Published on 05/20/2021
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations.
Zhao Yanan et al. Emerging microbes & infections 2021 5 1-11We developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 1135 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey between late December 2020 and March 2021. -
Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein.
Heinzelman Pete et al. PloS one 2021 5 (5) e0251585We experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. -
A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa
E Wilkinson et al, MEDRXIV, May 13, 2021We describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1 -
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.
Collier Ai-Ris Y et al. JAMA 2021 5In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern. -
Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.
Lopez Bernal Jamie et al. BMJ (Clinical research ed.) 2021 5 n1088Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found -
SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression.
A Nemundryi et al, Cell Reports, May 13, 2021Over 950,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral challenge experiments to link this isolate (ORF7a?115) to a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation negates anti-immune activities of the protein, which results in elevated type I interferon response to the viral infection. -
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection
DS Khoury et al, Nature Medicine, May 17, 2021Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from SARS-CoV-2 infection using data from seven current vaccines and from convalescent cohorts. we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. -
Rapidly emerging SARS-CoV-2 B.1.1.7 sub-lineage in the United States of America with spike protein D178H and membrane protein V70L mutations
L Shen et al, MEDRXIV, May 18 2021We recently identified several emerging SARS-CoV-2 variants of concerns, characterized by Membrane (M) protein mutations, including I82T and V70L. We now identify a sub-lineage of B.1.1.7 that emerged through sequential acquisitions of M:V70L in November 2020 followed by a novel S:D178H mutation first observed in early February 2021. The percentage of B.1.1.7 isolates in the U.S. that belong to this sub-lineage increased from 0.15% in February 2021 to 1.8% in April 2021. To date this sub-lineage appears to be U.S.-specific with reported cases in 31 states, including Hawaii. As of April 2021 it constituted 36.8% of all B.1.1.7 isolates in Washington. -
Diverse Functional Autoantibodies in Patients with COVID-19
EY Wang et al, Nature, May 19, 2021We used a high-throughput autoantibody (AAb) discovery technique called Rapid Extracellular Antigen Profiling (REAP)7 to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. -
ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.
Möhlendick Birte et al. Pharmacogenetics and genomics 2021 5We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease.
Non-Genomics Precision Health Studies
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A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations.
Zhao Yanan et al. Emerging microbes & infections 2021 5 1-11We developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 1135 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey between late December 2020 and March 2021. -
Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein.
Heinzelman Pete et al. PloS one 2021 5 (5) e0251585We experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. -
A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa
E Wilkinson et al, MEDRXIV, May 13, 2021We describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1 -
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.
Collier Ai-Ris Y et al. JAMA 2021 5In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern. -
Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.
Lopez Bernal Jamie et al. BMJ (Clinical research ed.) 2021 5 n1088Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found -
SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression.
A Nemundryi et al, Cell Reports, May 13, 2021Over 950,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral challenge experiments to link this isolate (ORF7a?115) to a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation negates anti-immune activities of the protein, which results in elevated type I interferon response to the viral infection. -
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection
DS Khoury et al, Nature Medicine, May 17, 2021Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from SARS-CoV-2 infection using data from seven current vaccines and from convalescent cohorts. we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. -
Rapidly emerging SARS-CoV-2 B.1.1.7 sub-lineage in the United States of America with spike protein D178H and membrane protein V70L mutations
L Shen et al, MEDRXIV, May 18 2021We recently identified several emerging SARS-CoV-2 variants of concerns, characterized by Membrane (M) protein mutations, including I82T and V70L. We now identify a sub-lineage of B.1.1.7 that emerged through sequential acquisitions of M:V70L in November 2020 followed by a novel S:D178H mutation first observed in early February 2021. The percentage of B.1.1.7 isolates in the U.S. that belong to this sub-lineage increased from 0.15% in February 2021 to 1.8% in April 2021. To date this sub-lineage appears to be U.S.-specific with reported cases in 31 states, including Hawaii. As of April 2021 it constituted 36.8% of all B.1.1.7 isolates in Washington. -
Diverse Functional Autoantibodies in Patients with COVID-19
EY Wang et al, Nature, May 19, 2021We used a high-throughput autoantibody (AAb) discovery technique called Rapid Extracellular Antigen Profiling (REAP)7 to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. -
ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.
Möhlendick Birte et al. Pharmacogenetics and genomics 2021 5We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease.
News, Reviews and Commentaries
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A Novel Diagnostic Test to Screen SARS-CoV-2 Variants Containing E484K and N501Y Mutations.
