Identification and trajectory of growth of concerning SARS-CoV-2 variants in Houston, Texas, January through April 2021 based on 11,568 genome sequences

Genetic variants of the SARS-CoV-2 virus are of substantial concern because they can detrimentally alter the trajectory of the ongoing pandemic, and disease course in individual patients. Here we report genome sequences from 11,568 COVID-19 patients in the Houston Methodist healthcare system dispersed throughout the metroplex that were diagnosed from January 1, 2021 through April 30, 2021. This sample represents 94% of Houston Methodist cases and 4.6% of all reported cases in the metropolitan area during this period. The SARS-CoV-2 variant designated UK B.1.1.7 increased very rapidly, and now causes 75%-90% of all new cases in the Houston area. Five of the 2,543 B.1.1.7 genomes had an E484K change in spike protein. Compared with non-B.1.1.7 patients, individuals infected with B.1.1.7 had a significantly lower cycle threshold value (considered to be a proxy for higher virus load) and higher rate of hospitalization. Other variants (e.g., B.1.429, B.1.427, P.1, P.2, and R.1) also increased rapidly in frequency, although the magnitude was less than for B.1.1.7. We also identified 42 patients with a recently described R.1 variant that has an E484K amino acid replacement, and seven patients with the B.1.617 "India" variants. In the aggregate, our study shows the occurrence of a diverse array of concerning SARS-CoV-2 variants circulating in a major metropolitan area, documents B.1.1.7 as the major cause of new cases in Houston and heralds the arrival and spread of B.1.617 variants in the metroplex.

[1]  J. Todd,et al.  Early Analysis of a potential link between viral load and the N501Y mutation in the SARS-COV-2 spike protein , 2021, medRxiv.

[2]  D. Stuart,et al.  Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine-induced sera , 2021, Cell.

[3]  D. Thoroughman,et al.  COVID-19 Outbreak Associated with a SARS-CoV-2 R.1 Lineage Variant in a Skilled Nursing Facility After Vaccination Program — Kentucky, March 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[4]  S. W. Long,et al.  Rapid, widespread, and preferential increase of SARS-CoV-2 B.1.1.7 variant in Houston, TX, revealed by 8,857 genome sequences , 2021, medRxiv.

[5]  Neville E. Sanjana,et al.  The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types , 2020, bioRxiv.

[6]  Fangfang Xia,et al.  Population Genomic Analysis of 1,777 Extended-Spectrum Beta-Lactamase-Producing Klebsiella pneumoniae Isolates, Houston, Texas: Unexpected Abundance of Clonal Group 307 , 2017, mBio.

[7]  Stephanie S. Chen,et al.  Emergence of a Novel SARS-CoV-2 Variant in Southern California. , 2021, JAMA.

[8]  R. Ahmed,et al.  Neutralizing Antibodies Against SARS-CoV-2 Variants After Infection and Vaccination. , 2021, JAMA.

[9]  P. Horby,et al.  A novel coronavirus outbreak of global health concern , 2020, The Lancet.

[10]  William L. Hamilton,et al.  SARS-CoV-2 B.1.617.2 Delta variant replication, sensitivity to neutralising antibodies and vaccine breakthrough , 2021 .

[11]  S. Atabani,et al.  S-variant SARS-CoV-2 lineage B1.1.7 is associated with significantly higher viral loads in samples tested by ThermoFisher TaqPath RT-qPCR , 2021, The Journal of infectious diseases.

[12]  David A. Drew,et al.  The effect of SARS-CoV-2 variant B.1.1.7 on symptomatology, re-infection and transmissibility , 2021, medRxiv.

[13]  D. Tandel,et al.  N440K variant of SARS-CoV-2 has Higher Infectious Fitness , 2021, bioRxiv.

[14]  S. Lo,et al.  A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster , 2020, The Lancet.

[15]  Stephanie S. Chen,et al.  Emergence of a novel SARS-CoV-2 strain in Southern California, USA , 2021, medRxiv.

[16]  N. Lennon,et al.  Estimating epidemiologic dynamics from cross-sectional viral load distributions , 2020, medRxiv.

