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Published on 01/28/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • Genome Sequencing of Sewage Detects Regionally Prevalent SARS-CoV-2 Variants.
    Crits-Christoph Alexander et al. mBio 2021 01 (1)
    we sequenced RNA directly from sewage collected by municipal utility districts in the San Francisco Bay Area to generate SARS-CoV-2 genomes. The genotypes detected in the sewage were identical to clinical genomes from the region. Observed wastewater variants were more similar to local California patient-derived genotypes than they were to those from other regions within the United States or globally.
  • Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking
    L Davo et al, MEDRXIV, January 22, 2021
    This study demonstrates that intermittent or persistent detection of SARS-CoV-2 RNA in nursing home sewers can provide an early warning of subsequent individual cases or outbreaks in these facilities.
  • Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020.
    Leung Kathy et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 01 (1)
    Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion ?69/?70, circulating mainly between early September and mid-November, was 10% (6-13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion ?69/?70, circulating since late September, was 75% (70-80%) more transmissible than 501N.
  • Investigation of novel SARS-CoV-2 variant: Variant of Concern 202012/01
    (Technical briefing document) Public Health England, UK. Updated Jan 15, 2021.
  • Global absence and targeting of protective immune states in severe COVID-19
    AJ Combes et al, NATURE, January 25, 2021
    We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease.
  • SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark
    Hammer AS, et al. Emerg Infect Dis, Feb 2021.
    Severe acute respiratory syndrome coronavirus 2 has caused a pandemic in humans. Farmed mink (Neovison vison) are also susceptible. In Denmark, this virus has spread rapidly among farmed mink, resulting in some respiratory disease. Full-length virus genome sequencing revealed novel virus variants in mink. These variants subsequently appeared within the local human community.
  • High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants
    RS Fontenele et al, MEDRXIV, January 25, 2021
    We analyzed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). We undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with >90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 5680 were novel SNVs that had not yet been identified in the global clinical-derived data.
  • Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
    PA Wang et al, BIORXIV, January 26, 2021
    Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD).
  • Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19
    H Vietzen et al, Genetics in Medicine, January 26, 2021
    We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19. Both were significantly overrepresented in hospitalized patients, particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms.
  • Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
    Z Liu et al, Host Cell and Microbe, January 27, 2021
    Summary: Generation of SARS-CoV-2 spike mutants that escape antibody neutralization. Mutant S477N is resistant to neutralization by multiple monoclonal antibodies. Mutant E484K is less sensitive to neutralization by convalescent human sera. Sequential selection identifies mutants that escape neutralization by antibody cocktails.
  • Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
    TN Starr et al, Science, January 25, 2021
    We map how mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2. The maps reveal that mutations escaping the individual antibodies are already present in circulating strains. Overall, these escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

Non-Genomics Precision Health Studies

  • Genome Sequencing of Sewage Detects Regionally Prevalent SARS-CoV-2 Variants.
    Crits-Christoph Alexander et al. mBio 2021 01 (1)
    we sequenced RNA directly from sewage collected by municipal utility districts in the San Francisco Bay Area to generate SARS-CoV-2 genomes. The genotypes detected in the sewage were identical to clinical genomes from the region. Observed wastewater variants were more similar to local California patient-derived genotypes than they were to those from other regions within the United States or globally.
  • Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking
    L Davo et al, MEDRXIV, January 22, 2021
    This study demonstrates that intermittent or persistent detection of SARS-CoV-2 RNA in nursing home sewers can provide an early warning of subsequent individual cases or outbreaks in these facilities.
  • Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020.
    Leung Kathy et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 01 (1)
    Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion ?69/?70, circulating mainly between early September and mid-November, was 10% (6-13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion ?69/?70, circulating since late September, was 75% (70-80%) more transmissible than 501N.
  • Investigation of novel SARS-CoV-2 variant: Variant of Concern 202012/01
    (Technical briefing document) Public Health England, UK. Updated Jan 15, 2021.
  • Global absence and targeting of protective immune states in severe COVID-19
    AJ Combes et al, NATURE, January 25, 2021
    We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease.
  • SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark
    Hammer AS, et al. Emerg Infect Dis, Feb 2021.
    Severe acute respiratory syndrome coronavirus 2 has caused a pandemic in humans. Farmed mink (Neovison vison) are also susceptible. In Denmark, this virus has spread rapidly among farmed mink, resulting in some respiratory disease. Full-length virus genome sequencing revealed novel virus variants in mink. These variants subsequently appeared within the local human community.
  • High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants
    RS Fontenele et al, MEDRXIV, January 25, 2021
    We analyzed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). We undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with >90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 5680 were novel SNVs that had not yet been identified in the global clinical-derived data.
  • Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
    PA Wang et al, BIORXIV, January 26, 2021
    Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD).
  • Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19
    H Vietzen et al, Genetics in Medicine, January 26, 2021
    We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19. Both were significantly overrepresented in hospitalized patients, particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms.
  • Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
    Z Liu et al, Host Cell and Microbe, January 27, 2021
    Summary: Generation of SARS-CoV-2 spike mutants that escape antibody neutralization. Mutant S477N is resistant to neutralization by multiple monoclonal antibodies. Mutant E484K is less sensitive to neutralization by convalescent human sera. Sequential selection identifies mutants that escape neutralization by antibody cocktails.
  • Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
    TN Starr et al, Science, January 25, 2021
    We map how mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2. The maps reveal that mutations escaping the individual antibodies are already present in circulating strains. Overall, these escape maps enable interpretation of the consequences of mutations observed during viral surveillance.

