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1.
Ann Pharmacother ; : 10600280221133577, 2022 Oct 29.
Article in English | MEDLINE | ID: covidwho-2098230

ABSTRACT

BACKGROUND: No study has yet systematically evaluated the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with type 2 diabetes (T2D). OBJECTIVE: We aimed to evaluate the effect of different antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. METHODS: We comprehensively retrieved the published research which examined the effect of antidiabetic therapy on clinical outcomes of COVID-19 patients with T2D. The odds ratio (OR) and its 95% confidence interval (95% CI) for clinical outcomes were calculated using the random-effects model, and meta-regression was adopted to evaluate the potential sources of heterogeneity between studies. RESULTS: A total of 54 studies were included in this study. We found that the use of metformin (OR = 0.66, 95% CI: 0.58-0.75), SGLT-2i (OR = 0.80, 95% CI: 0.73-0.88), and GLP-1ra (OR = 0.83, 95% CI: 0.70-0.98) were significantly associated with lower mortality risk in COVID-19 patients with T2D, while insulin use might unexpectedly increase the ICU admission rate (OR = 2.32, 95% CI: 1.34-4.01) and risk of death (OR = 1.52, 95% CI: 1.32-1.75). No statistically significant associations were identified for DPP-4i, SUs, AGIs, and TZDs. CONCLUSION AND RELEVANCE: We demonstrated that the usage of metformin, SGLT-2i, and GLP-1ra could significantly decrease mortality in COVID-19 patients with T2D. The heterogeneity across the studies, baseline characteristics of the included patients, shortage of dosage and the duration of antidiabetic drugs and autonomy of drug selection might limit the objectivity and accuracy of results. Further adequately powered and high-quality randomized controlled trials are warranted for conclusive findings.

2.
Health Commun ; : 1-11, 2022 Oct 17.
Article in English | MEDLINE | ID: covidwho-2077396

ABSTRACT

This research attempts to both replicate initial research on media prescriptions - the assignment of small doses of positively-valenced media for the purposes of reducing perceived stress - and, through the lens of the broaden-and-build theory, shed light on the process through which this effect might emerge. Two longitudinal data sets were collected, one with college students (N = 182) and one with U.S. adults (N = 197), in which participants were assigned to watch either comedic or inspiring media clips every day for 5 days. Findings indicated that both amusement and hope generated by media exposure reduced perceived stress over time. Specifically, inspiring media reduced perceived stress through its effect on felt hope for both samples, whereas comedic media reduced perceived stress via felt amusement for the general adult sample only. Further, as predicted, serial mediation through felt emotion and coping efficacy emerged for amusement in the student sample and for hope in the general sample. Given these data were collected during an inordinately stressful time in both the U.S. and the world with rising rates of COVID-19, a highly contentious political election, and tensions over racial inequity, these findings suggest that media, if harnessed appropriately, could be a useful tool in one's coping arsenal. A call for better understanding of the process through which media prescriptions have effect and their boundary conditions is advanced.

3.
Atmosphere ; 13(10):1597, 2022.
Article in English | MDPI | ID: covidwho-2065685

ABSTRACT

China has experienced a series of COVID-19 recurrences in different cities across the country since 2020, and relatively strict (full lockdown) or lenient closure (semi-lockdown) strategies have been employed accordingly in each city. The differences in detailed transmission control measures during lockdown periods led to distinct effects on air quality, which has rarely been studied. To fill this gap, we examined the effects of semi-lockdown and full lockdown on six major airborne pollutants, based on 55 lockdown cases. For all lockdown cases, the concentrations of PM2.5, PM10, SO2, NO2 and CO were much lower than in previous years. Specifically, due to the stricter transmission control, the concentration of the five airborne pollutants experienced a much sharper decline during full lockdown. However, O3 presented a different variation pattern during lockdown periods. Generally, O3 concentrations presented a slight increase in semi-lockdown cases and a notable increase in full lockdown cases. Meanwhile, O3 increased notably in northern China, particularly in the Beijing–Tianjin–Hebei region, while O3 had a slight variation in southern China. The unique variation of O3 across regions and lockdown types was mainly attributed to the spatial heterogeneity of O3 formation regimes, especially the VOCs-controlled O3 formation in northern China. Based on Geographical Detector, we examined the spatial continuity of natural and socio-economic factors on the variation of airborne pollutants during lockdown. In terms of meteorological factors, humidity and precipitation were the dominant factors for PM2.5 and PM10, respectively, while humidity and temperature were the dominant factors for O3. In terms of socio-economic factors, the numbers of taxis and private cars were the dominant factors for PM2.5 and O3 variations during lockdown. GD also revealed that the combination of natural and socio-economic factors had a significantly enhanced effect on airborne pollutants during lockdown. The combination of relative humidity and total area of urban built-up areas exerted the strongest interactive effects on both PM2.5 and O3. This research highlighted the challenge for urban O3 management, and suggested the control of VOCs emissions should be preferably considered, especially in northern China.

