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1.
J Clin Invest ; 132(4)2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1705312

ABSTRACT

Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.


Subject(s)
Antibodies, Viral/immunology , Broadly Neutralizing Antibodies/immunology , COVID-19/immunology , COVID-19/virology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Animals , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/genetics , Antibody Affinity , B-Lymphocytes/immunology , Binding Sites/genetics , Binding Sites/immunology , Broadly Neutralizing Antibodies/blood , Broadly Neutralizing Antibodies/genetics , COVID-19/therapy , Cloning, Molecular , Disease Models, Animal , Humans , Immunization, Passive , Immunoglobulin G/immunology , In Vitro Techniques , Lung/virology , Mice , Mice, Inbred BALB C , Mutation , Neutralization Tests , Receptors, Virus/immunology , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/immunology
2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-324548

ABSTRACT

Background: This study aims to investigate the comparative clinical characteristics of Covid-19 and non-Covid-19 patients. Methods: : Fifteen Covid-19 and 93 non-Covid-19 patients were included in RNA testing. All epidemiological and clinical data were collected and analyzed, and then comparative results were carried out. Results: : Covid-19 patients were older (46.40±18.21 years vs 34.43±18.80 years) and hada higher body weight (70.27±10.67 kg vs 60.54±12.33 kg, P <0.05). The main symptoms that were similar between Covid-19 and non-Covid-19 patients, and Covid-19 patients showed a lower incidence of sputum production (6.67% vs 45.16%, P <0.01) and a lower white-cell count (4.83×10 9 /L vs 7.43×10 9 /L) and lymphocyte count (0.90×10 9 /L vs 1.57×10 9 /L) ( P <0.01). Although there were no differences, C-reactive protein and interleukin-6 were elevated in Covid-19 patients. The sensitivity and negative predictive value of CT images were 0.87 and 0.97, respectively. Covid-19 patients showed a higher contact history of Wuhan residents (80% vs 30.11%) and higher familial clustering (53.33% vs 8.60%, P <0.001). Covid-19 patients showed a higher major adverse events (ARDS, 13.33%;death, 6.67%;P <0.05). Conclusion: Our results suggested that Covid-19 patients had a significant history of exposure and familial clustering and a higher rate of severe status;biochemical indicators showed lymphocyte depletion.

3.
Applied Economics Letters ; : 1-5, 2021.
Article in English | Taylor & Francis | ID: covidwho-1557054
4.
Front Psychol ; 12: 707667, 2021.
Article in English | MEDLINE | ID: covidwho-1376719

ABSTRACT

This study is aimed to examine the impact of WeChat use intensity on social isolation, loneliness, and well-being during the lockdown period of the COVID-19 pandemic. Drawing on the regulatory loop model of loneliness, the notions of Internet Paradox, the Time Displacement hypothesis and previous literature on WeChat use intensity, we propose that lockdown loneliness (partially) mediates the relationship between lockdown WeChat use intensity and well-being (i.e., lockdown stress and lockdown life satisfaction). Moreover, we assume that lockdown WeChat use intensity moderates the relationship between lockdown social isolation and well-being (i.e., lockdown stress and lockdown life satisfaction) in both a direct and in an indirect way, that is through lockdown loneliness. The results from our Structural Equation Modeling analyses, using a sample of 1,805 Chinese respondents, indicate that all of our research hypotheses are confirmed. From this empirical work, it becomes clear that online social interactions, which are believed by many people to be able to compensate for the lack of offline social interactions during the COVID-19 lockdown period, in fact are endangering their mental health and life satisfaction instead. This article concludes with theoretical and practical implications of our study, followed by its limitations and recommendations for future research.

5.
Disaster Med Public Health Prep ; : 1-9, 2021 Jan 08.
Article in English | MEDLINE | ID: covidwho-1014945

ABSTRACT

INTRODUCTION: Early identification of patients with novel corona virus disease 2019 (COVID-19) who may be at high mortality risk is of great importance. METHODS: In this retrospective study, we included all patients with COVID-19 at Huanggang Central Hospital from January 23 to March 5, 2020. Data on clinical characteristics and outcomes were compared between survivors and nonsurvivors. Univariable and multivariable logistic regression were used to explore risk factors associated with in-hospital death. A nomogram was established based on the risk factors selected by multivariable analysis. RESULTS: A total of 150 patients were enrolled, including 31 nonsurvivors and 119 survivors. The multivariable logistic analysis indicated that increasing the odds of in-hospital death associated with higher Sequential Organ Failure Assessment score (odds ratio [OR], 3.077; 95% confidence interval [CI]: 1.848-5.122; P < 0.001), diabetes (OR, 10.474; 95% CI: 1.554-70.617; P = 0.016), and lactate dehydrogenase greater than 245 U/L (OR, 13.169; 95% CI: 2.934-59.105; P = 0.001) on admission. A nomogram was established based on the results of the multivariable analysis. The AUC of the nomogram was 0.970 (95% CI: 0.947-0.992), showing good accuracy in predicting the risk of in-hospital death. CONCLUSIONS: This finding would facilitate the early identification of patients with COVID-19 who have a high-risk for fatal outcome.

6.
J Clin Nurs ; 29(21-22): 4217-4226, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-710079

ABSTRACT

AIMS AND OBJECTIVES: This study aimed to portray the prevalence and associated factors of psychological distress among frontline nurses during COVID-19 outbreak. BACKGROUND: The COVID-19 outbreak has posed great threat to public health worldwide. Nurses fighting against the epidemic on the frontline might be under great physical and psychological distress. This psychological distress was predominantly described as sleep disturbance, symptoms of anxiety and depression, post-traumatic stress, inability to make decisions and even somatic symptoms. DESIGN: Cross-sectional study. METHODS: Frontline nurses from designated hospitals for COVID-19 patients were invited to complete an online survey by convenience sampling, and the survey included six main sections: the General Health Questionnaire, the Perceived Social Support Scale, the Simplified Coping Style Scale, the Impact of Event Scale-Revised, socio-demographic, occupation and work history. Multiple logistic analysis was used to identify the potential risk factors of psychological distress. The study methods were compliant with the STROBE checklist. RESULTS: Of the 263 frontline nurses, 66 (25.1%) were identified as psychological distress. Multiple logistic analysis revealed that working in emergency department, concern for family, being treated differently, negative coping style and COVID-19-related stress symptom were positive related to psychological distress. Perceived more social support and effective precautionary measures were negatively associated with psychological distress. CONCLUSIONS: The study demonstrated that COVID-19 had a significant psychological impact on frontline nurses. Early detection of psychological distress and supportive intervention should be taken according to the associated factors to prevent more serious psychological impact on frontline nurses. RELEVANCE TO CLINICAL PRACTICE: This study highlighted that the frontline nurses were suffering from varying degrees of psychological distress, which needed early screening and supportive intervention for preventing more serious psychological impact on frontline nurses. Beside, more specific measurement should be combined with the GHQ-12 to assess the varying degrees of psychological distress in frontline nurses.


Subject(s)
Adaptation, Psychological , COVID-19/nursing , Nursing Staff, Hospital/psychology , Occupational Stress/psychology , Adult , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nursing Staff, Hospital/statistics & numerical data , Occupational Stress/epidemiology , Pandemics , SARS-CoV-2 , Surveys and Questionnaires
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