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1.
Ocean & Coastal Management ; 231:106414, 2023.
Article Dans Anglais | ScienceDirect | ID: covidwho-2105671

Résumé

Driven by globalization, the COVID-19 outbreak has severely impacted global transport and logistics systems. To better cope with this globalization crisis, the Belt and Road Initiative (BRI)—based on the concept of cooperation—is more important than ever in the post-pandemic era. Taking the BRI as the background, we design an intermodal hub-and-spoke network to provide reference for governments along BRI routes to improve their cross-border transportation system and promote economic recovery. In the context of the BRI, local governments at different nodes have incentives to subsidize hub construction and/or rail transportation to boost economic development. We consider co-opetition behavior among different levels of government caused by subsidies in this intermodal hub location problem, which we call the intermodal hub location problem based on government subsidies. We establish a two-stage mixed-integer programming model. In the first stage, local governments provide subsidies, then the central government decides the number and location of hubs. In the second stage, freight carriers choose the optimal route to transport the goods. To solve the model, we design an optimization method combining a population-based algorithm using contest theory. The results show that rail subsidies are positively correlated with construction subsidies but are not necessarily related to the choice of hubs. Compared with monomodal transportation, intermodal transportation can reduce costs more effectively when there are not too many hubs and the cost of different modes of transportation varies greatly. The influences of local government competition and hub construction investment on network design and government subsidies are further examined.

2.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-517609

Résumé

Bats are reservoir hosts for many zoonotic viruses. Despite this, relatively little is known about the diversity and abundance of viruses within bats at the level of individual animals, and hence the frequency of virus co-infection and inter-species transmission. Using an unbiased meta-transcriptomics approach we characterised the mammalian associated viruses present in 149 individual bats sampled from Yunnan province, China. This revealed a high frequency of virus co-infection and species spillover among the animals studied, with 12 viruses shared among different bat species, which in turn facilitates virus recombination and reassortment. Of note, we identified five viral species that are likely to be pathogenic to humans or livestock, including a novel recombinant SARS-like coronavirus that is closely related to both SARS-CoV-2 and SARS-CoV, with only five amino acid differences between its receptor-binding domain sequence and that of the earliest sequences of SARS-CoV-2. Functional analysis predicts that this recombinant coronavirus can utilize the human ACE2 receptor such that it is likely to be of high zoonotic risk. Our study highlights the common occurrence of inter-species transmission and co-infection of bat viruses, as well as their implications for virus emergence.

3.
Phytomedicine ; : 154514, 2022.
Article Dans Anglais | ScienceDirect | ID: covidwho-2086622

Résumé

Background A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). Purpose To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. Study Design and methods This study was a prospective, open‐label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. Results A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, P < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%;Day7: 65.3% vs. 55.2%, P<0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, P < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, P = 0.012), coughing (12.2% vs. 14.8%, P = 0.046), and expectoration (6.0% vs. 8.0%, P = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. Conclusion RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

4.
Frontiers in psychology ; 13, 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-2084318

Résumé

To help optimize online learning platforms for in-service teachers’ professional development, this study aims to develop an instrument to assess the quality of this type of platforms on teacher satisfaction. After reliability and validity tests and expert empowerment, the 27-item instrument was formed. Based on the information systems (IS) success model, this instrument was designed to measure teacher perceptions of the quality of online learning platforms from three dimensions, namely, content quality, technical quality, and service quality. Moreover, the developed instrument was used to analyze the effects of the National Teacher Training Platform amid the COVID-19 outbreak in China. The findings revealed that the improvement of the platform’s style, tool function, operating efficiency, and teaching methods could enhance teachers’ experience of online training.

