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1.
Journal of Affective Disorders ; 2022.
Article in English | ScienceDirect | ID: covidwho-2165451

ABSTRACT

Introduction Recently, in the view of network analysis, depression has been conceptualized as a complex and dynamic network model combining individual symptoms. To date, no studies have systematically examined and compared depressive symptom networks across different populations. Methods A total of 36,105 participants were recruited and asked to complete the Patient Health Questionnaire-9 among junior high school students, senior high school students, college students, and elderly adults who were more susceptible to depression during the COVID-19 lockdown in China. In the analysis, we applied the optimal cutoff score ≥ 8 for students and a score ≥ 6 for elderly adults to identify 5830 participants who were likely to be depressed. The index of "strength” was used to identify central symptoms in the network structure. Results The results showed that Sad Mood was the most central symptom among junior high school students, senior high school students, and college students, but the most central symptom in the elderly was Guilt. Among the top three central symptoms, Suicide Ideation was unique to senior high school students, while Anhedonia was most prevalent among college students. Guilt - Suicide Ideation, Anhedonia – Energy, Anhedonia - Sad Mood, and Sleep – Energy showed the strongest association among junior and senior high school students, college students, and elderly adults, respectively. NCT (i.e., Network Comparison Test) suggested that the network's global connectivity was ultimately inconsistent, but the network structure remained roughly intact. Conclusion In treatment, targeting central symptoms may be critical to alleviating depression.

2.
EClinicalMedicine ; 54: 101680, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2158748

ABSTRACT

Background: More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods: This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 µg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 µg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 µg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings: Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation: Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding: Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

3.
European journal of psychotraumatology ; 13(2), 2022.
Article in English | EuropePMC | ID: covidwho-2126035

ABSTRACT

Background: Suicide is a leading cause of death, and rates of attempted suicide have increased during the COVID-19 pandemic. The under-diagnosed psychiatric phenotype of dissociation is associated with elevated suicidal self-injury;however, it has largely been left out of attempts to predict and prevent suicide. Objective: We designed an artificial intelligence approach to identify dissociative patients and predict prior suicide attempts in an unbiased, data-driven manner. Method: Participants were 30 controls and 93 treatment-seeking female patients with posttraumatic stress disorder (PTSD) and various levels of dissociation, including some with the PTSD dissociative subtype and some with dissociative identity disorder (DID). Results: Unsupervised learning models identified patients along a spectrum of dissociation. Moreover, supervised learning models accurately predicted prior suicide attempts with an score up to 0.83. DID had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in PTSD and DID. Conclusions: These findings expand our understanding of the dissociative phenotype and underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury. HIGHLIGHTS Dissociation, feelings of detachment and disruption in one's sense of self and surroundings, is associated with an elevated risk of suicidal self-injury;however, it has largely been left out of attempts to predict and prevent suicide. Using machine learning techniques, we found dissociative identity disorder had the highest risk of prior suicide attempts, and distinct subtypes of dissociation predicted suicide attempts in posttraumatic stress disorder and dissociative identity disorder. These findings underscore the urgent need to assess for dissociation to identify individuals at high-risk of suicidal self-injury.

4.
Nucleic Acids Res ; 2022 Nov 18.
Article in English | MEDLINE | ID: covidwho-2135486

ABSTRACT

Many RNAs fold into multiple structures at equilibrium, and there is a need to sample these structures according to their probabilities in the ensemble. The conventional sampling algorithm suffers from two limitations: (i) the sampling phase is slow due to many repeated calculations; and (ii) the end-to-end runtime scales cubically with the sequence length. These issues make it difficult to be applied to long RNAs, such as the full genomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To address these problems, we devise a new sampling algorithm, LazySampling, which eliminates redundant work via on-demand caching. Based on LazySampling, we further derive LinearSampling, an end-to-end linear time sampling algorithm. Benchmarking on nine diverse RNA families, the sampled structures from LinearSampling correlate better with the well-established secondary structures than Vienna RNAsubopt and RNAplfold. More importantly, LinearSampling is orders of magnitude faster than standard tools, being 428× faster (72 s versus 8.6 h) than RNAsubopt on the full genome of SARS-CoV-2 (29 903 nt). The resulting sample landscape correlates well with the experimentally guided secondary structure models, and is closer to the alternative conformations revealed by experimentally driven analysis. Finally, LinearSampling finds 23 regions of 15 nt with high accessibilities in the SARS-CoV-2 genome, which are potential targets for COVID-19 diagnostics and therapeutics.

