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1.
Frontiers in Molecular Biosciences ; 9:871499, 2022.
Article in English | MEDLINE | ID: covidwho-1834465

ABSTRACT

Epidemics caused by coronaviruses (CoVs), namely the severe acute respiratory syndrome (SARS) (2003), Middle East respiratory syndrome (MERS) (2012), and coronavirus disease 2019 (COVID-19) (2019), have triggered a global public health emergency. Drug development against CoVs is inherently arduous. The nucleocapsid (N) protein forms an oligomer and facilitates binding with the viral RNA genome, which is critical in the life cycle of the virus. In the current study, we found a potential allosteric site (Site 1) using PARS, an online allosteric site predictor, in the CoV N-N-terminal RNA-binding domain (NTD) to modulate the N protein conformation. We identified 5-hydroxyindole as the lead via molecular docking to target Site 1. We designed and synthesized four 5-hydroxyindole derivatives, named P4-1 to P4-4, based on the pose of 5-hydroxyindole in the docking model complex. Small-angle X-ray scattering (SAXS) data indicate that two 5-hydroxyindole compounds with higher hydrophobic R-groups mediate the binding between N-NTD and N-C-terminal dimerization domain (CTD) and elicit high-order oligomerization of the whole N protein. Furthermore, the crystal structures suggested that these two compounds act on this novel cavity and create a flat surface with higher hydrophobicity, which may mediate the interaction between N-NTD and N-CTD. Taken together, we discovered an allosteric binding pocket targeting small molecules that induces abnormal aggregation of the CoV N protein. These novel concepts will facilitate protein-protein interaction (PPI)-based drug design against various CoVs.

2.
Frontiers in Immunology ; 13:822885, 2022.
Article in English | MEDLINE | ID: covidwho-1834400

ABSTRACT

Background: Vaccination is considered as most efficient strategy in controlling SARS-CoV-2 pandemic spread. Nevertheless, patients with autoimmune inflammatory rheumatic diseases receiving rituximab (RTX) are at increased risk to fail humoral and cellular responses upon vaccination. The ability to predict vaccination responses is essential to guide adequate safety and optimal protection in these patients. Methods: B- and T- cell data before vaccination were evaluated for characteristics predicting vaccine responses in altogether 15 patients with autoimmune inflammatory rheumatic diseases receiving RTX. Eleven patients with rheumatoid arthritis (RA) on other therapies, 11 kidney transplant recipients (KTR) on regular immunosuppression and 15 healthy controls (HC) served as controls. A multidimensional analysis of B cell subsets via UMAP algorithm and a correlation matrix were performed in order to identify predictive markers of response in patients under RTX therapy. Results: Significant differences regarding absolute B cell counts and specific subset distribution pattern between the groups were identified at baseline. In this context, the majority of B cells from vaccination responders of the RTX group (RTX IgG+) were naive and transitional B cells, whereas vaccination non-responders (RTX IgG-) carried preferentially plasmablasts and double negative (CD27-IgD-) B cells. Moreover, there was a positive correlation between neutralizing antibodies and B cells expressing HLA-DR and CXCR5 as well as an inverse correlation with CD95 expression and CD21low expression by B cells among vaccination responders. Summary: Substantial repopulation of the naive B cell compartment after RTX therapy appeared to be essential for an adequate vaccination response, which seem to require the additional capability of antigen presentation and germinal center formation. Moreover, expression of exhaustion markers represent negative predictors of vaccination responses.

