Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas

Long, Samuel; Olsen, Randall J.; Christensen, Paul; Bernard, David W.; Davis, James R.; Shukla, Maulik; Nguyen, M.; Saavedra, Matthew Ojeda; Cantu, Concepcion; Yerramilli, Prasanti; Pruitt, Layne; Subedi, Sishir; Hendrickson, Heather; Eskandari, Ghazaleh; Kumaraswami, Muthiah; McLellan, Jason S.; Musser, James M.

doi:10.1101/2020.05.01.072652

Cited by 18 publications

(24 citation statements)

References 36 publications

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“…Replacement of aspartate with glycine would eliminate both interactions, thereby substantively weakening the contact between the S1 and S2 subunits. We previously speculated ( 75 ) that this weakening produces a more fusogenic spike protein, as S1 must first dissociate from S2 before S2 can refold and mediate fusion of virus and cell membranes. Stated another way, virus strains with the Gly614 variant may be better able to enter host cells, potentially resulting in enhanced spread.…”

Section: Discussionmentioning

confidence: 99%

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

Long

Olsen

Christensen

et al. 2020

Preprint

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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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Section: Discussionmentioning

confidence: 99%

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

Long

Olsen

Christensen

et al. 2020

Preprint

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“…Trees were visualized and annotated with CLC Genomics Workbench v20 (QIAGEN). SARS-CoV-2 clade assignment was based on procedures described elsewhere (41).…”

Section: Methodsmentioning

confidence: 99%

Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization

Salazar¹,

Kuchipudi²,

Christensen³

et al. 2020

Journal of Clinical Investigation

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178

153

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The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), antireceptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.

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“…The 2,400-bed Houston Methodist Hospital health system has seven hospitals and serves a large, multiethnic, and socioeconomically diverse patient population throughout greater Houston ( 13 , 14 ). The first COVID-19 case in metropolitan Houston was reported on 5 March 2020, with community spread occurring 1 week later ( 15 ). Many of the first cases in our region were associated with national or international travel in areas known to have SARS-CoV-2 virus outbreaks ( 15 ).…”

Section: Introductionmentioning

confidence: 99%

“…The first COVID-19 case in metropolitan Houston was reported on 5 March 2020, with community spread occurring 1 week later ( 15 ). Many of the first cases in our region were associated with national or international travel in areas known to have SARS-CoV-2 virus outbreaks ( 15 ). A central molecular diagnostic laboratory serving all Houston Methodist hospitals and our very early adoption of a molecular test for the SARS-CoV-2 virus permitted us to rapidly identify SARS-CoV-2-positive patients and interrogate genomic variation among strains causing early infections in the greater Houston area.…”

Section: Introductionmentioning

confidence: 99%

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

Long

Olsen

Christensen

et al. 2020

mBio

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101

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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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Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas

Cited by 18 publications

References 36 publications

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

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

Convalescent plasma anti–SARS-CoV-2 spike protein ectodomain and receptor-binding domain IgG correlate with virus neutralization

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

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