5.
Sustainability ; 14(19):12837, 2022.
Article Dans Anglais | ProQuest Central | ID: covidwho-2066469

Résumé

This manuscript proposes an integrated system for treating hospital solid waste (H.S.W.) consisting of an incineration and frictional sterilization system capable of operating during normal and emergency situations. We analyzed the benefits of integrating different hospital solid waste (H.S.W.) treatment systems with the existing stand-alone incineration system, with a particular emphasis on the thermal friction sterilization integration system. The objective was to define the economic advantages and benefits in terms of resources recovery of using the thermal frictional sterilization–incineration integrated system during the hospital’s normal and emergency/pandemic operating conditions. We modeled three modeling scenarios based on normal and emergency operating conditions. The results show that the H.S.W. was composed of 74% general H.S.W. Existing incineration systems would be the most expensive process because the sanitary transportation cost represented approximately 96% of the H.S.W. costs. The hospital would realize 40–61% savings relative to the existing method if the integrated incineration–frictional systems were implemented to treat 50–70% of H.S.W.;the savings were better than in other scenarios. Proposed scenario 3 had a much better resources recovery factor than scenarios 1 and 2. This modeling study showed that a thermal frictional sterilization–incineration system could work well even under emergency conditions if the H.S.W. in-house sorting/transportation/storage process is modified to cater to other H.S.W. treatment/sterilization systems.

6.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22281532

Résumé

ImportanceActive monitoring of health outcomes following COVID-19 vaccination offers early detection of rare outcomes that may not be identified in pre-licensure trials. ObjectiveTo conduct near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years. DesignWe conducted rapid cycle analysis of 20 pre-specified health outcomes, 13 of which underwent sequential testing and 7 of which were monitored descriptively within a cohort of vaccinated individuals. We tested for increased risk of each health outcome following vaccination compared to a historical baseline, while adjusting for repeated looks at the data as well as claims processing delay. SettingThis is a population-based study in three large commercial claims databases conducted under the U.S. FDA public health surveillance mandate. ParticipantsThe study included over 3 million enrollees aged 5-17 years with BNT162b2 COVID-19 vaccination through mid-2022 in three commercial claims databases. We required continuous enrollment in a medical health insurance plan from the start of an outcome-specific clean window to the COVID-19 vaccination. ExposureExposure was defined as receipt of a BNT162b2 COVID-19 vaccine dose. The primary analysis assessed primary series doses together (Dose 1 + Dose 2), and dose-specific secondary analyses were conducted. Follow up time was censored for death, disenrollment, end of risk window, end of study period, or a subsequent vaccine dose. Main Outcome(s) and Measure(s)We monitored 20 pre-specified health outcomes. We performed descriptive monitoring for all outcomes and sequential testing for 13 outcomes. ResultsAmong 13 health outcomes evaluated by sequential testing, 12 did not meet the threshold for a statistical signal in any of the three databases. In our primary analysis, myocarditis/pericarditis signaled following primary series vaccination with BNT162b2 in ages 12-17 years across all three databases. Conclusions and RelevanceConsistent with published literature, our near-real time monitoring identified a signal for only myocarditis/pericarditis following BNT162b2 COVID-19 vaccination in children aged 12-17 years. This method is intended for early detection of safety signals. Our results are reassuring of the safety of the vaccine, and the potential benefits of vaccination outweigh the risks. Key PointsO_ST_ABSQuestionC_ST_ABSDid active monitoring detect potentially elevated risk of health outcomes following BNT162b2 COVID-19 vaccination in the U.S. pediatric population aged 5-17 years? FindingsTwelve of 13 health outcomes did not meet the safety signal threshold following BNT162b2 COVID-19 vaccination in three large commercial claims databases using near real-time monitoring. Myocarditis/pericarditis met the statistical threshold for a signal following primary series vaccination in ages 12-17 years. MeaningResults from near-real time monitoring of health outcomes following BNT162b2 COVID-19 vaccination provide additional reassuring evidence of vaccine safety in the pediatric population. The myocarditis/pericarditis signal is consistent with current evidence and is being further evaluated.

7.
Carbohydrate Polymers ; 299:120173, 2023.
Article Dans Anglais | ScienceDirect | ID: covidwho-2060487

Résumé

COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-β-d-Gal-(1 → 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-l-Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibite the infection with an EC50 of 37.52 μg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19.