3.
JMIR Public Health and Surveillance ; 27:27, 2022.
Article in English | MEDLINE | ID: covidwho-1834135

ABSTRACT

BACKGROUND: The COVID-19 pandemic creates disruptions on HIV prevention and sexual health services for men who have sex with men (MSM). OBJECTIVE: This study compared HIV testing utilization in three different reference periods (Period 1: before COVID-19 outbreak [November 2019 to January 2020], Period 2: after the outbreak [February to April 2020], and Period 3: after the pandemic was under initial control [May to July 2020]). Factors associated with HIV testing utilization after COVID-19 outbreak (combine Period 2 & 3) were also investigated. METHODS: Participants were MSM aged >=18 years living in Shenzhen, China. Those self-reported as HIV positive were excluded. A total of 595 participants recruited through multiple sources completed a self-administered online survey during August to September 2020. HIV testing uptake after COVID-19 outbreak was the dependent variable, and multivariate logistic regression models were fitted. RESULTS: HIV testing uptake was significantly lower during Period 2 than Period 1 (44.0% versus 61.0%, p<.001). However, HIV testing uptake was not significantly higher in Period 3 than Period 2 (46.6% versus 44.0%, p=.21). The prevalence of HIV testing uptake after COVID-19 outbreak was 55.6%. After adjusting for significant background characteristics, condomless anal intercourse (CAI) with regular male sex partners (AOR: 2.15, 95%CI: 1.29, 3.57) and sexualized drug use (AOR: 2.94, 95%CI: 1.41, 6.06) both before and after COVID-19 outbreak, CAI with regular (AOR: 2.07, 95%CI: 1.06, 4.07) and non-regular male sex partners (AOR: 3.57, 95%CI: 1.43, 8.89) were positively associated with the dependent variable. Regarding HIV prevention service utilization, HIV testing uptake before COVID-19 outbreak (AOR: 10.75, 95%CI: 7.22, 16.02), and use of sexually transmitted infections (STI) testing (AOR: 7.02, 95%CI: 4.10, 12.02), other HIV/STI prevention (AOR: 3.15, 95%CI: 2.16, 4.60) and PrEP (AOR: 3.58, 95%CI: 1.54, 8.34) after COVID-19 outbreak were associated with higher HIV testing uptake. Perceived risk of HIV infection at present was higher than the time before COVID-19 outbreak (AOR: 1.15, 95%CI: 1.01, 1.30), perceived COVID-19 preventive measures taken up by HIV testing service providers to be effective (AOR: 1.52, 95%CI: 1.29, 1.78), and perceived higher behavioral control to take up HIV testing (AOR: 1.18, 95%CI: 1.00, 1.40) were positively associated with HIV testing uptake. Concerns about COVID-19 infection during HIV testing (AOR: 0.78, 95%CI: 0.68, 0.89), avoiding crowed places (AOR: 0.68, 95%CI: 0.48, 0.98) and HIV testing service providers reduced their working hours (AOR: 0.59, 95%CI: 0.48, 0.98) were negatively associated with the dependent variable. CONCLUSIONS: HIV testing utilization among Chinese MSM declined after COVID-19 outbreak and did not increase after the pandemic received initial control. Removing structural barriers to access HIV testing caused by COVID-19, modifying perceptions related to HIV testing, and making use of HIV self-testing might be useful strategies to improve HIV testing among MSM during the pandemic. Clinicaltrial:

4.
Journal of multidisciplinary healthcare ; 14:3597-3606, 2021.
Article in English | MEDLINE | ID: covidwho-1833979

ABSTRACT

BACKGROUND: Vaccination is an effective strategy to mitigate the spread of COVID-19. This study aimed to compare predictors of vaccination intention between healthcare workers (HCWs) and non-healthcare workers (non-HCWs) in China. METHODS: A web-based cross-sectional survey was conducted among HCWs and non-HCWs. Several bivariate analysis techniques, eg, crosstab with Chi-square, independent t-test and single factor ANOVA, were performed to analyze the correlation. After that, a series of multivariate binary regressions were employed to determine predictors of vaccination intention. RESULTS: Intention was closely and significantly related with gender, perceived vaccination knowledge, perceived importance and effectiveness of vaccine to prevent COVID-19. HCWs and non-HCWs were heterogeneous, since vaccination intention, perceived knowledge, and attitudes (eg, importance, severity, risk) toward COVID-19 or vaccine had statistically significant difference between the two groups. With comparison of predictors of vaccination intention, for HCWs, demographic factors were the major predictors of COVID-19 vaccination intention. Female HCWs and HCWs with a Master's or higher degree were more hesitant about vaccination (P = 0.01 and P < 0.001, respectively), while HCWs had greater vaccination intention as their age increased (P = 0.02). For non-HCWs, perceived vaccination knowledge was the major predictor of COVID-19 vaccination intention (P < 0.001). Additionally, perceived importance and effectiveness of vaccine were predictors for both HCWs and non-HCWs. CONCLUSION: Vaccination intention of HCWs was greater than that of non-HCWs in China. Measures should be taken to improve the vaccination rate based on the predictors of vaccination intention identified in this study. For HCWs, especially those with a high level of education or who were females, the safety and effectiveness of vaccines in use may reinforce their vaccination intention. For non-HCWs, popularization of general medical knowledge, including of vaccine-preventable diseases, may increase their vaccination intention.

