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Published on 10/21/2021

COVID-19 Genomics and Precision Public Health Weekly Update Content

Pathogen and Human Genomics Studies

  • Genomic reconstruction of the SARS-CoV-2 epidemic in England
    HS Vohringer et al, Nature, October 14, 2021
    The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterization. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. Alpha grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed Alpha and eliminated nearly all other lineages in early 2021.
  • Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.
    Earnest Rebecca et al. medRxiv : the preprint server for health sciences 2021 10
    We formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont).
  • Impact of mRNA vaccines in curtailing SARS-CoV-2 infection and disability leave utilisation among healthcare workers during the COVID-19 pandemic: cross-sectional analysis from a tertiary healthcare system in the Greater Houston metropolitan area.
    Vahidy Farhaan S et al. BMJ open 2021 10 (10) e054332
    We provide an account of real-world effectiveness of COVID-19 vaccines among healthcare workers (HCWs) at a tertiary healthcare system and report trends in SARS-CoV-2 infections and subsequent utilisation of COVID-19-specific short-term disability leave (STDL).
  • Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), August-September 2021, the Netherlands
    P de Gier et al, MEDRXIV, October 14, 2021
    We estimated vaccine effectiveness against onward transmission by comparing secondary attack rates among household members between vaccinated and unvaccinated index cases, based on source and contact tracing data collected when Delta variant was dominant. Effectiveness of full vaccination of the index against transmission to fully vaccinated household contacts was 40% (95% confidence interval (CI) 20-54%), which is in addition to the direct protection of vaccination of contacts against infection. Effectiveness of full vaccination of the index against transmission to unvaccinated household contacts was 63% (95%CI 46-75%).
  • Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021
    BA Cohn et al, MEDRXIV, October 14, 2021
    National data on COVID-19 vaccine breakthrough infections is inadequate but urgently needed to determine U.S. policy during the emergence of the Delta variant. We address this gap by comparing SARS CoV-2 infection by vaccination status from February 1, 2021 to August 13, 2021 in the Veterans Health Administration, covering 2.7% of the U.S. population. Vaccine protection declined by mid-August 2021, decreasing from 91.9% in March to 53.9% (p<0.01, n=619,755). Declines were greatest for the Janssen vaccine followed by PfizerBioNTech and Moderna. Patterns of breakthrough infection over time were consistent by age, despite rolling vaccine eligibility, implicating the Delta variant as the primary determinant of infection.
  • mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
    Goel Rishi R et al. Science (New York, N.Y.) 2021 10 eabm0829
    The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity.
  • Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.
    Dhar Mahesh S et al. Science (New York, N.Y.) 2021 10 eabj9932
    Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates; ×1.5-fold, 20% reduction). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline.
  • Impact of the SARS-CoV-2 pandemic on cystic fibrosis centres and care: survey results from US centres.
    Muhlebach Marianne S et al. ERJ open research 2021 10 (4)
    Lessons learnt from the pandemic show that telehealth for cystic fibrosis allows multidisciplinary visits but better means for monitoring of lung function and microbiology are needed.
  • SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers
    F Rovida et al, Nature Comms, October 15, 2021
    Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58–93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p?=?0.01).
  • Duration of viral shedding and culture positivity with post-vaccination breakthrough delta variant infections
    MJ Siedner et al, MEDRXIV, October 17, 2021
    Isolation guidelines for SARS-CoV-2 are largely derived from data collected prior to emergence of the delta variant. We followed a cohort of ambulatory patients with post-vaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole genome sequencing, and viral culture. All delta variant infections (8/8, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR (median 13.5 vs 4 days, hazard ratio [HR] 0.45, 95%CI 0.17-1.17), greater likelihood of replication competent virus at early stages of infection (6/8 [75%] vs 3/14 [23%], P=0.03), and longer duration of culturable virus (median 7 vs 3 days, HR 0.38, 95%CI 0.14-1.02) compared to non-delta variants.