5.
Int J Colorectal Dis ; 37(11): 2277-2289, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2085359

ABSTRACT

BACKGROUND: Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear. METHODS: Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3. RESULTS: Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed. CONCLUSION: COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.


Subject(s)
COVID-19 , Colitis, Ulcerative , Inflammatory Bowel Diseases , Humans , SARS-CoV-2 , COVID-19/complications , Tumor Necrosis Factor Inhibitors , Inflammatory Bowel Diseases/complications , Inflammatory Bowel Diseases/drug therapy , Colitis, Ulcerative/drug therapy
6.
EClinicalMedicine ; 54:101680-101680, 2022.
Article in English | EuropePMC | ID: covidwho-2047143

ABSTRACT

Background More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 μg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 μg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 μg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Doub e irst-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

7.
J Clin Psychol ; 2022 Aug 29.
Article in English | MEDLINE | ID: covidwho-2013558

ABSTRACT

INTRODUCTION: In China, recurrent pandemics require frequent city-wide lockdowns and quarantine actions to contain the impact of COVID-19, exposing college students to psychological problems, including hopelessness. Hence, the purpose of helping problematic college students alleviate hopelessness symptoms motivates us to carry out the present study to explore their interrelationship. METHODS: Hopelessness (i.e., a complex phenomenon with important clinical consequences, such as depression and suicidality) was investigated in a large longitudinal sample of college students (N = 2787; 58.59% female; age mean ± SD = 18.34 ± 0.92) who were recruited during and after the COVID-19 lockdown using the Beck Hopelessness Scale (BHS). RESULTS: Applying the novel approach (i.e., symptom network analysis), the results indicated that the edge of #BHS1 (i.e., [NOT] hope-enthusiasm)-#BHS15 (i.e., [NOT] faith-in-the-future) showed the strongest association both in Wave 1 and Wave 2. Similarly, #BHS20 (i.e., not-trying) had the highest node expectedinfluence (centrality) in the hopelessness symptoms network both among Wave 1 and Wave 2. The Network Comparison Test indicated that the global network strength significantly differed between the two time points. As expected, college students' hopelessness will gradually dissipate with the end of segregation control. The stability and accuracy indicated that the network analysis results were trustworthy. CONCLUSIONS: The study findings provide evidence that central nodes and edges connecting symptoms should be addressed. Further interventions and treatments that may target these symptoms are essential to effectively alleviate the overall hopelessness level among college students. Theoretical and clinical potential consequences were discussed in detail.

