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Published on 01/20/2022

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape
    S Cele et al, Cell, January 13, 2022
    We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral but evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.
  • COVID infection severity in children under 5 years old before and after Omicron emergence in the US
    L Wang et al, MEDRXIV, January 13, 2022
    Among 7,201 infected children in the Omicron cohort (average age of 1.49 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]).
  • Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses
    BL Sievers et al, Science Trans Med, January 13, 2022
    Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization.
  • Ancestral SARS-CoV-2-specific T cells cross-recognize Omicron
    Y Gao et al, Nature Medicine, January 14, 2022
    We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529.
  • Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
    JE Huffman et al, Nature Genetics, January 13, 2022
    The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
  • Targeted vaccination and the speed of SARS-CoV-2 adaptation.
    Gandon Sylvain et al. Proceedings of the National Academy of Sciences of the United States of America 2022 1 (3)
    We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal.
  • The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste
    JF Shelton et al, Nature Genetics, January 17, 2022
    Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
  • The origin of SARS-CoV-2 variants of concern.
    Burki Talha et al. The Lancet. Infectious diseases 2022 1
  • Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.
    Munro Alasdair P S et al. Lancet (London, England) 2021 12 (10318) 2258-2276
    In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting
  • Effectiveness of mRNA-1273 and BNT162b2 Vaccines in Qatar
    LJ Abu-Raddad et al, NEJM, January 19, 2022
    We conducted a study to compare the protection afforded by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer–BioNTech) vaccine in Qatar.Using data from national Covid-19 electronic health databases, we designed two matched retrospective cohort studies to emulate a randomized, controlled trial and to assess the incidence of documented SARS-CoV-2 infection after the first and second doses of the mRNA-1273 and BNT162b2 vaccines. Vaccination with mRNA-1273 was associated with a lower incidence of SARS-CoV-2 breakthrough infection than vaccination with BNT162b2; this finding is consistent with the differences in neutralizing antibody titers. However, both vaccines elicited strong protection against Covid-19–related hospitalization and death.

Non-Genomics Precision Health Studies

  • SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape
    S Cele et al, Cell, January 13, 2022
    We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral but evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.
  • COVID infection severity in children under 5 years old before and after Omicron emergence in the US
    L Wang et al, MEDRXIV, January 13, 2022
    Among 7,201 infected children in the Omicron cohort (average age of 1.49 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]).
  • Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses
    BL Sievers et al, Science Trans Med, January 13, 2022
    Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization.
  • Ancestral SARS-CoV-2-specific T cells cross-recognize Omicron
    Y Gao et al, Nature Medicine, January 14, 2022
    We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529.
  • Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
    JE Huffman et al, Nature Genetics, January 13, 2022
    The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
  • Targeted vaccination and the speed of SARS-CoV-2 adaptation.
    Gandon Sylvain et al. Proceedings of the National Academy of Sciences of the United States of America 2022 1 (3)
    We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal.
  • The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste
    JF Shelton et al, Nature Genetics, January 17, 2022
    Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
  • The origin of SARS-CoV-2 variants of concern.
    Burki Talha et al. The Lancet. Infectious diseases 2022 1
  • Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.
    Munro Alasdair P S et al. Lancet (London, England) 2021 12 (10318) 2258-2276
    In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting
  • Effectiveness of mRNA-1273 and BNT162b2 Vaccines in Qatar
    LJ Abu-Raddad et al, NEJM, January 19, 2022
    We conducted a study to compare the protection afforded by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer–BioNTech) vaccine in Qatar.Using data from national Covid-19 electronic health databases, we designed two matched retrospective cohort studies to emulate a randomized, controlled trial and to assess the incidence of documented SARS-CoV-2 infection after the first and second doses of the mRNA-1273 and BNT162b2 vaccines. Vaccination with mRNA-1273 was associated with a lower incidence of SARS-CoV-2 breakthrough infection than vaccination with BNT162b2; this finding is consistent with the differences in neutralizing antibody titers. However, both vaccines elicited strong protection against Covid-19–related hospitalization and death.