5.
Blood Purification ; : 1-9, 2022.
Article in English | MEDLINE | ID: covidwho-1832797

ABSTRACT

INTRODUCTION: The efficacy of renal-replacement treatment (RRT) remains to be validated in COVID-19. In this retrospective cohort study, we aimed to assess the efficacy of early initiation of RRT in intensive care unit (ICU) adults with severe COVID-19. METHODS: Fifty-eight adult patients in ICU with critically ill or severe COVID-19 with a tendency of critical illness were recruited from February 9, 2020, to March 30, 2020. Early RRT were determined by the ICU medical team based on boom in cytokines levels, increased organs injury/failure, and rapid aggravation of condition. All participants were followed up from the first day of ICU admission to March 30, 2020. The primary outcome was all-cause mortality in ICU. RESULTS: The mean age of the cohort was 68.4 +/- 14.6 years, with 81.0% having at least one comorbidity before hospitalization. Twenty patients (34.5%) initiated early RRT after 24.1 +/- 10.4 days from the onset and 6.4 +/- 3.6 days from ICU admission. Thirty-four of 58 participants (58.6%) died during ICU follow-up. Univariate and multivariate Cox proportional-hazards model showed that early RRT was associated with a lower risk of all-cause mortality in ICU with an adjusted HR of 0.280 (95% CI: 0.106-0.738, p = 0.010). Sudden unexpected death (SUD) was remarkably reduced in the early RRT group, compared with the control group (0.2 vs. 2.9 per 100 person-day, p = 0.02). CONCLUSION: Early RRT can reduce the all-cause in-hospital mortality, especially SUD in patients with severe COVID-19, but not improve multi-organ impairment or increase the risk of AKI. Early initiation of RRT merits an optional strategy in critically ill patients with COVID-19 (ChiCTR2000030773).

6.
Computational Intelligence & Neuroscience ; 2022:8548534, 2022.
Article in English | MEDLINE | ID: covidwho-1832708

ABSTRACT

Covid-19 pandemic has ushered in a new school and academic year for students in a distance learning regime. This new daily routine was unprecedented and undoubtedly unusual, especially for the younger ones. At this point and at these ages, the risk of cyber fraud is even greater. The transition from the physical environment to the Internet took place quickly without the appropriate time to control potential risks and the proper information and training of teachers and students. Some common threats that need to be addressed to protect learners and their data when using e-learning methods are malicious remote access, malware, phishing, cyber fraud, etc. Considering the above situation, this work presents an innovative cyber risk recommendation system for digital education management platforms. The system in question is a distributed two-stage algorithm based on game theory and machine learning, which is trained by the constant change in the choice of recommendations by users to maximize security. We examine the algorithm's ability to simulate a user system in which everyone independently selects a user recommendation, assesses the environment and the implications of this choice, and then concludes whether it will continue to have that recommendation fixed. The methodology with which we have represented the digital e-learning system has been done with an approach that directly corresponds with their general view as a cyber-physical-social system. We consider the digital school as an environment that brings limitations, leading us to a pretty demanding personalization problem. Users coexist in this environment, in which everyone acts voluntarily but influences and is influenced by the surrounding environment. Our results lead us to conclude that this algorithm responds in a fully effective, flexible, and efficient way to the needs of protection and risk assessment of e-learning education systems.

