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Published on 09/09/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution
    R Ke et al, MEDRXIV, September 2, 2021
    we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases.
  • Surveillance for Adverse Events After COVID-19 mRNA Vaccination
    NP Klein et al, JAMA, September 3, 2021
    In this interim analysis of surveillance data from 6.2 million persons who received 11.8 million doses of an mRNA vaccine, event rates for 23 serious health outcomes were not significantly higher for individuals 1 to 21 days after vaccination compared with similar individuals at 22 to 42 days after vaccination.
  • Effectiveness of COVID-19 Vaccines Against SARS-CoV-2 Infection During a Delta Variant Epidemic Surge in Multnomah County, Oregon, July 2021
    RS Barlow et al, MEDRXIV, September 3, 2021
    500 case-control pairs were matched (n=1000). Overall effectiveness of any completed COVID-19 immunization was 73% (95% Confidence Interval [CI] 49-86%) and 74% (95% CI 65-85%) for mRNA immunizations and 72% (95% CI 47-85%) for individuals that had started but not completed mRNA immunizations. Our findings estimate high, yet reduced, VE during Delta variant dissemination.
  • Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021.
    Seppälä Elina et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 9 (35)
    Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0-27.4) and 64.6% (95% CI: 60.6-68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4-58.3) and 84.4% (95%CI: 81.8-86.5) against the Alpha variant.
  • COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases.
    Papadopoulou Areti et al. PloS one 2021 9 (9) e0256988
    We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10).
  • Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation
    CR Wells et al, MEDRXIV, September 5, 2021
    Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines shorter than five days, RA test on entry to and on exit from quarantine reduced onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the minimum testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to be every six days.
  • A year of Covid-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
    F Thibord et al, MEDRXIV, September 5, 2021
    Between May 2020 and June 2021, we used Covid-19 data released periodically by UK Biobank and performed 65 Genome-Wide Association Studies (GWAS) in up to 18 releases of Covid-19 susceptibility (N=18,481 cases in June 2021), hospitalization (N=3,260), severe outcomes (N=1,244) and death (N=1,104), stratified by sex and ancestry. In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26E-15 and rs71325088-C, OR=1.62, P=2.25E-9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30E-12).
  • SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
    P MIcochova et al, Nature, September 6, 2021
    B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7.
  • Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy
    N Dagan et al, Nature Medicine, September 7, 2021
    A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56?d after the second dose was 96% (95% confidence interval 89–100%) for any documented infection, 97% (91–100%) for infections with documented symptoms and 89% (43–100%) for COVID-19-related hospitalization.
  • The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages
    DP Martin et al, Cell, September 6, 2021
    The independent emergence late in 2020 of the B.1.1.7, B.1.351 and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three “501Y lineages” coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites: mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.
  • Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO
    J Kertes et al, MEDRXIV, September 7, 2021
    Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign. We carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. We found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups. An inverse relationship was found between IgG titer and subsequent CoVid-19 infection (PCR-positive). Those participants vaccinated in the first two months of the campaign were more likely to become infected than those subsequently vaccinated. The 60+ vaccinated had lower initial IgG levels, and were at greater risk of infection.
  • Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy
    EO Kharbanda et al, JAMA, September 8, 2021
    Of 105?446 unique pregnancies, 13?160 spontaneous abortions and 92?286 ongoing pregnancies were identified. Overall, 7.8% of women received 1 or more BNT162b2 (Pfizer-BioNTech) vaccines; 6.0% received 1 or more mRNA-1273 (Moderna) vaccines; and 0.5% received an Ad26.COV.2.S (Janssen) vaccine during pregnancy and before 20 weeks’ gestation. Spontaneous abortions did not have an increased odds of exposure to a COVID-19 vaccination in the prior 28 days compared with ongoing pregnancies (adjusted odds ratio, 1.02; 95% CI, 0.96-1.08). Results were consistent for mRNA-1273 and BNT162b2 and by gestational age group.
  • Effect of Vaccination on Transmission of SARS-CoV-2.
    Shah Anoop S V et al. The New England journal of medicine 2021 9
    Cases of Covid-19 were less common among household members of vaccinated health care workers during the period beginning 14 days after the first dose than during the unvaccinated period before the first dose (event rate per 100 person-years, 9.40 before the first dose and 5.93 beginning 14 days after the first dose). After the health care worker’s second dose, the rate in household members was lower still (2.98 cases per 100 person-years)
  • Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion.
    Zauche Lauren H et al. The New England journal of medicine 2021 9
    As compared with data from two historical cohorts that represent the lower and upper ranges of spontaneous-abortion risk,2,4 the cumulative risks of spontaneous abortion from our primary and sensitivity analyses were within the expected risk range.
  • On Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. Reply.
