Published on 12/02/2021
COVID-19 Genomics and Precision Public Health Weekly Update Content
Pathogen and Human Genomics Studies
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SARS-CoV-2 Genomic Surveillance Reveals Little Spread From a Large University Campus to the Surrounding Community.
Valesano Andrew L et al. Open forum infectious diseases 2021 11 (11) ofab518Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. -
Emergence of SARS-CoV-2 Delta Variant, Benin, May-July 2021.
Yadouleton Anges et al. Emerging infectious diseases 2021 11 (1)Severe acute respiratory syndrome coronavirus 2 Delta variant epidemiology in Africa is unknown. We found Delta variant was introduced in Benin during April-May 2021 and became predominant within 2 months, after which a steep increase in reported coronavirus disease incidence occurred. Benin might require increased nonpharmaceutical interventions and vaccination coverage. -
Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.
Kumar Deepali et al. Annals of internal medicine 2021 11total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). -
The N501Y spike substitution enhances SARS-CoV-2 infection and transmission
Y Liu et al, Nature, November 24, 2021The Alpha variant has 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 Alpha spike mutations, suggesting it is a major determinant of increased transmission of this variant. -
Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
SP Andeweg et al, MEDRXIV, November 24, 2021We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity. -
SARS-CoV-2 antigen-detecting rapid tests for the delta variant
M Bekliz et al, Lancet Microbe, November 24, 2021In this study, the accuracy of 11 Ag-RDTs to detect variants of concern was determined. Analytical validation with cultured virus might be a proxy for clinical accuracy, but it is not a replacement for clinical evaluations. Nevertheless, we showed that, despite slight differences in sensitivity, Ag-RDTs remain, in principle, effective to detect variants of concern, including the now-dominant delta variant. -
Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
PB Gilbert et al, Science, November 23, 2021In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at second vaccination and 4 weeks later, with values reported in standardized WHO International Units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. -
Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.
Kremsner Peter G et al. The Lancet. Infectious diseases 2021 11Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0-61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7%. -
Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans
BA Dickerman et al, NEJM, December 1, 2021Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval [CI], 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26). -
Covid-19 Vaccine Effectiveness in New York State
ES Rosenberg et al, NEJM, December 1,2021There were 150,865 cases of Covid-19 and 14,477 hospitalizations with Covid-19. During the week of May 1, 2021, when the delta variant made up 1.8% of the circulating variants, the median vaccine effectiveness against Covid-19 was 91.3% (range, 84.1 to 97.0) for BNT162b2, 96.9% (range, 93.7 to 98.0) for mRNA-1273, and 86.6% (range, 77.8 to 89.7) for Ad26.COV2.S. Subsequently, effectiveness declined contemporaneously in all cohorts, from a median of 93.4% (range, 77.8 to 98.0) during the week of May 1 to a nadir of 73.5% (range, 13.8 to 90.0) around July 10, when the prevalence of the delta variant was 85.3%. -
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization
G Witberg et al, NEJM, December 2, 2021Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. -
Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons
SM Kissler et al, NEJM, December 1,2021We compared SARS-CoV-2 viral dynamics among 36 participants who were infected with the B.1.1.7 (alpha) variant, 36 participants with the B.1.617.2 (delta) variant, and 41 participants with a variant that was not of current interest or concern, along with 37 vaccinated and 136 unvaccinated participants. We found no meaningful difference in the mean peak viral load (with a lower peak cycle threshold [Ct] indicating a higher viral load), proliferation duration, clearance duration, or duration of acute infection of either the alpha or the delta variant as compared with variants not of interest or concern.
Non-Genomics Precision Health Studies
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SARS-CoV-2 Genomic Surveillance Reveals Little Spread From a Large University Campus to the Surrounding Community.
Valesano Andrew L et al. Open forum infectious diseases 2021 11 (11) ofab518Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. -
Emergence of SARS-CoV-2 Delta Variant, Benin, May-July 2021.
Yadouleton Anges et al. Emerging infectious diseases 2021 11 (1)Severe acute respiratory syndrome coronavirus 2 Delta variant epidemiology in Africa is unknown. We found Delta variant was introduced in Benin during April-May 2021 and became predominant within 2 months, after which a steep increase in reported coronavirus disease incidence occurred. Benin might require increased nonpharmaceutical interventions and vaccination coverage. -
Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.
Kumar Deepali et al. Annals of internal medicine 2021 11total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). -
The N501Y spike substitution enhances SARS-CoV-2 infection and transmission
Y Liu et al, Nature, November 24, 2021The Alpha variant has 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 Alpha spike mutations, suggesting it is a major determinant of increased transmission of this variant. -
Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
SP Andeweg et al, MEDRXIV, November 24, 2021We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity. -
SARS-CoV-2 antigen-detecting rapid tests for the delta variant
M Bekliz et al, Lancet Microbe, November 24, 2021In this study, the accuracy of 11 Ag-RDTs to detect variants of concern was determined. Analytical validation with cultured virus might be a proxy for clinical accuracy, but it is not a replacement for clinical evaluations. Nevertheless, we showed that, despite slight differences in sensitivity, Ag-RDTs remain, in principle, effective to detect variants of concern, including the now-dominant delta variant. -
Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
PB Gilbert et al, Science, November 23, 2021In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at second vaccination and 4 weeks later, with values reported in standardized WHO International Units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. -
Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.