7.
Science immunology ; : eabo3425, 2022.
Article in English | MEDLINE | ID: covidwho-1832328

ABSTRACT

Neutralizing antibodies that recognize the SARS-CoV-2 spike glycoprotein are the principal host defense against viral invasion. Variants of SARS-CoV-2 bear mutations that allow escape from neutralization by many antibodies, especially those belonging to classes widely distributed in the human population. Identifying antibodies that neutralize these variants of concern and determining their prevalence are important goals for understanding immune protection. To determine the Delta- and Omicron BA.1-variant specificity of B cell repertoires established by an initial Wuhan strain infection, we measured neutralization potencies of 73 antibodies from an unbiased survey of the early memory B cell response. Antibodies recognizing each of three, previously defined, epitopic regions on the spike receptor-binding domain (RBD) varied in neutralization potency and variant-escape resistance. The ACE2 binding surface ("RBD-2") harbored the binding sites of the neutralizing antibodies with highest potency but with the greatest sensitivity to viral escape;two other epitopic regions on the RBD ("RBD-1 and "RBD-3") bound antibodies of more modest potency but greater breadth. The structures of several Fab:spike complexes that neutralized all five variants of concern tested, including one Fab each from the RBD-1, -2 and -3 clusters, illustrated the determinants of broad neutralization and showed that B cell repertoires can have specificities that avoid immune escape driven by widely distributed ("public") antibodies. The structure of the RBD-2-binding, broad neutralizer shows why it retains neutralizing activity for Omicron BA.1, unlike most others in the same public class. Our results correlate with real-world data on vaccine efficacy, which indicate mitigation of disease caused by Omicron BA.1.

8.
Construction Research Congress 2022: Health and Safety, Workforce, and Education, CRC 2022 ; 4-D:192-203, 2022.
Article in English | Scopus | ID: covidwho-1830306

ABSTRACT

Many college students had to switch to remote learning during the COVID-19 pandemic. Analyzing their workload and productivity after this major change is helpful to improve remote learning and teaching under these circumstances;however, there is limited quantitative evidence. Therefore, this study aims to quantitatively explore the impact of remote learning on college students' workload and productivity in the US during the pandemic. Within this issue, this research also asseses the impact of assistantships (i.e., students get paid for research, teaching, or other work) on students' workload and productivity, which has not been examined in remote learning during the pandemic. An online survey was developed and distributed, with 48 valid responses received. Descriptive analysis showed that total workload and overall productivity in remote learning were decreased, and students with assistantships had a higher total workload and higher productivity than those of students without assistantships. T-Test indicated that the overall productivity in remote learning was reduced, with the most significant decrease in lecture attendance. Specifically, no significant difference in total workload between face-To-face and remote learning was detected, while significant differences in total workload and overall productivity between students with and without assistantships were identified. Further exploration of participants' comments suggested the folloiwng major reasons for decreased productivity, including inadequate learning location, distraction, lack of self-motivation, and technology and connectivity issues. This study can help students and instructors better arrange study contents to improve remote learning productivity and further reduce the negative impact of the pandemic on education activities. © 2022 ASCE.

9.
Endocrine Practice ; 08:08, 2022.
Article in English | MEDLINE | ID: covidwho-1828470

ABSTRACT

OBJECTIVE: Continuous glucose monitoring (CGM) has demonstrated benefits in managing inpatient diabetes. We initiated this single-arm pilot feasibility study during the COVID-19 pandemic in 11 patients with diabetes to determine the feasibility and accuracy of real-time CGM in patients who underwent cardiac surgery and whose care was being transitioned from the intensive care unit. METHODS: A Clarke error grid analysis was used to compare CGM and point-of-care measurements. The mean absolute relative difference (MARD) of the paired measurements was calculated to assess the accuracy of CGM for glucose measurements during the first 24 hours on CGM, the remaining time on CGM, and for different chronic kidney disease (CKD) strata. RESULTS: Overall MARD between point-of-care and CGM measurements was 14.80%. MARD for patients without CKD IV and V with an estimated glomerular filtration rate (eGFR) of >=20 mL/min/1.73 m2 was 12.13%. Overall, 97% of the CGM values were within the no-risk zone of the Clarke error grid analysis. For the first 24 hours, a sensitivity analysis of the overall MARD for all patients and those with an eGFR of >=20 mL/min/1.73 m2 was 15.42% +/- 14.44% and 12.80% +/- 7.85%, respectively. Beyond the first 24 hours, overall MARD for all patients and those with an eGFR of >=20 mL/min/1.73 m2 was 14.54% +/- 13.21% and 11.86% +/- 7.64%, respectively. CONCLUSION: CGM has shown great promise in optimizing inpatient diabetes management in the noncritical care setting and after the transition of care from the intensive care unit with high clinical reliability and accuracy. More studies are needed to further assess CGM in patients with advanced CKD.

