Identification and trajectory of growth of concerning SARS-CoV-2 variants in Houston, Texas, January through April 2021 based on 11,568 genome sequences

Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the trajectory of the ongoing pandemic, and disease course in individual patients. Here we report genome sequences from 11,568 COVID-19 patients in the Houston Methodist healthcare system dispersed throughout the metroplex that were diagnosed from January 1, 2021 through April 30, 2021. This sample represents 94% of Houston Methodist cases and 4.6% of all reported cases in the metropolitan area during this period. The SARS-CoV-2 variant designated UK B.1.1.7 increased very rapidly, and now causes 75%-90% of all new cases in the Houston area. Five of the 2,543 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals infected with B.1.1.7 had a significantly lower cycle threshold value (considered to be a proxy for higher virus load) and higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly in frequency, although the magnitude was less than for B.1.1.7. We also identified 42 patients with a recently described R.1 variant that has an E484K amino acid replacement, and seven patients with the B.1.617 "India" variants. In the aggregate, our study shows the occurrence of a diverse array of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston and heralds the arrival and spread of B.1.617 variants in the metroplex.

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Rapid, widespread, and preferential increase of SARS-CoV-2 B.1.1.7 variant in Houston, TX, revealed by 8,857 genome sequences

10.1101/2021.03.16.21253753 ◽

2021 ◽

Author(s):

James M. Musser ◽

Randall J. Olsen ◽

Paul A. Christensen ◽

S. Wesley Long ◽

Sishir Subedi ◽

...

Keyword(s):

Genetic Variants ◽

Doubling Time ◽

Spike Protein ◽

Genome Sequences ◽

Houston Area

Genetic variants of the SARS-CoV-2 virus have become of great interest worldwide because they have the potential to detrimentally alter the course of the SARS-CoV-2 pandemic, and disease in individual patients. We recently sequenced 20,453 SARS-CoV-2 genomes from patients with COVID-19 disease in metropolitan Houston (population 7 million), dating from March 2020 to early February 2021. We discovered that all major variants of concern or interest are circulating in the region. To follow up on this discovery, we analyzed 8,857 genome sequences from patients in eight Houston Methodist hospitals dispersed throughout the metroplex diagnosed from January 1, 2021 to March 7, 2021. This sample represents 94% of Houston Methodist cases and 4.8% of all reported cases in metropolitan Houston during this period. We discovered rapid, widespread, and preferential increase of the SARS-CoV-2 UK B.1.1.7 throughout the region. The estimated case doubling time in the Houston area is 6.9 days. None of the 648 UK B.1.1.7 samples identified had the E484K change in spike protein that can cause decreased recognition by antibodies.

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Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences

10.1101/2020.07.27.222901 ◽

2020 ◽

Author(s):

Babatunde Olarenwaju Motayo ◽

Olukunle Oluwapamilerin Oluwasemowo ◽

Paul Akiniyi Akinduti ◽

Babatunde Adebiyi Olusola ◽

Olumide T Aerege ◽

...

Keyword(s):

Genetic Diversity ◽

Amino Acid ◽

Spike Protein ◽

Recent Common Ancestor ◽

Whole Genome ◽

Genome Sequences ◽

Protein Amino Acid ◽

Protein Variant ◽

Health Crisis ◽

Most Recent Common Ancestor

ABSTRACTThe ongoing SARSCoV-2 pandemic was introduced into Africa on 14th February 2020 and has rapidly spread across the continent causing severe public health crisis and mortality. We investigated the genetic diversity and evolution of this virus during the early outbreak months using whole genome sequences. We performed; recombination analysis against closely related CoV, Bayesian time scaled phylogeny and investigated spike protein amino acid mutations. Results from our analysis showed recombination signals between the AfrSARSCoV-2 sequences and reference sequences within the N and S genes. The evolutionary rate of the AfrSARSCoV-2 was 4.133 × 10−4 high posterior density HPD (4.132 × 10−4 to 4.134 × 10−4) substitutions/site/year. The time to most recent common ancestor TMRCA of the African strains was December 7th 2019. The AfrSARCoV-2 sequences diversified into two lineages A and B with B being more diverse with multiple sub-lineages confirmed by both maximum clade credibility MCC tree and PANGOLIN software. There was a high prevalence of the D614-G spike protein amino acid mutation (82.61%) among the African strains. Our study has revealed a rapidly diversifying viral population with the G614 spike protein variant dominating, we advocate for up scaling NGS sequencing platforms across Africa to enhance surveillance and aid control effort of SARSCoV-2 in Africa.