9.
Front Psychiatry ; 13: 919251, 2022.
Article in English | MEDLINE | ID: covidwho-1997482

ABSTRACT

Background: Besides physical changes, elderly adults are prone to have mental disorders such as anxiety, depression, and sleep disturbance, and the pandemic of COVID-19 worsened the situation. However, internal relationships and co-occurrence of psychopathologies were scarcely examined. Therefore, in the current study, through network analysis, we inspected relationships among symptoms of depression, anxiety, and sleep disturbance and identified key symptoms that espoused the disease. Methods: We asked 1,302 elderly adults to fill in Patient Health Questionnaire-2 (depressive symptoms), the Generalized Anxiety Disorder-2 (anxiety symptoms), and the Youth Self-rating Insomnia Scale (sleep disturbance) and then constructed three networks for elderly adults, male elderly, and female elderly. Via network analysis, we accomplished four goals. First, we identified symptom with the highest centrality (i.e., strength) index for each network; then, we found the strongest correlation (i.e., edges) in each network; thirdly, we confirmed specific nodes that could bridge anxiety, depression, and sleep disturbance; the last was to compare networks based on genders. Network stability and accuracy tests were performed. Results: Networks of elderly adults, male elderly, and female elderly were stable, accurate, and intelligible. Among all networks, "Nervousness"- "Excessive worry" (GAD-1- GAD-2) had the strongest correlation, and "Nervousness" (GAD-1) had the highest strength and bridge strength value. When we made a comparison between female elderly's and male elderly's networks, except for the significant difference in the mean value of "Difficulty initiating sleep" (YSIS-3), the findings showed that the two networks were similar. Network stability and accuracy proved to be reliable. Conclusions: In networks of anxiety, depression, and sleep disturbance, anxiety played a conspicuous role in comorbidity, which could be a target for practical intervention and prevention.

11.
Curr Psychol ; : 1-12, 2022 Aug 03.
Article in English | MEDLINE | ID: covidwho-1982348

ABSTRACT

Symptoms of depression and anxiety usually co-occur and are inextricably linked to sleep disturbance. However, little is known about the symptom-to-symptom relationships among these three mental disorders. Hence, to improve our understanding of concurrent depression, anxiety, and sleep disturbance, we used the network analysis approach to construct an interplay relationship among the above three mental disorders and identify which specific symptoms bridge these aggregations. We collected data from a large sample (N = 6710, male = 3074, female = 3636; mean age = 19.28) at a university. We estimated the symptom network structure of depression, anxiety, and sleep disturbance as assessed by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Youth Self-Rating Insomnia Scale during the COVID-19 lockdown. We further investigated four goals: first, identifying the individual core symptoms in the network by the index of "expected influence"; second, determining the bridge symptoms that play roles in linking different mental disorders by the index of bridge expected influence (1-step); third, examining the robustness of all results; and fourth, providing an overall structure that may or may not differ by sex. The network structure was stable, accurate, and predictable. Items referring to sleep dissatisfaction, poor sleep quality, and uncontrollable worry were potentially core symptoms in the interplay among depression, anxiety, and sleep disturbance. Sleep, guilt, restlessness, irritability, and feeling afraid can function as bridges among depression, anxiety, and sleep disturbance, which is clinically relevant and theoretically important. The results suggested that the network structures significantly differed between the female and male networks. Robustness tests also revealed that the results were reliable.

12.
Evid Based Complement Alternat Med ; 2022: 9152201, 2022.
Article in English | MEDLINE | ID: covidwho-1927683

ABSTRACT

Purpose: The possible mechanism of Xiyanping injection treatment COVID-19 is discussed through the network pharmacology. Methods: Obtaining the chemical structure of Xiyanping injection through the patent application and obtaining control compounds I, II, III, IV, V, Yanhuning injection (VI, VII), Chuanhuning injection (VIII, IX), 10 compounds were analyzed by D3Targets-2019-nCoV. The human anti-COVID-19 gene in COVID-19 DisGeNET was intersected with the CTD Andrographolide target gene and then combined with D3Targets-2019-nCoV, resulting in 93 genes, using the Venny 2.1 platform. The PPI network was constructed by the String platform and Cytoscape 3.8.2 platform. The GO, KEGG, and tissue of the target were analyzed using the Metascape platform and DAVID platform. The gene expression in the respiratory system was analyzed using the ePlant platform. The CB-Dock is used for the docking verification and degree values of the first 20 genes. Results: Finally, 1599 GO and 291 KEGG results were obtained. GO is mostly associated with the cell stress response to chemicals, the cell response to oxidative stress, and the cell response to reactive oxygen species. In total, 218 KEGG pathway concentrations were related to infection and other diseases and 73 signaling pathways mostly related to inflammation and immune pathways, such as TNF signaling pathway and MAPK signaling pathway. The molecular docking results show that Xiyanping injection, compound III, has a good docking relationship with 20 target proteins such as HSP90AA1. Tissue has 22 genes that are pooled in the lungs. Conclusion: Xiyanping injection may inhibit the release of various inflammatory factors by inhibiting intracellular pathways such as MAPK and TNF. It acts on protein targets such as HSP90AA1 and plays a potential therapeutic role in COVID-19. Thus, compound III may be treated as a potential new drug for the treatment of COVID-19 and the Xiyanping injection may treat patients with COVID-19 infection.

