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

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.

Genomic Epidemiology of SARS-CoV-2 Infection During the Initial Pandemic Wave and Association With Disease Severity

“… 26 Still, most investigations have found no significant difference in outcomes of hospitalization or death among major clades. 7 , 27 One explanation for these findings is that many clinical studies on SARS-CoV-2 occur when the genetic diversity within a community has diminished. Often, D614G genotype strains are disproportionately represented, impacting the ability to discern differences between clades in smaller studies.…”

Comparative molecular dynamics study of the receptor-binding domains in SARS-CoV-2 and SARS-CoV and the effects of mutations on the binding affinity

“…This has led to concerns that the virus may mutate into even less treatable forms than those that have spread through the community until now. Recent epidemiological analyses do confirm these expectations, indicating that mutated SARS-CoV-2 appearing in the most recent waves of infection in urban areas may be more contagious than the earlier versions (Long et al., 2020 ). Detailed analyses of the effects of mutations on the molecular characteristics of SARS-CoV-2 are therefore of benefit, like the one we undertake here.…”

SARS-CoV-2 Genomic Surveillance in Costa Rica: Evidence of a Divergent Population and an Increased Detection of a Spike T1117I Mutation

“…In our study, this mutation co-occurs with the H145Y and L291L variants in the Nucleocapsid. Interestingly, T1117I has been scarcely reported in other latitudes (GISAID, 2020;Long et al, 2020). According to GISAID (December 31 st , 2020), T1117I occurred merely 213 times worldwide (0.08% of all samples with Spike sequence in the database) in only 19 countries, including Colombia and New Zealand.…”