8.
Frontiers in cardiovascular medicine ; 9, 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-2057652

Résumé

Background Electrocardiography (ECG) plays a very important role in various cardiovascular diseases and elevated D-dimer in serum associated with thrombosis. In patients with coronavirus disease 2019 (COVID-19), immense pieces of evidence showed that ECG abnormalities or elevated D-dimer in serum occurred frequently. However, it remains unclear whether ECG abnormalities combined with elevated D-dimer could be a new risk predictor in patients with COVID-19. Methods and results This retrospective cohort study enrolled 416 patients with COVID-19 at Wuhan Tongji Hospital from 1 February to 20 March 2020. ECG manifestations, D-dimer levels, and in-hospital deaths were recorded for all patients. Logistic regression analysis was performed to examine the association between ECG manifestations and in-hospital mortality in patients with elevated D-dimer levels. In patients hospitalized for COVID-19, ST-T abnormalities (34.3%) were the most frequent ECG manifestations, whereas sinus tachycardia (ST) (13.3%) and atrial arrhythmias with rapid rhythms (8.5%) were the two most common cardiac arrhythmias. Compared to severely ill patients with COVID-19, ST-T abnormalities, ST and atrial arrhythmias (p<0.001) with rapid rhythms, D-dimer levels, and in-hospital deaths were significantly more frequent in critically ill patients with COVID-19. Moreover, elevated D-dimer levels were observed in all the patients who died. In the subgroup of 303 patients with elevated serum D-dimer levels, the patient's age, the incidence of ST-T abnormalities, ST, atrial fibrillation (AF), and atrial premature beat were significantly higher than those in the non-elevated D-dimer subgroup. Multivariate logistic regression analysis further revealed that ST and AF were risk factors for in-hospital mortality in COVID-19 patients with elevated D-dimer levels. Conclusions ECG abnormalities and elevated D-dimer levels were associated with a higher risk of critical illness and death in patients hospitalized for COVID-19. ECG abnormalities, including ST and AF, combined with elevated D-dimer levels, can be used to predict death in COVID-19.

9.
Carbohydrate polymers. ; 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-2045547

Résumé

COVID-19 caused by SARS-CoV-2 has spread around the world at an unprecedented rate. A more homogeneous oligo-porphyran with mean molecular weight of 2.1 kD, named OP145, was separated from Pyropia yezoensis. NMR analysis showed OP145 was mainly composed of →3)-β-d-Gal-(1 → 4)-α-l-Gal (6S) repeating units with few replacement of 3,6-anhydride, and the molar ratio was 1:0.85:0.11. MALDI-TOF MS revealed OP145 contained mainly tetrasulfate-oligogalactan with Dp range from 4 to 10 and with no more than two 3,6-anhydro-α-l-Gal replacement. The inhibitory activity of OP145 against SARS-CoV-2 was investigated in vitro and in silico. OP145 could bind to Spike glycoprotein (S-protein) through SPR result, and pseudovirus tests confirmed that OP145 could inhibited the infection with an EC50 of 37.52 μg/mL. Molecular docking simulated the interaction between the main component of OP145 and S-protein. All the results indicated that OP145 had the potency to treat and prevent COVID-19. Graphical Unlabelled Image

10.
Acta Medicinae Universitatis Scientiae et Technologiae Huazhong ; 49(6):716-720, 2020.
Article Dans Chinois | GIM | ID: covidwho-2040013

Résumé

Objective: To explore the features of bedside lung ultrasound images of severe and critical COVID-19.

11.
Chinese Journal of Nosocomiology ; 32(12):1880-1884, 2022.
Article Dans Anglais, Chinois | CAB Abstracts | ID: covidwho-2034518

