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1.
China Journal of Leprosy and Skin Diseases ; 38(8):499-502, 2022.
Article in Chinese | Scopus | ID: covidwho-1954980

ABSTRACT

Background: Eight pm on April 13, 2022,a10:1 mixed test tube was found to be positive in the COVID-19 nucleic acid test site set up outside the hospital. In order to identify the infected case and control the spread of COVID-19 rapidly, we conducted this emergency investigation. Methods: According to the National COVID-19 Control and Prevention Protocol (8th edition), Guideline on Emergency Response to COVID-19 Case Found in Hospital in Shandong Province, and the Emergency Response Plan for COVID-19 in our hospital, information reporting, hospitalblockading, potential COVID- 19 cases tracing, close contact screening, environmental sampling and disinfecting, COVID-19 nucleic acid testing and risk assessment were carried out by our team. Results: A female COVID-19 case aged 50 years was identified. She is aodd-jobber who works in the labour market near the hospital. The virus strain was sequenced as Omicron BA.2. A total of 65 close contacts was controlled in a hotel. The COVID-19 nucleic acid test results for all the staff of hospital, environmental samples were negative. The risk of COVID-19 spread was controlled and the hospital restarted of clinical activities as normal at 8 am on April 14 after blockaded for 12 hours. Inthe following 7 days, the staff of the hospital were tested for COVID-19 nucleic acid twice a day, and the results were negative. Then the testing frequency changed to once a day. Conclusion: Formulating detailed and feasible COVID-19 emergency response plans based on the requirements of the public documents and the actual conditions of the hospital, is useful to improve the efficiency of emergency response to COVID-19 cases and save time for control of COVID-19 spread and restart the clinical activities of hospital. © 2022 Shandong Yinbao Technology Co. Ltd. All Rights Reserved.

2.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(2): 172-178, 2022 Apr 13.
Article in Chinese | MEDLINE | ID: covidwho-1893445

ABSTRACT

OBJECTIVE: To investigate the health-seeking behaviors of imported malaria cases after returning to China, and to investigate the factors affecting the time to initial diagnosis, so as to provide the scientific evidence for early identification of imported malaria cases and prevention of severe cases development and secondary transmission. METHODS: The individual demographic features, and the disease onset and the time to initial diagnosis of imported malaria cases in Jiangsu Province in 2019 were captured from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The characteristics of health-seeking behaviors and epidemiological features of imported malaria cases were descriptively analyzed, and the factors affecting the time to initial diagnosis of imported malaria cases after returning to China were identified using multivariate logistic regression analysis. RESULTS: A total of 244 imported malaria cases were reported in Jiangsu Province in 2019, and the time to initial diagnosis of the cases were 1-12 days, with mean time of (1.53 ± 1.65) days, with median time of one day. The highest number of malaria cases seeking healthcare services were found on the day of developing primary symptoms (76 cases, 31.1%), followed by on the second day (68 cases, 27.9%), on the third day (46 cases, 18.9%), and 54 cases (22.1%) received initial diagnosis 3 days following presence of primary symptoms, including 3 cases with initial diagnosis at more than one week. High proportions of imported malaria cases with a delay in the time to initial diagnosis were seen in migrant workers who returned to China in January (14 cases, 5.7%) and December (13 cases, 5.3%) and those aged between 41 and 50 years (32 cases, 13.1%). Multivariate logistic regression analysis showed relative short time to initial diagnosis among imported malaria cases returning to China on March [odds ratio (OR) = 0.16, P = 0.03, 95% confidence interval (CI): (0.03, 0.85)] and those with a history of overseas malaria parasite infections [OR = 0.36, P = 0.001, 95% CI: (0.19, 0.67)]. CONCLUSIONS: Timely health-seeking behaviors should be improved among imported malaria cases in Jiangsu Province, patients with a history of overseas malaria infections require faster health-seeking activities.


