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2.
Sustainability ; 14(17):10949, 2022.
Article in English | MDPI | ID: covidwho-2010266

ABSTRACT

Remote work has become a new way of working due to the influence of the COVID-19 pandemic, which inevitably aggravates team conflicts caused by cognitive differences given the lack of face-to-face communication. With a team climate perspective, this paper investigates the impact of the team leader's conflict management style on team innovation performance in remote R&D teams in China based on social cognition theory and two-dimension theory. A theoretical model is constructed which describes the mediating effect of team psychological safety and the moderating impact of team trust. Paired data from 118 remote R&D teams in China including 118 leaders and 446 members were collected. The results show that team leader's cooperative conflict management style is conducive to enhancing team psychological safety and further effectively improves team innovation performance. Therefore, team psychological safety has a mediating effect between team leader's cooperative conflict management style and team innovation performance. In addition, team trust has a negative moderating effect between team leader's cooperative conflict management style and team psychological safety. Besides, this study obtains some valuable culture-related insights and provides more views for conflict management research in the cross-cultural context since the samples in this study are from China, a society with high collectivism, which is different from the western cultural context from which many conflict management theories develop.

3.
Preprint in English | medRxiv | ID: ppmedrxiv-22279589

ABSTRACT

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

4.
Front Immunol ; 13: 911859, 2022.
Article in English | MEDLINE | ID: covidwho-1952334

ABSTRACT

Safe and effective vaccines and therapeutics based on the understanding of antiviral immunity are urgently needed to end the COVID-19 pandemic. However, the understanding of these immune responses, especially cellular immune responses to SARS-CoV-2 infection, is limited. Here, we conducted a cohort study of COVID-19 patients who were followed and had blood collected to characterize the longitudinal dynamics of their cellular immune responses. Compared with healthy controls, the percentage of activation of SARS-CoV-2 S/N-specific T cells in recovered patients was significantly higher. And the activation percentage of S/N-specific CD8+ T cells in recovered patients was significantly higher than that of CD4+ T cells. Notably, SARS-CoV-2 specific T-cell responses were strongly biased toward the expression of Th1 cytokines, included the cytokines IFNγ, TNFα and IL2. Moreover, the secreted IFNγ and IL2 level in severe patients was higher than that in mild patients. Additionally, the number of IFNγ-secreting S-specific T cells in recovered patients were higher than that of N-specific T cells. Overall, the SARS-CoV-2 S/N-specific T-cell responses in recovered patients were strong, and virus-specific immunity was present until 14-16 weeks after symptom onset. Our work provides a basis for understanding the immune responses and pathogenesis of COVID-19. It also has implications for vaccine development and optimization and speeding up the licensing of the next generation of COVID-19 vaccines.


Subject(s)
COVID-19 , CD8-Positive T-Lymphocytes , COVID-19 Vaccines , Cohort Studies , Humans , Immunity, Cellular , Interleukin-2 , Pandemics , SARS-CoV-2
5.
BMC Psychol ; 10(1): 178, 2022 Jul 19.
Article in English | MEDLINE | ID: covidwho-1938356

ABSTRACT

BACKGROUND: Mindfulness-based intervention (MBI), an emotion-focused approach, has been shown promising and sustainable effects on enhancing the well-being of caregivers of patients with dementia (PWD). However, the conventional MBI was quite demanding, had high rates of attrition and inconsistent long-term effect. The social distancing measures introduced during the COVID-19 pandemic also restricted face-to-face psychosocial intervention. The study aims to evaluate the effectiveness of a 6-week hybrid MBI in caregivers of PWD over a 6-month follow up. METHODS: This is a single-blinded, parallel-group randomized controlled trial (RCT). Eligible participants from three local nongovernmental organizations (NGOs) will be randomly divided into intervention groups and control groups in a ratio of 1:1. The participants in the intervention group will receive 6 weekly 90-min group-based sessions delivered through a face-to-face and online approach. The participants in the control group will receive brief education on dementia care with the same group size, duration, and frequency as the sessions in the intervention group. Immediately after the intervention and at the 6-month follow-up, caring stress and other outcomes will be assessed. Besides, a focus group interview will be conducted to identify the strengths, limitations, and therapeutic components of the intervention from their perspectives. For quantitative data, intention-to-treat analysis and Generalized Estimating Equations (GEE) will be used. For qualitative data, content analysis will be used. DISCUSSION: This proposed hybrid model of MBI has several advantages, such as lower duration, longer follow-up period and easier access by family caregivers. Also, physiological indicators (e.g., heart rate viability and neuropsychiatric symptoms) will be measured in this study to show the body change after MBI. The quantitative and qualitative data of this research can also benefit the development of online or hybrid MBI for caregivers of PWD during the COVID-19 pandemic. Despite these strengths, it does have practical challenges and limitations. However, this proposed intervention has the potential to benefit not only the participants, but also the researcher as well as public health providers. TRIAL REGISTRATION: NCT05242614. Registered on 2022-02-16, https://clinicaltrials.gov/ct2/show/NCT05242614.