[17]  S. Panda,et al.  Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees , 2021, bioRxiv.

[18]  Carl A. B. Pearson,et al.  Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England , 2021, Science.

[19]  D. Bonsall,et al.  Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial , 2021, The Lancet.

[20]  S. W. Long,et al.  Evolutionary pathway to increased virulence and epidemic group A Streptococcus disease derived from 3,615 genome sequences , 2014, Proceedings of the National Academy of Sciences.

[21]  D. A. Jackson,et al.  Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity , 2020, Cell.

[22]  H. Jäck,et al.  SARS-CoV-2 variant B.1.617 is resistant to bamlanivimab and evades antibodies induced by infection and vaccination , 2021, bioRxiv.

[23]  Jessica E. Rothman,et al.  Early introductions and transmission of SARS-CoV-2 variant B.1.1.7 in the United States , 2021, Cell.

[24]  James J. Davis,et al.  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 , 2021, The American Journal of Pathology.

[25]  M. Nguyen,et al.  Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas , 2020, bioRxiv.

[26]  Noah R. Baker,et al.  Variants of Concern Are Overrepresented Among Postvaccination Breakthrough Infections of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Washington State , 2021, medRxiv.

[27]  M. Biggerstaff,et al.  Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[28]  M. Omata,et al.  Household transmission of SARS-CoV-2 R.1 lineage with spike E484K mutation in Japan , 2021, medRxiv.

[29]  J. Skehel,et al.  The effect of the D614G substitution on the structure of the spike glycoprotein of SARS-CoV-2 , 2021, Proceedings of the National Academy of Sciences.

[30]  Kimihito Ito,et al.  Estimating the increased transmissibility of the B.1.1.7 strain over previously circulating strains in England using fractions of GISAID sequences and the distribution of serial intervals , 2021, medRxiv.

[31]  Emily R. Davenport,et al.  Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis , 2019, Nature Genetics.

[32]  M. Stephens,et al.  Traces of Human Migrations in Helicobacter pylori Populations , 2003, Science.

[33]  Y. Hu,et al.  Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China , 2020, The Lancet.

[34]  N. Loman,et al.  Transmission of SARS-CoV-2 Lineage B.1.1.7 in England: Insights from linking epidemiological and genetic data , 2021, medRxiv.

[35]  D. Altmann,et al.  Immunity to SARS-CoV-2 variants of concern , 2021, Science.

[36]  Neville E. Sanjana,et al.  The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types , 2021, eLife.

[37]  K. Allel,et al.  Country-level factors associated with the early spread of COVID-19 cases at 5, 10 and 15 days since the onset , 2020, Global public health.

[38]  S. Panda,et al.  SARS CoV-2 variant B.1.617.1 is highly pathogenic in hamsters than B.1 variant , 2021, bioRxiv.

[39]  R. Walensky,et al.  SARS-CoV-2 Variants of Concern in the United States-Challenges and Opportunities. , 2021, JAMA.

[40]  S. Singh,et al.  Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India , 2021, bioRxiv.

[41]  P. Marrack,et al.  501Y.V2 and 501Y.V3 variants of SARS-CoV-2 lose binding to Bamlanivimab in vitro , 2021, bioRxiv.

[42]  A. Tanuri,et al.  Genomic Characterization of a Novel SARS-CoV-2 Lineage from Rio de Janeiro, Brazil , 2020, Journal of Virology.

[43]  L. Nolen,et al.  COVID-19 Vaccine Breakthrough Infections Reported to CDC — United States, January 1–April 30, 2021 , 2021, MMWR. Morbidity and mortality weekly report.

[44]  Lars B. Christoffersen,et al.  Increased Transmissibility of SARS-CoV-2 Lineage B.1.1.7 by Age and Viral Load: Evidence from Danish Households , 2021, medRxiv.

[45]  Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization , 2021, Cell Host & Microbe.

[46]  P. Horby,et al.  Analysis of severe outcomes associated with the SARS-CoV-2 Variant of Concern 202012/01 in England using ICNARC Case Mix Programme and QResearch databases. , 2021, medRxiv.

[47]  A. M. Leontovich,et al.  The species Severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2 , 2020, Nature Microbiology.