  • Time-varying effectiveness of the mRNA-1273, BNT162b2 and Ad26.COV2.S vaccines against SARS-CoV-2 infections and COVID-19 hospitalizations and deaths: an analysis based on observational data from Puerto Rico
    MM Robles-Fontan et al, MEDRXIV, October 18, 2021
    All vaccines were effective at reducing risks for all outcomes across all age groups. At the peak of their protection, mRNA-1273, BNT162b2, and Ad26.COV2.S had an effectiveness of 87% (85% - 89%), 85% (82% - 87%), and 65% (58% - 70%), with Ad26.COV2.S reaching this peak 32 days after the being considered fully vaccinated. After four months, effectiveness waned to about 73%, 58%, and 32% for mRNA-1273, BNT162b2, and Ad26.COV2.S, respectively. All vaccines had a lower effectiveness for those over 85 years, with the decrease in effectiveness particularly low for the Ad26.COV2.S vaccine. We found no clear evidence that effectiveness was different after the Delta variant became dominant.
  • Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants
    E Andreano et al, Nature, October 20, 2021
    We analyzed at single-cell level the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to dissect the nature of the B cell and antibody response. Almost six-thousands cells were sorted, over three-thousand of them produced monoclonal antibodies against the spike protein and more than four hundred neutralized the original Wuhan SARS-CoV-2 virus. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants showed to escape almost seventy per cent of these antibodies while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescent people and generated potent and broadly neutralizing antibodies. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants.
  • Effectiveness of BNT162b2 Vaccine against Delta Variant in Adolescents.
    Reis Ben Y et al. The New England journal of medicine 2021 10
    Our results show that the BNT162b2 mRNA vaccine was highly effective in the first few weeks after vaccination against both documented infection and symptomatic Covid-19 with the delta variant among adolescents between the ages of 12 and 18 years.he estimated vaccine effectiveness against documented SARS-CoV-2 infection was 59% (95% confidence interval [CI], 52 to 65) on days 14 through 20 after the first dose, 66% (95% CI, 59 to 72) on days 21 to 27 after the first dose, and 90% (95% CI, 88 to 92) on days 7 to 21 after the second dose. The estimated vaccine effectiveness against symptomatic Covid-19 was 57% (95% CI, 39 to 71) on days 14 to 20 after the first dose, 82% (95% CI, 73 to 91) on days 21 to 27 after the first dose, and 93% (95% CI, 88 to 97) on days 7 to 21 after the second dose.
  • Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage.
    Magnus Maria C et al. The New England journal of medicine 2021 10
    Our study found no evidence of an increased risk for early pregnancy loss after Covid-19 vaccination and adds to the findings from other reports supporting Covid-19 vaccination during pregnancy. Among 13,956 women with ongoing pregnancies (of whom 5.5% were vaccinated) and 4521 women with miscarriages (of whom 5.1% were vaccinated), the median number of days between vaccination and miscarriage or confirmation of ongoing pregnancy was 19 (Fig. S2). Among women with miscarriages, the adjusted odds ratios for Covid-19 vaccination were 0.91 (95% confidence interval [CI], 0.75 to 1.10) for vaccination in the previous 3 weeks and 0.81 (95% CI, 0.69 to 0.95) for vaccination in the previous 5 weeks.
  • Effectiveness of the mRNA-1273 Vaccine during a SARS-CoV-2 Delta Outbreak in a Prison.
    Chin Elizabeth T et al. The New England journal of medicine 2021 10
    Our results indicate that the mRNA-1273 vaccine was quite effective against SARS-CoV-2 infection during a delta variant–driven outbreak in this high-risk, congregate setting. Although the effectiveness against infection was substantially lower than that estimated in studies conducted before the emergence of the delta variant, protection against symptomatic illness remained robust — an outcome consistent with other recent reports. Notably, full vaccination also conferred additional substantial protection against infection in men with previous confirmed infections.
  • BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant.
    Sheikh Aziz et al. The New England journal of medicine 2021 10
    Among persons 16 to 39 years of age who had infections for which data on S gene status were available, no deaths occurred among those who were fully vaccinated, as compared with 17 deaths among those who were unvaccinated. Among those who were 40 to 59 years of age, vaccine effectiveness against death from Covid-19 was 88% (95% confidence interval [CI], 76 to 93) for ChAdOx1 nCoV-19 and 95% (95% CI, 79 to 99) for BNT162b2; vaccine effectiveness was 90% (95% CI, 84 to 94) and 87% (95% CI, 77 to 93), respectively, among those 60 years of age or older. Overall, vaccine effectiveness against death from the delta variant 14 or more days after the second vaccine dose was 90% (95% CI, 83 to 94) for BNT162b2 and 91% (95% CI, 86 to 94) for ChAdOx1 nCoV-19.

