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1.
IEEE Transactions on Automation Science & Engineering ; 19(2):709-723, 2022.
Article in English | Academic Search Complete | ID: covidwho-1788779

ABSTRACT

This article addresses a weekly physician scheduling problem in Covid-19. This problem has arisen in fever clinics in two collaborative hospitals located in Shanghai, China. Because of the coronavirus pandemic, the hospitals must consider some specific constraints in the scheduling problem. For example, due to social distance limitation, the patient queue lengths are much longer in the coronavirus pandemic, even with the same waiting patients. Thus, the hospitals must consider the maximum queue length in the physician scheduling problem. Moreover, the fever clinic’s scheduling rules are different from those in the common clinic, and some specific regulatory constraints have to be considered in the epidemic. We first build a mathematical model for this problem, in which a pointwise stationary fluid flow approximation method is used to compute the queue length. Some linearization techniques are designed to make the problem can be solved by commercial solvers, such as Gurobi. We find that solving this model from practical applications of the hospital within an acceptable computation time is challenging. Consequently, we develop an efficient two-phase approach to solve the problem. A staffing model and a branch-and-price algorithm are proposed in this approach. The performances of our models and approaches are discussed. The effectiveness of the proposed algorithms for real-life data from collaborative hospitals is validated. Note to Practitioners—This article is motivated by our collaborations with two hospitals in Shanghai, China. Covid-19 has swept the world since 2019 and is still raging in many regions, posing an unprecedented challenge to healthcare systems in countries worldwide. The hospitals are the frontlines of healthcare service, and the physicians are the most critical resource in the battles to coronavirus pandemic. In China, many large-scale hospitals establish fever clinics to serve fever patients. The physician scheduling for such clinics is different and complicated in the Covid-19 due to many specific constraints. We find that the managers are tough to give high-quality schedules to physicians. Thus, we propose a set of algorithms to solve this problem. Especially, a two-phase approach that consists of a staffing standard and a branch-and-price algorithm is designed. Based on hospitals’ real-life data, we show that the methods presented in this article can be used to help hospital managers obtain more reasonable scheduling solutions that can improve the service quality without increasing the workloads of physicians. [ FROM AUTHOR] Copyright of IEEE Transactions on Automation Science & Engineering is the property of IEEE and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

2.
Nature ; 602(7896): 307-313, 2022 02.
Article in English | MEDLINE | ID: covidwho-1585832

ABSTRACT

Emerging variants of concern (VOCs) are driving the COVID-19 pandemic1,2. Experimental assessments of replication and transmission of major VOCs and progenitors are needed to understand the mechanisms of replication and transmission of VOCs3. Here we show that the spike protein (S) from Alpha (also known as B.1.1.7) and Beta (B.1.351) VOCs had a greater affinity towards the human angiotensin-converting enzyme 2 (ACE2) receptor than that of the progenitor variant S(D614G) in vitro. Progenitor variant virus expressing S(D614G) (wt-S614G) and the Alpha variant showed similar replication kinetics in human nasal airway epithelial cultures, whereas the Beta variant was outcompeted by both. In vivo, competition experiments showed a clear fitness advantage of Alpha over wt-S614G in ferrets and two mouse models-the substitutions in S were major drivers of the fitness advantage. In hamsters, which support high viral replication levels, Alpha and wt-S614G showed similar fitness. By contrast, Beta was outcompeted by Alpha and wt-S614G in hamsters and in mice expressing human ACE2. Our study highlights the importance of using multiple models to characterize fitness of VOCs and demonstrates that Alpha is adapted for replication in the upper respiratory tract and shows enhanced transmission in vivo in restrictive models, whereas Beta does not overcome Alpha or wt-S614G in naive animals.


Subject(s)
COVID-19/transmission , COVID-19/virology , Mutation , SARS-CoV-2/classification , SARS-CoV-2/physiology , Virus Replication , Amino Acid Substitution , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Animals, Laboratory/virology , COVID-19/veterinary , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Humans , Male , Mesocricetus/virology , Mice , Mice, Transgenic , SARS-CoV-2/genetics , SARS-CoV-2/growth & development , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism , Virulence/genetics
3.
Sci Rep ; 11(1): 23561, 2021 12 07.
Article in English | MEDLINE | ID: covidwho-1559302

ABSTRACT

N-glycosylation plays an important role in the structure and function of membrane and secreted proteins. The spike protein on the surface of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, is heavily glycosylated and the major target for developing vaccines, therapeutic drugs and diagnostic tests. The first major SARS-CoV-2 variant carries a D614G substitution in the spike (S-D614G) that has been associated with altered conformation, enhanced ACE2 binding, and increased infectivity and transmission. In this report, we used mass spectrometry techniques to characterize and compare the N-glycosylation of the wild type (S-614D) or variant (S-614G) SARS-CoV-2 spike glycoproteins prepared under identical conditions. The data showed that half of the N-glycosylation sequons changed their distribution of glycans in the S-614G variant. The S-614G variant showed a decrease in the relative abundance of complex-type glycans (up to 45%) and an increase in oligomannose glycans (up to 33%) on all altered sequons. These changes led to a reduction in the overall complexity of the total N-glycosylation profile. All the glycosylation sites with altered patterns were in the spike head while the glycosylation of three sites in the stalk remained unchanged between S-614G and S-614D proteins.


