Published on 11/10/2022
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged =12 Years — United States, August 31–October 23, 2022
AM Hause et al, MMWR, November 3, 2022CDC recommended bivalent COVID-19 booster vaccination for persons aged =12 years in August 2022; approximately 22.6 million bivalent booster doses were administered during August 31–October 23, 2022. Early safety findings from v-safe and the Vaccine Adverse Event Reporting System for bivalent booster doses administered to persons aged =12 years during the first 7 weeks of vaccine availability are similar to those previously described for monovalent vaccine booster vaccines. -
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Matuozzo Daniela et al. medRxiv : the preprint server for health sciences 2022 11We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. We found that rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. -
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.
Butler-Laporte Guillaume et al. PLoS genetics 2022 11 (11) e1010367Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease -
Analysis of Genetic Variants Associated with COVID-19 Outcome Highlights Different Distributions among Populations
C Fabrizio et al, J Per Med, November 6, 2022 -
Quantifying the effect of inequitable global vaccine coverage on the COVID-19 pandemic.
et al. Nature medicine 2022 11We used a global mathematical model simulating different scenarios to study the effects of increased COVID-19 vaccine equity during 2021. Our results indicate that vaccine nationalism leads to increased infections and mortality worldwide, and by favoring the emergence of new viral variants, in the long term it may adversely affect all countries. -
Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection.
Woodbridge Yonatan et al. Nature communications 2022 11 (1) 6706By analyzing results of more than 460,000 individuals, we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, its relatively small effect on transmissibility of Omicron (as measured here by Ct) and its rapid waning call for reassessment of future booster campaigns. -
A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity
Me Kars et al, MEDRXIV, November 7, 2022We collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. -
Antibody response durability following three-dose COVID-19 vaccination in people with HIV receiving suppressive ART
HR LaPointe et al, MEDRXIV, November 7, 2022 -
Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation.
Wang Qian et al. The Lancet. Infectious diseases 2022 11Neutralization antibody titers in serum from healthy people with 3 doses of a COVID-19 mRNA vaccine (boosted cohort) and people with either BA.1, BA.2, or BA.4/5 breakthrough (infection cohorts) were similar against Omicron subvariants BA.4.6, BA.4.7, BA.5.9, and BF.7 and in BA.4/5. Bebtelovimab was the only one of 23 therapeutic monoclonal antibodies to retain potent activity against all circulating forms of SARS-CoV-2. -
Probable Aerosol Transmission of SARS-CoV-2 through Floors and Walls of Quarantine Hotel, Taiwan, 2021.
Wei Hsin-Yi et al. Emerging infectious diseases 2022 11 (12)A cluster of Omicron BA.1.1 infections among travelers quarantined in non-adjacent rooms (n=3, Taipei City, Dec 2021) was suspected to have spread via aerosol through structural defects. Two cases were from areas with no Omicron transmission at that time. Phylogenetic analysis showed similar viral genetic sequences for all 3 cases, and environmental investigation revealed 100% recirculated air and a possible route of airflow connecting the rooms. -
Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine
S Yamamoto et al, MEDRXIV, November 8, 2022 -
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
S Iketani et al, Nature, November 9, 2022Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both, and their sequences revealed a multitude of 3CL protease mutations. In the experiment done with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. -
Six-Month Follow-up after a Fourth BNT162b2 Vaccine Dose
M Canetti et al, NEJM, November 9, 2022In this prospective cohort study, a third dose of the BNT162b2 vaccine led to an improved and sustained immunologic response as compared with two doses, but the additional immunologic advantage of the fourth dose was much smaller and had waned completely by 13 weeks after vaccination. This finding correlated with waning vaccine effectiveness among recipients of a fourth dose, which culminated in no substantial additional effectiveness over a third dose at 15 to 26 weeks after vaccination. -
Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection
DD Flannery et al, JAMA Network Open, November 9, 2022Is placental antibody transfer after COVID-19 vaccination different from that after SARS-CoV-2 infection in pregnant individuals? In this cohort study of 585 maternal-newborn dyads, maternal and cord blood IgG antibody levels were higher after vaccination compared with after infection. An association was observed between time from infection or vaccination to delivery and transfer ratio. Findings of this study suggest that time from infection or vaccination to delivery was the most important factor in transfer ratio efficiency. -
Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome
W Ma et al, MEDRXIV, November 9, 2022Using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), robust consensus clustering identified six endophenotypes (EPs) present among 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19), with varying degrees of disease severity and times to intensive care unit (ICU) admission. In particular, one endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death.