Subject(s)
Malaria , Transients and Migrants , Adult , China/epidemiology , Humans , Malaria/diagnosis , Malaria/epidemiology , Malaria/parasitology , Middle Aged
3.
Forests ; 13(5), 2022.
Article in English | Scopus | ID: covidwho-1875526

ABSTRACT

Spatial analysis is essential to understand the spreading of the COVID-19 pandemic. Due to numerous factors of multi-disciplines involved, the current pandemic is yet fully known. Hence, the current study aimed to expand the knowledge on the pandemic by exploring the roles of forests and CO2 emission in the COVID-19 case-fatality rate (CFR) at the global level. Data were captured on the forest coverage rate and CO2 emission per capita from 237 countries. Meanwhile, extra demographic and socioeconomic variables were also included to adjust for potential confounding. Associations between the forest coverage rate and CO2 emission per capita and the COVID-19 CFR were assessed using spatial regression analysis, and the results were further stratified by country income levels. Although no distinct association between the COVID-19 CFR and forest coverage rate or CO2 emission per capita was found worldwide, we found that a 10% increase in forest coverage rates was associated with a 2.37‰ (95%CI: 3.12, 1.62) decrease in COVID-19 CFRs in low-income countries;and a 10% increase in CO2 emission per capita was associated with a 0.94‰ (95%CI: 1.46, 0.42) decrease in COVID-19 CFRs in low-middle-income countries. Since a strong correlation was observed between the CO2 emission per capita and GDP per capita (r = 0.89), we replaced CO2 emission with GDP and obtained similar results. Our findings suggest a higher forest coverage may be a protective factor in low-income countries, which may be related to their low urbanization levels and high forest accessibilities. On the other hand, CO2 can be a surrogate of GDP, which may be a critical factor likely to decrease the COVID-19 CFR in lower-middle-income countries. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

4.
ACM Transactions on Spatial Algorithms and Systems ; 8(2), 2022.
Article in English | Scopus | ID: covidwho-1874705

ABSTRACT

Existing Bluetooth-based private contact tracing (PCT) systems can privately detect whether people have come into direct contact with patients with COVID-19. However, we find that the existing systems lack functionality and flexibility, which may hurt the success of contact tracing. Specifically, they cannot detect indirect contact (e.g., people may be exposed to COVID-19 by using a contaminated sheet at a restaurant without making direct contact with the infected individual);they also cannot flexibly change the rules of "risky contact,"such as the duration of exposure or the distance (both spatially and temporally) from a patient with COVID-19 that is considered to result in a risk of exposure, which may vary with the environmental situation.In this article, we propose an efficient and secure contact tracing system that enables us to trace both direct contact and indirect contact. To address the above problems, we need to utilize users' trajectory data for PCT, which we call trajectory-based PCT. We formalize this problem as a spatiotemporal private set intersection that satisfies both the security and efficiency requirements. By analyzing different approaches such as homomorphic encryption, which could be extended to solve this problem, we identify the trusted execution environment (TEE) as a candidate method to achieve our requirements. The major challenge is how to design algorithms for a spatiotemporal private set intersection under the limited secure memory of the TEE. To this end, we design a TEE-based system with flexible trajectory data encoding algorithms. Our experiments on real-world data show that the proposed system can process hundreds of queries on tens of millions of records of trajectory data within a few seconds. © 2021 Copyright held by the owner/author(s). Publication rights licensed to ACM.