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Importation, circulation, and emergence of variants of SARS-CoV-2 in the South Indian State of Karnataka

10.1101/2021.03.17.21253810 ◽

2021 ◽

Author(s):

Chitra Pattabiraman ◽

Pramada Prasad ◽

Anson K George ◽

Darshan Sreenivas ◽

Risha Rasheed ◽

...

Keyword(s):

Amino Acid ◽

Immune Escape ◽

Severe Disease ◽

Warning System ◽

Amino Acid Replacement ◽

International Travel ◽

Spike Protein ◽

Local Circulation ◽

South Indian ◽

The Uk

As the pandemic of COVID-19 caused by the coronavirus SARS-CoV-2 continues, the selection of genomic variants which can influence how the pandemic progresses is of growing concern. Of particular concern, are those variants that carry mutations/amino acid changes conferring higher transmission, more severe disease, re-infection, and immune escape. These can broadly be classified as Variants of Concern (VOCs). VOCs have been reported from several parts of the world- UK (lineage B.1.1.7), South Africa (lineage B.1.351) and, Brazil (lineage P.1/B.1.1.28). The conditions that contribute to the emergence of VOCs are not well understood. International travel remains an important means of spread. To track importation, spread, and the emergence of variants locally; we sequenced whole genomes of SARS-CoV-2 from international travellers (n=75) entering Karnataka, a state in South India, between Dec 22, 2020- Jan 31, 2021, and from positive cases in the city of Bengaluru (n=108), between Nov 22, 2020- Jan 22, 2021. The resulting 176 SARS-CoV-2 genomes could be classified into 34 lineages, that were either imported (73/176) or circulating (103/176) in this time period. The lineage B.1.1.7 (a.k.a the UK variant) was the major lineage imported into the state (24/73, 32.9%), followed by B.1.36 (20/73, 27.4%) and B.1 (14/73, 19.2%). We identified B.1.36 (45/103; 43.7%), B.1 (26/103; 25.2%), B.1.1.74 (5/103; 4.9%) and B.1.468 (4/103; 3.9%) as the major variants circulating in Bengaluru city. A distinct clade within the B.1.36 lineage was associated with a local outbreak. Analysis of the complete genomes predicted multiple amino acid replacements in the Spike protein. In total, we identified nine amino acid changes (singly or in pairs) in the Receptor Binding Domain of the Spike protein. Of these, the amino acid replacement N440K was found in 37/65 (56.92%) sequences in the B.1.36 lineage. The E484K amino acid change which is present in both VOCs, B.1.351 and P.1/B.1.1.28, was found in a single circulating virus in the B.1.36 lineage. This study highlights the introduction of VOCs by travel and the local circulation of viruses with amino acid replacements in the Spike protein. These were spread across lineages, suggesting that multiple paths can lead to the emergence of VOCs, this, in turn, highlights the need to sequence and limit outbreaks of SARS-CoV-2 locally. Our data support the use of concentrated and continued genomic surveillance of SARS-CoV-2 to direct public health measures, suggest revisions to vaccines, and serve as an early warning system to prepare for a surge in COVID-19 cases.

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Molecular epidemiology of SARS-CoV-2 isolated from COVID-19 family clusters

BMC Medical Genomics ◽

10.1186/s12920-021-00990-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Gunadi ◽