    Meaney-Delman Dana M et al. The New England journal of medicine 2021 9
  • Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.
    Thompson Mark G et al. The New England journal of medicine 2021 9
    The effectiveness of full messenger RNA (mRNA) vaccination (=14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 85 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults.

Non-Genomics Precision Health Studies

  • Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution
    R Ke et al, MEDRXIV, September 2, 2021
    we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases.
  • Surveillance for Adverse Events After COVID-19 mRNA Vaccination
    NP Klein et al, JAMA, September 3, 2021
    In this interim analysis of surveillance data from 6.2 million persons who received 11.8 million doses of an mRNA vaccine, event rates for 23 serious health outcomes were not significantly higher for individuals 1 to 21 days after vaccination compared with similar individuals at 22 to 42 days after vaccination.
  • Effectiveness of COVID-19 Vaccines Against SARS-CoV-2 Infection During a Delta Variant Epidemic Surge in Multnomah County, Oregon, July 2021
    RS Barlow et al, MEDRXIV, September 3, 2021
    500 case-control pairs were matched (n=1000). Overall effectiveness of any completed COVID-19 immunization was 73% (95% Confidence Interval [CI] 49-86%) and 74% (95% CI 65-85%) for mRNA immunizations and 72% (95% CI 47-85%) for individuals that had started but not completed mRNA immunizations. Our findings estimate high, yet reduced, VE during Delta variant dissemination.
  • Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021.
    Seppälä Elina et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 9 (35)
    Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0-27.4) and 64.6% (95% CI: 60.6-68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4-58.3) and 84.4% (95%CI: 81.8-86.5) against the Alpha variant.
  • COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases.
    Papadopoulou Areti et al. PloS one 2021 9 (9) e0256988
    We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10).
  • Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation
    CR Wells et al, MEDRXIV, September 5, 2021
    Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines shorter than five days, RA test on entry to and on exit from quarantine reduced onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the minimum testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to be every six days.
  • A year of Covid-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
    F Thibord et al, MEDRXIV, September 5, 2021
    Between May 2020 and June 2021, we used Covid-19 data released periodically by UK Biobank and performed 65 Genome-Wide Association Studies (GWAS) in up to 18 releases of Covid-19 susceptibility (N=18,481 cases in June 2021), hospitalization (N=3,260), severe outcomes (N=1,244) and death (N=1,104), stratified by sex and ancestry. In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26E-15 and rs71325088-C, OR=1.62, P=2.25E-9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30E-12).
  • SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
    P MIcochova et al, Nature, September 6, 2021
    B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7.
  • Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy
    N Dagan et al, Nature Medicine, September 7, 2021
    A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56?d after the second dose was 96% (95% confidence interval 89–100%) for any documented infection, 97% (91–100%) for infections with documented symptoms and 89% (43–100%) for COVID-19-related hospitalization.
  • The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages
    DP Martin et al, Cell, September 6, 2021
    The independent emergence late in 2020 of the B.1.1.7, B.1.351 and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three “501Y lineages” coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites: mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.
  • Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO
    J Kertes et al, MEDRXIV, September 7, 2021
    Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign. We carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. We found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups. An inverse relationship was found between IgG titer and subsequent CoVid-19 infection (PCR-positive). Those participants vaccinated in the first two months of the campaign were more likely to become infected than those subsequently vaccinated. The 60+ vaccinated had lower initial IgG levels, and were at greater risk of infection.
  • Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy
    EO Kharbanda et al, JAMA, September 8, 2021
    Of 105?446 unique pregnancies, 13?160 spontaneous abortions and 92?286 ongoing pregnancies were identified. Overall, 7.8% of women received 1 or more BNT162b2 (Pfizer-BioNTech) vaccines; 6.0% received 1 or more mRNA-1273 (Moderna) vaccines; and 0.5% received an Ad26.COV.2.S (Janssen) vaccine during pregnancy and before 20 weeks’ gestation. Spontaneous abortions did not have an increased odds of exposure to a COVID-19 vaccination in the prior 28 days compared with ongoing pregnancies (adjusted odds ratio, 1.02; 95% CI, 0.96-1.08). Results were consistent for mRNA-1273 and BNT162b2 and by gestational age group.
  • Effect of Vaccination on Transmission of SARS-CoV-2.
    Shah Anoop S V et al. The New England journal of medicine 2021 9
    Cases of Covid-19 were less common among household members of vaccinated health care workers during the period beginning 14 days after the first dose than during the unvaccinated period before the first dose (event rate per 100 person-years, 9.40 before the first dose and 5.93 beginning 14 days after the first dose). After the health care worker’s second dose, the rate in household members was lower still (2.98 cases per 100 person-years)
  • Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion.