Non-Genomics Precision Health Studies

  • Genomic reconstruction of the SARS-CoV-2 epidemic in England
    HS Vohringer et al, Nature, October 14, 2021
    The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterization. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. Alpha grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed Alpha and eliminated nearly all other lineages in early 2021.
  • Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.
    Earnest Rebecca et al. medRxiv : the preprint server for health sciences 2021 10
    We formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont).
  • Impact of mRNA vaccines in curtailing SARS-CoV-2 infection and disability leave utilisation among healthcare workers during the COVID-19 pandemic: cross-sectional analysis from a tertiary healthcare system in the Greater Houston metropolitan area.
    Vahidy Farhaan S et al. BMJ open 2021 10 (10) e054332
    We provide an account of real-world effectiveness of COVID-19 vaccines among healthcare workers (HCWs) at a tertiary healthcare system and report trends in SARS-CoV-2 infections and subsequent utilisation of COVID-19-specific short-term disability leave (STDL).
  • Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), August-September 2021, the Netherlands
    P de Gier et al, MEDRXIV, October 14, 2021
    We estimated vaccine effectiveness against onward transmission by comparing secondary attack rates among household members between vaccinated and unvaccinated index cases, based on source and contact tracing data collected when Delta variant was dominant. Effectiveness of full vaccination of the index against transmission to fully vaccinated household contacts was 40% (95% confidence interval (CI) 20-54%), which is in addition to the direct protection of vaccination of contacts against infection. Effectiveness of full vaccination of the index against transmission to unvaccinated household contacts was 63% (95%CI 46-75%).
  • Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021
    BA Cohn et al, MEDRXIV, October 14, 2021
    National data on COVID-19 vaccine breakthrough infections is inadequate but urgently needed to determine U.S. policy during the emergence of the Delta variant. We address this gap by comparing SARS CoV-2 infection by vaccination status from February 1, 2021 to August 13, 2021 in the Veterans Health Administration, covering 2.7% of the U.S. population. Vaccine protection declined by mid-August 2021, decreasing from 91.9% in March to 53.9% (p<0.01, n=619,755). Declines were greatest for the Janssen vaccine followed by PfizerBioNTech and Moderna. Patterns of breakthrough infection over time were consistent by age, despite rolling vaccine eligibility, implicating the Delta variant as the primary determinant of infection.
  • mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
    Goel Rishi R et al. Science (New York, N.Y.) 2021 10 eabm0829
    The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity.
  • Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.
    Dhar Mahesh S et al. Science (New York, N.Y.) 2021 10 eabj9932
    Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates; ×1.5-fold, 20% reduction). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline.
  • Impact of the SARS-CoV-2 pandemic on cystic fibrosis centres and care: survey results from US centres.
    Muhlebach Marianne S et al. ERJ open research 2021 10 (4)
    Lessons learnt from the pandemic show that telehealth for cystic fibrosis allows multidisciplinary visits but better means for monitoring of lung function and microbiology are needed.
  • SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers
    F Rovida et al, Nature Comms, October 15, 2021
    Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58–93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p?=?0.01).
  • Duration of viral shedding and culture positivity with post-vaccination breakthrough delta variant infections
    MJ Siedner et al, MEDRXIV, October 17, 2021
    Isolation guidelines for SARS-CoV-2 are largely derived from data collected prior to emergence of the delta variant. We followed a cohort of ambulatory patients with post-vaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole genome sequencing, and viral culture. All delta variant infections (8/8, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR (median 13.5 vs 4 days, hazard ratio [HR] 0.45, 95%CI 0.17-1.17), greater likelihood of replication competent virus at early stages of infection (6/8 [75%] vs 3/14 [23%], P=0.03), and longer duration of culturable virus (median 7 vs 3 days, HR 0.38, 95%CI 0.14-1.02) compared to non-delta variants.