Non-Genomics Precision Health Studies
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Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged =12 Years — United States, August 31–October 23, 2022
AM Hause et al, MMWR, November 3, 2022CDC recommended bivalent COVID-19 booster vaccination for persons aged =12 years in August 2022; approximately 22.6 million bivalent booster doses were administered during August 31–October 23, 2022. Early safety findings from v-safe and the Vaccine Adverse Event Reporting System for bivalent booster doses administered to persons aged =12 years during the first 7 weeks of vaccine availability are similar to those previously described for monovalent vaccine booster vaccines. -
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Matuozzo Daniela et al. medRxiv : the preprint server for health sciences 2022 11We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. We found that rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. -
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.
Butler-Laporte Guillaume et al. PLoS genetics 2022 11 (11) e1010367Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease -
Analysis of Genetic Variants Associated with COVID-19 Outcome Highlights Different Distributions among Populations
C Fabrizio et al, J Per Med, November 6, 2022 -
Quantifying the effect of inequitable global vaccine coverage on the COVID-19 pandemic.
et al. Nature medicine 2022 11We used a global mathematical model simulating different scenarios to study the effects of increased COVID-19 vaccine equity during 2021. Our results indicate that vaccine nationalism leads to increased infections and mortality worldwide, and by favoring the emergence of new viral variants, in the long term it may adversely affect all countries. -
Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection.
Woodbridge Yonatan et al. Nature communications 2022 11 (1) 6706By analyzing results of more than 460,000 individuals, we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, its relatively small effect on transmissibility of Omicron (as measured here by Ct) and its rapid waning call for reassessment of future booster campaigns. -
A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity
Me Kars et al, MEDRXIV, November 7, 2022We collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. -
Antibody response durability following three-dose COVID-19 vaccination in people with HIV receiving suppressive ART
HR LaPointe et al, MEDRXIV, November 7, 2022 -
Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation.
Wang Qian et al. The Lancet. Infectious diseases 2022 11Neutralization antibody titers in serum from healthy people with 3 doses of a COVID-19 mRNA vaccine (boosted cohort) and people with either BA.1, BA.2, or BA.4/5 breakthrough (infection cohorts) were similar against Omicron subvariants BA.4.6, BA.4.7, BA.5.9, and BF.7 and in BA.4/5. Bebtelovimab was the only one of 23 therapeutic monoclonal antibodies to retain potent activity against all circulating forms of SARS-CoV-2. -
Probable Aerosol Transmission of SARS-CoV-2 through Floors and Walls of Quarantine Hotel, Taiwan, 2021.