Subject(s)
COVID-19 , Dementia , Mindfulness , Caregivers/psychology , Dementia/therapy , Emotions , Humans , Mindfulness/methods , Randomized Controlled Trials as Topic
6.
Frontiers in psychology ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1904956

ABSTRACT

Since the outbreak of the COVID-19 pandemic in December 2019, millions of people have been infected with the disease. The COVID-19 pandemic also produced severe mental health problems, such as loneliness and depression. The present study aimed to examine the mediating role of cognitive reappraisal and moderating role of resilience in the relationship between young adults’ loneliness and depression during the pandemic by adopting a cross-sectional research approach. In March 2020, 654 young adults (18–29 years old) were recruited to complete the measures for loneliness, depression, emotion regulation, and resilience. Results found that loneliness was positively and moderately associated with depression (r = 0.531, p < 0.001), and that both loneliness and depression were separately negatively associated with cognitive reappraisal (r = −0.348, p < 0.001;r = −0.424, p < 0.001) and resilience (r = −0.436, p < 0.001;r = −0.419, p < 0.001). The results indicated that both loneliness and depression were not associated with expressive suppression (r = 0.067, p = 0.087;r = −0.002, p = 0.961). The moderated mediation model results revealed that only cognitive reappraisal partially mediated the relationship between loneliness and depression (b = −0.301;Boot 95% CI = −0.388, −0.215). In addition, the results of the moderated mediation model indicated that resilience moderated the association between loneliness and depression (b = 0.035, p < 0.001, Boot 95% CI = 0.014, 0.055), while also moderated the impact of cognitive reappraisal on depression (b = −0.031, p < 0.001, Boot 95% CI = −0.058, −0.005). These findings have practical implications that broaden our understanding of depression in young adults and shed light on how to enhance cognitive reappraisal and resilience as a means of combating depression in this age group during the COVID-19 pandemic.

7.
Zool Res ; 43(3): 457-468, 2022 May 18.
Article in English | MEDLINE | ID: covidwho-1836354

ABSTRACT

COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions in vivo, and demonstrated the benefits of co-administration of antihistamines and antiviral drug remdesivir in SARS-CoV-2-infected mice. Specifically, SARS-CoV-2 spike protein-induced MC degranulation resulted in alveolar-capillary injury, while pretreatment of pulmonary microvascular endothelial cells with antihistamines prevented adhesion junction disruption; predictably, the combination of antiviral drug remdesivir with the antihistamine loratadine, a histamine receptor 1 (HR1) antagonist, dampened viral replication and inflammation, thereby greatly reducing lung injury. Our findings emphasize the crucial role of MCs in SARS-CoV-2-induced inflammation and lung injury and provide a feasible combination antiviral and anti-inflammatory therapy for COVID-19 treatment.