[48]  S. W. Long,et al.  Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case report, pathogen genome sequencing, pathology, and coordinated response. , 2011, Archives of pathology & laboratory medicine.

[49]  J. Snowdon,et al.  Introductions and evolutions of SARS-CoV-2 strains in Japan , 2021, medRxiv.

[50]  D. Ho,et al.  Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization , 2021, bioRxiv.

[51]  E. Holmes,et al.  A new coronavirus associated with human respiratory disease in China , 2020, Nature.

[52]  S. Rowland-Jones,et al.  Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus , 2020, Cell.

[53]  Randall J. Olsen,et al.  Absence of Patient-to-Patient Intrahospital Transmission of Staphylococcus aureus as Determined by Whole-Genome Sequencing , 2014, mBio.

[54]  Sergei L. Kosakovsky Pond,et al.  Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa , 2020, medRxiv.

[55]  P. Dormitzer,et al.  Neutralization of SARS-CoV-2 lineage B.1.1.7 pseudovirus by BNT162b2 vaccine–elicited human sera , 2021, Science.

[56]  S. Alizon,et al.  Epidemiological and clinical insights from SARS-CoV-2 RT-PCR cycle amplification values , 2021, medRxiv.

[57]  G. Rodger,et al.  An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status , 2021, medRxiv.

[58]  E. Hodcroft,et al.  Public health actions to control new SARS-CoV-2 variants , 2021, Cell.

[59]  Gene W. Yeo,et al.  Emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States , 2021, Cell.

[60]  J. Wise.  Covid-19: The E484K mutation and the risks it poses , 2021, BMJ.

[61]  William T. Harvey,et al.  Author Correction: Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies , 2021, Nature.

[62]  James J. Davis,et al.  Molecular Architecture of Early Dissemination and Massive Second Wave of the SARS-CoV-2 Virus in a Major Metropolitan Area , 2020, medRxiv.

[63]  Elisabeth Mahase.  Covid-19: Where are we on vaccines and variants? , 2021, BMJ.

[64]  M. Singer,et al.  Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study , 2021, The Lancet Infectious Diseases.

[65]  Vineet D. Menachery,et al.  Spike mutation D614G alters SARS-CoV-2 fitness , 2020, Nature.

[66]  J. Farrar,et al.  Increased infections, but not viral burden, with a new SARS-CoV-2 variant , 2021 .

[67]  L. Danon,et al.  Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study , 2021, BMJ.

[68]  James J. Davis,et al.  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 , 2021, The American Journal of Pathology.

[69]  M. Shankar-Hari,et al.  Virological and serological characterization of critically ill patient with COVID-19 in the UK: a special focus on variant detection , 2021, medRxiv.

[70]  V. Scaria,et al.  Symptomatic reinfection of SARS‐CoV‐2 with spike protein variant N440K associated with immune escape , 2021, Journal of medical virology.

[71]  S. Panda,et al.  Neutralization of variant under investigation B.1.617 with sera of BBV152 vaccinees. , 2021, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[72]  T. Kurth,et al.  Emergence of SARS-CoV-2 B.1.1.7 Lineage at Outpatient Testing Site, Berlin, Germany, January–March 2021 , 2021, Emerging infectious diseases.

[73]  S. Kissler,et al.  Densely sampled viral trajectories suggest longer duration of acute infection with B.1.1.7 variant relative to non-B.1.1.7 SARS-CoV-2 , 2021, medRxiv.

[74]  B. Graham,et al.  mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants , 2021, bioRxiv.

[75]  J. Mascola,et al.  SARS-CoV-2 Viral Variants-Tackling a Moving Target. , 2021, JAMA.

[76]  Haiyong Peng,et al.  SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity , 2020, Nature Communications.

[77]  D. Stuart,et al.  Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera , 2021, Cell.

[78]  G. Gao,et al.  A Novel Coronavirus from Patients with Pneumonia in China, 2019 , 2020, The New England journal of medicine.

[79]  R. Andino,et al.  Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant , 2021, Cell.

[80]  J. Bloom,et al.  Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies , 2021, bioRxiv.