Hendra Wibawa ◽

Mohamad Saifudin Hakim ◽

Marcellus ◽

Ika Trisnawati ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Amino Acid ◽

Epidemiological Data ◽

Spike Protein ◽

Full Genome ◽

Genome Sequences ◽

Family Cluster ◽

Protein Mutations ◽

Amino Acid Mutations ◽

Cluster 2

Abstract Background Transmission within families and multiple spike protein mutations have been associated with the rapid transmission of SARS-CoV-2. We aimed to: (1) describe full genome characterization of SARS-CoV-2 and correlate the sequences with epidemiological data within family clusters, and (2) conduct phylogenetic analysis of all samples from Yogyakarta and Central Java, Indonesia and other countries. Methods The study involved 17 patients with COVID-19, including two family clusters. We determined the full-genome sequences of SARS-CoV-2 using the Illumina MiSeq next-generation sequencer. Phylogenetic analysis was performed using a dataset of 142 full-genomes of SARS-CoV-2 from different regions. Results Ninety-four SNPs were detected throughout the open reading frame (ORF) of SARS-CoV-2 samples with 58% (54/94) of the nucleic acid changes resulting in amino acid mutations. About 94% (16/17) of the virus samples showed D614G on spike protein and 56% of these (9/16) showed other various amino acid mutations on this protein, including L5F, V83L, V213A, W258R, Q677H, and N811I. The virus samples from family cluster-1 (n = 3) belong to the same clade GH, in which two were collected from deceased patients, and the other from the survived patient. All samples from this family cluster revealed a combination of spike protein mutations of D614G and V213A. Virus samples from family cluster-2 (n = 3) also belonged to the clade GH and showed other spike protein mutations of L5F alongside the D614G mutation. Conclusions Our study is the first comprehensive report associating the full-genome sequences of SARS-CoV-2 with the epidemiological data within family clusters. Phylogenetic analysis revealed that the three viruses from family cluster-1 formed a monophyletic group, whereas viruses from family cluster-2 formed a polyphyletic group indicating there is the possibility of different sources of infection. This study highlights how the same spike protein mutations among members of the same family might show different disease outcomes.

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Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines

10.1101/2021.03.03.21252812 ◽

2021 ◽

Author(s):

Francis A. Tablizo ◽

Kenneth M. Kim ◽

Carlo M. Lapid ◽

Marc Jerrone R. Castro ◽

Maria Sofia L. Yangzon ◽

...

Keyword(s):

Public Health ◽

Amino Acid ◽

Protein A ◽

Amino Acid Replacement ◽

The Philippines ◽

Spike Protein ◽

Single Amino Acid ◽

Outbreak Management ◽

Public Health Agencies ◽

Management Measures

The emergence of SARS-CoV-2 variants of concern such as the B.1.1.7, B.1.351 and the P.1 have prompted calls for governments worldwide to increase their genomic biosurveillance efforts. Globally, quarantine and outbreak management measures have been implemented to stem the introduction of these variants and to monitor any emerging variants of potential clinical significance domestically. Here, we describe the emergence of a new SARS-CoV-2 lineage, mainly from the Central Visayas region of the Philippines. This emergent variant is characterized by 13 lineage-defining mutations, including the co-occurrence of the E484K, N501Y, and P681H mutations at the spike protein region, as well as three additional radical amino acid replacements towards the C-terminal end of the said protein. A three-amino acid deletion at positions 141 to 143 (LGV141_143del) in the spike protein was likewise seen in a region preceding the 144Y deletion found in the B.1.1.7 variant. A single amino acid replacement, K2Q, at the N-terminus of ORF8 was also shared by all 33 samples sequenced. The mutation profile of this new virus variant warrants closer investigation due to its potential public health implications. The current distribution of this emergent variant in the Philippines and its transmission are being monitored and addressed by relevant public health agencies to stem its spread in nearby islands and regions in the country.

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Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

10.1101/2020.09.22.20199125 ◽

2020 ◽

Cited By ~ 3

Author(s):

Scott Wesley Long ◽

Randall J Olsen ◽

Paul A. Christensen ◽

David W Bernard ◽

James J. Davis ◽

...

Keyword(s):

Amino Acid ◽

Protein A ◽

Potential Effect ◽

Amino Acid Replacement ◽

Spike Protein ◽

Metropolitan Region ◽

Single Amino Acid ◽

Molecular Architecture ◽

Virus Genotypes ◽

Second Wave

We sequenced the genomes of 5,085 SARS-CoV-2 strains causing two COVID-19 disease waves in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston, and an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotypes and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein - the primary target of global vaccine efforts - are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR30022. Our study is the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves, and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution.

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Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area

mBio ◽

10.1128/mbio.02707-20 ◽

2020 ◽

Vol 11 (6) ◽

Cited By ~ 2

Author(s):

S. Wesley Long ◽

Randall J. Olsen ◽

Paul A. Christensen ◽

David W. Bernard ◽

James J. Davis ◽

...