10.
Science China-Chemistry ; 65(3):497-513, 2022.
Article in English | MEDLINE | ID: covidwho-1826867

ABSTRACT

Cost-effective, rapid, and accurate virus detection technologies play key roles in reducing viral transmission. Prompt and accurate virus detection enables timely treatment and effective quarantine of virus carrier, and therefore effectively reduces the possibility of large-scale spread. However, conventional virus detection techniques often suffer from slow response, high cost or sophisticated procedures. Recently, two-dimensional (2D) materials have been used as promising sensing platforms for the high-performance detection of a variety of chemical and biological substances. The unique properties of 2D materials, such as large specific area, active surface interaction with biomolecules and facile surface functionalization, provide advantages in developing novel virus detection technologies with fast response and high sensitivity. Furthermore, 2D materials possess versatile and tunable electronic, electrochemical and optical properties, making them ideal platforms to demonstrate conceptual sensing techniques and explore complex sensing mechanisms in next-generation biosensors. In this review, we first briefly summarize the virus detection techniques with an emphasis on the current efforts in fighting again COVID-19. Then, we introduce the preparation methods and properties of 2D materials utilized in biosensors, including graphene, transition metal dichalcogenides (TMDs) and other 2D materials. Furthermore, we discuss the working principles of various virus detection technologies based on emerging 2D materials, such as field-effect transistor-based virus detection, electrochemical virus detection, optical virus detection and other virus detection techniques. Then, we elaborate on the essential works in 2D material-based high-performance virus detection. Finally, our perspective on the challenges and future research direction in this field is discussed.

11.
Advances in Biology Online ; : e2101327, 2022.
Article in English | MEDLINE | ID: covidwho-1825809

ABSTRACT

Sars-Cov-2 may trigger molecular and functional alterations of cardiomyocytes (CMs) of the heart due to the presence of receptor angiotensin-converting enzyme 2 (ACE2) of the host cells. While the endocytic itinerary of the virus via cleavage of the spike protein of Sars-Cov-2 is well understood, the role of the remaining part of the spike protein subunit and ACE2 complex is still elusive. Herein, the possible effects of this complex are investigated by using synthetic spike proteins of Sars-Cov-2, human-induced pluripotent stem cells (hiPSC), and a culture device made of an arrayed monolayer of cross-linked nanofibers. hiPSCs are first differentiated into CMs that form cardiac tissue-like constructs with regular beating and expression of both ACE2 and gap junction protein Connexin 43. When incubated with the spike proteins, the hiPSC-CMs undergo a rhythmic fluctuation with overstretched sarcomere structures and dispersed gap junction proteins. When incubated with the spike proteins and supplementary angiotensin II, the damage of the spike protein on hiPSC-CMs is enhanced due to downregulated ACE2, chromatin margination, altered Connexin 43 expression, sarcomere disruption, and beating break. This discovery may imply latent effects of the spike proteins on the heart.

12.
Chinese Journal of Disease Control and Prevention ; 26(3):343-346 and 356, 2022.
Article in Chinese | EMBASE | ID: covidwho-1822640

ABSTRACT

Objective To analyze the utilization of HIV testing services and related influencing factors among men who have sex with men (MSM) on COVID-19. Methods From September to November 2020, an electronic questionnaire survey was conducted on MSM in the AIDS Vct of Longhua CDC and the Third People's Hospital of Shenzhen, The rank sum test was used to compare the changes in the utilization of HIV testing services in different situations of various factors, and ordinal multinomial logistic regression model was established to analyze the influencing factors of the utilization of HIV testing services. Results A total of 30.4% MSM were reported reduction in the use of HIV testing services. Logistic regression analysis showed that highly panic of COVID-19 reducing the frequency of anal sex (OR=0.056, 95% CI: 0.021-0.150, P < 0.001), being advised not going to testing agency (OR=0.538, 95% CI: 0.297-0.975, P=0.041), and being infected of COVID-19 (OR=21.979, 95% CI: 4.369-110.559, P < 0.001) had higher chance of reduction in the used of HIV testing services. Conclusion The HIV testing service utilization is decreased in MSM during COVID-19. It is necessary to pay more attention to this convenience when formulating and implementing epidemic prevention and control measures.