  • Time-varying effectiveness of the mRNA-1273, BNT162b2 and Ad26.COV2.S vaccines against SARS-CoV-2 infections and COVID-19 hospitalizations and deaths: an analysis based on observational data from Puerto Rico
    MM Robles-Fontan et al, MEDRXIV, October 18, 2021
    All vaccines were effective at reducing risks for all outcomes across all age groups. At the peak of their protection, mRNA-1273, BNT162b2, and Ad26.COV2.S had an effectiveness of 87% (85% - 89%), 85% (82% - 87%), and 65% (58% - 70%), with Ad26.COV2.S reaching this peak 32 days after the being considered fully vaccinated. After four months, effectiveness waned to about 73%, 58%, and 32% for mRNA-1273, BNT162b2, and Ad26.COV2.S, respectively. All vaccines had a lower effectiveness for those over 85 years, with the decrease in effectiveness particularly low for the Ad26.COV2.S vaccine. We found no clear evidence that effectiveness was different after the Delta variant became dominant.
  • Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants
    E Andreano et al, Nature, October 20, 2021
    We analyzed at single-cell level the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to dissect the nature of the B cell and antibody response. Almost six-thousands cells were sorted, over three-thousand of them produced monoclonal antibodies against the spike protein and more than four hundred neutralized the original Wuhan SARS-CoV-2 virus. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants showed to escape almost seventy per cent of these antibodies while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescent people and generated potent and broadly neutralizing antibodies. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants.
  • Effectiveness of BNT162b2 Vaccine against Delta Variant in Adolescents.
    Reis Ben Y et al. The New England journal of medicine 2021 10
    Our results show that the BNT162b2 mRNA vaccine was highly effective in the first few weeks after vaccination against both documented infection and symptomatic Covid-19 with the delta variant among adolescents between the ages of 12 and 18 years.he estimated vaccine effectiveness against documented SARS-CoV-2 infection was 59% (95% confidence interval [CI], 52 to 65) on days 14 through 20 after the first dose, 66% (95% CI, 59 to 72) on days 21 to 27 after the first dose, and 90% (95% CI, 88 to 92) on days 7 to 21 after the second dose. The estimated vaccine effectiveness against symptomatic Covid-19 was 57% (95% CI, 39 to 71) on days 14 to 20 after the first dose, 82% (95% CI, 73 to 91) on days 21 to 27 after the first dose, and 93% (95% CI, 88 to 97) on days 7 to 21 after the second dose.
  • Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage.
    Magnus Maria C et al. The New England journal of medicine 2021 10
    Our study found no evidence of an increased risk for early pregnancy loss after Covid-19 vaccination and adds to the findings from other reports supporting Covid-19 vaccination during pregnancy. Among 13,956 women with ongoing pregnancies (of whom 5.5% were vaccinated) and 4521 women with miscarriages (of whom 5.1% were vaccinated), the median number of days between vaccination and miscarriage or confirmation of ongoing pregnancy was 19 (Fig. S2). Among women with miscarriages, the adjusted odds ratios for Covid-19 vaccination were 0.91 (95% confidence interval [CI], 0.75 to 1.10) for vaccination in the previous 3 weeks and 0.81 (95% CI, 0.69 to 0.95) for vaccination in the previous 5 weeks.
  • Effectiveness of the mRNA-1273 Vaccine during a SARS-CoV-2 Delta Outbreak in a Prison.
    Chin Elizabeth T et al. The New England journal of medicine 2021 10
    Our results indicate that the mRNA-1273 vaccine was quite effective against SARS-CoV-2 infection during a delta variant–driven outbreak in this high-risk, congregate setting. Although the effectiveness against infection was substantially lower than that estimated in studies conducted before the emergence of the delta variant, protection against symptomatic illness remained robust — an outcome consistent with other recent reports. Notably, full vaccination also conferred additional substantial protection against infection in men with previous confirmed infections.
  • BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant.
    Sheikh Aziz et al. The New England journal of medicine 2021 10
    Among persons 16 to 39 years of age who had infections for which data on S gene status were available, no deaths occurred among those who were fully vaccinated, as compared with 17 deaths among those who were unvaccinated. Among those who were 40 to 59 years of age, vaccine effectiveness against death from Covid-19 was 88% (95% confidence interval [CI], 76 to 93) for ChAdOx1 nCoV-19 and 95% (95% CI, 79 to 99) for BNT162b2; vaccine effectiveness was 90% (95% CI, 84 to 94) and 87% (95% CI, 77 to 93), respectively, among those 60 years of age or older. Overall, vaccine effectiveness against death from the delta variant 14 or more days after the second vaccine dose was 90% (95% CI, 83 to 94) for BNT162b2 and 91% (95% CI, 86 to 94) for ChAdOx1 nCoV-19.