    Zauche Lauren H et al. The New England journal of medicine 2021 9
    As compared with data from two historical cohorts that represent the lower and upper ranges of spontaneous-abortion risk,2,4 the cumulative risks of spontaneous abortion from our primary and sensitivity analyses were within the expected risk range.
  • On Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. Reply.
    Meaney-Delman Dana M et al. The New England journal of medicine 2021 9
  • Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.
    Thompson Mark G et al. The New England journal of medicine 2021 9
    The effectiveness of full messenger RNA (mRNA) vaccination (=14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 85 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults.

News, Reviews and Commentaries

  • Longitudinal analysis of SARS-CoV-2 vaccine breakthrough infections reveal limited infectious virus shedding and restricted tissue distribution
    R Ke et al, MEDRXIV, September 2, 2021
    we examined viral dynamics and infectious virus shedding through daily longitudinal sampling in a small cohort of adults infected with SARS-CoV-2 at varying stages of vaccination. The durations of both infectious virus shedding and symptoms were significantly reduced in vaccinated individuals compared with unvaccinated individuals. We also observed that breakthrough infections are associated with strong tissue compartmentalization and are only detectable in saliva in some cases.
  • Surveillance for Adverse Events After COVID-19 mRNA Vaccination
    NP Klein et al, JAMA, September 3, 2021
    In this interim analysis of surveillance data from 6.2 million persons who received 11.8 million doses of an mRNA vaccine, event rates for 23 serious health outcomes were not significantly higher for individuals 1 to 21 days after vaccination compared with similar individuals at 22 to 42 days after vaccination.
  • Effectiveness of COVID-19 Vaccines Against SARS-CoV-2 Infection During a Delta Variant Epidemic Surge in Multnomah County, Oregon, July 2021
    RS Barlow et al, MEDRXIV, September 3, 2021
    500 case-control pairs were matched (n=1000). Overall effectiveness of any completed COVID-19 immunization was 73% (95% Confidence Interval [CI] 49-86%) and 74% (95% CI 65-85%) for mRNA immunizations and 72% (95% CI 47-85%) for individuals that had started but not completed mRNA immunizations. Our findings estimate high, yet reduced, VE during Delta variant dissemination.
  • Vaccine effectiveness against infection with the Delta (B.1.617.2) variant, Norway, April to August 2021.
    Seppälä Elina et al. Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin 2021 9 (35)
    Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0-27.4) and 64.6% (95% CI: 60.6-68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4-58.3) and 84.4% (95%CI: 81.8-86.5) against the Alpha variant.
  • COVID-19 susceptibility variants associate with blood clots, thrombophlebitis and circulatory diseases.
    Papadopoulou Areti et al. PloS one 2021 9 (9) e0256988
    We utilised phenotypic data in up to 400,000 individuals from the UK Biobank, including Hospital Episode Statistics and General Practice data. We identified a spectrum of associations between both genetically determined COVID-19 susceptibility and severity with a number of traits. COVID-19 risk was associated with increased risk for phlebitis and thrombophlebitis (OR = 1.11, p = 5.36e-08). We also identified significant signals between COVID-19 susceptibility with blood clots in the leg (OR = 1.1, p = 1.66e-16) and with increased risk for blood clots in the lung (OR = 1.12, p = 1.45 e-10).
  • Comparative analyses of all FDA EUA-approved rapid antigen tests and RT-PCR for COVID-19 quarantine and surveillance-based isolation
    CR Wells et al, MEDRXIV, September 5, 2021
    Our results demonstrate that the relative effectiveness of RA and RT-PCR tests in reducing post-quarantine transmission depends on the quarantine duration and the turnaround time of testing results. For quarantines shorter than five days, RA test on entry to and on exit from quarantine reduced onward transmission more than a single RT-PCR test conducted upon exit. Conducting surveillance via serial RT-PCR testing with a 24-h turnaround time, the minimum testing frequency paired with isolation of positives that is required to suppress the effective reproduction number (RE) below one was found to be every six days.
  • A year of Covid-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
    F Thibord et al, MEDRXIV, September 5, 2021
    Between May 2020 and June 2021, we used Covid-19 data released periodically by UK Biobank and performed 65 Genome-Wide Association Studies (GWAS) in up to 18 releases of Covid-19 susceptibility (N=18,481 cases in June 2021), hospitalization (N=3,260), severe outcomes (N=1,244) and death (N=1,104), stratified by sex and ancestry. In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26E-15 and rs71325088-C, OR=1.62, P=2.25E-9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30E-12).
  • SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion
    P MIcochova et al, Nature, September 6, 2021
    B.1.617.2 is 6-fold less sensitive to serum neutralising antibodies from recovered individuals, and 8-fold less sensitive to vaccine-elicited antibodies as compared to wild type (WT) Wuhan-1 bearing D614G. Serum neutralising titres against B.1.617.2 were lower in ChAdOx-1 versus BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies against the receptor binding domain (RBD) and N- terminal domain (NTD). B.1.617.2 demonstrated higher replication efficiency in both airway organoid and human airway epithelial systems compared to B.1.1.7.