5.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-337444

ABSTRACT

Background SARS-CoV-2 Omicron variant BA.1 first emerged on the Chinese mainland in January 2022 in Tianjin and caused a large wave of infections. During mass PCR testing, a total of 430 cases infected with Omicron were recorded between January 8 and February 7, 2022, with no new infections detected for the following 16 days. Most patients had been vaccinated with SARSCoV-2 inactivated vaccines. The disease profile associated with BA.1 infection, especially after vaccination with inactivated vaccines, is unclear. Whether BA.1 breakthrough infection after receiving inactivated vaccine could create a strong enough humoral immunity barrier against Omicron is not yet investigated. Methods We collected the clinical information and vaccination history of the 430 COVID-19 patients infected with Omicron BA.1. Re-positive cases and inflammation markers were monitored during the patient’s convalescence phase. Ordered multiclass logistic regression model was used to identify risk factors for COVID-19 disease severity. Authentic virus neutralization assays against SARS-CoV-2 wildtype, Beta and Omicron BA.1 were conducted to examine the plasma neutralizing titers induced after post-vaccination Omicron BA.1 infection, and were compared to a group of uninfected healthy individuals who were selected to have a matched vaccination profile. Findings Among the 430 patients, 316 (73.5%) were adults with a median age of 47 years, and 114 (26.5%) were under-age with a median age of 10 years. Female and male patients account for 55.6% and 44.4%, respectively. Most of the patients presented with mild (47.7%) to moderate diseases (50.2%), with only 2 severe cases (0.5%) and 7 (1.6%) asymptomatic infections. No death was recorded. 341 (79.3%) of the 430 patients received inactivated vaccines (54.3% BBIBP-CorV vs. 45.5% CoronaVac), 49 (11.4%) received adenovirus-vectored vaccines (Ad5-nCoV), 2 (0.5%) received recombinant protein subunit vaccines (ZF2001), and 38 (8.8%) received no vaccination. No vaccination is associated with a substantially higher ICU admission rate among Omicron BA.1 infected patients (2.0% for vaccinated patients vs. 23.7% for unvaccinated patients, P<0.001). Compared with adults, child patients presented with less severe illness (82.5% mild cases for children vs. 35.1% for adults, P<0.001), no ICU admission, fewer comorbidities (3.5% vs. 53.2%, P<0.001), and less chance of turning re-positive on nucleic acid tests (12.3% vs. 22.5%, P=0.019). For adult patients, compared with no prior vaccination, receiving 3 doses of inactivated vaccine was associated with significantly lower risk of severe disease (OR 0.227 [0.065-0.787], P=0.020), less ICU admission (OR 0.023 [0.002-0.214], P=0.001), lower re-positive rate on PCR (OR 0.240 [0.098-0.587], P=0.002), and shorter duration of hospitalization and recovery (OR 0.233 [0.091-0.596], P=0.002). At the beginning of the convalescence phase, patients who had received 3 doses of inactivated vaccine had substantially lower systemic immune-inflammation index (SII) and C-reactive protein than unvaccinated patients, while CD4+/CD8+ ratio, activated Treg cells and Th1/Th2 ratio were higher compared to their 2-dose counterparts, suggesting that receipt of 3 doses of inactivated vaccine could step up inflammation resolution after infection. Plasma neutralization titers against Omicron, Beta, and wildtype significantly increased after breakthrough infection with Omicron. Moderate symptoms were associated with higher plasma neutralization titers than mild symptoms. However, vaccination profiles prior to infection, whether 2 doses versus 3 doses or types of vaccines, had no significant effect on post-infection neutralization titer. Among recipients of 3 doses of CoronaVac, infection with Omicron BA.1 largely increased neutralization titers against Omicron BA.1 (8.7x), Beta (4.5x), and wildtype (2.2x), compared with uninfected healthy individuals who have a matched vaccination profile. Interpretation Receipt of 3-dose inactivated vaccines can substantially reduce the disease severity of Omicr n BA.1 infection, with most vaccinated patients presenting with mild to moderate illness. Child patients present with less severe disease than adult patients after infection. Omicron BA.1 convalescents who had received inactivated vaccines showed significantly increased plasma neutralizing antibody titers against Omicron BA.1, Beta, and wildtype SARS-CoV-2 compared with vaccinated healthy individuals.

