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Published on 02/25/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.
    Zeberg Hugo et al. Proceedings of the National Academy of Sciences of the United States of America 2021 03 (9)
    Using data from the GenOMICC consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease
  • High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing.
    Bhoyar Rahul C et al. PloS one 2021 (2) e0247115
    The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2.
  • Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677.
    Hodcroft Emma B et al. medRxiv : the preprint server for health sciences 2021 Feb
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2).
  • Genomic Evidence of SARS-CoV-2 Reinfection Involving E484K Spike Mutation, Brazil.
    Nonaka Carolina K V et al. Emerging infectious diseases 2021 Feb (5)
    Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies
  • Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
    J Masoli et al, MEDRXIV, February 19, 2021
    Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests. Findings Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns
  • SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts
    RN Tasakis et al, BIORXIV, February 19,2021
    Our study focuses on a representative set of sequences from the United States throughout 2020 and early 2021. We show that the driving force behind the variants of public health concern, is widespread infection and superspreader events. In particular, we show accumulation of mutations over time with little loss from genetic drift, including in the Spike region, which could be problematic for vaccines and therapies.
  • Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.
    Bénard Alan et al. Nature communications 2021 02 (1) 1112
    In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNa and IFN? levels when compared to non-severe COVID-19 patients
  • Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
    V Tchesnokova et al, BIORXIV, February 22, 2021
    Ee investigated genetic variations in a 414-583 amino acid region of the Spike protein, across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with multiple outbreaks.
  • Estimating the spreading and dominance of SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) across Europe
    N Gozzi et al, MEDRXIV, February 23, 2021
    We develop a two strain,compartmental model to assess the spreading potential of the B.1.1.7 variant across several European countries. The model accounts for B.1.1.7 introductions from the UK and different locations, as well as local mitigation policies in the time period 2020/09-2021/02. In the case of an increase of transmissibility of 50%, the B.1.1.7 variant has the potential to become dominant in all investigated areas by the end of March 2021.
  • Wastewater Monitoring of SARS-CoV-2 from Acute Care Hospitals Identifies Nosocomial Transmission and Outbreaks
    N Acosta et al, MEDRXIV, February 23, 2021
    SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Methods: Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totalling >2100 dedicated inpatient beds) were collected.
  • No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants
    Q Li et al, Cell, February 23, 2021
    The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed.
  • Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera
    D Zhou et al, Cell, February 23, 2021
    We describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.
  • BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
    N Dagan et al, NEJM, February 24, 2021
    In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% and 92% for symptomatic Covid-19, 57% and 94% for hospitalization, 74% and 87% and for severe disease, 62% and 92%, respectively.

Non-Genomics Precision Health Studies

  • A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.
    Zeberg Hugo et al. Proceedings of the National Academy of Sciences of the United States of America 2021 03 (9)
    Using data from the GenOMICC consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease
  • High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing.
    Bhoyar Rahul C et al. PloS one 2021 (2) e0247115
    The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2.
  • Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677.
    Hodcroft Emma B et al. medRxiv : the preprint server for health sciences 2021 Feb
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2).
  • Genomic Evidence of SARS-CoV-2 Reinfection Involving E484K Spike Mutation, Brazil.
    Nonaka Carolina K V et al. Emerging infectious diseases 2021 Feb (5)
    Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies
  • Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
    J Masoli et al, MEDRXIV, February 19, 2021
    Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests. Findings Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns
  • SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts
    RN Tasakis et al, BIORXIV, February 19,2021
    Our study focuses on a representative set of sequences from the United States throughout 2020 and early 2021. We show that the driving force behind the variants of public health concern, is widespread infection and superspreader events. In particular, we show accumulation of mutations over time with little loss from genetic drift, including in the Spike region, which could be problematic for vaccines and therapies.
  • Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.
    Bénard Alan et al. Nature communications 2021 02 (1) 1112
    In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNa and IFN? levels when compared to non-severe COVID-19 patients
  • Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
    V Tchesnokova et al, BIORXIV, February 22, 2021
    Ee investigated genetic variations in a 414-583 amino acid region of the Spike protein, across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with multiple outbreaks.
  • Estimating the spreading and dominance of SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) across Europe
    N Gozzi et al, MEDRXIV, February 23, 2021
    We develop a two strain,compartmental model to assess the spreading potential of the B.1.1.7 variant across several European countries. The model accounts for B.1.1.7 introductions from the UK and different locations, as well as local mitigation policies in the time period 2020/09-2021/02. In the case of an increase of transmissibility of 50%, the B.1.1.7 variant has the potential to become dominant in all investigated areas by the end of March 2021.
  • Wastewater Monitoring of SARS-CoV-2 from Acute Care Hospitals Identifies Nosocomial Transmission and Outbreaks
    N Acosta et al, MEDRXIV, February 23, 2021
    SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Methods: Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totalling >2100 dedicated inpatient beds) were collected.
  • No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants
    Q Li et al, Cell, February 23, 2021
    The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed.
  • Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera
    D Zhou et al, Cell, February 23, 2021
    We describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.
  • BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
    N Dagan et al, NEJM, February 24, 2021
    In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% and 92% for symptomatic Covid-19, 57% and 94% for hospitalization, 74% and 87% and for severe disease, 62% and 92%, respectively.