Subject(s)
COVID-19 , Lung Injury , Rodent Diseases , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , COVID-19/veterinary , Endothelial Cells , Histamine Antagonists/therapeutic use , Inflammation/drug therapy , Inflammation/etiology , Inflammation/veterinary , Lung Injury/drug therapy , Lung Injury/veterinary , Mice , Rodent Diseases/drug therapy , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
8.
Journal of Medical Virology ; 94(5):i-i, 2022.
Article in English | Wiley | ID: covidwho-1750403

ABSTRACT

Front Cover Caption: The cover image is based on the Research Article Aggregation of high-frequency RBD mutations of SARS-CoV-2 with three VOCs did not cause significant antigenic drift by Tao Li et al., https://doi.org/10.1002/jmv.27596.

9.
Preprint in English | medRxiv | ID: ppmedrxiv-22272062

ABSTRACT

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with immune escape ability raises the urgent need for developing cross-neutralizing vaccines against the virus. NVSI-06-08 is a potential broad-spectrum recombinant COVID-19 vaccine that integrates the antigens from multiple SARS-CoV-2 strains into a single immunogen. Here, we evaluated the safety and immunogenicity of NVSI-06-08 as a heterologous booster dose in adults previously vaccinated with the inactivated vaccine BBIBP-CorV in a randomized, double-blind, controlled, phase 2 trial conducted in the United Arab Emirates (NCT05069129). Three groups of healthy adults over 18 years of age (600 participants per group) who had administered two doses of BBIBP-CorV 4-6-month, 7-9-month and >9-month earlier, respectively, were vaccinated with either a homologous booster of BBIBP-CorV or a heterologous booster of NVSI-06-08. The primary outcome was immunogenicity and safety of booster vaccinations. The exploratory outcome was cross-reactive immunogenicity against multiple SARS-CoV-2 variants of concerns (VOCs). The incidence of adverse reactions was low in both booster vaccinations, and the overall safety profile of heterologous boost was quite similar to that of homologous boost. Heterologous NVSI-06-08 booster was immunogenically superior to homologous booster of BBIBP-CorV. Both Neutralizing and IgG antibodies elicited by NVSI-06-08 booster were significantly higher than by the booster of BBIBP-CorV against not only SARS-CoV-2 prototype strain but also multiple VOCs. Especially, the neutralizing activity induced by NVSI-06-08 booster against the immune-evasive Beta variant was no less than that against the prototype strain, and a considerable level of neutralizing antibodies against Omicron (GMT: 367.67; 95%CI, 295.50-457.47) was induced by heterologous booster, which was substantially higher than that boosted by BBIBP-CorV (GMT: 45.03; 95%CI, 36.37-55.74). Our findings showed that NVSI-06-08 was safe and immunogenic as a booster dose following two doses of BBIBP-CorV, which was immunogenically superior to homologous boost with another dose of BBIBP-CorV. Our study also indicated that the design of hybrid antigen may provide an effective strategy for broad-spectrum vaccine developments.

10.
Lancet Microbe ; 3(3): e193-e202, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1721237

ABSTRACT

BACKGROUND: Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). METHODS: This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 µg, 10 µg, 15 µg, 20 µg, and 25 µg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). FINDINGS: Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 µg group, 13 [65%] of 20 in the 10 µg group, 17 [85%] of 20 in the 15 µg group, 19 [95%] of 20 in the 20 µg group, 16 [100%] of 16 in the 25 µg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 µg group, three (15%) of 20 in the 10 µg group, six (30%) of 20 in the 15 µg group, seven (35%) of 20 in the 20 µg group, five (31%) of 16 in the 25 µg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 µg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. INTERPRETATION: ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. FUNDING: National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.


Subject(s)
COVID-19 , SARS-CoV-2 , Adult , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , China , Humans , Immunogenicity, Vaccine , Immunoglobulin G , Pandemics/prevention & control , Spike Glycoprotein, Coronavirus , Vaccines, Synthetic , mRNA Vaccines
11.
ACS ES&T engineering ; 2022.
Article in English | EuropePMC | ID: covidwho-1695810