13.
Viruses ; 14(5), 2022.
Article in English | EMBASE | ID: covidwho-1822446

ABSTRACT

Coronaviruses (CoVs) consist of a large group of RNA viruses causing various diseases in humans and in lots of animals. Human coronavirus (HCoV) OC43, the prototype of beta-coronavirus discovered in the 1960s, has been circulating in humans for long time, and infection with other emerging strains of beta-coronavirus (SARS-CoV, SARS-CoV-2, and MERS-CoV) can lead to severe illness and death. In this study, we found that montelukast, a leukotriene receptor antagonist, potently inhibited the infection of HCoV-OC43 in distinct cells in a dose-and time-dependent manner. Additionally, the results showed that montelukast induced release of HCoV-OC43 genomic RNA by disrupting the integrity of the viral lipid membrane, and irreversibly inhibited viral infection. Considering the similarity among HCoV-OC43, MERS-CoV, and SARS-CoV-2, it suggests that montelukast may be a potential candidate for the treatment of human beta-coronavirus infection.

14.
Iscience ; 25(4):24, 2022.
Article in English | Web of Science | ID: covidwho-1821313

ABSTRACT

Mesenchymal stem cells (MSCs) have shown some efficacy in the COVID-19 treatment. We proposed that exogenous supplementation of ACE2 via MSCs (ACE2-MSCs) might have better therapeutic effects. We constructed SARS-CoV-2 spike glycoprotein stably transfected AT-II and Beas-2B cells and used SARS-CoV-2 spike pseudovirus to infect hACE2 transgenic mice. The results showed that spike glycoprotein transfection triggers the release of apoptotic bodies and formation of membrane pores in pyroptosis. Inflammatory factors and pyroptosis factors were highly upregulated by spike glycoprotein transfection. SARS-CoV-2 spike pseudovirus worsened lung injury and increased the main factors of cytokine storm and pyroptosis. Compared to using MSCs or rh-ACE2 alone, the administration of ACE2-MSCs could significantly reduce these factors better and alleviate lung injury in vivo and in vitro, which might be because of the increased activities of secretory ACE2. Our proposal is a promising therapeutic solution for preclinical or clinical research.

15.
Zhonghua kou qiang yi xue za zhi = Zhonghua kouqiang yixue zazhi = Chinese journal of stomatology ; 57(5):455-461, 2022.
Article in Chinese | EuropePMC | ID: covidwho-1818247

ABSTRACT

Today, there is greater awareness on the association between oral diseases and respiration diseases after the outbreak of COVID-19. However, confusion regarding the oral health management and medical risk prevention for patients with chronic airway diseases has been remained among dental clinicians. Therefore, the dental experts of the Fifth General Dentistry Special Committee, Chinese Stomatological Association, combined with the experts of respiratory and critical care medicine, undertook the formation of consensus on the oral health management of patients with chronic airway diseases in order to help dental clinicians to evaluate medical risks and make better treatment decision in clinical practice. In the present consensus report, the relationship of oral diseases and chronic airway diseases, the oral health management and the treatment recommendations of patients with chronic airway diseases are provided.

16.
Am J Public Health ; : e1-e10, 2022.
Article in English | PubMed | ID: covidwho-1817598

ABSTRACT

We analyzed COVID-19 influences on the design, implementation, and validity of assessing the quality of primary health care using unannounced standardized patients (USPs) in China. Because of the pandemic, we crowdsourced our funding, removed tuberculosis from the USP case roster, adjusted common cold and asthma cases, used hybrid online-offline training for USPs, shared USPs across provinces, and strengthened ethical considerations. With those changes, we were able to conduct fieldwork despite frequent COVID-19 interruptions. Furthermore, the USP assessment tool maintained high validity in the quality checklist (criteria), USP role fidelity, checklist completion, and physician detection of USPs. Our experiences suggest that the pandemic created not only barriers but also opportunities to innovate ways to build a resilient data collection system. To build data system reliance, we recommend harnessing the power of technology for a hybrid model of remote and in-person work, learning from the sharing economy to pool strengths and optimize resources, and dedicating individual and group leadership to problem-solving and results. (Am J Public Health. Published online ahead of print April 28, 2022:e1-e10. https://doi.org/10.2105/AJPH.2022.306779).