4.
Disease Surveillance ; 37(4):435-439, 2022.
Article in English | GIM | ID: covidwho-1994241

ABSTRACT

Objective: To analyze the epidemiological characteristics of a COVID-19 case imported from Nepal in Chongqing of China, and provide evidence for the prevention and control of imported COVID-19.

5.
J Med Virol ; 94(12): 5746-5757, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1976742

ABSTRACT

We evaluated and compared humoral immune responses after inactivated coronavirus disease 2019 (COVID-19) vaccination among naïve individuals, asymptomatically infected individuals, and recovered patients with varying severity. In this multicenter, prospective cohort study, blood samples from 666 participants were collected before and after 2 doses of inactivated COVID-19 vaccination. Among 392 severe acute respiratory syndrome coronavirus 2-naïve individuals, the seroconversion rate increased significantly from 51.8% (median antispike protein pan-immunoglobulins [S-Igs] titer: 0.8 U/ml) after the first dose to 96% (median S-Igs titer: 79.5 U/ml) after the second dose. Thirty-two percent of naïve individuals had detectable neutralizing antibodies (NAbs) against the original strain but all of them lost neutralizing activity against the Omicron variant. In 274 individuals with natural infection, humoral immunity was significantly improved after a single vaccine dose, with median S-Igs titers of 596.7, 1176, 1086.5, and 1828 U/ml for asymptomatic infections, mild cases, moderate cases, and severe/critical cases, respectively. NAb titers also improved significantly. However, the second dose did not substantially increase antibody levels. Although a booster dose is needed for those without infection, our findings indicate that recovered patients should receive only a single dose of the vaccine, regardless of the clinical severity, until there is sufficient evidence to confirm the benefits of a second dose.


Subject(s)
COVID-19 , Viral Vaccines , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19 Vaccines , Humans , Prospective Studies , SARS-CoV-2 , Vaccination , Vaccines, Inactivated
6.
ACS omega ; 7(28):24824-24837, 2022.
Article in English | EuropePMC | ID: covidwho-1957868

ABSTRACT

A late-stage functionalization (LSF) of the natural product andrographolide for the efficient assembly of a range of structurally interesting and diverse tricyclic-aza derivatives was developed. The key to the diversification is a photo-catalyzed intramolecular hydroamination reaction, and acridinium derivatives were demonstrated to be the optimal catalysts. Additionally, the synthesized tricyclic aza-andrographolide derivatives were found to inhibit human coronavirus with high potency.

7.
Frontiers in psychiatry ; 13, 2022.
Article in English | EuropePMC | ID: covidwho-1787183

ABSTRACT

Background Under the threat of COVID-19, many universities offer online courses to avoid student gatherings, which prevent teachers from collecting responses and optimizing courses. This work collected eye movement data to analyze attention allocation and proposed instruction for improving the courses. Methods Subjects were recruited to watch three online courses. Meanwhile, their eye movement data were collected through Dikablis Glasses. Mayer’s multimedia cognitive theory was adopted to discriminate the pivotal components of online course, and the Mann–Whitney relevance analysis demonstrated that different representations of courses affected the viewers’ attention differently. Results Three subjects watched three different types of political courses. Course 1, which combined text and explanation, attracted the most attention. Course 2 was shown to be less attractive than course 1 and better than course 3, but the subjects were distracted by the animations in course 2. Course 3, which did not use any technique to present learning content, attracts the least attention from the subjects. A correlation analysis shows that course 1 and course 3 have similar results compared with course 2. Conclusion Online courses have become a norm during the COVID-19 pandemic. Improving the quality of online courses can effectively reduce the impact of the epidemic on teaching. These experiment results suggest that text + commentary in the design of online courses can effectively attract the attention of the listeners and achieve better learning results. Attention gradually rises in the early stage and then falls after reaching a peak. At this time, the proper introduction of animation can effectively reverse the attention curve, while individual text or commentary results in quickly losing the listener’s attention.