ABSTRACT

In indoor environments with limited ventilation, recirculating portable air filtration (PAF) units may reduce COVID-19 infection risk via not only the direct aerosol route (i.e., inhalation) but also via an indirect aerosol route (i.e., contact with the surface where aerosol particles deposited). We systematically investigated the impact of PAF units in a mock classroom, as a supplement to background ventilation, on localized and whole-room surface deposition and particle concentration. Fluorescently tagged particles with a volumetric mean diameter near 2 μm were continuously introduced into the classroom environment via a breathing simulator with a prescribed inhalation–exhalation waveform. Deposition velocities were inferred on >50 horizontal and vertical surfaces throughout the classroom, while aerosol concentrations were spatially monitored via optical particle spectrometry. Results revealed a particle decay rate consistent with expectations based upon the reported clean air delivery rates of the PAF units. Additionally, the PAF units reduced peak concentrations by a factor of around 2.5 compared to the highest concentrations observed and led to a statistically significant reduction in deposition velocities for horizontal surfaces >2.5 m from the aerosol source. Our results not only confirm that PAF units can reduce particle concentrations but also demonstrate that they may lead to reduced particle deposition throughout an indoor environment when properly positioned with respect to the location of the particle source(s) within the room (e.g., where the largest group of students sit) and the predominant air distribution profile of the room.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325244

ABSTRACT

Objective: Based on differences in populations and prevention and control measures, the spread of new coronary pneumonia in different countries and regions also differs. This study aimed to calculate the transmissibility of coronavirus disease 2019 (COVID-19), and to evaluate the effectiveness of countermeasures to control the disease in Jilin Province, China. Methods: : The data of reported COVID-19 cases were collected, including imported and local cases from Jilin Province as of March 14, 2019. A Susceptible–Exposed–Infectious–Asymptomatic–Recovered (SEIAR) model was developed to fit the data, and the effective reproduction number ( R eff ) was calculated at different stages in the province. Finally, the effectiveness of the countermeasures was assessed. Results: : A total of 97 COVID-19 infections were reported in Jilin Province, among which 45 were imported infections (including one asymptomatic infection) and 52 were local infections (including three asymptomatic infections). The model fit well with the reported data ( R 2 = 0.593, P < 0.001). The R eff of COVID-19 before and after February 1, 2020 was 1.64 and 0.05, respectively. Without the intervention taken on February 1, 2020, the predicted cases would reach a peak of 177,011 on October 22, 2020 (284 days from the first case). The projected number of cases until the end of the outbreak (on October 9, 2021) would be 17,129,367, with a total attack rate of 63.66%. Based on the comparison between the predicted incidence of the model and the actual incidence, the comprehensive intervention measures implemented in Jilin Province on February 1 reduced the incidence of cases by 99.99%. Therefore, according to the current measures and implementation efforts, Jilin Province can achieve good control of the virus’s spread. Conclusions: : COVID-19 has a moderate transmissibility in Jilin Province, China. The interventions implemented in the province had proved effective, increasing social distancing and a rapid response by the prevention and control system will help control the spread of the disease.

13.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-325239

ABSTRACT

Backgrounds: : The COVID-19 pandemic has great impact on hospitals and patients. The fourteen-day quarantine caused surgery of RRD postponed. To explore the risk factors of rhegmatogenous retinal detachment (RRD) progression in a group of patients whose surgery was postponed during the top-level emergency response of COVID-19. Methods: : Retrospective case series study. The information on RRD patients who received surgeries in Beijing Tongren Hospital's retina service from February 16, 2020, to April 30, 2020 has been collected retrospectively. The history, manifestation on presentation and admission, and progression of RRD were recorded. RRD progression was defined as the presence of either choroidal detachment (CD) or proliferative vitreoretinopathy (PVR) progression during the quarantine period. Risk factors were analyzed using the Cox proportional hazards model, survival analysis, and logistic regression. Results: : There were 79 cases enrolled in this study. The median time from the patients' presentation at the clinic to admission for surgery was 14 days (3–61 days). There were 70 cases (88.6%) who did not present to the hospital within one week of the onset of visual symptoms. There were 69 (87.3%) macular-off cases at the presentation. There were 27 (34.2%) cases combined with choroidal detachment. There were 49 (62.0%) cases with PVR B, 22 (27.8%) cases with PVR C, 4 (5.1%) cases with PVR D, and 4 (5.1%) cases with PVR A. After the 14-day quarantine, 21 (26.6%) cases showed RRD progression, and 9 cases showed RD regression at the time of surgery. Neither the time of onset of the visual symptom ( p =0.46) nor the time between presentation and admission ( p =0.31) was significantly different between the patients with RRD progression and patients without RRD progression. The combination of CD (3.61, 1.86-6.99, p =0.001) and retinal breaks located posterior to the equator (3.78, 1.25-11.45, p =0.02) were factors related to the progression of RRD. Conclusions: : In the cases enrolled in our study during the COVID-19 outbreak period, the RRD progression risk factors included a combination of CD and retinal breaks posterior to the equator. Ophthalmologists should schedule the surgeries for RRD patients with these signs as soon as possible.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-318614