News, Reviews and Commentaries

  • A genomic region associated with protection against severe COVID-19 is inherited from Neandertals.
    Zeberg Hugo et al. Proceedings of the National Academy of Sciences of the United States of America 2021 03 (9)
    Using data from the GenOMICC consortium, we show that a haplotype at a region on chromosome 12 associated with requiring intensive care when infected with the virus is inherited from Neandertals. This region encodes proteins that activate enzymes that are important during infections with RNA viruses. In contrast to the previously described Neandertal haplotype that increases the risk for severe COVID-19, this Neandertal haplotype is protective against severe disease
  • High throughput detection and genetic epidemiology of SARS-CoV-2 using COVIDSeq next-generation sequencing.
    Bhoyar Rahul C et al. PloS one 2021 (2) e0247115
    The rapid emergence of coronavirus disease 2019 (COVID-19) as a global pandemic affecting millions of individuals globally has necessitated sensitive and high-throughput approaches for the diagnosis, surveillance, and determining the genetic epidemiology of SARS-CoV-2. In the present study, we used the COVIDSeq protocol, which involves multiplex-PCR, barcoding, and sequencing of samples for high-throughput detection and deciphering the genetic epidemiology of SARS-CoV-2.
  • Emergence in late 2020 of multiple lineages of SARS-CoV-2 Spike protein variants affecting amino acid position 677.
    Hodcroft Emma B et al. medRxiv : the preprint server for health sciences 2021 Feb
    The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) plays critical roles in host cell entry. Non-synonymous substitutions affecting S are not uncommon and have become fixed in a number of SARS-CoV-2 lineages. A subset of such mutations enable escape from neutralizing antibodies or are thought to enhance transmission through mechanisms such as increased affinity for the cell entry receptor, angiotensin-converting enzyme 2 (ACE2).
  • Genomic Evidence of SARS-CoV-2 Reinfection Involving E484K Spike Mutation, Brazil.
    Nonaka Carolina K V et al. Emerging infectious diseases 2021 Feb (5)
    Uncertainty remains about how long the protective immune responses against severe acute respiratory syndrome coronavirus 2 persists, and suspected reinfection in recovered patients has been reported. We describe a case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies
  • Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak
    J Masoli et al, MEDRXIV, February 19, 2021
    Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests. Findings Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns
  • SARS-CoV-2 variant evolution in the United States: High accumulation of viral mutations over time likely through serial Founder Events and mutational bursts
    RN Tasakis et al, BIORXIV, February 19,2021
    Our study focuses on a representative set of sequences from the United States throughout 2020 and early 2021. We show that the driving force behind the variants of public health concern, is widespread infection and superspreader events. In particular, we show accumulation of mutations over time with little loss from genetic drift, including in the Spike region, which could be problematic for vaccines and therapies.
  • Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections.
    Bénard Alan et al. Nature communications 2021 02 (1) 1112
    In a prospective multicentric study, we identify IL-3 as an independent prognostic marker for the outcome during SARS-CoV-2 infections. Specifically, low plasma IL-3 levels is associated with increased severity, viral load, and mortality during SARS-CoV-2 infections. Patients with severe COVID-19 exhibit also reduced circulating plasmacytoid dendritic cells (pDCs) and low plasma IFNa and IFN? levels when compared to non-severe COVID-19 patients
  • Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants
    V Tchesnokova et al, BIORXIV, February 22, 2021
    Ee investigated genetic variations in a 414-583 amino acid region of the Spike protein, across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with multiple outbreaks.
  • Estimating the spreading and dominance of SARS-CoV-2 VOC 202012/01 (lineage B.1.1.7) across Europe
    N Gozzi et al, MEDRXIV, February 23, 2021
    We develop a two strain,compartmental model to assess the spreading potential of the B.1.1.7 variant across several European countries. The model accounts for B.1.1.7 introductions from the UK and different locations, as well as local mitigation policies in the time period 2020/09-2021/02. In the case of an increase of transmissibility of 50%, the B.1.1.7 variant has the potential to become dominant in all investigated areas by the end of March 2021.
  • Wastewater Monitoring of SARS-CoV-2 from Acute Care Hospitals Identifies Nosocomial Transmission and Outbreaks
    N Acosta et al, MEDRXIV, February 23, 2021
    SARS-CoV-2 has been detected in wastewater and its abundance correlated with community COVID-19 cases, hospitalizations and deaths. We sought to use wastewater-based detection of SARS-CoV-2 to assess the epidemiology of SARS-CoV-2 in hospitals. Methods: Between August and December 2020, twice-weekly wastewater samples from three tertiary-care hospitals (totalling >2100 dedicated inpatient beds) were collected.
  • No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants
    Q Li et al, Cell, February 23, 2021
    The 501Y.V2 variants of SARS-CoV-2 containing multiple mutations in Spike are now dominant in South Africa and are rapidly spreading to other countries. Here, experiments with 18 pseudotyped viruses showed that the 501Y.V2 variants do not confer increased infectivity in multiple cell types except for murine ACE2-overexpressing cells, where a substantial increase in infectivity was observed.
  • Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera
    D Zhou et al, Cell, February 23, 2021
    We describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. In a number of cases it would appear that convalescent and some vaccine serum offers limited protection against this variant.
  • BNT162b2 mRNA Covid-19 Vaccine in a Nationwide Mass Vaccination Setting
    N Dagan et al, NEJM, February 24, 2021
    In this study, data from Israel’s largest health care organization were used to evaluate the effectiveness of the BNT162b2 mRNA vaccine. Estimated vaccine effectiveness for the study outcomes at days 14 through 20 after the first dose and at 7 or more days after the second dose was as follows: for documented infection, 46% and 92% for symptomatic Covid-19, 57% and 94% for hospitalization, 74% and 87% and for severe disease, 62% and 92%, respectively.
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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