8.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-325257

ABSTRACT

Background: As a new infectious disease, coronavirus disease 2019 (COVID-19) is not fully understood. During January - July 2020, there were two clusters infections in Beijing, China. This study was to analyze the features of the two COVID-19 infections in Beijing. Methods: : In this retrospective single-center study, 89 cases with the positive novel coronavirus nucleic acid test were collected from January to July 2020 in Beijing. They were divided into January-March group and June-July group. Two groups of data were compared. Results: : The eighty-nine cases, 47 males and 42 females, mean age (41±14 years), were used for our study. The most common symptoms were fever (46/89, 52%) and cough (34/89, 38%). The clinical classification were moderate type (56/89,63%), mild type (24/89, 27%), severe type (4/89, 4%), critical type (0), respectively. Ground glass opacity (GGO) (47%) was the majority CT pattern. The frequency of involvement of lower lobe was higher than that of upper lobe ( P <0.01). In January - March group, there were 5 patients (18%) exposure to Wuhan, 15 patients (54%) family clusters, 5 patients (18%) colleague clusters, 3 patients (11%) imported cases. In June-July group, 41 patients (68%) had an exposure to Xinfadi market of Beijing, 6 patients (10%) family clusters, and 14 patients (23%) colleague clusters. The number of patients with fever, cough, chest CT severity score and the number of lesion lung lobes in January-March group was higher than that in June-July group ( P <0.05). Conclusions: : Two COVID-19 clusters were dominated moderate and mild type, but few severe types. Patients in June-July group had less symptoms, imaging and family clusters than that in January-March group. This suggested that closely monitoring, early quarantined, nucleic acid test of COVID-19 and chest CT were important measures to prevent epidemic.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323719

ABSTRACT

The SARS-CoV-2 has led to a worldwide health crisis. The ACE2 has been identified as the entry receptor in a species-specific manner. Classic laboratory mice were insusceptible since the virus cannot use murine ACE2 orthologue. Animal models rely on gene modification on the virus or the host. However, these mice were restricted in limited genetic backgrounds and did not support natural infection. Here we showed two wild-type inbred lines (CAST and FEW) from Genetic Diversity mice supported authentic SARS-CoV-2 infection, and developed mild to moderate interstitial pneumonia, along with infiltrating inflammatory cells. Particularly, FEW featured age-dependent damages, while CAST charactered by pulmonary fibrosis. Genome and transcriptome comparative analysis suggested the mutated ACE2 was not responsible for SARS-CoV-2 infection in CAST and FEW, and the differential gene expressions in immune response and immune cell may be risk factors for the infection. In summary, the GD mice, derived from the multi-parental panel, provided promising murine models for exploring sophisticated pathogenesis in SARS-CoV-2.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-323518

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic conditions increased GP73 production and secretion. Secreted GP73 then trafficked to the liver and kidney to stimulate gluconeogenesis through the cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of the PKA kinase hub exerted by GP73. Notably, plasma GP73 levels were elevated and positively correlated with blood glucose in patients with COVID19 and diabetes. Neutralization of circulating GP73 in serum of individuals infected with SARS-CoV-2 or with diabetes reduced excessive gluconeogenesis in cultured hepatocytes, and lowered blood glucose levels in animal models of diabetes. Ablation of GP73 from whole animals has a profound glucose-lowering effect secondary to reduced gluconeogenesis. Thus, GP73 is a key glucogenic hormone contributing to SARS-CoV-2-induced glucose abnormality.