13.
Lancet Respir Med ; 10(8): 749-760, 2022 08.
Article in English | MEDLINE | ID: covidwho-1867947

ABSTRACT

BACKGROUND: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults. METHODS: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0-44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316). FINDINGS: Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42-51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31-49]) of 120 vaccine recipients compared with one (1% [0-5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8-13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4-4·3] in responders), and in 31 (22% [15-29]) of 143 vaccine recipients (GMT 4·4 [3·3-5·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9-16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5-4·1] in responders) in the phase 2 trial, as did 18 (13% [8-19]) of 143 vaccine recipients (GMT 5·2 [4·0-6·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. INTERPRETATION: dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration. FUNDING: National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.


Subject(s)
COVID-19 Vaccines , COVID-19 , Orthomyxoviridae , Viral Vaccines , Adult , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Double-Blind Method , Humans , Immunoglobulin A , Immunoglobulin G , SARS-CoV-2 , Vaccines, Attenuated/adverse effects
14.
Sci Bull (Beijing) ; 67(13): 1372-1387, 2022 Jul 15.
Article in English | MEDLINE | ID: covidwho-1867754

ABSTRACT

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

15.
Front Public Health ; 10: 855633, 2022.
Article in English | MEDLINE | ID: covidwho-1847239

ABSTRACT

COVID-19, which occurred at the end of December 2019, has evolved into a global public health threat and affects every aspect of human life. COVID-19's high infectivity and mortality prompted governments and the scientific community to respond quickly to the pandemic outbreak. The application of personal protective equipment (PPE) is of great significance in overcoming the epidemic situation. Since the discovery of severe acute respiratory coronavirus 2 (SARS-CoV-2), bibliometric analysis has been widely used in many aspects of the COVID-19 epidemic. Although there are many reported studies about PPE and COVID-19, there is no study on the bibliometric analysis of these studies. The citation can be used as an indicator of the scientific influence of an article in its field. The aim of this study was to track the research trends and latest hotspots of COVID-19 in PPE by means of bibliometrics and visualization maps.


Subject(s)
COVID-19 , Bibliometrics , COVID-19/prevention & control , Humans , Pandemics/prevention & control , Personal Protective Equipment , SARS-CoV-2
16.
Inflammation ; 45(3): 1076-1088, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1838368

ABSTRACT

The emergence of severe acute syndrome coronavirus 2 (SARS-CoV-2) in December 2019 has led to the global COVID-19 pandemic. Although the symptoms of most COVID-19 patients are mild or self-curable, most of severe patients have sepsis caused by cytokine storms, which greatly increases the case fatality rate. Moreover, there is no effective drug that can limit the novel coronavirus thus far, so it is more needed to develop antiviral drugs for the SARS-CoV-2. In our research, we employed the techniques of molecular docking to screen 35 flavonoid compounds among which 29 compounds have Z-scores lower than - 6. Then, ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein were identified to have potent inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 5.774 ± 0.805 µM, 13.14 ± 2.081 µM and 5.158 ± 0.928 µM respectively by FRET assay. Molecular docking results also showed that ( -)-gallocatechin gallate, ( +)-gallocatechin and baicalein can non-covalently bind to Mpro through π-π stacking and hydrogen bonds in the Cys145 catalytic site. We further evaluated the effect of ( -)-gallocatechin gallate and baicalein on cytokine storms using a mouse model of sepsis. ( -)-Gallocatechin gallate and baicalein significantly reduced sepsis of mouse models on weight, murine sepsis score, and survival rate and reduced the inflammatory factor levels, such as TNF-α, IL-1α, IL-4, and IL-10. Overall, ( -)-gallocatechin gallate and baicalein show certain potential of treatment against COVID-19.