7.
Embase; 2022.
Preprint in English | EMBASE | ID: ppcovidwho-334805

ABSTRACT

Omicron sub-lineage BA.2 has rapidly surged globally, accounting for over 60% of recent SARS-CoV-2 infections. Newly acquired RBD mutations and high transmission advantage over BA.1 urge the investigation of BA.2's immune evasion capability. Here, we show that BA.2 causes strong neutralization resistance, comparable to BA.1, in vaccinated individuals' plasma. However, BA.2 displays more severe antibody evasion in BA.1 convalescents, and most prominently, in vaccinated SARS convalescents' plasma, suggesting a substantial antigenicity difference between BA.2 and BA.1. To specify, we determined the escaping mutation profiles1,2 of 714 SARS-CoV-2 RBD neutralizing antibodies, including 241 broad sarbecovirus neutralizing antibodies isolated from SARS convalescents, and measured their neutralization efficacy against BA.1, BA.1.1, BA.2. Importantly, BA.2 specifically induces large-scale escape of BA.1/BA.1.1effective broad sarbecovirus neutralizing antibodies via novel mutations T376A, D405N, and R408S. These sites were highly conserved across sarbecoviruses, suggesting that Omicron BA.2 arose from immune pressure selection instead of zoonotic spillover. Moreover, BA.2 reduces the efficacy of S309 (Sotrovimab)3,4 and broad sarbecovirus neutralizing antibodies targeting the similar epitope region, including BD55-5840. Structural comparisons of BD55-5840 in complexes with BA.1 and BA.2 spike suggest that BA.2 could hinder antibody binding through S371F-induced N343-glycan displacement. Intriguingly, the absence of G446S mutation in BA.2 enabled a proportion of 440-449 linear epitope targeting antibodies to retain neutralizing efficacy, including COV2-2130 (Cilgavimab)5. Together, we showed that BA.2 exhibits distinct antigenicity compared to BA.1 and provided a comprehensive profile of SARS-CoV-2 antibody escaping mutations. Our study offers critical insights into the humoral immune evading mechanism of current and future variants.

8.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-334688

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. It is known that the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with the human angiotensin-converting enzyme 2 (ACE2) receptor, initiating the entry of SARS-CoV-2. Since its emergence, a number of SARS-CoV-2 variants have been reported, and the variants that show high infectivity are classified as the variants of concern according to the US CDC. In this study, we performed both all-atom steered molecular dynamics (SMD) simulations and microscale thermophoresis (MST) experiments to characterize the binding interactions between ACE2 and RBD of all current variants of concern (Alpha, Beta, Gamma, and Delta) and two variants of interest (Epsilon and Kappa). We report that the RBD of the Alpha (N501Y) variant requires the highest amount of force initially to be detached from ACE2 due to the N501Y mutation in addition to the role of N90-glycan, followed by Beta/Gamma (K417N/T, E484K, and N501Y) or Delta (L452R and T478K) variant. Among all variants investigated in this work, the RBD of the Epsilon (L452R) variant is relatively easily detached from ACE2. Our results combined SMD simulations and MST experiments indicate what makes each variant more contagious in terms of RBD and ACE2 interactions. This study could help develop new drugs to inhibit SARS-CoV-2 entry effectively. Abstract figure:

9.
Annals of Surgical Oncology ; 29(SUPPL 1):277-277, 2022.
Article in English | Web of Science | ID: covidwho-1812927
10.
Environmental Science-Nano ; : 11, 2022.
Article in English | Web of Science | ID: covidwho-1778647

ABSTRACT

Hydrogen peroxide (H2O2) solution and its aerosols are common disinfectants, especially for urgent reuse of personal protective equipment during the COVID-19 pandemic. Highly sensitive and selective evaluation of the H2O2 concentration is key to customizing the sufficient disinfection process and avoiding disinfection overuse. Amperometric electrochemical detection is an effective means but poses challenges originated from the precarious state of H2O2. Here, an atomic Co-N-x-C site anchored neuronal-like carbon modified amperometric sensor (denoted as the CoSA-N/C@rGO sensor) is designed, which exhibits a broad detection range (from 250 nM to 50 mM), superior sensitivity (743.3 mu A mM(-1) cm(-2), the best among carbon-based amperometric sensors), strong selectivity (no response to interferents), powerful reliability (only 2.86% decay for one week) and fast response (just 5 s) for residual H2O2 detection. We validated the accuracy and practicability of the CoSA-N/C@rGO sensor in the actual H2O2 disinfection process of personal protective equipment. Further characterization verifies that the electrocatalytic activity and selective reduction of H2O2 is determined by the atomically dispersed Co-N-x-C sites and the high oxygen content of CoSA-N/C@rGO, where the response time and reliability of H2O2 detection is determined by the neuronal-like structure with high nitrogen content. Our findings pave the way for developing a sensor with superior sensitivity, selectivity and stability, rendering promising applications such as medical care and environmental treatment.