11.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-321377

ABSTRACT

Background: The prognosis of children and adolescents with COVID-19 obtain increasing attention worldwide. This study provides the first systematic review and meta-analysis to identify risk factors which predict poor prognosis in this group.Methods: Electronic databases from inception to March, 2021 were searched for cohort studies, case-control studies and case series that investigated risk factors for poor prognosis of children and adolescents with COVID-19. We estimated the summary effect size by use of random-effects models and the 95% confidential interval (CI).Findings: We identified 33 studies, comprising 32,225 individuals. The risk of bias were generally high. In children and adolescents with COVID-19, risk of death was significantly increased in patients with MIS-C complication (odds ratio [OR]=58.00, 95% CI 6.39 to 526.79) and in need for intensive care (OR=15.25, 95% CI 1.98 to 117.44). Congenital heart disease (OR=2.90, 95% CI 1.26 to 6.67), chronic pulmonary disease (OR=3.45, 95% CI 1.47 to 8.07), and gastrointestinal symptoms (OR=2.11, 95% CI 1.43 to 3.12) increased the odds to be admitted to ICU;MIS-C complication (OR=70.00, 95% CI 6.51 to 752.27) and neurological diseases (OR=2.51, 95% CI 1.03 to 6.15) increased the odds of respiratory support;neurological diseases (OR=4.59, 95% CI 1.99 to 10.61), obesity (OR=2.51, 95% CI 2.02 to 3.12), C-reactive protein (CRP) level ≥80mg/L (OR=11.70, 95% CI 4.37 to 31.37) and D-dimer level ≥0.5ug/mL (OR=20.40, 95% CI 1.76 to 236.44) on admission increased the odds of progression to severe/critical disease.Interpretation: Very low to moderate quality evidence found that MIS-C, congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, and gastrointestinal symptoms, in need for intensive care, elevated CRP and D-dimer are risk factors for poor prognosis in children and adolescents with COVID-19.Funding: None.Declaration of Interests: The authors declare that they have no competing interests.

12.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315161

ABSTRACT

Background: The COVID-19 mortality is very low in the regions with a low transmission rate and sufficient medical resources. However, strict prevention measures greatly altered people’s social activities, diet, and hygienic habits, which had potential impact on non-COVID-19 deaths. Therefore, this study is to evaluate the impact of short-term lifestyle change on non-COVID deaths in the region with a low COVID-19 transmission rate.Methods: We performed a retropective observational study with statiscal analysis via Student’s t-test (significance defined as P-value < 0.05). The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were sourced from Xuzhou Center for Disease Control and Prevention. Death rates were calculated and compared by weeks, months, and years with a focus on the period of COVID-19 pandemic from Jan 24 to March 27, 2020 in Xuzhou, Jiangsu Province, China.Findings: Within the COVID-19 timeframe, all-cause mortality (138.03/105 vs. 158.28/105 vs. 152.57/105, P < 0.001), respiratory disorders (13.99/105 vs. 24.48/105 vs. 21.22/105, P < 0.001), cerebrovascular diseases (36.35/105 vs. 38.69/105 vs. 38.61/105, P < 0.05), and cardiovascular diseases (35.70/105 vs. 42.06/105 vs. 39.55/105, P < 0.001) are consistently lower than those in the same period in 2018 and 2019. The traffic death dropped significantly, while mortalities of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time.Interpretation: Our study suggests the short-term lifestyle alteration can have significant impact on all-cause mortality. This could provide evidences for adjusting future healthcare policies to reduce specific-cause mortalities such as respiratory, cardiovascular and cerebrovascular diseases.Trial Registration: This study was registered at the ClinicalTrials.gov (NCT 04550312). Funding: Xuzhou Talent Fellowship Program 2019.Conflict of Interest: We declare no competing interests.Ethical Approval: The medical research ethics committee of the affiliated hospital of Xuzhou Medical University, Xuzhou, approved the study (9th, September 2020, No. XYFY2020-KL142-01).