Résumé

OBJECTIVE: To explore a new method for detecting respiratory viruses by extracting residual virus on mask, and verify its reliability and sensitivity. METHODS: The novel coronavirus analogs-s La Sota strains of chicken Newcastle disease virus and H120 strains of infectious bronchitis virus with different diluted concentrations were sprayed onto surgical masks and N95 masks through a respiratory simulator, and they were left standing at room temperature for 2 hours and 12 hours, respectively. The cDNA and its amplification cycle(CT) values of the nucleoocapsid protein(N) of chicken Newcastle disease virus and the nucleoprotein(NP) genes of infectious bronchitis virus were detected by ordinary polymerase chain reaction(PCR) and quantitative real-time PCR(qRT-PCR). The minimum detectable virus concentration and viral content in masks under different retention times were compared. RESULTS: The gene bands of the Newcastle disease virus La Sota strains and the infectious bronchitis virus H120 strains were detected on the masks stored for different times, and the total RNA of the virus had good amplification curves in the range of 10 pg-10 ng. The mean CT values of N gene and NP gene of the residual virus on the general medical surgical mask and N95 masks placed for 2 h were 22.547+or-0.342,23.698+or-0.501 and 22.855+or-0.308,24.036+or-0.338, respectively. However, only part of them could be detected after 12 h. respectively, and there was no significant difference in CT values between the two masks during the same period of time(P2 h=0.452, P12 h=0.355). The minimum detectable concentration of virus in the masks was 1:800, and the number of residual viruses on the mask that can be detected was 6.75x10~3. CONCLUSION: The method of screening coronavirus by detecting virus residues on masks within 2 hours was feasible and suitable for medical surgical masks and N95 masks, which can be used for preliminary screening of respiratory viruses.

12.
Chinese Journal of Nosocomiology ; 32(8):1271-1275, 2022.
Article Dans Anglais, Chinois | CAB Abstracts | ID: covidwho-2011252

Résumé

OBJECTIVE: COVID-19 continues to spread globally, which poses a significant threat to global public health security. Recently, the emergence of new variant strains of SARS-CoV-2 complicates the containment of COVID-19 due to its rapid transmission, high infectivity, high viral load, atypical symptoms and high number of severe cases. In order to further understand the transmission route, pathogenesis and pathological changes of COVID-19, and accelerate the research and development of antiviral drugs and vaccines, animal models of COVID-19 have played an important role in this process. The status of research on different animal models of COVID-19 was reviewed, the characteristics were compared among the models so as to provide theoretical basis for selecting appropriate animal models of COVID-19.

13.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-507787

Résumé

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA. 5. Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such convergent evolution and its impact on humoral immunity remain unclear. Here, we demonstrate that these convergent mutations can cause striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2 binding capability. BQ.1.1.10, BA.4.6.3, XBB, and CH. 1.1 are the most antibody-evasive strain tested, even exceeding SARS-CoV-1 level. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies (mAbs) isolated from BA.2 and BA.5 breakthrough-infection convalescents. Importantly, due to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection caused significant reductions in the epitope diversity of NAbs and increased proportion of non-neutralizing mAbs, which in turn concentrated humoral immune pressure and promoted convergent evolution. Moreover, we showed that the convergent RBD mutations could be accurately inferred by integrated deep mutational scanning (DMS) profiles, and the evolution trends of BA.2.75/BA.5 subvariants could be well-simulated through constructed convergent pseudovirus mutants. Together, our results suggest current herd immunity and BA.5 vaccine boosters may not provide good protection against infection. Broad-spectrum SARS-CoV-2 vaccines and NAb drugs development should be highly prioritized, and the constructed mutants could help to examine their effectiveness in advance.

14.
Frontiers in psychology ; 13, 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-1999680

Résumé

This study intended to explore the current status of psychological problems of preschool teachers in Southwest China 1 year after the COVID-19 pandemic and to assess the association between mental health education and psychological problems and symptoms of psychopathology. A total of 614 preschool teachers from Southwest China were enrolled to complete the questionnaires of the Chinese Symptom Checklist (SCL-90). Notably, 60% of the respondents reported psychological distress with GSI T-scores ≥ 63, especially the high score was reported on obsessive-compulsive disorder, interpersonal sensitivity, and phobic anxiety. Although less than half of the respondents have received mental health education last year, the teachers who received the mental health education reported lower GSI T-scores(β = −1.303, 95% CI: −2.208, −0.397). The results demonstrated the significance of constructing the education of promoting mental health of preschool teachers, and enlightening government or managers of kindergartens to relieve the psychological problems of preschool teachers through mental health education, especially for those with the pressure of overtime. It is recommended that local governments or kindergartens should organize more mental health education for kindergarten teachers to improve their mental health as well as their teaching professionalism.