11.
12th International Conference on Applications and Technologies in Information Security, ATIS 2021 ; 1554 CCIS:21-36, 2022.
Article in English | Scopus | ID: covidwho-1772872

ABSTRACT

During the COVID-19 pandemic, artificial intelligence (AI) plays a major role to detect and distinguish between several lungs diseases and diagnose COVID-19 cases accurately. This article studies the feasibility of the federated learning (FL) approach for identifying and distinguishing COVID-19 X-ray images. We trained and tested FL components by using the data sets that collect images of three different lungs conditions, COVID-19, common lungs and viral pneumonia. We develop and evaluate FL model horizontally with same parameters and compare the performance with the classic CNN model and the transfer learning approaches. We found that FL can quickly train artificial intelligence models on different devices during a pandemic, avoiding privacy leaks that may be caused by such a high resolution personal and private X-ray data. © 2022, Springer Nature Singapore Pte Ltd.

12.
Biophysical Journal ; 121(3):42-42, 2022.
Article in English | Web of Science | ID: covidwho-1755835
13.
2021 International Conference on Applied Mathematics, Modeling and Computer Simulation, AMMCS 2021 ; 20:530-538, 2022.
Article in English | Scopus | ID: covidwho-1753331

ABSTRACT

A susceptible-infected-susceptible (SIS) model with a nonlinear infection rate, a forecast model based on autoregressive integrated moving average (ARIMA), and a forecast model based on long short-term memory (LSTM) artificial neural networks were developed using the COVID-19 epidemic data from four countries (China, Italy, the United Kingdom, Germany, France, and Poland) to simulate and forecast the epidemic trends in these countries. The models were compared in terms of forecast errors, and the LSTM model was found to forecast virus transmission very well. © 2022 The authors and IOS Press.

14.
Open Forum Infectious Diseases ; 8(SUPPL 1):S362-S363, 2021.
Article in English | EMBASE | ID: covidwho-1746474

ABSTRACT

Background. Molnupiravir (MOV) is an orally administered ribonucleoside prodrug of β-D-N4-hydroxycytidine (NHC) against SARS-CoV-2. Here we present viral dynamics analysis of Phase 2 clinical virology data to inform MOV Phase 3 study design and development strategy. Methods. An Immune-Viral Dynamics Model (IVDM) was developed with mechanisms of SARS-CoV-2 infection, replication, and induced immunity, which together describe the dynamics of viral load (VL) during disease progression. Longitudinal virology data from ferret studies (Cox, et al. Nat. Microbiol 2021:6-11) were used to inform IVDM, which was further translated to human by adjusting parameter values to capture clinical data from MOVe-IN/MOVe-OUT studies. Different placements of drug effects (on viral infectivity vs. productivity) and representations of immune response were explored to identify the best ones to describe data. A simplified 95% drug effect was implemented to represent a highly effective dose of MOV. Results. IVDM showed data were best described when MOV acts on viral infectivity, consistent with the error catastrophe mechanism of action. A cascade of innate and adaptive immune response and a basal level activation enabled durable immunity and continued viral decay after treatment end. IVDM reasonably describes VL and viral titer data from animals and humans. Influence of MOV start time was explored using simulations. Consistent with the ferret studies, simulations showed when treatment is started within the first week post infection, MOV reduces viral growth, resulting in a lower and shortened duration of detectable VL. When started later (e.g. >7 days since symptom onset), the magnitude of drug effect is substantially diminished in a typical patient with an effective immune response which reduces VL prior to treatment start. Further work is needed to model response in patients with longer term infection, where MOV drug effects may have more persistent utility. Conclusion. A COVID-19 IVDM developed using multiscale MOV virology data supports drug action on viral infectivity and importance of interplay of treatment and immune response and can describe infection time course and drug effect. IVDM provided mechanistic interpretations for VL drug effect in clinical studies.