13.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315160

ABSTRACT

Background: The increase of all-cause mortality in the areas with high COVID-19 transmission rate due to COVID-19 deaths and the collateral damage to other healthcare problems is well-known. However, the COVID-19 mortality is low in the regions with a low transmission rate and sufficient medical resources. In such regions, strict prevention measures altered people’s lifestyle and hygienic habits and had an impact on non-COVID-19 deaths. Yet, this aspect needs to be elucidated further.Methods: The number of registered deaths among 8.8 million permanent residents with specific causes from January 2018 to June 2020 were estimated. Death rates were calculated and compared by weeks, months, seasons and years with a focus on the period of the COVID-19 pandemic from January 24 to March 27, 2020. The numerical values of all-cause death and the death rates of non-COVID diseases were compared in various time points.Findings: During the pandemic in Xuzhou region, a total of 79 COVID-19 infected patients were diagnosed and treated. Meanwhile, stringent public health measures were taken to contain the virus transmission. Surprisingly, mortalities of all-cause casualty, respiratory disorders, cerebrovascular disease, and cardiovascular disease are consistently lower than those in the same periods in 2018 and 2019. Moreover, the first two weeks in the lunar new year presented the highest death rates from 2018–2020 and lowest in 2020 due to COVID-19 control. The traffic death dropped significantly, while mortality of mental health disorders and out-of-hospital sudden death significantly increased during the pandemic time.Interpretation: Control strategies in the region of low SARS-CoV-2 transmission rate during the COVID-19 outbreak alter the lifestyles of people and further exert an impact on non-COVID deaths, which could have a practical value in guiding clinical work and future management of chronic diseases.Funding Statement: Xuzhou Talent Fellowship Program 2019Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Review Board at the affiliated hospital of Xuzhou Medical University.

14.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-309015

ABSTRACT

The outbreak of the COVID-19 pandemic has plunged the world into a crisis. To contain the crisis, it is essential to build full cooperation between the government and the public. However, it is unclear which governmental and individual factors are the determinants and how they interact on protective behaviors against COVID-19. To resolve this issue, this study built a multiple mediation model and found government emergency management as information transparency and positive propaganda had more important impacts on protective behaviors than refuting rumors and supplies. Moreover, governmental factors could indirectly affect protective behaviors through individual factors such as perceived control, positive emotions, and risk perception. These findings suggest that systematic intervention programs for governmental factors need to be integrated with individual factors to finally achieve effective prevention and control of the COVID-19 pandemic among the public.

15.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-308248

ABSTRACT

Background: The aim of this study was to survey the general public in China to better understand their levels of psychological state and its influencing factors after the Wuhan shutdown on 23 Jan. Methods: : A survey was conducted on Feb 20-24, using an online self-administrated questionnaire among 4071 participants. Data on subjective indicators of daily-life change was collected, and individual scores on changes in anxiety, depression, and stress were generated by 8-item, 11-item, and 6-item questions. After bivariate analyses, multiple linear regression analyses were conducted to investigate independent associations between socio-demographic variables, subjective indicators of changes in daily life, and summary scores including anxiety, depression, and stress scores. Results: : Information from 3803 participants was available for analysis. Multivariable regression analyses showed that the anxiety (B=-1.27, 95%CI=-1.71 to -0.82), depression (B=-1.47, 95%CI=-2.06 to -0.88), and stress (B=-0.79, 95%CI=-1.13 to -0.46) scores of people in rural areas are lower than those in urban areas. People living in the other regions except Hubei, higher education were independent correlates of less negative emotions, while people with relatively high incomes had poor psychological status in anxiety (B=0.73, 95%CI=0.08 to 1.38),depression (B=1.45, 95%CI=0.60 to 2.30) and stress (B=0.65, 95%CI=0.17 to 1.13). Married people were less anxious (B=-0.67, 95%CI=-1.30 to -0.05), depressed (B=-1.14, 95%CI=-1.96 to -0.33), and stressed (B=-0.47, 95%CI=-0.93 to 0.00) than single people. The level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking tended to be positively associated with the scores of anxiety, depression, and stress (p<0.001). Conclusions: : Usual residence, education, marital status, monthly income, the level of attention, self-assessed infection risk, impact of the daily life and mental-health help-seeking are important correlates of the scores of anxiety, depression, and stress. Awareness of these relevant factors could help the government and related personnel to prevent more severe psychological trauma in the later period.

