Coronavirus Disease 2019 (COVID-19) Re-infection by a Phylogenetically Distinct Severe Acute Respiratory Syndrome Coronavirus 2 Strain Confirmed by Whole Genome Sequencing

Abstract Background Waning immunity occurs in patients who have recovered from Coronavirus Disease 2019 (COVID-19). However, it remains unclear whether true re-infection occurs. Methods Whole genome sequencing was performed directly on respiratory specimens collected during 2 episodes of COVID-19 in a patient. Comparative genome analysis was conducted to differentiate re-infection from persistent viral shedding. Laboratory results, including RT-PCR Ct values and serum Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG, were analyzed. Results The second episode of asymptomatic infection occurred 142 days after the first symptomatic episode in an apparently immunocompetent patient. During the second episode, there was evidence of acute infection including elevated C-reactive protein and SARS-CoV-2 IgG seroconversion. Viral genomes from first and second episodes belong to different clades/lineages. The virus genome from the first episode contained a a stop codon at position 64 of ORF8, leading to a truncation of 58 amino acids. Another 23 nucleotide and 13 amino acid differences located in 9 different proteins, including positions of B and T cell epitopes, were found between viruses from the first and second episodes. Compared to viral genomes in GISAID, the first virus genome was phylogenetically closely related to strains collected in March/April 2020, while the second virus genome was closely related to strains collected in July/August 2020. Conclusions Epidemiological, clinical, serological, and genomic analyses confirmed that the patient had re-infection instead of persistent viral shedding from first infection. Our results suggest SARS-CoV-2 may continue to circulate among humans despite herd immunity due to natural infection. Further studies of patients with re-infection will shed light on protective immunological correlates for guiding vaccine design.

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Identification and Whole-Genome Sequencing of Four Enterovirus D68 Strains in Southern China in Late 2015

Genome Announcements ◽

10.1128/genomea.01014-16 ◽

2016 ◽

Vol 4 (5) ◽

Cited By ~ 4

Author(s):

Long Chen ◽

Lei Shi ◽

Hong Yang ◽

Da-Yong Gu ◽

Jun Meng ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Phylogenetic Relationship ◽

Genome Sequencing ◽

Southern China ◽

Northern China ◽

Genomic Sequences ◽

Whole Genome ◽

Influenza Like Illness ◽

Viral Genomes ◽

Enterovirus D68

Four enterovirus D68 (EV-D68) strains from four children with influenza-like illness were identified in Shenzhen, southern China, in late 2015. Here, we announce the availability of these viral genomes in GenBank. The genomic sequences of these EV-D68 strains showed the closest phylogenetic relationship to strains from northern China.

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The Emergence and Spread of Novel SARS-CoV-2 Variants

Frontiers in Public Health ◽

10.3389/fpubh.2021.696664 ◽

2021 ◽

Vol 9 ◽

Author(s):

Huaimin Yi ◽

Jin Wang ◽

Jiong Wang ◽

Yuying Lu ◽

Yali Zhang ◽

...

Keyword(s):

Immune Response ◽

Severe Acute Respiratory Syndrome ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Neutralizing Antibodies ◽

Whole Genome ◽

Distribution Characteristics ◽

S Protein ◽

The World ◽

Viral Genes

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in late 2019, laboratories around the world have widely used whole genome sequencing (WGS) to continuously monitor the changes in the viral genes and discovered multiple subtypes or branches evolved from SARS-CoV-2. Recently, several novel SARS-CoV-2 variants have been found to be more transmissible. They may affect the immune response caused by vaccines and natural infections and reduce the sensitivity to neutralizing antibodies. We analyze the distribution characteristics of prevalent SARS-CoV-2 variants and the frequency of mutant sites based on the data available from GISAID and PANGO by R 4.0.2 and ArcGIS 10.2. Our analysis suggests that B.1.1.7, B.1.351, and P.1 are more easily spreading than other variants, and the key mutations of S protein, including N501Y, E484K, and K417N/T, have high mutant frequencies, which may have become the main genotypes for the spread of SARS-CoV-2.