Kremsner Peter G et al. The Lancet. Infectious diseases 2021 11Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0-61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7%. -
Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans
BA Dickerman et al, NEJM, December 1, 2021Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval [CI], 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26). -
Covid-19 Vaccine Effectiveness in New York State
ES Rosenberg et al, NEJM, December 1,2021There were 150,865 cases of Covid-19 and 14,477 hospitalizations with Covid-19. During the week of May 1, 2021, when the delta variant made up 1.8% of the circulating variants, the median vaccine effectiveness against Covid-19 was 91.3% (range, 84.1 to 97.0) for BNT162b2, 96.9% (range, 93.7 to 98.0) for mRNA-1273, and 86.6% (range, 77.8 to 89.7) for Ad26.COV2.S. Subsequently, effectiveness declined contemporaneously in all cohorts, from a median of 93.4% (range, 77.8 to 98.0) during the week of May 1 to a nadir of 73.5% (range, 13.8 to 90.0) around July 10, when the prevalence of the delta variant was 85.3%. -
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization
G Witberg et al, NEJM, December 2, 2021Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. -
Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons
SM Kissler et al, NEJM, December 1,2021We compared SARS-CoV-2 viral dynamics among 36 participants who were infected with the B.1.1.7 (alpha) variant, 36 participants with the B.1.617.2 (delta) variant, and 41 participants with a variant that was not of current interest or concern, along with 37 vaccinated and 136 unvaccinated participants. We found no meaningful difference in the mean peak viral load (with a lower peak cycle threshold [Ct] indicating a higher viral load), proliferation duration, clearance duration, or duration of acute infection of either the alpha or the delta variant as compared with variants not of interest or concern.
News, Reviews and Commentaries
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SARS-CoV-2 Genomic Surveillance Reveals Little Spread From a Large University Campus to the Surrounding Community.
Valesano Andrew L et al. Open forum infectious diseases 2021 11 (11) ofab518Phylogenetic analysis identified >200 introductions into the student population, most of which were not related to other student cases. There were 2 prolonged student transmission clusters, of 115 and 73 individuals, that spanned multiple on-campus residences. Remarkably, <5% of nonstudent genomes were descended from student clusters, and viral descendants of student cases were rare during a subsequent wave of infections in the community. -
Emergence of SARS-CoV-2 Delta Variant, Benin, May-July 2021.
Yadouleton Anges et al. Emerging infectious diseases 2021 11 (1)Severe acute respiratory syndrome coronavirus 2 Delta variant epidemiology in Africa is unknown. We found Delta variant was introduced in Benin during April-May 2021 and became predominant within 2 months, after which a steep increase in reported coronavirus disease incidence occurred. Benin might require increased nonpharmaceutical interventions and vaccination coverage. -
Neutralization of SARS-CoV-2 Variants in Transplant Recipients After Two and Three Doses of mRNA-1273 Vaccine : Secondary Analysis of a Randomized Trial.
Kumar Deepali et al. Annals of internal medicine 2021 11total of 117 transplant recipients were analyzed (60 in the mRNA-1273 group and 57 in the placebo group). Sera were obtained before and 4 to 6 weeks after the third dose. After 2 doses, the proportion of patients with positive neutralization for all 3 variants was small compared with wild-type virus. After the third dose of mRNA-1273 vaccine, the proportion with a positive neutralization response versus placebo was improved for all 3 variants as measured by both assays. Based on the pseudovirus neutralization assay against the Delta variant, 33 of 60 (55%) patients were positive in the mRNA-1273 group versus 10 of 57 (18%) in the placebo group (difference, 37 [95% CI, 19 to 53] percentage points). -
The N501Y spike substitution enhances SARS-CoV-2 infection and transmission
Y Liu et al, Nature, November 24, 2021The Alpha variant has 19 nonsynonymous mutations across its viral genome, including 8 substitutions or deletions in the spike protein, which interacts with cellular receptors to mediate infection and tropism. Here, using a reverse genetics approach, we show that, of the 8 individual spike protein substitutions, only N501Y exhibited consistent fitness gains for replication in the upper airway in the hamster model as well as primary human airway epithelial cells. The N501Y substitution recapitulated the phenotype of enhanced viral transmission seen with the combined 8 Alpha spike mutations, suggesting it is a major determinant of increased transmission of this variant. -
Increased risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals
SP Andeweg et al, MEDRXIV, November 24, 2021We find evidence for an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to 60 days and longer. In contrast to vaccine-induced immunity, no increased risk for reinfection with Beta, Gamma or Delta variants relative to Alpha variant was found in individuals with infection-induced immunity. -
SARS-CoV-2 antigen-detecting rapid tests for the delta variant
M Bekliz et al, Lancet Microbe, November 24, 2021In this study, the accuracy of 11 Ag-RDTs to detect variants of concern was determined. Analytical validation with cultured virus might be a proxy for clinical accuracy, but it is not a replacement for clinical evaluations. Nevertheless, we showed that, despite slight differences in sensitivity, Ag-RDTs remain, in principle, effective to detect variants of concern, including the now-dominant delta variant. -
Immune correlates analysis of the mRNA-1273 COVID-19 vaccine efficacy clinical trial
PB Gilbert et al, Science, November 23, 2021In the coronavirus efficacy (COVE) phase 3 clinical trial, vaccine recipients were assessed for neutralizing and binding antibodies as correlates of risk for COVID-19 disease and as correlates of protection. These immune markers were measured at second vaccination and 4 weeks later, with values reported in standardized WHO International Units. All markers were inversely associated with COVID-19 risk and directly associated with vaccine efficacy. -
Efficacy and safety of the CVnCoV SARS-CoV-2 mRNA vaccine candidate in ten countries in Europe and Latin America (HERALD): a randomised, observer-blinded, placebo-controlled, phase 2b/3 trial.
