Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area

S. Wesley Long, Randall J. Olsen, Paul A. Christensen, David W. Bernard, James J. Davis, Maulik Shukla, Marcus Nguyen, Matthew Ojeda Saavedra, Prasanti Yerramilli, Layne Pruitt, Sishir Subedi, Hung Che Kuo, Heather Hendrickson, Ghazaleh Eskandari, Hoang A.T. Nguyen, J. Hunter Long, Muthiah Kumaraswami, Jule Goike, Daniel Boutz, Jimmy GolliharJason S. McLellan, Chia Wei Chou, Kamyab Javanmardi, Ilya J. Finkelstein, James M. Musser

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


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.

Original languageEnglish (US)
Article numbere02707-20
Pages (from-to)1-30
Number of pages30
Issue number6
StatePublished - Oct 30 2020


  • COVID-19
  • COVID-19 disease
  • Evolution
  • Genome sequencing
  • Molecular population genomics
  • SARS-CoV-2
  • Betacoronavirus/genetics
  • Pandemics
  • COVID-19 Testing
  • Clinical Laboratory Techniques
  • Humans
  • Spike Glycoprotein, Coronavirus/chemistry
  • Phylogeny
  • Machine Learning
  • Sequence Analysis, Protein
  • Molecular Diagnostic Techniques
  • Base Sequence
  • Pneumonia, Viral/epidemiology
  • Antibodies, Neutralizing/immunology
  • Amino Acid Sequence
  • Genome, Viral
  • Viral Nonstructural Proteins/chemistry
  • Models, Molecular
  • Genotype
  • Coronavirus Infections/diagnosis
  • Coronavirus RNA-Dependent RNA Polymerase
  • Texas/epidemiology
  • RNA-Dependent RNA Polymerase/chemistry
  • Amino Acid Substitution

ASJC Scopus subject areas

  • Virology
  • Microbiology


Dive into the research topics of 'Molecular architecture of early dissemination and massive second wave of the SARS-CoV-2 virus in a major metropolitan area'. Together they form a unique fingerprint.

Cite this