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1.
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.

2.
PubMed; 2021.
Preprint in English | PubMed | ID: ppcovidwho-330088

ABSTRACT

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect additional cell types expressing low levels of ACE2. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness and immune evasion. They may guide intervention strategies to control the pandemic.

3.
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.

4.
21st COTA International Conference of Transportation Professionals: Advanced Transportation, Enhanced Connection, CICTP 2021 ; : 691-702, 2021.
Article in English | Scopus | ID: covidwho-1628028

ABSTRACT

In 2020, the outbreak of COVID-19 pneumonia has had a great impact on China's economic and social life. The construction and transportation industries have been greatly impacted and suffered from its high mobility. This paper studies the big data of migration between Xi'an and Chengdu from January 1, 2020 to March 15, 2020 and divides the epidemic situation into four stages according to the introduction of the elastic coefficient according to the development of the epidemic situation. In each stage, the elastic coefficient of index change is introduced in combination with the decreasing impact of epidemic prevention and control measures on transportation. Finally, a modified moving average method is formed, which is compared with the ordinary moving average method. The results show that the modified moving average method combined with Hadoop big data platform can improve the accuracy and efficiency of the intercity transportation flow prediction under the epidemic situation. © 2021 CICTP 2021: Advanced Transportation, Enhanced Connection - Proceedings of the 21st COTA International Conference of Transportation Professionals. All rights reserved.

5.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293483

ABSTRACT

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report here structure, function and antigenicity of its full-length spike (S) trimer in comparison with those of other variants, including Gamma, Kappa, and previously characterized Alpha and Beta. Delta S can fuse membranes more efficiently at low levels of cellular receptor ACE2 and its pseudotyped viruses infect target cells substantially faster than all other variants tested, possibly accounting for its heightened transmissibility. Mutations of each variant rearrange the antigenic surface of the N-terminal domain of the S protein in a unique way, but only cause local changes in the receptor-binding domain, consistent with greater resistance particular to neutralizing antibodies. These results advance our molecular understanding of distinct properties of these viruses and may guide intervention strategies.

6.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-293189

ABSTRACT

The Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has outcompeted previously prevalent variants and become a dominant strain worldwide. We report here structure, function and antigenicity of its full-length spike (S) trimer in comparison with those of other variants, including Gamma, Kappa, and previously characterized Alpha and Beta. Delta S can fuse membranes more efficiently at low levels of cellular receptor ACE2 and its pseudotyped viruses infect target cells substantially faster than all other variants tested, possibly accounting for its heightened transmissibility. Mutations of each variant rearrange the antigenic surface of the N-terminal domain of the S protein in a unique way, but only cause local changes in the receptor-binding domain, consistent with greater resistance particular to neutralizing antibodies. These results advance our molecular understanding of distinct properties of these viruses and may guide intervention strategies.

7.
PUBMED; 2021.
Preprint in English | PUBMED | ID: ppcovidwho-292872

ABSTRACT

Several fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the dominant circulating strains that continue to fuel the COVID-19 pandemic despite intensive vaccination efforts throughout the world. We report here cryo-EM structures of the full-length spike (S) trimers of the B.1.1.7 and B.1.351 variants, as well as their biochemical and antigenic properties. Mutations in the B.1.1.7 protein increase the accessibility of its receptor binding domain and also the binding affinity for receptor angiotensin-converting enzyme 2 (ACE2). The enhanced receptor engagement can account for the increased transmissibility and risk of mortality as the variant may begin to infect efficiently infect additional cell types expressing low levels of ACE2. The B.1.351 variant has evolved to reshape antigenic surfaces of the major neutralizing sites on the S protein, rendering complete resistance to some potent neutralizing antibodies. These findings provide structural details on how the wide spread of SARS-CoV-2 enables rapid evolution to enhance viral fitness and immune evasion. They may guide intervention strategies to control the pandemic.

8.
Arthroplast Today ; 11: 113-121, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1347495

ABSTRACT

BACKGROUND: Total joint arthroplasty (TJA) practices have been dramatically impacted by the COVID-19 pandemic. To date, no study has assessed trends in patient perceptions regarding the safety of elective TJA. METHODS: A single-institution, prospective cohort study was conducted between May 11th and August 10th, 2020. All patients who underwent elective hip and knee arthroplasty were contacted via telephone or emailed surveys. Two-hundred and thirty-five consecutive patients were screened, and 158 agreed to participate. The average age was 65.9 ± 11.5 years, with 51.0% of patients being female. The percentage of participants who underwent total knee, total hip, and unicompartmental knee arthroplasty was 41.4%, 37.6%, and 21.0%, respectively. Survey components assessed demographic data, level of concern and specific concerns about the pandemic, and factors increasing patient comfort in proceeding with surgery. RESULTS: Older age (P = .029) and female sex (P = .004) independently predicted higher concern on multivariate analysis. Race (P = .343), surgical site (knee vs hip, P = .58), and procedure type (primary vs revision, P = .26) were not significantly related to degree of concern. Most participants (71.5%) disagreed that the pandemic would negatively affect the outcome of their surgery. Patient concern mirrored statewide COVID-19 cases and deaths, rather than local municipal trends. The most cited reassuring factors were preoperative COVID-19 testing, personal protective equipment usage by hospital staff, and surgeon support. CONCLUSIONS: Patient concern regarding the safety of elective TJA may follow broader policy-level events rather than local trends. Surgeons should note that universal preoperative COVID-19 testing, adequate personal protective equipment, and surgeon support were reassuring to patients. LEVEL OF EVIDENCE: Level IV Therapeutic.

9.
14th IEEE Pacific Visualization Symposium, PacificVis 2021 ; 2021-April:216-220, 2021.
Article in English | Scopus | ID: covidwho-1270797

ABSTRACT

Social networking services (SNSs) have become the main avenue, where people speak their thoughts. Accordingly, we can explore people's thoughts by analyzing topics in SNS. When do topics change? Do they ever come back? What do people mainly talk about? In this study, we design and propose a novel visual analytics system to answer these interesting questions. We abstract the topic per unit time as a point in a two-dimensional space through document embedding and dimensionality reduction techniques and provide supplemented charts that represent words appearing at a certain time and the time-series change of word occurrence over the entire period. We employ a novel text visualization technique, called semantic preserving word bubbles, to visualize words at a certain time. In addition, we demonstrate the effectiveness of our system using Twitter data about early COVID-19 trends in Japan. We propose our system to help users to explore and understand transitions in posted contents on SNS. © 2021 IEEE.

10.
Chinese Journal of General Practitioners ; 19(10):904-907, 2020.
Article in Chinese | Scopus | ID: covidwho-1154590
11.
Chinese Journal of Clinical Infectious Diseases ; 13(2):92-101, 2020.
Article in Chinese | Scopus | ID: covidwho-1143643

ABSTRACT

In December 2019, the endemic of COVID-19 broke out in Wuhan, China. The disease is highly contagious and quickly spreads at home and abroad, causing great concern. However, there are no definite effective antiviral drugs in clinical use. Given the urgency of the COVID-19 outbreak, based on the diagnosis and treatment recommendation and relavant researches, this article describes the optional antiviral drugs such as remdesivir, oseltamivir, arbidol, lopinavir/ritonavir, ribavirin, and interferon-α to provide a reference for treatment of COVID-19. Copyright © 2020 by the Chinese Medical Association.

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