Subject(s)
COVID-19 , Sepsis , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Catechin/analogs & derivatives , Coronavirus 3C Proteases , Cytokine Release Syndrome , Flavanones , Humans , Mice , Molecular Docking Simulation , Pandemics , Protease Inhibitors/pharmacology , SARS-CoV-2 , Sepsis/drug therapy
17.
Clin Lab ; 67(11)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1818667

ABSTRACT

BACKGROUND: Immunoglobulin D multiple myeloma (IgD-MM) is a rare but aggressive disease. The safety and effectiveness of anti-CD38 monoclonal antibody (daratumumab) have not been known in either IgD-MM or MM complicated with secondary neoplasm. METHODS: A fragile IgD-MM patient had an aggressively relapsed disease concurrent with lung cancer and severe thrombocytopenia, which led to a dilemma for management. After a failure of ixazomib-based chemotherapy, a salvage therapy with daratumumab unexpectedly induced complete remission and platelet recovery, and the patient successfully proceeded to lung cancer surgery. CONCLUSIONS: Our case indicates daratumumab is both safe and effective for refractory IgD-MM with severe complications.


Subject(s)
Lung Neoplasms , Multiple Myeloma , Thrombocytopenia , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Immunoglobulin D , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
18.
Front Public Health ; 9: 727829, 2021.
Article in English | MEDLINE | ID: covidwho-1775854

ABSTRACT

Background: Hypertension has become the second-leading risk factor for death worldwide. However, the fragmented three-level "county-township-village" medical and healthcare system in rural China cannot provide continuous, coordinated, and comprehensive health care for patients with hypertension, as a result of which rural China has a low rate of hypertension control. This study aimed to explore the costs and benefits of an integrated care model using three intervention modes-multidisciplinary teams (MDT), multi-institutional pathway (MIP), and system global budget and performance-based payments (SGB-P4P)-for hypertension management in rural China. Methods: A Markov model with 1-year per cycle was adopted to simulate the lifetime medical costs and quality-adjusted life-years (QALYs) for patients. The interventions included Option 1 (MDT + MIP), Option 2 (MDT + MIP + SGB-P4P), and the Usual practice (usual care). We used the incremental cost-effectiveness ratio (ICER), net monetary benefit (NMB), and net health benefit (NHB) to make economic decisions and a 5% discount rate. One-way and probability sensitivity analyses were performed to test model robustness. Data on the blood pressure control rate, transition probability, utility, annual treatment costs, and project costs were from the community intervention trial (CMB-OC) project. Results: Compared with the Usual practice, Option 1 yielded an additional 0.068 QALYs and an additional cost of $229.99, resulting in an ICER of $3,373.75/QALY, the NMB was -$120.97, and the NHB was -0.076 QALYs. Compared with the Usual practice, Option 2 yielded an additional 0.545 QALYs, and the cost decreased by $2,007.31, yielding an ICER of -$3,680.72/QALY. The NMB was $2,879.42, and the NHB was 1.801 QALYs. Compared with Option 1, Option 2 yielded an additional 0.477 QALYs, and the cost decreased by $2,237.30, so the ICER was -$4,688.50/QALY, the NMB was $3,000.40, and the NHB was 1.876 QALYs. The one-way sensitivity analysis showed that the most sensitive factors in the model were treatment cost of ESRD, human cost, and discount rate. The probability sensitivity analysis showed that when willingness to pay was $1,599.16/QALY, the cost-effectiveness probability of Option 1, Option 2, and the Usual practice was 0.008, 0.813, and 0.179, respectively. Conclusions: The integrated care model with performance-based prepaid payments was the most beneficial intervention, whereas the general integrated care model (MDT + MIP) was not cost-effective. The integrated care model (MDT + MIP + SGB-P4P) was suggested for use in the community management of hypertension in rural China as a continuous, patient-centered care system to improve the efficiency of hypertension management.