15.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22278967

Résumé

Serum antibodies IgM and IgG are elevated during COVID-19 to defend against viral attack. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their two-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense, and that high titers of IgM might not be favorable to COVID-19 recovery.

16.
Preprint Dans Anglais | medRxiv | ID: ppmedrxiv-22278425

Résumé

The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines. Here, we report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain. These were tested in conjunction with three different adjuvants: a TLR2 agonist R4-Pam2Cys, an NKT cell agonist glycolipid -Galactosylceramide, or MF59(R) squalene oil-in-water adjuvant. Each formulation drove strong neutralising antibody (nAb) responses and provided durable and highly protective immunity against lower and upper airway infection in mouse models of COVID-19. We have also developed an RBD-human IgG1 Fc vaccine with an RBD sequence of the highly immuno-evasive beta variant (N501Y, E484K, K417N). This beta variant RBD vaccine, combined with MF59(R) adjuvant, induced strong protection in mice against the beta strain as well as the ancestral strain. Furthermore, when used as a third dose booster vaccine following priming with whole spike vaccine, anti-sera from beta-RBD-Fc immunised mice increased titres of nAb against other variants including alpha, delta, delta+, gamma, lambda, mu, and omicron BA.1 and BA.2. These results demonstrated that an RBD-Fc protein subunit/MF59(R) adjuvanted vaccine can induce high levels of broad nAbs, including when used as a booster following prior immunisation of mice with whole ancestral-strain Spike vaccines. This vaccine platform offers a potential approach to augment some of the currently approved vaccines in the face of emerging variants of concern, and it has now entered a phase I clinical trial.

17.
Clinical eHealth ; 2022.
Article Dans Anglais | ScienceDirect | ID: covidwho-1936135

Résumé

Background The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic acute infectious disease, especially with the features of possible asymptomatic carriers and high contagiousness. Currently, it is difficult to quickly identify asymptomatic cases or COVID-19 patients with pneumonia due to limited access to reverse transcription-polymerase chain reaction (RT-PCR) nucleic acid tests and CT scans. Goal This study aimed to develop a scientific and rigorous clinical diagnostic tool for the rapid prediction of COVID-19 cases based on a COVID-19 clinical case database in China, and to assist doctors to efficiently and precisely diagnose asymptomatic COVID-19 patients and cases who had a false-negative RT-PCR test result. Methods With online consent, and the approval of the ethics committee of Zhongshan Hospital Fudan University (NCT04275947, B2020-032R) to ensure that patient privacy is protected, clinical information has been uploaded in real-time through the New Coronavirus Intelligent Auto-diagnostic Assistant Application of cloud plus terminal (nCapp) by doctors from different cities (Wuhan, Shanghai, Harbin, Dalian, Wuxi, Qingdao, Rizhao, and Bengbu) during the COVID-19 outbreak in China. By quality control and data anonymization on the platform, a total of 3,249 cases from COVID-19 high-risk groups were collected. The effects of different diagnostic factors were ranked based on the results from a single factor analysis, with 0.05 as the significance level for factor inclusion and 0.1 as the significance level for factor exclusion. Independent variables were selected by the step-forward multivariate logistic regression analysis to obtain the probability model. Findings We applied the statistical method of a multivariate regression model to the training dataset (1,624 cases) and developed a prediction model for COVID-19 with 9 clinical indicators that are accessible. The area under the receiver operating characteristic (ROC) curve (AUC) for the model was 0.88 (95% CI: 0.86, 0.89) in the training dataset and 0.84 (95% CI: 0.82, 0.86) in the validation dataset (1,625 cases). Discussion With the assistance of nCapp, a mobile-based diagnostic tool developed from a large database that we collected from COVID-19 high-risk groups in China, frontline doctors can rapidly identify asymptomatic patients and avoid misdiagnoses of cases with false-negative RT-PCR results.

