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1.
Med Sci Monit ; 28: e934102, 2022 Jan 25.
Article in English | MEDLINE | ID: covidwho-1651076

ABSTRACT

BACKGROUND Heat-clearing and detoxifying herbs (HDHs) play an important role in the prevention and treatment of coronavirus infection. However, their mechanism of action needs further study. This study aimed to explore the anti-coronavirus basis and mechanism of HDHs. MATERIAL AND METHODS Database mining was performed on 7 HDHs. Core ingredients and targets were screened according to ADME rules combined with Neighborhood, Co-occurrence, Co-expression, and other algorithms. GO enrichment and KEGG pathway analyses were performed using the R language. Finally, high-throughput molecular docking was used for verification. RESULTS HDHs mainly acts on NOS3, EGFR, IL-6, MAPK8, PTGS2, MAPK14, NFKB1, and CASP3 through quercetin, luteolin, wogonin, indirubin alkaloids, ß-sitosterol, and isolariciresinol. These targets are mainly involved in the regulation of biological processes such as inflammation, activation of MAPK activity, and positive regulation of NF-kappaB transcription factor activity. Pathway analysis further revealed that the pathways regulated by these targets mainly include: signaling pathways related to viral and bacterial infections such as tuberculosis, influenza A, Ras signaling pathways; inflammation-related pathways such as the TLR, TNF, MAPK, and HIF-1 signaling pathways; and immune-related pathways such as NOD receptor signaling pathways. These pathways play a synergistic role in inhibiting lung inflammation and regulating immunity and antiviral activity. CONCLUSIONS HDHs play a role in the treatment of coronavirus infection by regulating the body's immunity, fighting inflammation, and antiviral activities, suggesting a molecular basis and new strategies for the treatment of COVID-19 and a foundation for the screening of new antiviral drugs.


Subject(s)
COVID-19/drug therapy , Coronavirus/drug effects , Drugs, Chinese Herbal/pharmacology , SARS-CoV-2/drug effects , Alkaloids/chemistry , Alkaloids/pharmacology , Caspase 3/drug effects , Caspase 3/genetics , Coronavirus/metabolism , Coronavirus Infections/drug therapy , Cyclooxygenase 2/drug effects , Cyclooxygenase 2/genetics , Databases, Pharmaceutical , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/therapeutic use , Flavanones/chemistry , Flavanones/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacology , Interleukin-6/genetics , Lignin/chemistry , Lignin/pharmacology , Luteolin/chemistry , Luteolin/pharmacology , Mitogen-Activated Protein Kinase 14/drug effects , Mitogen-Activated Protein Kinase 14/genetics , Mitogen-Activated Protein Kinase 8/drug effects , Mitogen-Activated Protein Kinase 8/genetics , Molecular Docking Simulation , NF-kappa B p50 Subunit/drug effects , NF-kappa B p50 Subunit/genetics , Naphthols/chemistry , Naphthols/pharmacology , Nitric Oxide Synthase Type III/drug effects , Nitric Oxide Synthase Type III/genetics , Protein Interaction Maps , Quercetin/chemistry , Quercetin/pharmacology , SARS-CoV-2/metabolism , Signal Transduction , Sitosterols/chemistry , Sitosterols/pharmacology , Transcriptome/drug effects , Transcriptome/genetics
2.
Land ; 10(11):1169, 2021.
Article in English | ProQuest Central | ID: covidwho-1534138

ABSTRACT

The implementation of China’s Beautiful Village Initiative was an extraordinary achievement and aroused extensive public attention. However, existing research mostly focuses on the construction and seldom on public attention towards the Beautiful Village Initiative. For this reason, this paper investigated the spatiotemporal characteristics of public attention based on the Baidu index using time-constrained clustering and the spatial autocorrelation test. Our results showed that the evolutionary process can be divided into three stages: very little national attention (2011–2012), injection of a strong impetus (2013–2015), and rooted in the people’s minds (2016–2020). Spatially, provincial public attention demonstrated obvious spatial differentiation and stable spatial autocorrelation, with Low–Low clusters in Northwest China and High–High Clusters in East, Central, and North China. Spatial econometric models were further utilized to quantify the effects of socioeconomic factors on public attention. The results of the SEM model proved the existence of spatial spillover effects and indicated that the urbanization rate, population density, education level, and network popularity rate all positively affected public attention. The relationship between Beautiful Village construction and public attention was uncoordinated and, in most provinces, advances in public attention were ahead of the construction level. Our findings contribute to the understanding of public attention towards the Beautiful Village Initiative, and policy suggestions we proposed would be applied to increasing public awareness and participation.

3.
Int J Environ Res Public Health ; 18(9)2021 04 30.
Article in English | MEDLINE | ID: covidwho-1526814

ABSTRACT

Major public health emergencies would have a negative influence on the psychology of the public, and an effective psychological intervention can help them to relieve some emotions, such as tension and panic. However, differences in individual environments affect people's psychological intervention demands and intervention mode choices. Therefore, it is of great theoretical and practical value to analyze and identify the key factors affecting these demands and choices. Based on a nationwide sample of 24,188 respondents from the "Internet Survey of Residents' Behavioral Changes and Psychological Conditions during the Epidemic," the different characteristics of public psychological intervention demands and choices under different factors are explored in this paper. The results demonstrate that: (1) the psychological status of Chinese people was relatively stable during the epidemic period, and there were 1016 respondents who had subjective demands for a psychological intervention, (2) age, gender, occupation type, residence, family size, risk perception, psychological status, education level, and fixed expenditure all significantly affect public psychological intervention demands, and (3) risk perception, psychological status, age, gender, and family size will impact the choice of psychological intervention methods. The above results can provide a decision-making basis for the construction of a psychological intervention system in psychological crisis management during the post-epidemic prevention and control period, as well as reference and suggestions for handling psychological stress of similar sudden crisis events in the future.