Kremsner Peter G et al. The Lancet. Infectious diseases 2021 11Between Dec 11, 2020, and April 12, 2021, 39 680 participants were enrolled and randomly assigned to receive either CVnCoV (n=19 846) or placebo (n=19 834), of whom 19 783 received at least one dose of CVnCoV and 19 746 received at least one dose of placebo. After a mean observation period of 48·2 days (SE 0·2), 83 cases of COVID-19 occurred in the CVnCoV group (n=12 851) in 1735·29 person-years and 145 cases occurred in the placebo group (n=12 211) in 1569·87 person-years, resulting in an overall vaccine efficacy against symptomatic COVID-19 of 48·2% (95·826% CI 31·0-61·4; p=0·016). Vaccine efficacy against moderate-to-severe COVID-19 was 70·7%. -
Comparative Effectiveness of BNT162b2 and mRNA-1273 Vaccines in U.S. Veterans
BA Dickerman et al, NEJM, December 1, 2021Each vaccine group included 219,842 persons. Over 24 weeks of follow-up in a period marked by alpha-variant predominance, the estimated risk of documented infection was 5.75 events per 1000 persons (95% confidence interval [CI], 5.39 to 6.23) in the BNT162b2 group and 4.52 events per 1000 persons (95% CI, 4.17 to 4.84) in the mRNA-1273 group. The excess number of events per 1000 persons for BNT162b2 as compared with mRNA-1273 was 1.23 (95% CI, 0.72 to 1.81) for documented infection, 0.44 (95% CI, 0.25 to 0.70) for symptomatic Covid-19, 0.55 (95% CI, 0.36 to 0.83) for hospitalization for Covid-19, 0.10 (95% CI, 0.00 to 0.26). -
Covid-19 Vaccine Effectiveness in New York State
ES Rosenberg et al, NEJM, December 1,2021There were 150,865 cases of Covid-19 and 14,477 hospitalizations with Covid-19. During the week of May 1, 2021, when the delta variant made up 1.8% of the circulating variants, the median vaccine effectiveness against Covid-19 was 91.3% (range, 84.1 to 97.0) for BNT162b2, 96.9% (range, 93.7 to 98.0) for mRNA-1273, and 86.6% (range, 77.8 to 89.7) for Ad26.COV2.S. Subsequently, effectiveness declined contemporaneously in all cohorts, from a median of 93.4% (range, 77.8 to 98.0) during the week of May 1 to a nadir of 73.5% (range, 13.8 to 90.0) around July 10, when the prevalence of the delta variant was 85.3%. -
Myocarditis after Covid-19 Vaccination in a Large Health Care Organization
G Witberg et al, NEJM, December 2, 2021Among more than 2.5 million vaccinated HCO members who were 16 years of age or older, 54 cases met the criteria for myocarditis. The estimated incidence per 100,000 persons who had received at least one dose of vaccine was 2.13 cases (95% confidence interval [CI], 1.56 to 2.70). The highest incidence of myocarditis (10.69 cases per 100,000 persons; 95% CI, 6.93 to 14.46) was reported in male patients between the ages of 16 and 29 years. -
Viral Dynamics of SARS-CoV-2 Variants in Vaccinated and Unvaccinated Persons
SM Kissler et al, NEJM, December 1,2021We compared SARS-CoV-2 viral dynamics among 36 participants who were infected with the B.1.1.7 (alpha) variant, 36 participants with the B.1.617.2 (delta) variant, and 41 participants with a variant that was not of current interest or concern, along with 37 vaccinated and 136 unvaccinated participants. We found no meaningful difference in the mean peak viral load (with a lower peak cycle threshold [Ct] indicating a higher viral load), proliferation duration, clearance duration, or duration of acute infection of either the alpha or the delta variant as compared with variants not of interest or concern.
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- Page last updated:Mar 28, 2024
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