There is a need for wastewater based epidemiological (WBE) methods that integrate multiple, variously sized surveillance sites across geographic areas. We developed a novel indexing method, Melvin's Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin's Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF's) of varying sizes and served populations across the state of Minnesota during the Summer of 2020.

In a case-control study that included 4513 hospitalized adults in 18 US states, hospitalization for a COVID-19 diagnosis compared with an alternative diagnosis was associated with an adjusted odds ratio (aOR) of 0.15 for full vaccination with an authorized or approved mRNA COVID-19 vaccine. Among adults hospitalized for COVID-19, progression to death or invasive mechanical ventilation was associated with an aOR of 0.33 for full vaccination; both ORs were statistically significant. Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and with disease progression, consistent with risk reduction among vaccine breakthrough infections.

Vaccines not only decrease transmission rates, but also decrease disease severity among individuals who do acquire infection. Vaccinated people with breakthrough infections, including infection with the Delta variant, are less likely to develop symptoms, less likely to develop severe symptoms, more likely to recover from their illness quickly, and much less likely to require hospitalization compared with unvaccinated people.

We report SARS-CoV-2 vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type (n = 780,225) in the Veterans Health Administration, covering 2.7% of the U.S. population. From February to October 2021, VE-I declined from 87.9% to 48.1%, and the decline was greatest for the Janssen vaccine resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta surge. From July to October 2021, VE-D for age 65 years was 73.0% for Janssen, 81.5% for Moderna, and 84.3% for Pfizer-BioNTech; VE-D for age =65 years was 52.2% for Janssen, 75.5% for Moderna, and 70.1% for Pfizer-BioNTech.

Using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1.

We assessed antispike (anti-S) IgG antibody titers before and after a third BNT162b2 dose in individuals aged 60 years and older because this population is at high risk of developing severe SARS-CoV-2 disease and was the first to receive authorization for a third dose. We found that a third BNT162b2 dose in adults aged 60 years and older was associated with significantly increased IgG titers after 10 to 19 days, with no major adverse events.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern which is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and B.1.617.2 (Delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the B.1.617.2 (Delta) N-terminal domain. The ACE2 binding affinities of the B.1.617.1 (Kappa) and B.1.617.2 (Delta) receptor-binding domains are comparable to the Wuhan-Hu-1 isolate whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.

At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, =0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. We found that a single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern.

There is a need for wastewater based epidemiological (WBE) methods that integrate multiple, variously sized surveillance sites across geographic areas. We developed a novel indexing method, Melvin's Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin's Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF's) of varying sizes and served populations across the state of Minnesota during the Summer of 2020.

In a case-control study that included 4513 hospitalized adults in 18 US states, hospitalization for a COVID-19 diagnosis compared with an alternative diagnosis was associated with an adjusted odds ratio (aOR) of 0.15 for full vaccination with an authorized or approved mRNA COVID-19 vaccine. Among adults hospitalized for COVID-19, progression to death or invasive mechanical ventilation was associated with an aOR of 0.33 for full vaccination; both ORs were statistically significant. Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and with disease progression, consistent with risk reduction among vaccine breakthrough infections.

Vaccines not only decrease transmission rates, but also decrease disease severity among individuals who do acquire infection. Vaccinated people with breakthrough infections, including infection with the Delta variant, are less likely to develop symptoms, less likely to develop severe symptoms, more likely to recover from their illness quickly, and much less likely to require hospitalization compared with unvaccinated people.

We report SARS-CoV-2 vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type (n = 780,225) in the Veterans Health Administration, covering 2.7% of the U.S. population. From February to October 2021, VE-I declined from 87.9% to 48.1%, and the decline was greatest for the Janssen vaccine resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta surge. From July to October 2021, VE-D for age 65 years was 73.0% for Janssen, 81.5% for Moderna, and 84.3% for Pfizer-BioNTech; VE-D for age =65 years was 52.2% for Janssen, 75.5% for Moderna, and 70.1% for Pfizer-BioNTech.

Using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1.

We assessed antispike (anti-S) IgG antibody titers before and after a third BNT162b2 dose in individuals aged 60 years and older because this population is at high risk of developing severe SARS-CoV-2 disease and was the first to receive authorization for a third dose. We found that a third BNT162b2 dose in adults aged 60 years and older was associated with significantly increased IgG titers after 10 to 19 days, with no major adverse events.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern which is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and B.1.617.2 (Delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the B.1.617.2 (Delta) N-terminal domain. The ACE2 binding affinities of the B.1.617.1 (Kappa) and B.1.617.2 (Delta) receptor-binding domains are comparable to the Wuhan-Hu-1 isolate whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.