17.
Journal of Bio-X Research ; 5(1):7-13, 2022.
Article in English | EMBASE | ID: covidwho-1816310

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has been an unmitigated disaster for society and the economy worldwide. However, much remains unknown about the pathogenesis of, treatment methods for, and preventive measures against COVID-19. Single-cell sequencing is a novel sequencing technology whose use has recently become prevalent in various life-science fields. This high-resolution technology is being used to analyze the COVID-19 pandemic at a single-cell level. In this review, we summarize the application of single-cell sequencing technology to the field of COVID-19-related research, including the biology of severe acute respiratory syndrome coronavirus 2, clinical concerns associated with COVID-19, neutralizing antibody screening, and vaccine development. We also address challenges to, and improvements in, existing single-cell research related to COVID-19.

18.
Nature ; 2022.
Article in English | PubMed | ID: covidwho-1815563

ABSTRACT

Severe COVID-19 is characterized by persistent lung inflammation, inflammatory cytokine production, viral RNA, and sustained interferon (IFN) response all of which are recapitulated and required for pathology in the SARS-CoV-2 infected MISTRG6-hACE2 humanized mouse model of COVID-19 with a human immune system(1-20). Blocking either viral replication with Remdesivir(21-23) or the downstream IFN stimulated cascade with anti-IFNAR2 in vivo in the chronic stages of disease attenuated the overactive immune-inflammatory response, especially inflammatory macrophages. Here, we show SARS-CoV-2 infection and replication in lung-resident human macrophages is a critical driver of disease. In response to infection mediated by CD16 and ACE2 receptors, human macrophages activate inflammasomes, release IL-1 and IL-18 and undergo pyroptosis thereby contributing to the hyperinflammatory state of the lungs. Inflammasome activation and its accompanying inflammatory response is necessary for lung inflammation, as inhibition of the NLRP3 inflammasome pathway reverses chronic lung pathology. Remarkably, this same blockade of inflammasome activation leads to the release of infectious virus by the infected macrophages. Thus, inflammasomes oppose host infection by SARS-CoV-2 by production of inflammatory cytokines and suicide by pyroptosis to prevent a productive viral cycle.

19.
Signal Transduction and Targeted Therapy ; 7(1):139, 2022.
Article in English | MEDLINE | ID: covidwho-1815514

ABSTRACT

The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection- and vaccination-induced antibodies, highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies (bnAbs). Here, we developed a panel of bnAbs against Omicron and other variants of concern (VOCs) elicited by vaccination of adenovirus-vectored COVID-19 vaccine (Ad5-nCoV). We also investigated the human longitudinal antibody responses following vaccination and demonstrated how the bnAbs evolved over time. A monoclonal antibody (mAb), named ZWD12, exhibited potent and broad neutralization against SARS-CoV-2 variants Alpha, Beta, Gamma, Kappa, Delta, and Omicron by blocking the spike protein binding to the angiotensin-converting enzyme 2 (ACE2) and provided complete protection in the challenged prophylactic and therapeutic K18-hACE2 transgenic mouse model. We defined the ZWD12 epitope by determining its structure in complex with the spike (S) protein via cryo-electron microscopy. This study affords the potential to develop broadly therapeutic mAb drugs and suggests that the RBD epitope bound by ZWD12 is a rational target for the design of a broad spectrum of vaccines.

20.
Acupuncture & Electro-Therapeutics Research ; 47(2):195-201, 2022.
Article in English | Web of Science | ID: covidwho-1810380

ABSTRACT

Objective : Summarize the experience of transporting patients in the pre-hospital emergency center of our hospital from January 20, 2020 to May 2020 during the outbreak of novel coronavirus pneumonia in Zhuzhou City, and formulate a series of transport strategics. Methods: During the novel coronavirus pneumonia epidemic, review the relevant experience of the medical staff and drivers in the pre-hospital emergency center of Zhuzhou Central Hospital to improve the procedures for the transfer of patients during the epidemic. Results: As of the time when patients with novel coronavirus pneumonia in our city are cleared, none of the medical staff in the pre-hospital emergency center of Zhuzhou Central Hospital has been infected, and the city's patients in need of pre-hospital emergency treatment have been treated in an orderly manner. In conjunction with our hospital's epidemic prevention and control expert team, combined with the actual situation in the region, we jointly formulated a series of transfer procedures for Zhuzhou Central Hospital to comply with the region during the epidemic. Conclusion: During the novel coronavirus pneumonia epidemic, all patients received by the pre-hospital emergency center of our hospital were transferred in a timely and safe manner, and a series of transfer procedures were developed.

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