16.
Preprint in English | bioRxiv | ID: ppbiorxiv-474593

ABSTRACT

Novel pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an imminent global threat since its initial outbreak in December 2019. A simple in vitro model system using cell lines highly susceptible to SARS-CoV-2 infection are critical to facilitate the study of the virus cycle and to discover effective antivirals against the virus. Human lung alveolar A549 cells are regarded as a useful and valuable model for respiratory virus infection. However, SARS-CoV-2 uses the ACE2 as receptor for viral entry and the TMPRSS2 to prime the Spike protein, both of which are negligibly expressed in A549 cells. Here, we report the generation of a robust human lung epithelial cell-based model by transducing ACE2 and TMPRSS2 into A549 cells and show that the ACE2 enriched A549ACE2/TMPRSS2 cells (ACE2plus) and its single-cell-derived subclone (ACE2plusC3) are highly susceptible to SARS-CoV-2 infection. These engineered ACE2plus showed higher ACE2 and TMPRSS2 mRNA expression levels than currently used Calu3 and commercial A549ACE2/TMPRSS2 cells. ACE2 and TMPRSS2 proteins were also highly and ubiquitously expressed in ACE2plusC3 cells. Additionally, antiviral drugs like Camostat mesylate, EIDD-1931, and Remdesivir strongly inhibited SARS-CoV-2 replication. Notably, multinucleated syncytia, a clinical feature commonly observed in severe COVID-19 patients was induced in ACE2plusC3 cells either by virus infection or by overexpressing the Spike proteins of different variants of SARS-CoV-2. Syncytial process was effectively blocked by the furin protease inhibitor, Decanoyl-RVKR-CMK. Taken together, we have developed a robust human A549 lung epithelial cell-based model that can be applied to probe SARS-CoV-2 replication and to facilitate the discovery of SARS-CoV-2 inhibitors.

17.
Preprint in English | bioRxiv | ID: ppbiorxiv-469747

ABSTRACT

Therapeutic inhibition of critical viral functions is important for curtailing coronavirus disease-2019 (COVID-19). We sought to identify antiviral targets through genome-wide characterization of SARS-CoV-2 proteins that are crucial for viral pathogenesis and that cause harmful cytopathic effects. All twenty-nine viral proteins were tested in a fission yeast cell-based system using inducible gene expression. Twelve proteins including eight non-structural proteins (NSP1, NSP3, NSP4, NSP5, NSP6, NSP13, NSP14 and NSP15) and four accessory proteins (ORF3a, ORF6, ORF7a and ORF7b) were identified that altered cellular proliferation and integrity, and induced cell death. Cell death correlated with the activation of cellular oxidative stress. Of the twelve proteins, ORF3a was chosen for further study in mammalian cells. In human pulmonary and kidney epithelial cells, ORF3a induced cellular oxidative stress associated with apoptosis and necrosis, and caused activation of pro-inflammatory response with production of the cytokines TNF-, IL-6, and IFN-{beta}1, possibly through the activation of NF-{kappa}B. To further characterize the mechanism, we tested a natural ORF3a Beta variant, Q57H, and a mutant with deletion of the highly conserved residue, {Delta}G188. Compared to wild type ORF3a, the {Delta}G188 variant yielded more robust activation of cellular oxidative stress, cell death, and innate immune response. Since cellular oxidative stress and inflammation contribute to cell death and tissue damage linked to the severity of COVID-19, our findings suggest that ORF3a is a promising, novel therapeutic target against COVID-19. SignificanceThe ongoing SARS-CoV-2 pandemic has claimed over 5 million lives with more than 250 million people infected world-wide. While vaccines are effective, the emergence of new viral variants could jeopardize vaccine protection. Antiviral drugs provide an alternative to battle against COVID-19. Our goal was to identify viral therapeutic targets that can be used in antiviral drug discovery. Utilizing a genome-wide functional analysis in a fission yeast cell-based system, we identified twelve viral candidates, including ORF3a, which cause cellular oxidative stress, inflammation and apoptosis and necrosis that contribute to COVID-19. Our findings indicate that antiviral agents targeting ORF3a could greatly impact COVID-19.