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Use of whole genome sequencing to investigate a cluster of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections in emergency department personnel

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2021.208 ◽

2021 ◽

pp. 1-10

Author(s):

Ernest R. Chan ◽

Lucas D. Jones ◽

Sarah N. Redmond ◽

Maria E. Navas ◽

Nataliya M. Kachaluba ◽

...

Keyword(s):

Emergency Department ◽

Severe Acute Respiratory Syndrome ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Healthcare Personnel ◽

Whole Genome ◽

Suspected Outbreak

Abstract Several recent reports have raised concern that infected co-workers may be an important source of SARS-CoV-2 acquisition by healthcare personnel. In a suspected outbreak among emergency department personnel, sequencing of SARS-CoV-2 confirmed transmission among co-workers. The suspected 6-person outbreak included 2 distinct transmission clusters and 1 unrelated infection.

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Flight-Associated Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 Corroborated by Whole-Genome Sequencing

Emerging Infectious Diseases ◽

10.3201/eid2612.203910 ◽

2020 ◽

Vol 26 (12) ◽

pp. 2872-2880 ◽

Cited By ~ 8

Author(s):

Hollie Speake ◽

Anastasia Phillips ◽

Tracie Chong ◽

Chisha Sikazwe ◽

Avram Levy ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Whole Genome

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Clinical and Genetic Characteristics of Extended-Spectrum Beta-Lactamase–Producing Enterobacteriaceae Among Canadian Children

Infection Control and Hospital Epidemiology ◽

10.1017/ice.2020.693 ◽

2020 ◽

Vol 41 (S1) ◽

pp. s167-s168

Author(s):

Nisha Thampi ◽

Jennifer Bowes ◽

Roberto Melano ◽

Nathalie Tijet ◽

Robert Slinger

Keyword(s):

Public Health ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Multidrug Resistant ◽

Clinical Isolates ◽

First Episode ◽

Whole Genome ◽

Comorbid Conditions ◽

Genetic Characteristics ◽

E Coli

Background: Infections with extended-spectrum β-lactamase–producing Enterobacteriaceae (ESBL-E) in nonoutbreak settings have not demonstrated the presence of dominant strains. Our objective was to determine the incidence, clinical characteristics, and genetic characteristics of ESBL-E infections among a group of Canadian children. Methods: From 2012 through 2017, patients aged ≤18 years with first-episode ESBL-E infections who presented at a pediatric center were reviewed. All clinical isolates were phenotypically identified in the laboratory as ESBL-producers. Demographic and clinical data were collected, including comorbid conditions, presence of devices, and previous antibacterial exposure. Community-associated infection was defined as a positive culture from a sterile site within the first 48 hours of hospital admission and no healthcare exposure during the preceding year. Isolates were sent to the Public Health Ontario Laboratory for whole-genome sequencing. Multilocus sequence typing was used to determine clonal relationship. Results: During the study period, 102 patients were identified with first-episode ESBL-E infection, and the proportion of ESBL-E isolates among all clinical isolates of E. coli and Klebsiella spp increased from 0.6% to 2.6% between 2012 and 2017, respectively (P = .001). The median age was 1 year (interquartile range, 0.8–5 years). Women comprised 66% of cases. No comorbid conditions were noted among 58 patients (57%), and 24% had previous antibiotic exposure, most frequently a cephalosporin (16%). ESBL-E was most frequently isolated in the urine (91%) and least frequently in the blood (2.2%) and was predominantly Escherichia coli (90%). Infection was most frequently diagnosed in the outpatient setting (61%); there were 11 healthcare-associated infections. Whole-genome sequencing of ESBL-E isolates revealed predominance of blaCTX-M-15 (63 isolates, 62%) and blaCTX-M-27 (16%) genes, and sequence type (ST) 131 (41%). Mutations conferring fluoroquinolone nonsusceptibility were noted among 62 isolates (61%), most frequently associated with ST131 (38 of 62 isolates, 61%) and among all 5 isolates with ST1193, an emerging multidrug-resistant E. coli clone. In addition, 15 patients had recurrence of ESBL-E infection at median of 113 days (IQR, 26–208); blaCTX-M-27 was found in 33% of recurrent infections compared to 12% of primary infections (P = 0.045). Conclusions: This study is the first in Canada to provide whole-genome sequencing data regarding ESBL-E in a pediatric population. The gene blaCTX-M-15 and ST131 clone were predominant. More than 60% of infections were community associated and demonstrated cross resistance to fluoroquinolones. With 76% of infections in antibiotic-naïve children, ESBL-E is a public health concern, and a One Health approach is critical to understanding the epidemiology and curbing the spread of multidrug-resistant Enterobacteriaceae.Funding: NoneDisclosures: None