Wei Hsin-Yi et al. Emerging infectious diseases 2022 11 (12)A cluster of Omicron BA.1.1 infections among travelers quarantined in non-adjacent rooms (n=3, Taipei City, Dec 2021) was suspected to have spread via aerosol through structural defects. Two cases were from areas with no Omicron transmission at that time. Phylogenetic analysis showed similar viral genetic sequences for all 3 cases, and environmental investigation revealed 100% recirculated air and a possible route of airflow connecting the rooms. -
Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine
S Yamamoto et al, MEDRXIV, November 8, 2022 -
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
S Iketani et al, Nature, November 9, 2022Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both, and their sequences revealed a multitude of 3CL protease mutations. In the experiment done with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. -
Six-Month Follow-up after a Fourth BNT162b2 Vaccine Dose
M Canetti et al, NEJM, November 9, 2022In this prospective cohort study, a third dose of the BNT162b2 vaccine led to an improved and sustained immunologic response as compared with two doses, but the additional immunologic advantage of the fourth dose was much smaller and had waned completely by 13 weeks after vaccination. This finding correlated with waning vaccine effectiveness among recipients of a fourth dose, which culminated in no substantial additional effectiveness over a third dose at 15 to 26 weeks after vaccination. -
Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection
DD Flannery et al, JAMA Network Open, November 9, 2022Is placental antibody transfer after COVID-19 vaccination different from that after SARS-CoV-2 infection in pregnant individuals? In this cohort study of 585 maternal-newborn dyads, maternal and cord blood IgG antibody levels were higher after vaccination compared with after infection. An association was observed between time from infection or vaccination to delivery and transfer ratio. Findings of this study suggest that time from infection or vaccination to delivery was the most important factor in transfer ratio efficiency. -
Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome
W Ma et al, MEDRXIV, November 9, 2022Using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), robust consensus clustering identified six endophenotypes (EPs) present among 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19), with varying degrees of disease severity and times to intensive care unit (ICU) admission. In particular, one endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death.
News, Reviews and Commentaries
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Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Persons Aged =12 Years — United States, August 31–October 23, 2022
AM Hause et al, MMWR, November 3, 2022CDC recommended bivalent COVID-19 booster vaccination for persons aged =12 years in August 2022; approximately 22.6 million bivalent booster doses were administered during August 31–October 23, 2022. Early safety findings from v-safe and the Vaccine Adverse Event Reporting System for bivalent booster doses administered to persons aged =12 years during the first 7 weeks of vaccine availability are similar to those previously described for monovalent vaccine booster vaccines. -
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Matuozzo Daniela et al. medRxiv : the preprint server for health sciences 2022 11We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. We found that rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old. -
Exome-wide association study to identify rare variants influencing COVID-19 outcomes: Results from the Host Genetics Initiative.
Butler-Laporte Guillaume et al. PLoS genetics 2022 11 (11) e1010367Here, we combined whole-exome and whole-genome sequencing from 21 cohorts across 12 countries and performed rare variant exome-wide burden analyses for COVID-19 outcomes. In an analysis of 5,085 severe disease cases and 571,737 controls, we observed that carrying a rare deleterious variant in the SARS-CoV-2 sensor toll-like receptor TLR7 (on chromosome X) was associated with a 5.3-fold increase in severe disease -
Analysis of Genetic Variants Associated with COVID-19 Outcome Highlights Different Distributions among Populations
C Fabrizio et al, J Per Med, November 6, 2022 -
Quantifying the effect of inequitable global vaccine coverage on the COVID-19 pandemic.
et al. Nature medicine 2022 11We used a global mathematical model simulating different scenarios to study the effects of increased COVID-19 vaccine equity during 2021. Our results indicate that vaccine nationalism leads to increased infections and mortality worldwide, and by favoring the emergence of new viral variants, in the long term it may adversely affect all countries. -
Viral load dynamics of SARS-CoV-2 Delta and Omicron variants following multiple vaccine doses and previous infection.
Woodbridge Yonatan et al. Nature communications 2022 11 (1) 6706By analyzing results of more than 460,000 individuals, we show that while recent vaccination reduces Omicron viral load, its effect wanes rapidly. In contrast, a significantly slower waning rate is demonstrated for recovered COVID-19 individuals. Thus, while the vaccine is effective in decreasing morbidity and mortality, its relatively small effect on transmissibility of Omicron (as measured here by Ct) and its rapid waning call for reassessment of future booster campaigns. -
A comprehensive knowledgebase of known and predicted human genetic variants associated with COVID-19 susceptibility and severity
Me Kars et al, MEDRXIV, November 7, 2022We collated 820 host genetic variants reported to affect COVID-19 susceptibility by means of a systematic literature search and confidence evaluation, and obtained 196 high-confidence variants. We then developed the first machine learning classifier of severe COVID-19 variants to perform a genome-wide prediction of COVID-19 severity for 82,468,698 missense variants in the human genome. -
Antibody response durability following three-dose COVID-19 vaccination in people with HIV receiving suppressive ART
HR LaPointe et al, MEDRXIV, November 7, 2022 -
Resistance of SARS-CoV-2 omicron subvariant BA.4.6 to antibody neutralisation.