At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, =0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. We found that a single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern.

There is a need for wastewater based epidemiological (WBE) methods that integrate multiple, variously sized surveillance sites across geographic areas. We developed a novel indexing method, Melvin's Index, that provides a normalized and standardized metric of wastewater pathogen load for qPCR assays that is resilient to surveillance site variation. To demonstrate the utility of Melvin's Index, we used qRT-PCR to measure SARS-CoV-2 genomic RNA levels in influent wastewater from 19 municipal wastewater treatment facilities (WWTF's) of varying sizes and served populations across the state of Minnesota during the Summer of 2020.

In a case-control study that included 4513 hospitalized adults in 18 US states, hospitalization for a COVID-19 diagnosis compared with an alternative diagnosis was associated with an adjusted odds ratio (aOR) of 0.15 for full vaccination with an authorized or approved mRNA COVID-19 vaccine. Among adults hospitalized for COVID-19, progression to death or invasive mechanical ventilation was associated with an aOR of 0.33 for full vaccination; both ORs were statistically significant. Vaccination with an mRNA COVID-19 vaccine was significantly less likely among patients with COVID-19 hospitalization and with disease progression, consistent with risk reduction among vaccine breakthrough infections.

Vaccines not only decrease transmission rates, but also decrease disease severity among individuals who do acquire infection. Vaccinated people with breakthrough infections, including infection with the Delta variant, are less likely to develop symptoms, less likely to develop severe symptoms, more likely to recover from their illness quickly, and much less likely to require hospitalization compared with unvaccinated people.

We report SARS-CoV-2 vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type (n = 780,225) in the Veterans Health Administration, covering 2.7% of the U.S. population. From February to October 2021, VE-I declined from 87.9% to 48.1%, and the decline was greatest for the Janssen vaccine resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta surge. From July to October 2021, VE-D for age 65 years was 73.0% for Janssen, 81.5% for Moderna, and 84.3% for Pfizer-BioNTech; VE-D for age =65 years was 52.2% for Janssen, 75.5% for Moderna, and 70.1% for Pfizer-BioNTech.

Using a combined multiomics and machine learning approach, we identify the gain-of-function risk A allele of an SNP, rs17713054G>A, as a probable causative variant. We show with chromosome conformation capture and gene-expression analysis that the rs17713054-affected enhancer upregulates the interacting gene, leucine zipper transcription factor like 1 (LZTFL1). Selective spatial transcriptomic analysis of lung biopsies from patients with COVID-19 shows the presence of signals associated with epithelial–mesenchymal transition (EMT), a viral response pathway that is regulated by LZTFL1.

We assessed antispike (anti-S) IgG antibody titers before and after a third BNT162b2 dose in individuals aged 60 years and older because this population is at high risk of developing severe SARS-CoV-2 disease and was the first to receive authorization for a third dose. We found that a third BNT162b2 dose in adults aged 60 years and older was associated with significantly increased IgG titers after 10 to 19 days, with no major adverse events.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission leads to the emergence of variants, including the B.1.617.2 (Delta) variant of concern which is causing a new wave of infections and has become globally dominant. We show that these variants dampen the in vitro potency of vaccine-elicited serum neutralizing antibodies and provide a structural framework for describing their immune evasion. Mutations in the B.1.617.1 (Kappa) and B.1.617.2 (Delta) spike glycoproteins abrogate recognition by several monoclonal antibodies via alteration of key antigenic sites, including remodeling of the B.1.617.2 (Delta) N-terminal domain. The ACE2 binding affinities of the B.1.617.1 (Kappa) and B.1.617.2 (Delta) receptor-binding domains are comparable to the Wuhan-Hu-1 isolate whereas B.1.617.2+ (Delta+) exhibits markedly reduced affinity.

At data cutoff, the median follow-up was 2.3 months. In the 5-to-11-year-olds, as in other age groups, the BNT162b2 vaccine had a favorable safety profile. No vaccine-related serious adverse events were noted. One month after the second dose, the geometric mean ratio of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% confidence interval [CI], 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion (lower bound of two-sided 95% CI, >0.67; geometric mean ratio point estimate, =0.8). Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients (vaccine efficacy, 90.7%; 95% CI, 67.7 to 98.3).

Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer–BioNTech) mRNA vaccine. We found that a single dose of the BNT162b2 vaccine is likely to provide greater protection against SARS-CoV-2 infection in individuals with previous SARS-CoV-2 infection, than in SARS-CoV-2-naive individuals, including against variants of concern.