News, Reviews and Commentaries

  • Genome Sequencing of Sewage Detects Regionally Prevalent SARS-CoV-2 Variants.
    Crits-Christoph Alexander et al. mBio 2021 01 (1)
    we sequenced RNA directly from sewage collected by municipal utility districts in the San Francisco Bay Area to generate SARS-CoV-2 genomes. The genotypes detected in the sewage were identical to clinical genomes from the region. Observed wastewater variants were more similar to local California patient-derived genotypes than they were to those from other regions within the United States or globally.
  • Early detection of SARS-CoV-2 infection cases or outbreaks at nursing homes by targeted wastewater tracking
    L Davo et al, MEDRXIV, January 22, 2021
    This study demonstrates that intermittent or persistent detection of SARS-CoV-2 RNA in nursing home sewers can provide an early warning of subsequent individual cases or outbreaks in these facilities.
  • Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020.
    Leung Kathy et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 01 (1)
    Two new SARS-CoV-2 lineages with the N501Y mutation in the receptor-binding domain of the spike protein spread rapidly in the United Kingdom. We estimated that the earlier 501Y lineage without amino acid deletion ?69/?70, circulating mainly between early September and mid-November, was 10% (6-13%) more transmissible than the 501N lineage, and the 501Y lineage with amino acid deletion ?69/?70, circulating since late September, was 75% (70-80%) more transmissible than 501N.
  • Investigation of novel SARS-CoV-2 variant: Variant of Concern 202012/01
    (Technical briefing document) Public Health England, UK. Updated Jan 15, 2021.
  • Global absence and targeting of protective immune states in severe COVID-19
    AJ Combes et al, NATURE, January 25, 2021
    We performed a whole-blood preserving single-cell analysis protocol to integrate contributions from all major cell types including neutrophils, monocytes, platelets, lymphocytes and the contents of serum. Patients with mild COVID-19 disease display a coordinated pattern of interferon-stimulated gene (ISG) expression across every cell population and these cells are systemically absent in patients with severe disease. Severe COVID-19 patients also paradoxically produce very high anti-SARS-CoV-2 antibody titers and have lower viral load as compared to mild disease.
  • SARS-CoV-2 Transmission between Mink (Neovison vison) and Humans, Denmark
    Hammer AS, et al. Emerg Infect Dis, Feb 2021.
    Severe acute respiratory syndrome coronavirus 2 has caused a pandemic in humans. Farmed mink (Neovison vison) are also susceptible. In Denmark, this virus has spread rapidly among farmed mink, resulting in some respiratory disease. Full-length virus genome sequencing revealed novel virus variants in mink. These variants subsequently appeared within the local human community.
  • High-throughput sequencing of SARS-CoV-2 in wastewater provides insights into circulating variants
    RS Fontenele et al, MEDRXIV, January 25, 2021
    We analyzed 91 wastewater samples from 11 states in the USA, where the majority of samples represent Maricopa County, Arizona (USA). We undertook a single-nucleotide variant (SNV) analysis on data from 52 samples with >90% SARS-CoV-2 genome coverage of sequence reads, and compared these SNVs with those detected in genomes sequenced from clinical patients. We identified 7973 SNVs, of which 5680 were novel SNVs that had not yet been identified in the global clinical-derived data.
  • Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
    PA Wang et al, BIORXIV, January 26, 2021
    Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK and B.1.351 in South Africa is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD).
  • Deletion of the NKG2C receptor encoding KLRC2 gene and HLA-E variants are risk factors for severe COVID-19
    H Vietzen et al, Genetics in Medicine, January 26, 2021
    We investigated the distribution of KLRC2 deletion and HLA-E*0101/0103 allelic variants in a study cohort of 361 patients with either mild (N = 92) or severe (N = 269) COVID-19. Both were significantly overrepresented in hospitalized patients, particularly in patients requiring intensive care (p < 0.0001 and p = 0.01), compared with patients with mild symptoms.
  • Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization
    Z Liu et al, Host Cell and Microbe, January 27, 2021
    Summary: Generation of SARS-CoV-2 spike mutants that escape antibody neutralization. Mutant S477N is resistant to neutralization by multiple monoclonal antibodies. Mutant E484K is less sensitive to neutralization by convalescent human sera. Sequential selection identifies mutants that escape neutralization by antibody cocktails.
  • Prospective mapping of viral mutations that escape antibodies used to treat COVID-19
    TN Starr et al, Science, January 25, 2021
    We map how mutations to SARS-CoV-2’s receptor-binding domain (RBD) affect binding by the antibodies in the REGN-COV2 cocktail and the antibody LY-CoV016. These complete maps uncover a single amino-acid mutation that fully escapes the REGN-COV2 cocktail. The maps also identify viral mutations that are selected in a persistently infected patient treated with REGN-COV2. The maps reveal that mutations escaping the individual antibodies are already present in circulating strains. Overall, these escape maps enable interpretation of the consequences of mutations observed during viral surveillance.
Disclaimer: Articles listed in COVID-19 Genomics and Precision Public Health Weekly Update are selected by Public Health Genomics Branch to provide current awareness of the scientific literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the Clips, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.
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