Subject(s)
Delivery of Health Care, Integrated , Hypertension , Cost-Benefit Analysis , Humans , Hypertension/therapy , Quality-Adjusted Life Years
19.
Stem Cell Reports ; 17(2): 307-320, 2022 02 08.
Article in English | MEDLINE | ID: covidwho-1712991

ABSTRACT

Neurological complications are common in COVID-19. Although SARS-CoV-2 has been detected in patients' brain tissues, its entry routes and resulting consequences are not well understood. Here, we show a pronounced upregulation of interferon signaling pathways of the neurovascular unit in fatal COVID-19. By investigating the susceptibility of human induced pluripotent stem cell (hiPSC)-derived brain capillary endothelial-like cells (BCECs) to SARS-CoV-2 infection, we found that BCECs were infected and recapitulated transcriptional changes detected in vivo. While BCECs were not compromised in their paracellular tightness, we found SARS-CoV-2 in the basolateral compartment in transwell assays after apical infection, suggesting active replication and transcellular transport of virus across the blood-brain barrier (BBB) in vitro. Moreover, entry of SARS-CoV-2 into BCECs could be reduced by anti-spike-, anti-angiotensin-converting enzyme 2 (ACE2)-, and anti-neuropilin-1 (NRP1)-specific antibodies or the transmembrane protease serine subtype 2 (TMPRSS2) inhibitor nafamostat. Together, our data provide strong support for SARS-CoV-2 brain entry across the BBB resulting in increased interferon signaling.


Subject(s)
Blood-Brain Barrier/virology , Central Nervous System/virology , SARS-CoV-2/physiology , Virus Internalization , Antibodies/pharmacology , Benzamidines/pharmacology , COVID-19/pathology , COVID-19/virology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Endothelial Cells/virology , Guanidines/pharmacology , Humans , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Models, Biological , RNA, Viral/metabolism , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Virus Internalization/drug effects
20.
Int J Environ Res Public Health ; 19(2)2022 01 06.
Article in English | MEDLINE | ID: covidwho-1631096

ABSTRACT

This study aimed to explore the health service needs of empty nest families from a household perspective. A multistage random sampling strategy was conducted to select 1606 individuals in 803 empty nest households in this study. A questionnaire was used to ask each individual about their health service needs in each household. The consistency rate was calculated based on their consistent answers to the questionnaire. We used a collective household model to analyze individuals' public health service needs on the family level. According to the results, individuals' consistency rates of health service needs in empty nest households, such as diagnosis and treatment service (H1), chronic disease management service (H2), telemedicine care (H3), physical examination service (H4), health education service (H5), mental healthcare (H6), and traditional Chinese medicine service (H7) were 40.30%, 89.13%, 98.85%, 58.93%, 57.95%, 72.84%, and 63.40%, respectively. Therefore, family-level health service needs could be studied from a family level. Health service needs of H1, H3, H4, H5, and H7 for individuals in empty nest households have significant correlations with each other (r = 0.404, 0.177, 0.286, 0.265, 0.220, p < 0.001). This will be helpful for health management in primary care in rural China; the concordance will alleviate the pressure of primary care and increase the effectiveness of doctor-patient communication. Health service needs in empty nest households who took individuals' public needs as household needs (n = 746) included the H4 (43.3%) and H5 (24.9%) and were always with a male householder (94.0%) or at least one had chronic diseases (82.4%). Health service needs in empty nest households that considered one member's needs as household needs (n = 46) included the H1 (56.5%), H4 (65.2%), H5 (63.0%), and H7 (45.7%), and the member would be the householder of the family (90.5%) or had a disease within two weeks (100.0%). In conclusion, family members' roles and health status play an important role in health service needs in empty nest households. Additionally, physical examination and health education services are the two health services that are most needed by empty nest households, and are suitable for delivering within a household unit.


Subject(s)
Family Characteristics , Rural Population , China , Health Services , Health Status , Humans , Male
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