18.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-292232

ABSTRACT

Introduction: The purpose of this systematic review is to evaluate the efficacy and safety of using potential drugs: remdesivir and glucocorticoid in treating children and adolescents with COVID-19 and intravenous immunoglobulin (IVIG) in treating MIS-C. Methods: : We searched seven databases, three preprint platform, ClinicalTrials.gov, and Google from December 1, 2019, to August 5, 2021, to collect evidence of remdesivir, glucocorticoid, and IVIG which were used in children and adolescents with COVID-19 or MIS-C. Results: : A total of nine cohort studies and one case series study were included in this systematic review. In terms of remdesivir, the meta-analysis of single-arm cohort studies have shown that, after the treatment, 54.7% (95%CI, 10.3% to 99.1%) experienced adverse events, 5.6% (95%CI, 1.2% to 10.1%) died, 27.0% (95%CI, 0% to 73.0%) needed extracorporeal membrane oxygenation or invasive mechanical ventilation. As for glucocorticoids, the results of the meta-analysis showed that the fixed-effect summary odds ratio for the association with mortality was 2.79 (95%CI, 0.13 to 60.87), and the mechanical ventilation rate was 3.12 (95%CI, 0.80 to 12.08) for glucocorticoids compared with the control group. In terms of IVIG, most of the included cohort studies showed that for MIS-C patients with more severe clinical symptoms, IVIG combined with methylprednisolone could achieve better clinical efficacy than IVIG alone. Conclusions: : Overall, the current evidence in the included studies is insignificant and of low quality. It is recommended to conduct high-quality randomized controlled trials of remdesivir, glucocorticoids, and IVIG in children and adolescents with COVID-19 or MIS-C to provide substantial evidence for the development of guidelines.

19.
Vaccines (Basel) ; 9(11)2021 Nov 06.
Article in English | MEDLINE | ID: covidwho-1502551

ABSTRACT

The COVID-19 vaccination behavior of people living with HIV (PLWH) was examined via a cross-sectional web-based survey of PLWH aged 18 years and older. The survey was conducted from l May to 20 June 2021. The survey included social demographic information; vaccination behavior (B); and questions related to perceived usefulness (PU), perceived risk (PR), subjective norms (SNs), perceived behavior control (PBC), and behavior intention (BI). The associations between the questionnaire variables and COVID-19 vaccination behavior were assessed by calculating the descriptive data, correlation analysis, and structural equation modeling. In total, 43.71% of the 350 eligible respondents had received a COVID-19 vaccine. The differences in COVID-19 vaccination behavior according to age, gender, religious belief, marital status, income, education level, and occupation were not obvious (p > 0.05). PU had a significantly negative effect on PR (p < 0.05). PR had a significantly negative effect on BI (p < 0.05). SNs had a significantly positive effect on BI (p < 0.05). BI had a significantly positive effect on B (p < 0.05). PR fully mediated the effects of PU on BI, BI fully mediated the effects of PR on B, and BI fully mediated the effects of SNs on B (p < 0.05). Health policymakers and medical workers should provide more information about the risks of vaccine application to improve the vaccination behavior of PLWH.

20.
Preprint in English | bioRxiv | ID: ppbiorxiv-466470

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects cells through binding to angiotensin-converting enzyme 2 (ACE2). This interaction is mediated by the receptor-binding domain (RBD) of the viral spike (S) glycoprotein. Structural and dynamic data have shown that S can adopt multiple conformations, which controls the exposure of the ACE2-binding site in the RBD. Here, using single-molecule Forster resonance energy transfer (smFRET) imaging we report the effects of ACE2 and antibody binding on the conformational dynamics of S from the Wuhan-1 strain and the B.1 variant (D614G). We find that D614G modulates the energetics of the RBD position in a manner similar to ACE2 binding. We also find that antibodies that target diverse epitopes, including those distal to the RBD, stabilize the RBD in a position competent for ACE2 binding. Parallel solution-based binding experiments using fluorescence correlation spectroscopy (FCS) indicate antibody-mediated enhancement of ACE2 binding. These findings inform on novel strategies for therapeutic antibody cocktails.

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