ABSTRACT

Excessive inflammatory responses induced upon SARS-CoV-2 infection interlocks with severe symptoms and acute lung injury in patients with Severe Coronavirus Disease 2019 (COVID-19). Revealing the mechanism underlying the control of SARS-CoV-2-triggered immune-inflammatory responses would help us to understand the pathological process and guide clinical treatment. However, the effect of the NLRP3 inflammasome on regulating SARS-CoV-2-induced inflammatory responses has not been reported. Here, we revealed a distinct mechanism by which SARS-CoV-2 nucleocapsid (N) protein promotes the NLRP3 inflammasome activation to induce hyperinflammation. We demonstrated that N protein facilitates the maturation of proinflammatory cytokines IL-1β and IL-6 and induces proinflammatory responses in cultured cells and mice tissues. In team of molecular mechanism, N protein interacts directly with NLRP3 protein, promotes the binding of NLRP3 with ASC, and facilitates the assemble of the inflammasome complex. More importantly, N protein aggravates lung injury, accelerated death in sepsis and acute inflammation mouse models, and promotes IL-1β and IL-6 activation in mice. Notably, N-induced lung injury and cytokine production were blocked by Ac-YVAD-cmk, an inhibitor of the NLRP3 inflammasome. Therefore, this study revealed a distinct mechanism by which SARS-CoV-2 N protein promotes the NLRP3 inflammasome activation and induces excessive inflammatory responses.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-312690

ABSTRACT

Background: Despite worldwide calls for precautionary measures to combat COVID-19, the public's preventive intention still varies significantly among different regions. Exploring the influencing factors of the public's preventive intention is very important to curtail the spread of COVID-19. Previous studies have found that fear can effectively improve the public's preventive intention, but they ignore the impact of differences in cultural values. The present study examines the combined effect of fear and collectivism on the public's preventive intention towards COVID-19 through the analysis of social media big data. Methods: : The Sina microblog posts of 108,914 active users from Chinese mainland 31 provinces were downloaded. The data was retrieved from January 11 to February 21 2020. Afterwards, we conducted a province-level analysis of the contents of downloaded posts. Three lexicons were applied to automatically recognise the scores of fear, collectivism, and preventive intention of 31 provinces. After that, a multiple regression model was established to examine the combined effect of fear and collectivism on the public's preventive intention towards COVID-19. The simple slope test and the Johnson-Neyman technique were used to test the interaction of fear and collectivism on preventive intention. Results: : The study reveals that: (a) both fear and collectivism can positively predict people's preventive intention and (b) there is an interaction of fear and collectivism on people's preventive intention, where fear and collectivism reduce each other's positive influence on people's preventive intention. Conclusion: The promotion of fear on people's preventive intention may be limited and conditional, and values of collectivism can well compensate for the promotion of fear on preventive intention. These results provide scientific inspiration on how to enhance the public's preventive intention towards COVID-19 effectively.

