104 on viral assembly. Drug resin affinity chromatography was performed to study the interaction between PAV-104 and N. Glycerol gradient sedimentation was used to assess N oligomerization. Total RNA-seq and the REACTOME database were used to evaluate PAV-104 effects on the host transcriptome. Result(s): PAV-104 reached 50% cytotoxicity in Calu-3 cells at 3732 nM (Fig.1A). 50 nM PAV-104 inhibited >99% of SARS-CoV-2 infection in Calu-3 cells (p< 0.01) and in primary AECs (p< 0.01) (Fig.1B-E). PAV-104 specifically inhibited SARS-CoV-2 post entry, and suppressed production of SARS-CoV-2 VLPs without affecting viral protein synthesis. PAV-104 interacted with SARS-CoV-2 N and interfered with N oligomerization. Transcriptome analysis revealed that PAV-104 treatment reversed SARS-CoV-2 induction of the interferon and maturation of nucleoprotein signaling pathways. Conclusion(s): PAV-104 is a pan-respiratory virus small molecule inhibitor with promising activity against SARS-CoV-2 in human airway epithelial cells that should be explored in animal models and clinical studies.

A Practical Study on Foreign Language Anxiety of College Students in Online Classes

In the spring of 2020, due to the outbreak of COVID-19, college students in China had to take online classes at home. The present paper aims to explore whether college students suffer more anxiety in online classes and what factors may affect students' anxiety. The study finds that in addition to demographic variables like age and gender, factors such as grade, English test scores, self-concept, and network stability can lead to students' anxiety. Constructive suggestions are given to alleviate students' anxiety and improve learning effect. © 2023 ACADEMY PUBLICATION.

Online learning-related screen use and associated factors in school-aged children in Shanghai during the COVID-19 epi-demic

Objective To understand the online learning-related screen use duration and screen types in school-aged children in Shanghai during the COVID-19 epidemic. Methods Random clustering sampling was used to select 5 591 parents of students from 8 primary and junior schools that are in the sampling pool of the national myopia survey in districts of Jiading, Pudong and Baoshan in Shanghai in April 2020. Electronic questionnaire was administered to parents regarding their child's online learning-related screen use. Results On average, the median weekly duration of online learning-related screen use was 13.33 hours, the curricular and extracurricular parts of which were 10(8.75, 16.67) and 0(0, 3.33) hours, respectively. About 29.44% of investigated school-aged children only used small-size screen for online learning. Children in higher grades, being myopic and parents neither being myopic were associated with reporting higher weekly duration(P<0.05);children in higher grades of primary school and parents neither being myopic were associated with a higher likelihood of using small-size screen for online learning(P<0.05). Conclusion At the early stage of the COVID-19 epidemic, the burden associated with online-learning-related screen use was high in school-aged children in Shanghai. Health education regarding online learning-related screen use should be addressed in parents to guide their children to use screen appropriately. © 2022 Ｃｈｉｎ Ｊ Ｓｃｈ Ｈｅａｌｔｈ. All rights reserved.

Emergency management in university students during coronavirus disease 2019 epidemics: West China urgent recommendation.

During the coronavirus disease 2019 (COVID-19) epidemics, universities take responsibility for the health of their students and epidemic control. Our urgent recommendation focuses on four key questions of emergency management in universities following rigorous evidence-based approaches and provides timely suggestions to university managers, academic faculties and student affairs managers. We recommend universities during the COVID-19 epidemics should: 1) suspend offline lectures;2) provide proper health education on the disease;3) encourage face masks, however oppose using N95 masks on the campus;4) encourage hand hygiene and provide sanitizing products on the campus. Copyright © 2020 West China University of Medical Science. All rights reserved.

Graded personal protection scheme for preventing medical staffs from 2019-novel coronavirus infection in West China Hospital.

To reduce the infection risk of 2019-novel coronavirus and to protect medical staffs, "Graded personal protection scheme for preventing medical staffs from 2019-novel coronavirus infection in West China hospital" was formulated according to the guidance and notice issued by the National Health Commission combined with the actual situation of West China Hospital. This scheme could provide reference for preventing such disease for medical staffs. Copyright © 2020 West China University of Medical Science. All rights reserved.

A Novel Host-Targeted Viral Assembly Inhibitor Blocks SARS-CoV-2 in Airway Epithelial Cells