15.
Open Forum Infectious Diseases ; 8(SUPPL 1):S373, 2021.
Article in English | EMBASE | ID: covidwho-1746454

ABSTRACT

Background. Molnupiravir (MOV, MK-4482, EIDD-2801) is an orally administered prodrug of N-hydroxycytidine (NHC, EIDD-1931), a nucleoside with broad antiviral activity against a range of RNA viruses. MOV acts by driving viral error catastrophe following its incorporation by the viral RdRp into the viral genome. Given its mechanism of action, MOV activity should not be affected by substitutions in the spike protein present in SARS-CoV-2 variants of concern which impact efficacy of therapeutic neutralizing antibodies and vaccine induced immunity. We characterized MOV activity against variants by assessing antiviral activity in vitro and virologic response from the Phase 2/3 clinical trials (MOVe-In, MOVe-Out) for treatment of COVID-19. Methods. MOV activity against several SARS-CoV-2 variants, was evaluated in an in vitro infection assay. Antiviral potency of NHC (IC50) was determined in Vero E6 cells infected with virus at MOI ~0.1 by monitoring CPE. Longitudinal SARSCoV-2 RNA viral load measures in participants enrolled in MOVe-In and MOVe-Out were analyzed based on SARS-CoV-2 genotype. Sequences of SARS-CoV-2 from study participants were amplified from nasal swabs by PCR and NGS was performed on samples with viral genome RNA of >22,000 copies/ml amplified by primers covering full length genome with Ion Torrent sequencing to identify clades represented in trial participants. SARS-CoV-2 clades were assigned using clade.nextstrain.org. Results. In vitro, NHC was equally effective against SARS-CoV-2 variants B.1.1.7 (20I), B.1351 (20H), and P1 (20J), compared with the original WA1 (19B) isolate. In clinical trials, no discernable difference was observed in magnitude of viral response measured by change from baseline in RNA titer over time across all clades represented including 20A through 20E and 20G to 20I. No participants at the time of the study presented with 20F, 20J, or 21A. Conclusion. Distribution of clades in participants in MOVe-In and MOVe-Out was representative of those circulating globally at the time of collection (Oct 2020 -Jan 2021). Both in vitro and clinical data suggest that spike protein substitutions do not impact antiviral activity of MOV and suggest its potential use for the treatment of SARS-CoV-2 variants.

16.
Jisuanji Jicheng Zhizao Xitong/Computer Integrated Manufacturing Systems, CIMS ; 28(1):242-257, 2022.
Article in Chinese | Scopus | ID: covidwho-1698657

ABSTRACT

COVID-19 has an impact on the global supply chain, which is mainly manifested in the simultaneous interruption of production capacity and demand. To explore the impact of government subsidy strategies on recovery in the context of supply chain interruption, the low-demand products during the epidemic were used as the research object, and the government's choice of subsidies for production capacity and demand interruption as a recovery strategy. The cumulative profit of supply chain members was taken as the recovery index, and system dynamics was used to construct the "manufacturer-distribution center" secondary supply chain. The changes in cumulative profits for different subsidy options were simulate under partial and complete interruption scenarios. The simulation results showed that the choice of government subsidy strategies under different interruption scenarios had different effects on the supply chain recovery effect. In the scenario of partial demand interruption, government subsidies for manufacturers with interrupted production capacity would make the supply chain recovery better. In the scenario of complete demand interruption, government subsidies for distribution centers with interrupted demand would make the supply chain recovery better. © 2022, Editorial Department of CIMS. All right reserved.