News, Reviews and Commentaries

  • Genomic reconstruction of the SARS-CoV-2 epidemic in England
    HS Vohringer et al, Nature, October 14, 2021
    The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterization. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of sub-epidemics that peaked in the early autumn of 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. Alpha grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed Alpha and eliminated nearly all other lineages in early 2021.
  • Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.
    Earnest Rebecca et al. medRxiv : the preprint server for health sciences 2021 10
    We formed a partnership with SARS-CoV-2 genomic surveillance programs from all six New England US states. By comparing logistic growth rates, we found that Delta emerged 37-163% faster than Alpha in early 2021 (37% Massachusetts, 75% New Hampshire, 95% Maine, 98% Rhode Island, 151% Connecticut, and 163% Vermont). We next computed variant-specific effective reproductive numbers and estimated that Delta was 58-120% more transmissible than Alpha across New England (58% New Hampshire, 68% Massachusetts, 76% Connecticut, 85% Rhode Island, 98% Maine, and 120% Vermont).
  • Impact of mRNA vaccines in curtailing SARS-CoV-2 infection and disability leave utilisation among healthcare workers during the COVID-19 pandemic: cross-sectional analysis from a tertiary healthcare system in the Greater Houston metropolitan area.
    Vahidy Farhaan S et al. BMJ open 2021 10 (10) e054332
    We provide an account of real-world effectiveness of COVID-19 vaccines among healthcare workers (HCWs) at a tertiary healthcare system and report trends in SARS-CoV-2 infections and subsequent utilisation of COVID-19-specific short-term disability leave (STDL).
  • Vaccine effectiveness against SARS-CoV-2 transmission to household contacts during dominance of Delta variant (B.1.617.2), August-September 2021, the Netherlands
    P de Gier et al, MEDRXIV, October 14, 2021
    We estimated vaccine effectiveness against onward transmission by comparing secondary attack rates among household members between vaccinated and unvaccinated index cases, based on source and contact tracing data collected when Delta variant was dominant. Effectiveness of full vaccination of the index against transmission to fully vaccinated household contacts was 40% (95% confidence interval (CI) 20-54%), which is in addition to the direct protection of vaccination of contacts against infection. Effectiveness of full vaccination of the index against transmission to unvaccinated household contacts was 63% (95%CI 46-75%).
  • Breakthrough SARS-CoV-2 infections in 620,000 U.S. Veterans, February 1, 2021 to August 13, 2021
    BA Cohn et al, MEDRXIV, October 14, 2021
    National data on COVID-19 vaccine breakthrough infections is inadequate but urgently needed to determine U.S. policy during the emergence of the Delta variant. We address this gap by comparing SARS CoV-2 infection by vaccination status from February 1, 2021 to August 13, 2021 in the Veterans Health Administration, covering 2.7% of the U.S. population. Vaccine protection declined by mid-August 2021, decreasing from 91.9% in March to 53.9% (p<0.01, n=619,755). Declines were greatest for the Janssen vaccine followed by PfizerBioNTech and Moderna. Patterns of breakthrough infection over time were consistent by age, despite rolling vaccine eligibility, implicating the Delta variant as the primary determinant of infection.
  • mRNA vaccines induce durable immune memory to SARS-CoV-2 and variants of concern.
    Goel Rishi R et al. Science (New York, N.Y.) 2021 10 eabm0829
    The durability of immune memory after SARS-CoV-2 mRNA vaccination remains unclear. Here, we longitudinally profiled vaccine responses in SARS-CoV-2 naïve and recovered individuals for 6 months after vaccination. Antibodies declined from peak levels but remained detectable in most subjects at 6 months. We found mRNA vaccines generated functional memory B cells that increased from 3-6 months post-vaccination, with the majority of these cells cross-binding the Alpha, Beta, and Delta variants. mRNA vaccination further induced antigen-specific CD4+ and CD8+ T cells, and early CD4+ T cell responses correlated with long-term humoral immunity.
  • Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.
    Dhar Mahesh S et al. Science (New York, N.Y.) 2021 10 eabj9932
    Delhi, the national capital of India, has experienced multiple SARS-CoV-2 outbreaks in 2020 and reached population seropositivity of over 50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant B.1.617.2 (Delta) replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates; ×1.5-fold, 20% reduction). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline.
  • Impact of the SARS-CoV-2 pandemic on cystic fibrosis centres and care: survey results from US centres.
    Muhlebach Marianne S et al. ERJ open research 2021 10 (4)
    Lessons learnt from the pandemic show that telehealth for cystic fibrosis allows multidisciplinary visits but better means for monitoring of lung function and microbiology are needed.
  • SARS-CoV-2 vaccine breakthrough infections with the alpha variant are asymptomatic or mildly symptomatic among health care workers
    F Rovida et al, Nature Comms, October 15, 2021
    Vaccine breakthrough SARS-CoV-2 infection has been monitored in 3720 healthcare workers receiving 2 doses of BNT162b2. SARS-CoV-2 infection is detected in 33 subjects, with a 100-day cumulative incidence of 0.93%. Vaccine protection against acquisition of SARS-CoV-2 infection is 83% (95%CI: 58–93%) in the overall population and 93% (95%CI: 69-99%) in SARS-CoV-2-experienced subjects, when compared with a non-vaccinated control group from the same Institution, in which SARS-CoV-2 infection occurs in 20/346 subjects (100-day cumulative incidence: 5.78%). The infection is symptomatic in 16 (48%) vaccinated subjects vs 17 (85%) controls (p?=?0.01).
  • Duration of viral shedding and culture positivity with post-vaccination breakthrough delta variant infections
    MJ Siedner et al, MEDRXIV, October 17, 2021
    Isolation guidelines for SARS-CoV-2 are largely derived from data collected prior to emergence of the delta variant. We followed a cohort of ambulatory patients with post-vaccination breakthrough SARS-CoV-2 infections with longitudinal collection of nasal swabs for SARS-CoV-2 viral load quantification, whole genome sequencing, and viral culture. All delta variant infections (8/8, 100%) in our cohort were symptomatic, compared with 64% (9/14) of non-delta variant infections. Delta variant breakthrough infections were characterized by higher initial viral load, longer duration of virologic shedding by PCR (median 13.5 vs 4 days, hazard ratio [HR] 0.45, 95%CI 0.17-1.17), greater likelihood of replication competent virus at early stages of infection (6/8 [75%] vs 3/14 [23%], P=0.03), and longer duration of culturable virus (median 7 vs 3 days, HR 0.38, 95%CI 0.14-1.02) compared to non-delta variants.
  • Time-varying effectiveness of the mRNA-1273, BNT162b2 and Ad26.COV2.S vaccines against SARS-CoV-2 infections and COVID-19 hospitalizations and deaths: an analysis based on observational data from Puerto Rico
    MM Robles-Fontan et al, MEDRXIV, October 18, 2021
    All vaccines were effective at reducing risks for all outcomes across all age groups. At the peak of their protection, mRNA-1273, BNT162b2, and Ad26.COV2.S had an effectiveness of 87% (85% - 89%), 85% (82% - 87%), and 65% (58% - 70%), with Ad26.COV2.S reaching this peak 32 days after the being considered fully vaccinated. After four months, effectiveness waned to about 73%, 58%, and 32% for mRNA-1273, BNT162b2, and Ad26.COV2.S, respectively. All vaccines had a lower effectiveness for those over 85 years, with the decrease in effectiveness particularly low for the Ad26.COV2.S vaccine. We found no clear evidence that effectiveness was different after the Delta variant became dominant.