  • Effectiveness of the BNT162b2 mRNA COVID-19 vaccine in pregnancy
    N Dagan et al, Nature Medicine, September 7, 2021
    A total of 10,861 vaccinated pregnant women were matched to 10,861 unvaccinated pregnant controls using demographic and clinical characteristics. Study outcomes included documented infection with SARS-CoV-2, symptomatic COVID-19, COVID-19-related hospitalization, severe illness and death. Estimated vaccine effectiveness from 7 through to 56?d after the second dose was 96% (95% confidence interval 89–100%) for any documented infection, 97% (91–100%) for infections with documented symptoms and 89% (43–100%) for COVID-19-related hospitalization.
  • The emergence and ongoing convergent evolution of the SARS-CoV-2 N501Y lineages
    DP Martin et al, Cell, September 6, 2021
    The independent emergence late in 2020 of the B.1.1.7, B.1.351 and P.1 lineages of SARS-CoV-2 prompted renewed concerns about the evolutionary capacity of this virus to overcome public health interventions and rising population immunity. Here, by examining patterns of synonymous and non-synonymous mutations that have accumulated in SARS-CoV-2 genomes since the pandemic began, we find that the emergence of these three “501Y lineages” coincided with a major global shift in the selective forces acting on various SARS-CoV-2 genes. Following their emergence, the adaptive evolution of 501Y lineage viruses has involved repeated selectively favored convergent mutations at 35 genome sites: mutations we refer to as the 501Y meta-signature. The ongoing convergence of viruses in many other lineages on this meta-signature suggests that it includes multiple mutation combinations capable of promoting the persistence of diverse SARS-CoV-2 lineages in the face of mounting host immune recognition.
  • Effectiveness of the mRNA BNT162b2 vaccine six months after vaccination: findings from a large Israeli HMO
    J Kertes et al, MEDRXIV, September 7, 2021
    Israel is currently experiencing a new wave of CoVid-19 infection, six months after implementing a national vaccination campaign. We carried out three discrete analyses using data from a large Israeli HMO to determine whether IgG levels of those fully vaccinated drop over time, the relationship between IgG titer and subsequent PCR-confirmed infection, and compare PCR-confirmed infection rates by period of vaccination. We found that mean IgG antibody levels steadily decreased over the six-month period in the total tested population, and in all age groups. An inverse relationship was found between IgG titer and subsequent CoVid-19 infection (PCR-positive). Those participants vaccinated in the first two months of the campaign were more likely to become infected than those subsequently vaccinated. The 60+ vaccinated had lower initial IgG levels, and were at greater risk of infection.
  • Spontaneous Abortion Following COVID-19 Vaccination During Pregnancy
    EO Kharbanda et al, JAMA, September 8, 2021
    Of 105?446 unique pregnancies, 13?160 spontaneous abortions and 92?286 ongoing pregnancies were identified. Overall, 7.8% of women received 1 or more BNT162b2 (Pfizer-BioNTech) vaccines; 6.0% received 1 or more mRNA-1273 (Moderna) vaccines; and 0.5% received an Ad26.COV.2.S (Janssen) vaccine during pregnancy and before 20 weeks’ gestation. Spontaneous abortions did not have an increased odds of exposure to a COVID-19 vaccination in the prior 28 days compared with ongoing pregnancies (adjusted odds ratio, 1.02; 95% CI, 0.96-1.08). Results were consistent for mRNA-1273 and BNT162b2 and by gestational age group.
  • Effect of Vaccination on Transmission of SARS-CoV-2.
    Shah Anoop S V et al. The New England journal of medicine 2021 9
    Cases of Covid-19 were less common among household members of vaccinated health care workers during the period beginning 14 days after the first dose than during the unvaccinated period before the first dose (event rate per 100 person-years, 9.40 before the first dose and 5.93 beginning 14 days after the first dose). After the health care worker’s second dose, the rate in household members was lower still (2.98 cases per 100 person-years)
  • Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion.
    Zauche Lauren H et al. The New England journal of medicine 2021 9
    As compared with data from two historical cohorts that represent the lower and upper ranges of spontaneous-abortion risk,2,4 the cumulative risks of spontaneous abortion from our primary and sensitivity analyses were within the expected risk range.
  • On Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons. Reply.
    Meaney-Delman Dana M et al. The New England journal of medicine 2021 9
  • Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.
    Thompson Mark G et al. The New England journal of medicine 2021 9
    The effectiveness of full messenger RNA (mRNA) vaccination (=14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 85 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults.
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