Introduction: The rapid emergence of the SARS-CoV-2 Omicron variant that evades many monoclonal antibody therapies illustrates the need for anti-viral treatments with low susceptibility to evolutionary escape. The small molecule PAV-104, identified through a moderate-throughput screen involving cell-free protein synthesis, was recently shown to target a subset of host protein assembly machinery in a manner specific to viral assembly. This compound has minimal host toxicity, including once daily oral dosing in rats that achieves >200-fold of the 90% effective concentration (EC90) in blood. The chemotype shows broad activity against respiratory viral pathogens, including Orthomyxoviridae, Paramyxoviridae, Adenoviridae, Herpesviridae, and Picornaviridae, with low suceptability to evolutionary escape. We hypothesized that PAV-104 would be active against SARSCoV- 2 variants in human airway epithelial cells. Methods: Airway epithelial cells were differentiated from lung transplant tissue at air-liquid interface (ALI) for four weeks prior to challenge with Alpha (Pango lineage designation B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) SARS-CoV-2 variants. Viral replication was determined by quantitative PCR measurement of the SARS-CoV-2 nucleocapsid (N) gene. Dose-dependent virus inhibition and cytotoxicity of PAV-104 in the Calu-3 airway epithelial cell line was determined by PCR and MTT assay. Student's t-tests were used to evaluate statistical significance. Results: Alpha, Beta, Gamma, and Delta variants of SARS-CoV-2 showed comparable infectivity in human primary airway epithelial cells at ALI (N=3 donors), 47- to 550-fold higher than the parent (USA-WA1/2020) strain. PAV-104 reached 50% cytotoxicity in Calu-3 cells at 240 nM (Fig. 1A). Dose-response studies in Calu-3 cells demonstrated PAV-104 has a 6 nM 50% inhibitory concentration (IC50) for blocking replication of SARS-CoV-2 (USA-WA1/2020) (Fig.1B). In primary cells at ALI from 3 donors tested, there was >99% inhibition of infection by SARS-CoV-2 Gamma variant (N=3, MOI 0.1, P <0.01) with 100 nM PAV-104 (Fig. 1C). Addition of 100 nM PAV-104 2-hours post-infection, but not pre-infection, resulted in >99% suppression of viral replication, indicating a post-entry drug mechanism. PAV-104 bound a small subset of the known allosteric modulator 14-3-3, itself implicated in the interactome of SARS-CoV-2. Conclusion: PAV-104 is a host-targeted, orally bioavailable, pan-viral small molecule inhibitor with promising activity against SARS-CoV-2 variants in human primary airway epithelial cells. (Figure Presented).

GALECTIN-9 INDUCES SARS-CoV-2 REPLICATION and INFLAMMATION in AIRWAY EPITHELIAL CELLS

Background: Galectin-9 (Gal-9) is a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis. Multiple recent reports demonstrate that plasma levels of Gal-9 are elevated in the setting of severe COVID-19 disease. However, a causal role of Gal-9 in SARS-CoV-2 pathology remains to be elucidated. Here, we determined the impact of Gal-9 on SARS-CoV-2 replication and pro-inflammatory signaling in immortalized and primary human airway epithelial cells (AECs). Methods: Dose-dependent cytotoxicity of recombinant human Gal-9 in the Calu-3 AEC line was determined by MTT assay. Calu-3 cells were infected with SARS-CoV-2 isolate USA-WA1/2020 (MOI=0.01). Primary AECs were isolated from healthy donor lung transplant tissue, cultured at air liquid interface (ALI), and infected with SARS-CoV-2 lineage P.1 (MOI=0.1). SARS-CoV-2 replication was assessed by RT-PCR quantitation of the nucleocapsid (N) gene, immunofluorescence assay (IFA) of N protein, and titration of supernatant (TCID50). Viral entry was measured using luciferase activity of VSV-SARS-CoV-2 S-ΔG-Luciferase reporter pseudovirus. ACE2 and TMPRSS2 cell-surface expression were measured by flow cytometry. Pro-inflammatory factors (IL-6, IL-8, and TNFα) were detected by RT-PCR. Total RNA-seq was used to evaluate Gal-9 effects on the host transcriptome. Groups were compared by Student's t-test, and differential expression analyses were performed using DESeq2. Results: Gal-9 reached 50% cytotoxicity in Calu-3 cells at 597 nM. Gal-9 significantly increased SARS-CoV-2 expression (8.1 to 25.5 fold;p<0.0001) and infectious virus release (1.9 to 17.8 fold;p<0.038) in a dose-dependent manner in Calu-3 cells. Pseudovirus entry into Calu-3 cells was enhanced by Gal-9 (2.4 to 5.6 fold;p<0.0016), and the enhanced entry was inhibited by anti-ACE2 antibody (p<0.0027). Cell surface ACE2 and TMPRSS2 expression were unaffected by Gal-9. Gal-9 treatment accelerated virus-induced expression of IL-6, IL-8, and TNFα (p<0.018) in Calu-3 cells. Gal-9 increased SARS-CoV-2 production (p=0.03) and pro-inflammatory factor expression (p<0.05) in primary AECs (N=5 donors). RNA-seq data revealed that Gal-9 significantly induced IL-17, EIF2, IL-8 and IL-6 signaling pathways in the setting of SARS-CoV-2 infection. Conclusion: Gal-9 facilitates SARS-CoV-2 entry, replication, and virus-induced pro-inflammatory signaling in AECs ex vivo. Our data suggest that pharmacologic manipulation of Gal-9 should be explored as a SARS-CoV-2 therapeutic strategy.