18.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-499114

Résumé

SARS-CoV-2 Omicron sublineages have escaped most RBD-targeting therapeutic neutralizing antibodies (NAbs), which proves the previous NAb drug screening strategies deficient against the fast-evolving SARS-CoV-2. Better broad NAb drug candidate selection methods are needed. Here, we describe a rational approach for identifying RBD-targeting broad SARS-CoV-2 NAb cocktails. Based on high-throughput epitope determination, we propose that broad NAb drugs should target non-immunodominant RBD epitopes to avoid herd immunity-directed escape mutations. Also, their interacting antigen residues should focus on sarbecovirus conserved sites and associate with critical viral functions, making the antibody-escaping mutations less likely to appear. Following the criteria, a featured non-competing antibody cocktail, SA55+SA58, is identified from a large collection of broad sarbecovirus NAbs isolated from SARS convalescents. SA55+SA58 potently neutralizes ACE2-utilizing sarbecoviruses, including circulating Omicron variants, and could serve as broad SARS-CoV-2 prophylactics to offer long-term protection. Our screening strategy can also be applied to identify broad-spectrum NAb drugs against other fast-evolving viruses, such as influenza viruses.

19.
Frontiers in immunology ; 13, 2022.
Article Dans Anglais | EuropePMC | ID: covidwho-1918699

Résumé

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is one of the fastest-evolving viral diseases that has instigated a worldwide pandemic. Severe inflammatory syndrome and venous thrombosis are commonly noted in COVID-19 patients with severe and critical illness, contributing to the poor prognosis. Interleukin (IL)-6, a major complex inflammatory cytokine, is an independent factor in predicting the severity of COVID-19 disease in patients. IL-6 and tumor necrosis factor (TNF)-α participate in COVID-19-induced cytokine storm, causing endothelial cell damage and upregulation of plasminogen activator inhibitor-1 (PAI-1) levels. In addition, IL-6 and PAI-1 form a vicious cycle of inflammation and thrombosis, which may contribute to the poor prognosis of patients with severe COVID-19. Targeted inhibition of IL-6 and PAI-1 signal transduction appears to improve treatment outcomes in severely and critically ill COVID-19 patients suffering from cytokine storms and venous thrombosis. Motivated by studies highlighting the relationship between inflammatory cytokines and thrombosis in viral immunology, we provide an overview of the immunothrombosis and immunoinflammation vicious loop between IL-6 and PAI-1. Our goal is that understanding this ferocious circle will benefit critically ill patients with COVID-19 worldwide.

20.
Preprint Dans Anglais | bioRxiv | ID: ppbiorxiv-500332

Résumé

Recently emerged SARS-CoV-2 Omicron subvariant, BA.2.75, displayed a local growth advantage over BA.2.38, BA.2.76 and BA.5 in India. The underlying mechanism of BA.2.75s enhanced infectivity, especially compared to BA.5, remains unclear. Here, we show that BA.2.75 exhibits substantially higher ACE2-binding affinity than BA.5. Also, BA.2.75 spike shows decreased thermostability and increased "up" RBD conformation in acidic conditions, suggesting enhanced low-pH-endosomal cell-entry pathway utilization. BA.2.75 is less humoral immune evasive than BA.4/BA.5 in BA.1/BA.2 breakthrough-infection convalescents; however, BA.2.75 shows heavier neutralization evasion in Delta breakthrough-infection convalescents. Importantly, plasma from BA.5 breakthrough infection exhibit significantly weaker neutralization against BA.2.75 than BA.5, mainly due to BA.2.75s distinct RBD and NTD-targeting antibody escaping pattern from BA.4/BA.5. Additionally, Evusheld and Bebtelovimab remain effective against BA.2.75, and Sotrovimab recovered RBD-binding affinity. Together, our results suggest BA.2.75 may prevail after the global BA.4/BA.5 wave, and its increased receptor-binding capability could allow further incorporation of immune-evasive mutations.

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