  • Hybrid immunity improves B cells and antibodies against SARS-CoV-2 variants
    E Andreano et al, Nature, October 20, 2021
    We analyzed at single-cell level the memory B cells of five naive and five convalescent people vaccinated with the BNT162b2 mRNA vaccine to dissect the nature of the B cell and antibody response. Almost six-thousands cells were sorted, over three-thousand of them produced monoclonal antibodies against the spike protein and more than four hundred neutralized the original Wuhan SARS-CoV-2 virus. The B.1.351 (Beta) and B.1.1.248 (Gamma) variants showed to escape almost seventy per cent of these antibodies while a much smaller portion was impacted by the B.1.1.7 (Alpha) and B.1.617.2 (Delta) variants. The overall loss of neutralization was always significantly higher in the antibodies from naive people. In part this was due to the IGHV2-5;IGHJ4-1 germline, which was found only in convalescent people and generated potent and broadly neutralizing antibodies. Our data suggest that people that are seropositive following infection or primary vaccination will produce antibodies with increased potency and breadth and will be able to better control SARS-CoV-2 emerging variants.
  • Effectiveness of BNT162b2 Vaccine against Delta Variant in Adolescents.
    Reis Ben Y et al. The New England journal of medicine 2021 10
    Our results show that the BNT162b2 mRNA vaccine was highly effective in the first few weeks after vaccination against both documented infection and symptomatic Covid-19 with the delta variant among adolescents between the ages of 12 and 18 years.he estimated vaccine effectiveness against documented SARS-CoV-2 infection was 59% (95% confidence interval [CI], 52 to 65) on days 14 through 20 after the first dose, 66% (95% CI, 59 to 72) on days 21 to 27 after the first dose, and 90% (95% CI, 88 to 92) on days 7 to 21 after the second dose. The estimated vaccine effectiveness against symptomatic Covid-19 was 57% (95% CI, 39 to 71) on days 14 to 20 after the first dose, 82% (95% CI, 73 to 91) on days 21 to 27 after the first dose, and 93% (95% CI, 88 to 97) on days 7 to 21 after the second dose.
  • Covid-19 Vaccination during Pregnancy and First-Trimester Miscarriage.
    Magnus Maria C et al. The New England journal of medicine 2021 10
    Our study found no evidence of an increased risk for early pregnancy loss after Covid-19 vaccination and adds to the findings from other reports supporting Covid-19 vaccination during pregnancy. Among 13,956 women with ongoing pregnancies (of whom 5.5% were vaccinated) and 4521 women with miscarriages (of whom 5.1% were vaccinated), the median number of days between vaccination and miscarriage or confirmation of ongoing pregnancy was 19 (Fig. S2). Among women with miscarriages, the adjusted odds ratios for Covid-19 vaccination were 0.91 (95% confidence interval [CI], 0.75 to 1.10) for vaccination in the previous 3 weeks and 0.81 (95% CI, 0.69 to 0.95) for vaccination in the previous 5 weeks.
  • Effectiveness of the mRNA-1273 Vaccine during a SARS-CoV-2 Delta Outbreak in a Prison.
    Chin Elizabeth T et al. The New England journal of medicine 2021 10
    Our results indicate that the mRNA-1273 vaccine was quite effective against SARS-CoV-2 infection during a delta variant–driven outbreak in this high-risk, congregate setting. Although the effectiveness against infection was substantially lower than that estimated in studies conducted before the emergence of the delta variant, protection against symptomatic illness remained robust — an outcome consistent with other recent reports. Notably, full vaccination also conferred additional substantial protection against infection in men with previous confirmed infections.
  • BNT162b2 and ChAdOx1 nCoV-19 Vaccine Effectiveness against Death from the Delta Variant.
    Sheikh Aziz et al. The New England journal of medicine 2021 10
    Among persons 16 to 39 years of age who had infections for which data on S gene status were available, no deaths occurred among those who were fully vaccinated, as compared with 17 deaths among those who were unvaccinated. Among those who were 40 to 59 years of age, vaccine effectiveness against death from Covid-19 was 88% (95% confidence interval [CI], 76 to 93) for ChAdOx1 nCoV-19 and 95% (95% CI, 79 to 99) for BNT162b2; vaccine effectiveness was 90% (95% CI, 84 to 94) and 87% (95% CI, 77 to 93), respectively, among those 60 years of age or older. Overall, vaccine effectiveness against death from the delta variant 14 or more days after the second vaccine dose was 90% (95% CI, 83 to 94) for BNT162b2 and 91% (95% CI, 86 to 94) for ChAdOx1 nCoV-19.
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