Sequence Analysis of 20,453 Severe Acute Respiratory Syndrome Coronavirus 2 Genomes from the Houston Metropolitan Area Identifies the Emergence and Widespread Distribution of Multiple Isolates of All Major Variants of Concern

Abstract

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, there has been international concern about the emergence of virus variants with mutations that increase transmissibility, enhance escape from the human immune response, or otherwise alter biologically important phenotypes. In late 2020, several variants of concern emerged globally, including the UK variant (B.1.1.7), the South Africa variant (B.1.351), Brazil variants (P.1 and P.2), and two related California variants of interest (B.1.429 and B.1.427). These variants are believed to have enhanced transmissibility. For the South Africa and Brazil variants, there is evidence that mutations in spike protein permit it to escape from some vaccines and therapeutic monoclonal antibodies. On the basis of our extensive genome sequencing program involving 20,453 coronavirus disease 2019 patient samples collected from March 2020 to February 2021, we report identification of all six of these SARS-CoV-2 variants among Houston Methodist Hospital (Houston, TX) patients residing in the greater metropolitan area. Although these variants are currently at relatively low frequency (aggregate of 1.1%) in the population, they are geographically widespread. Houston is the first city in the United States in which active circulation of all six current variants of concern has been documented by genome sequencing. As vaccine deployment accelerates, increased genomic surveillance of SARS-CoV-2 is essential to understanding the presence, frequency, and medical impact of consequential variants and their patterns and trajectory of dissemination.

Figure 1

A: Schematic showing structural changes present in the spike protein of the major severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants identified in the study. B: Mapping of important changes onto the cryoEM structure of spike protein. The color scheme matches that used in A. Blue, amino-terminal domain (NTD); purple, receptor-binding domain (RBD); orange, S1 domain (S1); and yellow, S2 domain (S2). Aggregate mutations present in variants of concern are colored in red when amino acid residues are present in the resolved structure. Left panel: Side view of SARS-CoV-2 prefusion-stabilized spike. Right panel, top view: Structure of PDB 6vsb was used as reference.

Figure 2

Geospatial distribution for each variant of concern identified in the study. The home address zip code for each patient was used, and figures were generated using Tableau version 2020.3.4.