Zhao Yanan et al. Emerging microbes & infections 2021 5 1-11We developed a single-tube duplex molecular assay for rapid and simultaneous identification of E484K and N501Y mutations from nasopharyngeal swab (NS) samples within 2.5 h from sample preparation to report. Using this tool, we screened a total of 1135 clinical NS samples collected from COVID patients at 8 hospitals within the Hackensack Meridian Health network in New Jersey between late December 2020 and March 2021. -
Discovery of human ACE2 variants with altered recognition by the SARS-CoV-2 spike protein.
Heinzelman Pete et al. PloS one 2021 5 (5) e0251585We experimentally interrogate thousands of ACE2 mutants to identify over one hundred human single-nucleotide variants (SNVs) that are likely to have altered recognition by the virus, and make the complementary discovery that ACE2 residues distant from the spike interface influence the ACE2-spike interaction. -
A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa
E Wilkinson et al, MEDRXIV, May 13, 2021We describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations, predominantly from Europe, which diminished following the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1 and C.1.1 -
Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women.
Collier Ai-Ris Y et al. JAMA 2021 5In this cohort study involving 103 women who received a COVID-19 mRNA vaccine, 30 of whom were pregnant and 16 of whom were lactating, immunogenicity was demonstrated in all, and vaccine-elicited antibodies were found in infant cord blood and breast milk. Pregnant and nonpregnant vaccinated women developed cross-reactive immune responses against SARS-CoV-2 variants of concern. -
Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study.
Lopez Bernal Jamie et al. BMJ (Clinical research ed.) 2021 5 n1088Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found -
SARS-CoV-2 genomic surveillance identifies naturally occurring truncation of ORF7a that limits immune suppression.
A Nemundryi et al, Cell Reports, May 13, 2021Over 950,000 whole genome sequences of SARS-CoV-2 have been determined for viruses isolated from around the world. These sequences have been critical for understanding the spread and evolution of SARS-CoV-2. Using global phylogenomics, we show that mutations frequently occur in the C-terminal end of ORF7a. We have isolated one of these mutant viruses from a patient sample and used viral challenge experiments to link this isolate (ORF7a?115) to a growth defect. ORF7a has been implicated in immune modulation, and we show that the C-terminal truncation negates anti-immune activities of the protein, which results in elevated type I interferon response to the viral infection. -
Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection
DS Khoury et al, Nature Medicine, May 17, 2021Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from SARS-CoV-2 infection using data from seven current vaccines and from convalescent cohorts. we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. -
Rapidly emerging SARS-CoV-2 B.1.1.7 sub-lineage in the United States of America with spike protein D178H and membrane protein V70L mutations
L Shen et al, MEDRXIV, May 18 2021We recently identified several emerging SARS-CoV-2 variants of concerns, characterized by Membrane (M) protein mutations, including I82T and V70L. We now identify a sub-lineage of B.1.1.7 that emerged through sequential acquisitions of M:V70L in November 2020 followed by a novel S:D178H mutation first observed in early February 2021. The percentage of B.1.1.7 isolates in the U.S. that belong to this sub-lineage increased from 0.15% in February 2021 to 1.8% in April 2021. To date this sub-lineage appears to be U.S.-specific with reported cases in 31 states, including Hawaii. As of April 2021 it constituted 36.8% of all B.1.1.7 isolates in Washington. -
Diverse Functional Autoantibodies in Patients with COVID-19
EY Wang et al, Nature, May 19, 2021We used a high-throughput autoantibody (AAb) discovery technique called Rapid Extracellular Antigen Profiling (REAP)7 to screen a cohort of 194 SARS-CoV-2 infected COVID-19 patients and healthcare workers for autoantibodies against 2,770 extracellular and secreted proteins (the “exoproteome”). We found that COVID-19 patients exhibit dramatic increases in autoantibody reactivities compared to uninfected controls, with a high prevalence of autoantibodies against immunomodulatory proteins including cytokines, chemokines, complement components, and cell surface proteins. -
ACE2 polymorphism and susceptibility for SARS-CoV-2 infection and severity of COVID-19.
Möhlendick Birte et al. Pharmacogenetics and genomics 2021 5We performed genotyping of SNPs in the genes ACE2 and ACE in 297 SARS-CoV-2-positive and 253 SARS-CoV-2-negative tested patients. We analyzed the association of the SNPs with susceptibility for SARS-CoV-2 infection and the severity of COVID-19. For ACE2 rs2285666, the GG genotype or G-allele was significantly associated with an almost two-fold increased SARS-CoV-2 infection risk and a three-fold increased risk to develop serious disease or COVID-19 fatality. In contrast, the ACE polymorphism was not related to infection risk or severity of disease.
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- Page last updated:Mar 28, 2024
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