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Published on 02/11/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.
    Ng Dianna L et al. Science advances 2021 02 (6)
    We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 86% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for diagnosis.
  • Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality.
    Dumonteil Eric et al. Viruses 2021 Feb (2)
    Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality.
  • SARS-CoV-2 Worldwide Replication Drives Rapid Rise and Selection of Mutations across the Viral Genome: A Time-Course Study Potential Challenge for Vaccines and Therapies
    S Weber et al, MEDRXIV, February 6, 2021
    We have followed time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries. We examined complete SARS-CoV-2 nucleotide sequences in GISAID with sampling extending until January 20, 2021. These sequences originated from ten different countries. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations.
  • Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants
    CY Tang et al, MEDRXIV, February 5, 2021
    In this study, we investigated the emergence and spread of SARS-CoV-2 genetic variants in Missouri, examined viral shedding over time, and analyzed the associations among emerging genetic variants, viral shedding, and disease severity. We found that COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.
  • Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
    NL Washington et al, MEDRXIV, February 7, 2021
    We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant.
  • Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
    X Xie et al, Nature Medicine, February 8, 2021
    We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y?+?D614G from UK; and E484K?+?N501Y?+?D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.
  • Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
    M DeVitt, MEDRXIV, February 9, 2021
    Several cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021. This variant has been associated with higher levels of transmissibility. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number.
  • Coronavirus Likely Came From Animal, Not Leaked From Laboratory, WHO Says
    Page J, et al. Wall Street Journal, Feb 9, 2021.
  • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
    Z Wang et al, Nature, February 10, 2021
    Activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors5–8. Neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations.
  • Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2
    D Yu et al, MEDRXIV, February 10, 2021
    We developed the Coronavirus GenBrowser (CGB)using 178,765 high quality SARS-CoV-2 genomic sequences. 121,522 mutations were identified. In total, 1,041 mutation cold spots were found, suggesting that these spots are key functional elements of SARS-CoV-2 and can be used for detection and vaccine development. CGB revealed 203 accelerated evolutions of SARS-CoV-2, but variants with accelerated evolution were not highly contagious, suggesting that most of these evolutions are neutral.

Non-Genomics Precision Health Studies

  • A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.
    Ng Dianna L et al. Science advances 2021 02 (6)
    We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 86% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for diagnosis.
  • Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality.
    Dumonteil Eric et al. Viruses 2021 Feb (2)
    Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality.
  • SARS-CoV-2 Worldwide Replication Drives Rapid Rise and Selection of Mutations across the Viral Genome: A Time-Course Study Potential Challenge for Vaccines and Therapies
    S Weber et al, MEDRXIV, February 6, 2021
    We have followed time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries. We examined complete SARS-CoV-2 nucleotide sequences in GISAID with sampling extending until January 20, 2021. These sequences originated from ten different countries. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations.
  • Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants
    CY Tang et al, MEDRXIV, February 5, 2021
    In this study, we investigated the emergence and spread of SARS-CoV-2 genetic variants in Missouri, examined viral shedding over time, and analyzed the associations among emerging genetic variants, viral shedding, and disease severity. We found that COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.
  • Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
    NL Washington et al, MEDRXIV, February 7, 2021
    We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant.
  • Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
    X Xie et al, Nature Medicine, February 8, 2021
    We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y?+?D614G from UK; and E484K?+?N501Y?+?D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.
  • Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
    M DeVitt, MEDRXIV, February 9, 2021
    Several cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021. This variant has been associated with higher levels of transmissibility. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number.
  • Coronavirus Likely Came From Animal, Not Leaked From Laboratory, WHO Says
    Page J, et al. Wall Street Journal, Feb 9, 2021.
  • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
    Z Wang et al, Nature, February 10, 2021
    Activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors5–8. Neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations.
  • Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2
    D Yu et al, MEDRXIV, February 10, 2021
    We developed the Coronavirus GenBrowser (CGB)using 178,765 high quality SARS-CoV-2 genomic sequences. 121,522 mutations were identified. In total, 1,041 mutation cold spots were found, suggesting that these spots are key functional elements of SARS-CoV-2 and can be used for detection and vaccine development. CGB revealed 203 accelerated evolutions of SARS-CoV-2, but variants with accelerated evolution were not highly contagious, suggesting that most of these evolutions are neutral.

News, Reviews and Commentaries

  • A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.
    Ng Dianna L et al. Science advances 2021 02 (6)
    We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 86% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for diagnosis.
  • Genomic Signatures of SARS-CoV-2 Associated with Patient Mortality.
    Dumonteil Eric et al. Viruses 2021 Feb (2)
    Phylogenetic analysis of SARS-CoV-2 genome sequences revealed four well-resolved clades which had significantly different mortality rates, even after adjusting for patient demographic and geographic characteristics. We further identified ten single-nucleotide polymorphisms (SNPs) in the SARS-CoV-2 genome that were associated with patient mortality.
  • SARS-CoV-2 Worldwide Replication Drives Rapid Rise and Selection of Mutations across the Viral Genome: A Time-Course Study Potential Challenge for Vaccines and Therapies
    S Weber et al, MEDRXIV, February 6, 2021
    We have followed time course of emerging viral mutants and variants during the SARS-CoV-2 pandemic in ten countries. We examined complete SARS-CoV-2 nucleotide sequences in GISAID with sampling extending until January 20, 2021. These sequences originated from ten different countries. Despite lockdowns, worldwide active replication in genetically and socio-economically diverse populations facilitated selection of new mutations.
  • Increased SAR-CoV-2 shedding associated with reduced disease severity despite continually emerging genetic variants
    CY Tang et al, MEDRXIV, February 5, 2021
    In this study, we investigated the emergence and spread of SARS-CoV-2 genetic variants in Missouri, examined viral shedding over time, and analyzed the associations among emerging genetic variants, viral shedding, and disease severity. We found that COVID-positive individuals that presented with increased viral shedding had less severe disease by several measures.
  • Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States
    NL Washington et al, MEDRXIV, February 7, 2021
    We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant.
  • Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera
    X Xie et al, Nature Medicine, February 8, 2021
    We engineered three severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses containing key spike mutations from the newly emerged United Kingdom (UK) and South African (SA) variants: N501Y from UK and SA; 69/70-deletion + N501Y?+?D614G from UK; and E484K?+?N501Y?+?D614G from SA. Neutralization geometric mean titers (GMTs) of 20 BTN162b2 vaccine-elicited human sera against the three mutant viruses were 0.81- to 1.46-fold of the GMTs against parental virus, indicating small effects of these mutations on neutralization by sera elicited by two BNT162b2 doses.
  • Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
    M DeVitt, MEDRXIV, February 9, 2021
    Several cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021. This variant has been associated with higher levels of transmissibility. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number.
  • Coronavirus Likely Came From Animal, Not Leaked From Laboratory, WHO Says
    Page J, et al. Wall Street Journal, Feb 9, 2021.
  • mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants
    Z Wang et al, Nature, February 10, 2021
    Activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors5–8. Neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations.
  • Coronavirus GenBrowser for monitoring the transmission and evolution of SARS-CoV-2
    D Yu et al, MEDRXIV, February 10, 2021
    We developed the Coronavirus GenBrowser (CGB)using 178,765 high quality SARS-CoV-2 genomic sequences. 121,522 mutations were identified. In total, 1,041 mutation cold spots were found, suggesting that these spots are key functional elements of SARS-CoV-2 and can be used for detection and vaccine development. CGB revealed 203 accelerated evolutions of SARS-CoV-2, but variants with accelerated evolution were not highly contagious, suggesting that most of these evolutions are neutral.
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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