Subject(s)
Glycopeptides/analysis , Mass Spectrometry/methods , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/chemistry , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/pathology , COVID-19/virology , Chromatography, High Pressure Liquid , Glycosylation , Humans , Mutation , Protein Binding , Protein Structure, Tertiary , SARS-CoV-2/isolation & purification , Spike Glycoprotein, Coronavirus/chemistry
4.
Emerg Infect Dis ; 27(5): 1380-1392, 2021 05.
Article in English | MEDLINE | ID: covidwho-1202277

ABSTRACT

Co-infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other viruses has been reported. We evaluated cell lines commonly used to isolate viruses and diagnose related diseases for their susceptibility to SARS-CoV-2. Although multiple kidney cell lines from monkeys were susceptible to SARS-CoV-2, we found many cell types derived from humans, dogs, minks, cats, mice, and chicken were not. We analyzed MDCK cells, which are most commonly used for surveillance and study of influenza viruses, and found that they were not susceptible to SARS-CoV-2. The low expression level of the angiotensin converting enzyme 2 receptor and lower receptor affinity to SARS-CoV-2 spike, which could be overcome by overexpression of canine angiotensin converting enzyme 2 in trans, strengthened the cellular barrier to productive infection. Moreover, a D614G mutation in the spike protein did not appear to affect SARS-CoV-2 cell tropism. Our findings should help avert inadvertent propagation of SARS-CoV-2 from diagnostic cell lines.


Subject(s)
COVID-19 , Influenza, Human , Animals , Cats , Cell Line , Dogs , Humans , Mice , Peptidyl-Dipeptidase A , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/genetics
5.
Nature ; 592(7852): 122-127, 2021 04.
Article in English | MEDLINE | ID: covidwho-1104508

ABSTRACT

During the evolution of SARS-CoV-2 in humans, a D614G substitution in the spike glycoprotein (S) has emerged; virus containing this substitution has become the predominant circulating variant in the COVID-19 pandemic1. However, whether the increasing prevalence of this variant reflects a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains unknown. Here we use isogenic SARS-CoV-2 variants to demonstrate that the variant that contains S(D614G) has enhanced binding to the human cell-surface receptor angiotensin-converting enzyme 2 (ACE2), increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a human ACE2 knock-in mouse model, and markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Our data show that the D614G substitution in S results in subtle increases in binding and replication in vitro, and provides a real competitive advantage in vivo-particularly during the transmission bottleneck. Our data therefore provide an explanation for the global predominance of the variant that contains S(D614G) among the SARS-CoV-2 viruses that are currently circulating.


Subject(s)
COVID-19/transmission , COVID-19/virology , Mutation , SARS-CoV-2/genetics , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/genetics , Virus Replication/genetics , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Animals , Bronchi/cytology , Bronchi/virology , COVID-19/epidemiology , Cell Line , Cells, Cultured , Cricetinae , Disease Models, Animal , Epithelial Cells/virology , Female , Ferrets/virology , Founder Effect , Gene Knock-In Techniques , Genetic Fitness , Humans , Male , Mesocricetus , Mice , Nasal Mucosa/cytology , Nasal Mucosa/virology , Protein Binding , RNA, Viral/analysis , Receptors, Coronavirus/metabolism , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
6.
bioRxiv ; 2020 Oct 27.
Article in English | MEDLINE | ID: covidwho-915978

ABSTRACT

During the evolution of SARS-CoV-2 in humans a D614G substitution in the spike (S) protein emerged and became the predominant circulating variant (S-614G) of the COVID-19 pandemic 1 . However, whether the increasing prevalence of the S-614G variant represents a fitness advantage that improves replication and/or transmission in humans or is merely due to founder effects remains elusive. Here, we generated isogenic SARS-CoV-2 variants and demonstrate that the S-614G variant has (i) enhanced binding to human ACE2, (ii) increased replication in primary human bronchial and nasal airway epithelial cultures as well as in a novel human ACE2 knock-in mouse model, and (iii) markedly increased replication and transmissibility in hamster and ferret models of SARS-CoV-2 infection. Collectively, our data show that while the S-614G substitution results in subtle increases in binding and replication in vitro , it provides a real competitive advantage in vivo , particularly during the transmission bottle neck, providing an explanation for the global predominance of S-614G variant among the SARS-CoV-2 viruses currently circulating.

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