Analysis of the characteristics of ocular trauma diseases during the novel coronavirus epidemic

AIM: To analyze the epidemiological characteristics of patients hospitalized for ocular trauma during the novel coronavirus (COVID-19) epidemic. METHODS: A retrospective case analysis. Totally 876 cases (905 eyes) of ocular trauma were analyzed in this study, including 545 cases (565 eyes) from January to June 2019 were enrolled ascontrol group, and 331 cases (340 eyes) from January to June 2020 were enrolled in the research group. Information regarding age, sex, location of injury, cause of injury, place of residence, and type of injury were collected and analyzed. RESULTS: The number of hospitalisation for ocular trauma in the research group decreased by 39.3% compared with the control group. The age distribution of patients showed a double peak, at 0-10 years (20.55%, 21.45%) and 41-50 years (17.98%, 19.03%) in the control group and research group, respectively. There was no statistically significant difference in the age distribution between the two groups (P=0.907). Men were predominantly injured in both the control and the research groups, accounting for 80.37% and 83.69%, respectively (P=0.219). The proportion of home injuries in the research group (28.40%) was higher than the control group (11.38%) (P<0.001). The proportion of mechanical eye injuries in the research group (98.19%) was higher than the control group (95.60%) (P=0.041), and the proportion of open globe injuries (85.54%) was also higher than the control group (76.58%) (P=0.001). The proportion of patients with no light perception in the research group (18.86%) was higher than that of the control group (9.53%) (P<0.001). CONCLUSION: During the COVID-19 epidemic period, the total number of ocular trauma cases was significantly reduced. Mechanical eye injuries are still the main type for hospitalisation of patients with eye injuries. The awareness of eye injury prevention should be strengthened during the period of epidemic. Copyright 2022 by the IJO Press.

Evidence-based Chinese medicine for the response to public health emergencies: The Guangzhou declaration

Traditional Chinese medicine has been used for the treatment of many diseases including acute infections often associated with public health emergencies for thousands of years. However, clinical evidence supporting the use of these treatments is insufficient, and the mechanism for using Chinese medicine therapy in the public health setting has not been fully established. In this report, the Evidence-based Traditional and Integrative Chinese medicine Responding to Public Health Emergencies Working Group proposed five recommendations to facilitate the inclusion of Chinese medicine as part of our responses to public health emergencies. It is expected that the Working Group’s proposals may promote the investigation and practice of Chinese Medicine in public health settings.

Impact of the “ncp” on the catering industry through the sars perspective based on the perspective of big data

The NCP epidemic has inevitably negatively affected China’s economy in a short period of time, causing the catering industry to also experience the shock of the epidemic, especially at the current stage, consumer demand has fallen in the short term, which has caused many regions Significant impact, some companies in the catering industry are also facing bankruptcy, so it is extremely important for companies to avoid risks in all areas of life. This article passes the 2003 SARS epidemic caused by the virus was compared with the pneumonia epidemic caused by the new coronavirus, with the English translation “Novel Coronavirus Pneumonia” (hereinafter referred to as: NCP). Analyze the current situation of the catering industry during the SARS epidemic and the survival and development of catering companies during the NCP epidemic. The catering industry suffered during the NCP epidemic. Through the comparison of the two outbreak catering industry conditions, the forecast of the catering industry after the NCP epidemic is made, and related Reasonable amendment proposals to improve the anti-risk ability of catering companies. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021.

[Investigation on demands for antenatal care services among 2 002 pregnant women during the epidemic of COVID-19 in Shanghai].

Objective: To identify problems and demands for antenatal care (ANC) among pregnant women in different trimesters of pregnancy in Shanghai for optimizing ANC service during the epidemic of COVID-19. Method: s Organized by maternal and child health care institute in the 16 districts of Shanghai, a cross sectional study was conducted among pregnant women who came to pregnancy registration in the community health centers or attended ANC in midwifery hospitals from February 7 to February 12, 2020. Consented participating women completed a semi-structured online questionnaire voluntarily. Data was analyzed using frequency,chi-square test and scoring. Result: s A total of 2 002 valid questionnaires were collected from 183 community health centers and 67 midwifery hospitals. About 94.6%(1 894/2 002) of the pregnant women worried about being infected during the COVID-19 epidemic, and 14.7% (294/2 002) demanded for psychological consultation. Time-lapse appointments for ANC were requested by 87.7% (1 756/2 002) of the participants for avoiding presenting themselves in people-density places. Compared with other pregnancy trimesters, pregnant women in the second trimester were more willing to reduce the frequency of ANC (35.2% versus 39.5% versus 48.1%, P<0.01). Compared with multiparas, primiparas were more willing to have online consultation and guidance (49.2% versus 63.8%, P<0.01). Regarding the needs for health knowledge on COVID-19, personal protection against 2019 novel coronavirus (2019-nCoV) was the most concerned for pregnant women, and 71.0% (1 421/2 002) of them preferred to obtain knowledge through health applications, official Weibo and WeChat. Conclusions: Pregnant women in Shanghai critically concern about the risk of 2019-nCoV infections, and highly demand knowledge and measures on prevention and protection from COVID-19. They ask for having time-lapse appointments for ANC and online access to health information and services. Maternal and child care institutes should understand the demands of pregnant women, optimize the means of ANC service, and provide tailored and accessible health education and service for the safety of mother and child.