Wang Qian et al. The Lancet. Infectious diseases 2022 11Neutralization antibody titers in serum from healthy people with 3 doses of a COVID-19 mRNA vaccine (boosted cohort) and people with either BA.1, BA.2, or BA.4/5 breakthrough (infection cohorts) were similar against Omicron subvariants BA.4.6, BA.4.7, BA.5.9, and BF.7 and in BA.4/5. Bebtelovimab was the only one of 23 therapeutic monoclonal antibodies to retain potent activity against all circulating forms of SARS-CoV-2. -
Probable Aerosol Transmission of SARS-CoV-2 through Floors and Walls of Quarantine Hotel, Taiwan, 2021.
Wei Hsin-Yi et al. Emerging infectious diseases 2022 11 (12)A cluster of Omicron BA.1.1 infections among travelers quarantined in non-adjacent rooms (n=3, Taipei City, Dec 2021) was suspected to have spread via aerosol through structural defects. Two cases were from areas with no Omicron transmission at that time. Phylogenetic analysis showed similar viral genetic sequences for all 3 cases, and environmental investigation revealed 100% recirculated air and a possible route of airflow connecting the rooms. -
Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine
S Yamamoto et al, MEDRXIV, November 8, 2022 -
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
S Iketani et al, Nature, November 9, 2022Nirmatrelvir, an oral antiviral targeting the 3CL protease of SARS-CoV-2, has been demonstrated to be clinically useful against COVID-19. However, as SARS-CoV-2 has evolved to become resistant to other therapeutic modalities, there is a concern that the same could occur for nirmatrelvir. Here, we have examined this possibility by in vitro passaging of SARS-CoV-2 in nirmatrelvir using two independent approaches, including one on a large scale. Indeed, highly resistant viruses emerged from both, and their sequences revealed a multitude of 3CL protease mutations. In the experiment done with many replicates, 53 independent viral lineages were selected with mutations observed at 23 different residues of the enzyme. -
Six-Month Follow-up after a Fourth BNT162b2 Vaccine Dose
M Canetti et al, NEJM, November 9, 2022In this prospective cohort study, a third dose of the BNT162b2 vaccine led to an improved and sustained immunologic response as compared with two doses, but the additional immunologic advantage of the fourth dose was much smaller and had waned completely by 13 weeks after vaccination. This finding correlated with waning vaccine effectiveness among recipients of a fourth dose, which culminated in no substantial additional effectiveness over a third dose at 15 to 26 weeks after vaccination. -
Comparison of Maternal and Neonatal Antibody Levels After COVID-19 Vaccination vs SARS-CoV-2 Infection
DD Flannery et al, JAMA Network Open, November 9, 2022Is placental antibody transfer after COVID-19 vaccination different from that after SARS-CoV-2 infection in pregnant individuals? In this cohort study of 585 maternal-newborn dyads, maternal and cord blood IgG antibody levels were higher after vaccination compared with after infection. An association was observed between time from infection or vaccination to delivery and transfer ratio. Findings of this study suggest that time from infection or vaccination to delivery was the most important factor in transfer ratio efficiency. -
Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome
W Ma et al, MEDRXIV, November 9, 2022Using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), robust consensus clustering identified six endophenotypes (EPs) present among 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19), with varying degrees of disease severity and times to intensive care unit (ICU) admission. In particular, one endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death.
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- Page last updated:Apr 29, 2024
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