TY - JOUR
T1 - Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area
AU - Long, S. Wesley
AU - Olsen, Randall J.
AU - Christensen, Paul A.
AU - Bernard, David W.
AU - Davis, James J.
AU - Shukla, Maulik
AU - Nguyen, Marcus
AU - Saavedra, Matthew Ojeda
AU - Yerramilli, Prasanti
AU - Pruitt, Layne
AU - Subedi, Sishir
AU - Kuo, Hung Che
AU - Hendrickson, Heather
AU - Eskandari, Ghazaleh
AU - Nguyen, Hoang A.T.
AU - Long, J. Hunter
AU - Kumaraswami, Muthiah
AU - Goike, Jule
AU - Boutz, Daniel
AU - Gollihar, Jimmy
AU - McLellan, Jason S.
AU - Chou, Chia Wei
AU - Javanmardi, Kamyab
AU - Finkelstein, Ilya J.
AU - Musser, James M.
N1 - Copyright © 2020 Long et al.
PY - 2020/10/30
Y1 - 2020/10/30
N2 - 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 al-tered 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 find-ings 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.
AB - 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 al-tered 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 find-ings 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.
KW - COVID-19
KW - COVID-19 disease
KW - Evolution
KW - Genome sequencing
KW - Molecular population genomics
KW - SARS-CoV-2
KW - Betacoronavirus/genetics
KW - Pandemics
KW - COVID-19 Testing
KW - Clinical Laboratory Techniques
KW - Humans
KW - Spike Glycoprotein, Coronavirus/chemistry
KW - Phylogeny
KW - Machine Learning
KW - Sequence Analysis, Protein
KW - Molecular Diagnostic Techniques
KW - Base Sequence
KW - Pneumonia, Viral/epidemiology
KW - Antibodies, Neutralizing/immunology
KW - Amino Acid Sequence
KW - Genome, Viral
KW - Viral Nonstructural Proteins/chemistry
KW - Models, Molecular
KW - Genotype
KW - Coronavirus Infections/diagnosis
KW - Coronavirus RNA-Dependent RNA Polymerase
KW - Texas/epidemiology
KW - RNA-Dependent RNA Polymerase/chemistry
KW - Amino Acid Substitution
UR - http://www.scopus.com/inward/record.url?scp=85095393359&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85095393359&partnerID=8YFLogxK
U2 - 10.1128/mBio.02707-20
DO - 10.1128/mBio.02707-20
M3 - Article
C2 - 33127862
AN - SCOPUS:85095393359
SN - 2161-2129
VL - 11
SP - 1
EP - 30
JO - mBio
JF - mBio
IS - 6
M1 - e02707-20
ER -