Keyword(s):

Amino Acid ◽

Protein A ◽

Potential Effect ◽

Amino Acid Replacement ◽

Spike Protein ◽

Metropolitan Region ◽

Single Amino Acid ◽

Molecular Architecture ◽

Virus Genotype ◽

Second Wave

ABSTRACT We sequenced the genomes of 5,085 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains causing two coronavirus disease 2019 (COVID-19) disease waves in metropolitan Houston, TX, an ethnically diverse region with 7 million residents. The genomes were from viruses recovered in the earliest recognized phase of the pandemic in Houston and from viruses recovered in an ongoing massive second wave of infections. The virus was originally introduced into Houston many times independently. Virtually all strains in the second wave have a Gly614 amino acid replacement in the spike protein, a polymorphism that has been linked to increased transmission and infectivity. Patients infected with the Gly614 variant strains had significantly higher virus loads in the nasopharynx on initial diagnosis. We found little evidence of a significant relationship between virus genotype and altered virulence, stressing the linkage between disease severity, underlying medical conditions, and host genetics. Some regions of the spike protein—the primary target of global vaccine efforts—are replete with amino acid replacements, perhaps indicating the action of selection. We exploited the genomic data to generate defined single amino acid replacements in the receptor binding domain of spike protein that, importantly, produced decreased recognition by the neutralizing monoclonal antibody CR3022. Our report represents the first analysis of the molecular architecture of SARS-CoV-2 in two infection waves in a major metropolitan region. The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution. IMPORTANCE There is concern about second and subsequent waves of COVID-19 caused by the SARS-CoV-2 coronavirus occurring in communities globally that had an initial disease wave. Metropolitan Houston, TX, with a population of 7 million, is experiencing a massive second disease wave that began in late May 2020. To understand SARS-CoV-2 molecular population genomic architecture and evolution and the relationship between virus genotypes and patient features, we sequenced the genomes of 5,085 SARS-CoV-2 strains from these two waves. Our report provides the first molecular characterization of SARS-CoV-2 strains causing two distinct COVID-19 disease waves.

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A Novel Polymorphism in Exon 10 of the Factor V Gene Inducing an Amino Acid Replacement of Arginine to Lysine at Codon 485

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665424 ◽

1997 ◽

Vol 78 (05) ◽

pp. 1419-1420 ◽

Cited By ~ 1

Author(s):

Tetsuo Ozawa ◽

Kenji Niiya ◽

Naoko Ejiri ◽

Nobuo Sakuragawa

Keyword(s):

Amino Acid ◽

Amino Acid Replacement ◽

Factor V ◽

Factor V Gene ◽

V Gene ◽

Exon 10

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Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

PLoS ONE ◽

10.1371/journal.pone.0006130 ◽

2009 ◽

Vol 4 (7) ◽

pp. e6130 ◽

Cited By ~ 22

Author(s):

Yoshiyuki Yamada ◽

Xiao Bo Liu ◽

Shou Guo Fang ◽

Felicia P. L. Tay ◽

Ding Xiang Liu

Keyword(s):

Amino Acid ◽

Cell Fusion ◽

Cultured Cells ◽

Spike Protein ◽

Amino Acid Substitutions ◽

Fusion Activity ◽

Cell Cell

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Assessing the Impact of Secondary Structure and Solvent Accessibility on Protein Evolution

Genetics ◽

10.1093/genetics/149.1.445 ◽

1998 ◽

Vol 149 (1) ◽

pp. 445-458 ◽

Cited By ~ 21

Author(s):

Nick Goldman ◽

Jeffrey L Thorne ◽

David T Jones

Keyword(s):

Amino Acid ◽

Secondary Structure ◽

Protein Evolution ◽

Solvent Accessibility ◽

Strong Association ◽

Length Distribution ◽

Parametric Bootstrap ◽

Amino Acid Replacement ◽

Physical Constraints ◽

The Impact

Abstract Empirically derived models of amino acid replacement are employed to study the association between various physical features of proteins and evolution. The strengths of these associations are statistically evaluated by applying the models of protein evolution to 11 diverse sets of protein sequences. Parametric bootstrap tests indicate that the solvent accessibility status of a site has a particularly strong association with the process of amino acid replacement that it experiences. Significant association between secondary structure environment and the amino acid replacement process is also observed. Careful description of the length distribution of secondary structure elements and of the organization of secondary structure and solvent accessibility along a protein did not always significantly improve the fit of the evolutionary models to the data sets that were analyzed. As indicated by the strength of the association of both solvent accessibility and secondary structure with amino acid replacement, the process of protein evolution—both above and below the species level—will not be well understood until the physical constraints that affect protein evolution are identified and characterized.

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