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SARS-CoV-2 B.1.1.7 lineage rapidly spreads and overwhelms R.1 lineage in Japan: serial and stationary observation in a community

10.1101/2021.06.30.21259820 ◽

2021 ◽

Author(s):

Yosuke Hirotsu ◽

Masao Omata

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Whole Genome Sequencing ◽

Genome Sequencing ◽

Genome Analysis ◽

Whole Genome ◽

Community Based ◽

The World ◽

Viral Lineage

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulates in the world and acquires mutations during evolution. To identify the new emergent variants, the surveillance of the variants of concern (VOC) and variants of interest (VOI) is ongoing. This study aimed to determine how the transition of viral lineage occurred by stationary genome analysis in Yamanashi, Japan. Methods We performed the whole genome sequencing using SARS-CoV-2 positive samples (n=325) collected from February 2020 to the end of June 2021. The number of analyzed samples accounted for 15.4% of the total 2,109 samples identified in our community. Viral lineage was defined by the Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages. Results We identified 13 types of viral lineages including R.1, P.1, B.1.1.7 (Alpha) and B.1.617.2 (Delta) These virus lineages had distinct periods of expansion and decline. After the emerging of the R.1 lineage harboring E484K variant (designated VOI in Japan), the prevalent B.1.1.214 lineage were no longer identified. The R.1 lineages were temporarily prevalent afterwards, but the influx of B.1.1.7 lineage (designated VOC) led to a decline in R.1. Currently, B.1.1.7 has become dominant after mid-April, 2021. Conclusion We clearly elucidated the transition and replacement of viral lineage by the community-based analysis. The virus completely replaced by more infectious lineages, therefore, it will be necessary to continue to monitor the VOC and VOI.

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Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India

10.1101/2021.04.22.440932 ◽

2021 ◽

Author(s):

Sarah Cherian ◽

Varsha Potdar ◽

Santosh Jadhav ◽

Pragya Yadav ◽

Nivedita Gupta ◽

...

Keyword(s):

Whole Genome Sequencing ◽

Genome Sequencing ◽

Natural Infection ◽

Health Impact ◽

Spike Protein ◽

Whole Genome ◽

Furin Cleavage ◽

Genomic Epidemiology ◽

Furin Cleavage Site ◽

Second Wave

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being constantly used to investigate its transmissions and evolution. In the backdrop of the global emergence of variants of concern (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches was undertaken to identify possible new variants and gauge the fitness of current circulating strains. Phylogenetic analysis revealed that the predominant clade in circulation was a distinct newly identified lineage B.1.617 possessing common signature mutations D111D, G142D, L452R, E484Q, D614G and P681R, in the spike protein including within the receptor binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R and E484Q along with P681R in the furin cleavage site, revealed that these may possibly result in increased ACE2 binding and rate of S1-S2 cleavage resulting in better transmissibility. The same two RBD mutations indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Experimental validation against a wider panel of mAbs, sera from vaccinees and those that recovered from natural infection needs to be studied. The emergence of such local variants through the accumulation of convergent mutations during the COVID-19 second wave needs to be further investigated for their public health impact in the rest of the country and its possibility of becoming a VOC.

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