16.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308334

ABSTRACT

Objective: Based on the Prevention and Control of COVID-19, this paper points out the shortcomings of China's current medical insurance system, and puts forward the concept of establishing emergency medical insurance system. Methods: : This paper analyzes the characteristics of the modern epidemic and its special requirements for medical insurance. Putting forward the idea of mechanism construction. Results: : The operation of China's national medical insurance system is mainly operated by the insured, the government, medical institutions and medical institutions. However, the rapid spread of the epidemic has caused great disasters to the society. In the face of major public health events, medical insurance should have four characteristics: the "normalization" of the emergency medical insurance system, the fairness of guarantees, the public quality of treatment and positive externalities. China should establish an emergency system in line with these four characteristics from the four parties. Therefore, this paper analyzes the characteristics of modern epidemic risk, its development process and the requirements for the insurance industry in combination with the situation of China's response to dealing with COVID-19, and puts forward that China should further improve the universal medical insurance system and establish an emergency medical security system to better deal with all kinds of sudden public health events, which will still happen in the future. Conclusions: : China's national medical insurance system should not be limited to meet people's conventional medical needs. When public health emergencies occur, it is also necessary to establish a sound medical insurance system to operate.The establishment of emergency medical security system is one of the important development directions of our country in the future.

17.
Internet Research ; 32(1):90-119, 2022.
Article in English | ProQuest Central | ID: covidwho-1626537

ABSTRACT

PurposeThis paper aims to investigate the impacts of rumors' information characteristics on people's believing and spreading of rumors online.Design/methodology/approachThis study employed a mixed-methods approach by combining qualitative and quantitative methods. In study 1, the authors explored different types of rumors and their information source characteristics through qualitative research. In study 2, the authors utilized the findings from study 1 to develop an empirical model to verify the impact of these characteristics on the public's behaviors of believing and spreading rumors by content analysis and quantitative research.FindingsThe results show that five information source characteristics – credibility, professionalism, attractiveness, mystery and concreteness – influence the spreading effect of different types of rumors.Research limitations/implicationsThis study contributes to rumor spreading research by deepening the theory of information source characteristics and adding to the emerging literature on the COVID-19 pandemic.Practical implicationsInsights from this research offer important practical implications for policymakers and online-platform operators by highlighting how to suppress the spread of rumors, particularly those associated with COVID-19.Originality/valueThis research introduces the theory of information source characteristics into the field of rumor spreading and adopts a mixed-methods approach, taking COVID-19 rumors as a typical case, which provides a unique perspective for a deeper understanding of rumor spreading's antecedences.

18.
Signal Transduct Target Ther ; 6(1): 428, 2021 12 17.
Article in English | MEDLINE | ID: covidwho-1585884

ABSTRACT

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. In this study, we showed that SARS-CoV-2-triggered MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation altered various signaling pathways in alveolar epithelial cells, particularly, the induction of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.


Subject(s)
COVID-19/metabolism , Cell Degranulation , Lung Injury/metabolism , Mast Cells/metabolism , Pulmonary Alveoli/metabolism , SARS-CoV-2/metabolism , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , COVID-19/genetics , Cell Line, Tumor , Female , Humans , Lung Injury/genetics , Lung Injury/virology , Macaca mulatta , Male , Mice, Inbred BALB C , Mice, Transgenic , Pulmonary Alveoli/virology , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
19.
Signal Transduct Target Ther ; 6(1): 438, 2021 12 24.
Article in English | MEDLINE | ID: covidwho-1585880

ABSTRACT

Messenger RNA (mRNA) vaccine technology has shown its power in preventing the ongoing COVID-19 pandemic. Two mRNA vaccines targeting the full-length S protein of SARS-CoV-2 have been authorized for emergency use. Recently, we have developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor-binding domain (RBD) of SARS-CoV-2 (termed ARCoV), which confers complete protection in mouse model. Herein, we further characterized the protection efficacy of ARCoV in nonhuman primates and the long-term stability under normal refrigerator temperature. Intramuscular immunization of two doses of ARCoV elicited robust neutralizing antibodies as well as cellular response against SARS-CoV-2 in cynomolgus macaques. More importantly, ARCoV vaccination in macaques significantly protected animals from acute lung lesions caused by SARS-CoV-2, and viral replication in lungs and secretion in nasal swabs were completely cleared in all animals immunized with low or high doses of ARCoV. No evidence of antibody-dependent enhancement of infection was observed throughout the study. Finally, extensive stability assays showed that ARCoV can be stored at 2-8 °C for at least 6 months without decrease of immunogenicity. All these promising results strongly support the ongoing clinical trial.