News, Reviews and Commentaries

  • SARS-CoV-2 prolonged infection during advanced HIV disease evolves extensive immune escape
    S Cele et al, Cell, January 13, 2022
    We longitudinally tracked the evolved virus and tested it against self-plasma and convalescent plasma from ancestral, Beta, and Delta infections. Early virus was similar to ancestral but evolved a multitude of mutations found in Omicron and other variants. It showed substantial but incomplete Pfizer BNT162b2 escape, weak neutralization by self-plasma, and despite pre-dating Delta, extensive escape of Delta infection-elicited neutralization. This example is consistent with the notion SARS-CoV-2 evolving in individual immune-compromised hosts, including those with advanced HIV disease, may gain immune escape of vaccines and enhanced escape of Delta immunity, with implications for vaccine breakthrough and reinfections.
  • COVID infection severity in children under 5 years old before and after Omicron emergence in the US
    L Wang et al, MEDRXIV, January 13, 2022
    Among 7,201 infected children in the Omicron cohort (average age of 1.49 years), 47.4% were female, 2.4% Asian, 26.1% Black, 13.7% Hispanic, and 44.0% White. Before propensity score matching, the Omicron cohort were younger than the Delta cohort (average age 1.49 vs 1.73 years), comprised of more Black children, and had fewer comorbidities. After propensity-score matching for demographics, socio-economic determinants of health, comorbidities and medications, risks for severe clinical outcomes in the Omicron cohort were significantly lower than those in the Delta cohort: ED visits: 18.83% vs. 26.67% (risk ratio or RR: 0.71 [0.66-0.75]); hospitalizations: 1.04% vs. 3.14% (RR: 0.33 [0.26-0.43]); ICU admissions: 0.14% vs. 0.43% (RR: 0.32 [0.16-0.66]); mechanical ventilation: 0.33% vs. 1.15% (RR: 0.29 [0.18-0.46]).
  • Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses
    BL Sievers et al, Science Trans Med, January 13, 2022
    Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization.
  • Ancestral SARS-CoV-2-specific T cells cross-recognize Omicron
    Y Gao et al, Nature Medicine, January 14, 2022
    We report here that SARS-CoV-2 spike-specific CD4+ and CD8+ T cells induced by prior infection and, more extensively, by mRNA vaccination provide comprehensive heterologous immune reactivity against B.1.1.529. Pairwise comparisons across groups further revealed that SARS-CoV-2 spike-reactive CD4+ and CD8+ T cells exhibited similar functional attributes, memory distributions, and phenotypic traits in response to the ancestral strain or B.1.1.529.
  • Multi-ancestry fine mapping implicates OAS1 splicing in risk of severe COVID-19
    JE Huffman et al, Nature Genetics, January 13, 2022
    The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.
  • Targeted vaccination and the speed of SARS-CoV-2 adaptation.
    Gandon Sylvain et al. Proceedings of the National Academy of Sciences of the United States of America 2022 1 (3)
    We clarify the consequences of different vaccination strategies through the analysis of the speed of viral adaptation measured as the rate of change of the frequency of a vaccine-adapted variant. We show that such a variant is expected to spread faster if vaccination targets individuals who are likely to be involved in a higher number of contacts. We also discuss the pros and cons of dose-sparing strategies. Because delaying the second dose increases the proportion of the population vaccinated with a single dose, this strategy can both speed up the spread of the vaccine-adapted variant and reduce the cumulative number of deaths. Hence, strategies that are most effective at slowing viral adaptation may not always be epidemiologically optimal.
  • The UGT2A1/UGT2A2 locus is associated with COVID-19-related loss of smell or taste
    JF Shelton et al, Nature Genetics, January 17, 2022
    Using online surveys, we collected data regarding COVID-19-related loss of smell or taste from 69,841 individuals. We performed a multi-ancestry genome-wide association study and identified a genome-wide significant locus in the vicinity of the UGT2A1 and UGT2A2 genes. Both genes are expressed in the olfactory epithelium and play a role in metabolizing odorants. These findings provide a genetic link to the biological mechanisms underlying COVID-19-related loss of smell or taste.
  • The origin of SARS-CoV-2 variants of concern.
    Burki Talha et al. The Lancet. Infectious diseases 2022 1
  • Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.
    Munro Alasdair P S et al. Lancet (London, England) 2021 12 (10318) 2258-2276
    In this single-blind, multicenter, randomized, controlled trial involving health care workers who had received a priming dose of Ad26.COV2.S vaccine, we assessed immunogenicity and reactogenicity 28 days after a homologous or heterologous booster vaccination. The Ad26.COV2.S and mRNA boosters had an acceptable safety profile and were immunogenic in health care workers who had received a priming dose of Ad26.COV2.S vaccine. The strongest responses occurred after boosting with mRNA-based vaccines. Boosting with any available vaccine was better than not boosting
  • Effectiveness of mRNA-1273 and BNT162b2 Vaccines in Qatar
    LJ Abu-Raddad et al, NEJM, January 19, 2022
    We conducted a study to compare the protection afforded by the mRNA-1273 (Moderna) vaccine with that of the BNT162b2 (Pfizer–BioNTech) vaccine in Qatar.Using data from national Covid-19 electronic health databases, we designed two matched retrospective cohort studies to emulate a randomized, controlled trial and to assess the incidence of documented SARS-CoV-2 infection after the first and second doses of the mRNA-1273 and BNT162b2 vaccines. Vaccination with mRNA-1273 was associated with a lower incidence of SARS-CoV-2 breakthrough infection than vaccination with BNT162b2; this finding is consistent with the differences in neutralizing antibody titers. However, both vaccines elicited strong protection against Covid-19–related hospitalization and death.
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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