17.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-327041

ABSTRACT

The SARS-CoV-2 Omicron with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures of the Spike (S) from Omicron reveals amino acid substitutions forging new interactions that stably maintain an “active” conformation for receptor recognition. The relatively more compact domain organization confers improved stability and enhances attachment but compromises the efficiency of viral fusion step. Alterations in local conformation, charge and hydrophobic microenvironments underpin the modulation of the epitopes such that they are not recognized by most NTD- and RBD-antibodies, facilitating viral immune escape. Apart from already existing mutations, we have identified three new immune escape sites: 1) Q493R, 2) G446S and 3) S371L/S373P/S375F that confers greater resistance to five of the six classes of RBD-antibodies. Structure of the Omicron S bound with human ACE2, together with analysis of sequence conservation in ACE2 binding region of 25 sarbecovirus members as well as heatmaps of the immunogenic sites and their corresponding mutational frequencies sheds light on conserved and structurally restrained regions that can be used for the development of broad-spectrum vaccines and therapeutics.

18.
Embase;
Preprint in English | EMBASE | ID: ppcovidwho-326764

ABSTRACT

The SARS-CoV-2 B.1.1.529 variant (Omicron) contains 15 mutations on the receptor-binding domain (RBD). How Omicron would evade RBD neutralizing antibodies (NAbs) requires immediate investigation. Here, we used high-throughput yeast display screening1,2 to determine the RBD escaping mutation profiles for 247 human anti-RBD NAbs and showed that the NAbs could be unsupervised clustered into six epitope groups (A-F), which is highly concordant with knowledge-based structural classifications3-5. Strikingly, various single mutations of Omicron could impair NAbs of different epitope groups. Specifically, NAbs in Group A-D, whose epitope overlap with ACE2-binding motif, are largely escaped by K417N, G446S, E484A, and Q493R. Group E (S309 site)6 and F (CR3022 site)7 NAbs, which often exhibit broad sarbecovirus neutralizing activity, are less affected by Omicron, but still, a subset of NAbs are escaped by G339D, N440K, and S371L. Furthermore, Omicron pseudovirus neutralization showed that single mutation tolerating NAbs could also be escaped due to multiple synergetic mutations on their epitopes. In total, over 85% of the tested NAbs are escaped by Omicron. Regarding NAb drugs, the neutralization potency of LYCoV016/LY-CoV555, REGN10933/REGN10987, AZD1061/AZD8895, and BRII-196 were greatly reduced by Omicron, while VIR-7831 and DXP-604 still function at reduced efficacy. Together, data suggest Omicron would cause significant humoral immune evasion, while NAbs targeting the sarbecovirus conserved region remain most effective. Our results offer instructions for developing NAb drugs and vaccines against Omicron and future variants.

19.
European Journal of Public Health ; 31:10-10, 2021.
Article in English | Web of Science | ID: covidwho-1609832
20.
BMJ Open ; 11(12), 2021.
Article in English | ProQuest Central | ID: covidwho-1594463

ABSTRACT

ObjectivesThe COVID-19 pandemic has changed the way people are accessing healthcare. The aim of this study was to examine the impact of COVID-19 on emergency department (ED) attendance for frequent attenders and to explore potential reasons for changes in attendance.DesignThis convergent parallel mixed methods study comprised two parts.SettingAn interrupted time-series analysis evaluated changes in ED presentation rates;interviews investigated reasons for changes for frequent ED users in a culturally and linguistically diverse setting.ParticipantsA total of 4868 patients were included in the time series. A subgroup of 200 patients were interviewed, mean age 66 years (range 23–99).ResultsInterrupted time-series analysis from 4868 eligible participants showed an instantaneous decrease in weekly ED presentations by 36% (p<0.001), with reduction between 45% and 67% across emergency triage categories. 32% did not know they could leave home to seek care with differences seen in English versus non-English speakers (p<0.001). 35% reported postponing medical care. There was a high fear about the health system becoming overloaded (mean 4.2 (±2) on 6-point scale). Four key themes emerged influencing health-seeking behaviour: fear and/or avoidance of hospital care;use of telehealth for remote assessment;no fear or avoidance of hospital care;not leaving the house for any reason.ConclusionsThis study demonstrated reduced ED use by a vulnerable population of previously frequent attenders. COVID-19 has resulted in some fear and avoidance of hospitals, but has also offered new opportunity for alternative care through telehealth.

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