Subject(s)
Epidemics , Psychosocial Intervention , Humans , Public Health , Stress, Psychological , Surveys and Questionnaires
4.
Lancet Infect Dis ; 22(2): 196-208, 2022 02.
Article in English | MEDLINE | ID: covidwho-1414105

ABSTRACT

BACKGROUND: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years. METHODS: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 µg, 4 µg, or 8 µg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing. FINDINGS: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination. INTERPRETATION: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 µg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19 Vaccines/standards , COVID-19/prevention & control , Adolescent , COVID-19 Vaccines/administration & dosage , Child , Child, Preschool , Cohort Studies , Double-Blind Method , Female , Humans , Male , Vaccines, Inactivated/immunology , Vaccines, Inactivated/standards
5.
EClinicalMedicine ; 38: 101010, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1300745

ABSTRACT

BACKGROUND: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years. METHODS: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants (n = 336 in 18-59 age group and n = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809. FINDINGS: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups. INTERPRETATION: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.

6.
JAMA ; 324(10): 951-960, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-911581

ABSTRACT

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.


Subject(s)
Betacoronavirus/immunology , Coronavirus Infections/prevention & control , Immunogenicity, Vaccine , Pandemics/prevention & control , Pneumonia, Viral/prevention & control , Viral Vaccines/immunology , Adjuvants, Immunologic/administration & dosage , Adjuvants, Immunologic/adverse effects , Adolescent , Adult , Aluminum Hydroxide/administration & dosage , Aluminum Hydroxide/adverse effects , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Betacoronavirus/genetics , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Dose-Response Relationship, Immunologic , Double-Blind Method , Female , Humans , Injections, Intramuscular , Male , Pneumonia, Viral/immunology , Propiolactone , SARS-CoV-2 , Vaccines, Inactivated/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/adverse effects , Young Adult
7.
Lancet Infect Dis ; 21(1): 39-51, 2021 01.
Article in English | MEDLINE | ID: covidwho-863722

ABSTRACT

BACKGROUND: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 µg, 4 µg, or 8 µg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 µg on day 0 or on a two-dose schedule of 4 µg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. FINDINGS: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 µg [n=24], 4 µg [n=24], or 8 µg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 µg group, one [4%] in the 4 µg group, and two [8%] in the 8 µg group; ≥60 years, one [4%] in the 8 µg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87·7 [95% CI 64·9-118·6], 2 µg group; 211·2 [158·9-280·6], 4 µg group; and 228·7 [186·1-281·1], 8 µg group) and the group aged 60 years and older (80·7 [65·4-99·6], 2 µg group; 131·5 [108·2-159·7], 4 µg group; and 170·87 [133·0-219·5], 8 µg group) compared with the placebo group (2·0 [2·0-2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 µg on day 0 [n=84] or 4 µg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 µg day 0; 18 [21%], 4 µg days 0 and 14; 15 [18%], 4 µg days 0 and 21; and ten [12%], 4 µg days 0 and 28). One placebo recipient in the 4 µg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 µg day 0; one [1%], 4 µg days 0 and 14; three [4%], 4 µg days 0 and 21; two [2%], 4 µg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 µg days 0 and 14 (169·5, 95% CI 132·2-217·1), days 0 and 21 (282·7, 221·2-361·4), and days 0 and 28 (218·0, 181·8-261·3) schedules than the 8 µg day 0 schedule (14·7, 11·6-18·8; all p<0·001). INTERPRETATION: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 µg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 µg dose or 4 µg dose on days 0 and 14. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.


Subject(s)
COVID-19 Vaccines/immunology , COVID-19/prevention & control , SARS-CoV-2/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , Double-Blind Method , Female , Humans , Immunization Schedule , Male , Middle Aged , Vaccines, Inactivated/immunology , Young Adult
8.
Front Psychiatry ; 11: 568329, 2020.
Article in English | MEDLINE | ID: covidwho-776222

ABSTRACT

BACKGROUND: Anxiety has been a common mental state during the epidemic of Coronavirus Disease 2019 (COVID-19) and is usually closely related to somatization. However, no study on somatization in anxiety and its relationship with insomnia has been conducted. Therefore, this study aimed to identify the prevalence of anxiety, somatization and insomnia and explore the relationships between different psychological states in the general population during the COVID-19 outbreak. METHODS: A total of 1,172 respondents were recruited from 125 cities in mainland China by an online questionnaire survey. All subjects were evaluated with the 7-item Generalized Anxiety Disorder (GAD-7) scale, the somatization subscale of the Symptom Checklist 90-Revised (SCL-90-R), and the 7-item Insomnia Severity Index (ISI). RESULTS: The percentages of anxiety, somatization, and insomnia were 33.02%, 7.59%, and 24.66%, respectively. The prevalence of somatization was 19.38% in participants with anxiety. Compared to the anxiety without somatization group, the anxiety with somatization group had a significantly higher percentage of patients with a history of physical disease and insomnia, as well as higher GAD-7 scores and SCL-90 somatization subscores (all p < 0.001). The SCL-90 somatization subscores were positively correlated with age, history of physical disease, GAD-7 scores, and ISI scores (all p < 0.001). Furthermore, multivariate logistic regression showed that GAD-7 score, ISI score, and age were risk factors for somatization in the anxious population. CONCLUSIONS: Somatic and psychological symptoms were common in the general population during the COVID-19 outbreak. Somatic symptoms, anxiety, and insomnia are closely related, and improving anxiety and sleep quality may help relieve somatic symptoms.

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