Subject(s)
COVID-19 Vaccines/pharmacology , COVID-19/immunology , Immunogenicity, Vaccine , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/immunology , /pharmacology , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Chlorocebus aethiops , Humans , Macaca fascicularis , Vero Cells , /immunology
20.
Preprint in English | medRxiv | ID: ppmedrxiv-21268499

ABSTRACT

BackgroundThe increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccinations. In this study, we reported the safety and immunogenicity of a heterologous boost with a recombinant COVID-19 vaccine (CHO cells), named NVSI-06-07, as a third dose in participants who have previously received two doses of the inactivated vaccine (BBIBP-CorV) at pre-specified time intervals. Using homologous boost with BBIBP-CorV as control, the safety and immunogenicity of the heterologous boost with NVSI-06-07 against various SARS-CoV-2 strains, including Omicron, were characterized. MethodsThis study is a single-center, randomised, double-blinded, controlled phase 2 trial for heterologous boost of NVSI-06-07 in BBIBP-CorV recipients from the United Arab Emirates (UAE). Healthy adults (aged [≥]18 years) were enrolled and grouped by the specified prior vaccination interval of BBIBP-CorV, i.e., 1-3 months, 4-6 months or [≥]6 months, respectively, with 600 individuals per group. For each group, participants were randomly assigned at 1:1 ratio to receive either a heterologous boost of NVSI-06-07 or a homologous booster dose of BBIBP-CorV. The primary outcome was to comparatively assess the immunogenicity between heterologous and homologous boosts at 14 and 28 days post-boosting immunization, by evaluation of the geometric mean titers (GMTs) of IgG and neutralizing antibodies as well as the corresponding seroconversion rate ([≥]4-fold rise in antibody titers). The secondary outcomes were the safety profile of the boosting strategies within 30 days post vaccination. The exploratory outcome was the immune efficacy against Omicron and other variants of concern (VOCs) of SARS-CoV-2. This trial is registered with ClinicalTrials.gov, NCT05033847. FindingsA total of 1800 individuals who have received two doses of BBIBP-CorV were enrolled, of which 899 participants received a heterologous boost of NVSI-06-07 and 901 received a homologous boost for comparison. No vaccine-related serious adverse event (SAE) and no adverse events of special interest (AESI) were reported. 184 (20{middle dot}47%) participants in the heterologous boost groups and 177 (19{middle dot}64%) in the homologous boost groups reported at least one adverse reaction within 30 days. Most of the local and systemic adverse reactions reported were grades 1 (mild) or 2 (moderate), and there was no significant difference in the overall safety between heterologous and homologous boosts. Immunogenicity assays showed that the seroconversion rates in neutralizing antibodies against prototype SARS-CoV-2 elicited by heterologous boost were 89{middle dot}96% - 97{middle dot}52% on day 28 post-boosting vaccination, which was much higher than what was induced by homologous boost (36{middle dot}80% - 81{middle dot}75%). Similarly, in heterologous NVSI-06-07 booster groups, the neutralizing geometric mean titers (GMTs) against the prototype strain increased by 21{middle dot}01 - 63{middle dot}85 folds from baseline to 28 days post-boosting vaccination, whereas only 4{middle dot}20 - 16{middle dot}78 folds of increases were observed in homologous BBIBP-CorV booster group. For Omicron variant, the neutralizing antibody GMT elicited by the homologous boost of BBIBP-CorV was 37{middle dot}91 (95%CI, 30{middle dot}35-47{middle dot}35), however, a significantly higher level of neutralizing antibodies with GMT 292{middle dot}53 (95%CI, 222{middle dot}81-384{middle dot}07) was induced by the heterologous boost of NVSI-06-07, suggesting that it may serve as an effective boosting strategy combating the pandemic of Omicron. The similar results were obtained for other VOCs, including Alpha, Beta and Delta, in which the neutralizing response elicited by the heterologous boost was also significantly greater than that of the homologous boost. In the participants primed with BBIBP-CorV over 6 months, the largest increase in the neutralizing GMTs was obtained both in the heterologous and homologous boost groups, and thus the booster vaccination with over 6 months intervals was optimal. InterpretationOur findings indicated that the heterologous boost with NVSI-06-07 was safe, well-tolerated and immunogenic in adults primed with a full regimen of BBIBP-CorV. Compared to homologous boost with a third dose of BBIBP-CorV, incremental increases in immune responses were achieved by the heterologous boost with NVSI-06-07 against SARS-CoV-2 prototype strain, Omicron variant, and other VOCs. The heterologous BBIBP-CorV/NVSI-06-07 prime-boosting vaccination may be valuable in preventing the pandemic of Omicron. The optimal booster strategy was the heterologous boost with NVSI-06-07 over 6 months after a priming with two doses of BBIBP-CorV. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed for clinical trials or prospective/cohort studies involving heterologous booster vaccination in non-immunocompromised population published up to Dec 25, 2021, using the term "(COVID) AND (vaccin*) AND (clinical trial OR cohort OR prospective) AND (heterologous) AND (booster OR prime-boost OR third dose)" with no language restrictions. Nine studies of heterologous prime-boost vaccinations with adenovirus-vector vaccines (ChAdOx1 nCov-19, Oxford-AstraZeneca, Ad26.COV2.S, Janssen) and mRNA vaccines (BNT162b2, Pfizer-BioNtech; mRNA1273, Moderna) were identified. The adenovirus-vector and mRNA heterologous prime-boost vaccination was found to be well tolerated and immunogenic. In individuals primed with adenovirus-vector vaccine, mRNA booster vaccination led to greater immune response than homologous boost. However, varied results were obtained on whether heterologous boost was immunogenically superior to the homologous mRNA prime-boost vaccination. Besides that, A preprint trial in population previously immunized with inactivated vaccines (CoronaVac, Sinovac Biotech) showed that the heterologous boost with adenovirus-vector vaccine (Convidecia, CanSino Biologicals) was safe and induced higher level of live-virus neutralizing antibodies than by the homogeneous boost. A pilot study reported that boosting with BNT162b2 in individuals primed with two doses of inactivated vaccines (BBIBP-CorV) was significantly more immunogenic than homologous vaccination with two-dose of BNT162b2. In addition, a preprint paper demonstrated that heterologous boost of ZF2001, a recombinant protein subunit vaccine, after CoronaVac or BBIBP-CorV vaccination potently improved the immunogenicity. But only a small size of samples was tested in this study and the live-virus neutralization was not detected. Till now, it is still lacking a formal clinical trial to evaluate the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit-based vaccine. Added value of this studyTo our knowledge, this is the first reported result of a large-scale randomised, controlled clinical trial of heterologous prime-boost vaccination with an inactivated vaccine followed by a recombinant protein subunit vaccine. This trial demonstrated that the heterologous prime-booster vaccination with BBIBP-CorV/NVSI-06-07 is safe and immunogenic. Its immunoreactivity is similar to that of homologous vaccination with BBIBP-CorV. Compared to homologous boost, heterologous boost with NVSI-06-07 in BBIBP-CorV recipients elicited significantly higher immunogenicity not only against the SARS-CoV-2 prototype strain but also against Omicron and other variants of concern (VOCs). Implications of all the available evidenceBooster vaccination is considered an effective strategy to improve the protection efficacy of COVID-19 vaccines and control the epidemic waves of SARS-CoV-2. Data from our trial suggested that the booster vaccination of NVSI-06-07 in BBIBP-CorV recipients significantly improved the immune responses against various SARS-CoV-2 strains, including Omicron. Due to no Omicron-specific vaccine available currently, the BBIBP-CorV/NVSI-06-07 heterologous prime-boost might serve as an effective strategy combating Omicron variant. Besides that, BBIBP-CorV has been widely inoculated in population, and thus further boosting vaccination with NVSI-06-07 is valuable in preventing the COVID-19 pandemic. But further studies are needed to assess the long-term protection of BBIBP-CorV/NVSI-06-07 prime-booster vaccination.

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