The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19.

The cohort included 897932 individuals. Comirnaty (BioNTech/Pfizer) VE against Covid-19-related hospitalization was 93% (95% CI90%–95%) and 87% (95% CI 84%–89%) 14–90 and 91–180 days after the second dose; VE increased to 96% (95% CI 95%–97%) 14–60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe Covid-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 91% (95% CI 79%–96%) and 76% (95% CI 56%–86%) 14–90 and 91–180 days after the second and 95% (95% CI 94%–97%) 14–60 days after the third dose.

Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against beta and omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron.

People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21- 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65-5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61-10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60-11.08]).

Measuring COVID-19 disease severity in a population has been important for understanding the public health impact of each variant of concern. It also impacts immunologists and virologists closely as it reflects population immunity and the mechanisms of viral infection. The Omicron variant of SARS-CoV-2 has been reported to cause milder disease in adults but lead to increased hospital admissions in children. How can we compare disease severity in Omicron and Delta infections, and how should differences be interpreted?

We developed a web-based bioinformatic pipeline ("COVID-Profiler") that inputs raw or assembled sequencing data, displays raw alignments for quality control, annotates mutations found and performs phylogenetic analysis. The pipeline software can be applied to other (re-) emerging pathogens.

Using data from the UK Biobank, which contains in-depth genotyping data and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants identified from a previous large genome-wide association study. We prospectively assessed associations between PRS and incident VTE after first and the second-dose vaccination separately. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (95% CI 1.15 to 1.73) in 28 days and 1.36 (95% CI 1.22 to 1.52) in 90 days). Similar associations were found after stratification by vaccine type, in the two-dose cohort and across the historical unvaccinated cohorts.

COVID-19 can cause severe illness in children. Children aged 5–11 years became eligible for COVID-19 vaccination on November 2, 2021. During the period of Omicron predominance (December 19, 2021–February 28, 2022), COVID-19–associated hospitalization rates in children aged 5–11 years were approximately twice as high among unvaccinated as among vaccinated children. Non-Hispanic Black children represented the largest group of unvaccinated children. Thirty percent of hospitalized children had no underlying medical conditions, and 19% were admitted to an intensive care unit. Children with diabetes and obesity were more likely to experience severe COVID-19.

Did the effectiveness of the mRNA-1273, BNT162b2, and JNJ-78436735 COVID-19 vaccines change among US-based military personnel before and during the predominance of the SARS-CoV-2 Delta (B.1.617.2) variant? In this case-control study of 441?379 active US military personnel, overall COVID-19 vaccine effectiveness decreased by 19% from the pre-Delta to the Delta period. JNJ-78436735 had the lowest overall vaccine effectiveness in the pre-Delta (81.8%) and Delta (38.3%) periods.

The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19.

The cohort included 897932 individuals. Comirnaty (BioNTech/Pfizer) VE against Covid-19-related hospitalization was 93% (95% CI90%–95%) and 87% (95% CI 84%–89%) 14–90 and 91–180 days after the second dose; VE increased to 96% (95% CI 95%–97%) 14–60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe Covid-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 91% (95% CI 79%–96%) and 76% (95% CI 56%–86%) 14–90 and 91–180 days after the second and 95% (95% CI 94%–97%) 14–60 days after the third dose.

Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against beta and omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron.

People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21- 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65-5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61-10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60-11.08]).

Measuring COVID-19 disease severity in a population has been important for understanding the public health impact of each variant of concern. It also impacts immunologists and virologists closely as it reflects population immunity and the mechanisms of viral infection. The Omicron variant of SARS-CoV-2 has been reported to cause milder disease in adults but lead to increased hospital admissions in children. How can we compare disease severity in Omicron and Delta infections, and how should differences be interpreted?

We developed a web-based bioinformatic pipeline ("COVID-Profiler") that inputs raw or assembled sequencing data, displays raw alignments for quality control, annotates mutations found and performs phylogenetic analysis. The pipeline software can be applied to other (re-) emerging pathogens.

Using data from the UK Biobank, which contains in-depth genotyping data and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants identified from a previous large genome-wide association study. We prospectively assessed associations between PRS and incident VTE after first and the second-dose vaccination separately. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (95% CI 1.15 to 1.73) in 28 days and 1.36 (95% CI 1.22 to 1.52) in 90 days). Similar associations were found after stratification by vaccine type, in the two-dose cohort and across the historical unvaccinated cohorts.

COVID-19 can cause severe illness in children. Children aged 5–11 years became eligible for COVID-19 vaccination on November 2, 2021. During the period of Omicron predominance (December 19, 2021–February 28, 2022), COVID-19–associated hospitalization rates in children aged 5–11 years were approximately twice as high among unvaccinated as among vaccinated children. Non-Hispanic Black children represented the largest group of unvaccinated children. Thirty percent of hospitalized children had no underlying medical conditions, and 19% were admitted to an intensive care unit. Children with diabetes and obesity were more likely to experience severe COVID-19.

Did the effectiveness of the mRNA-1273, BNT162b2, and JNJ-78436735 COVID-19 vaccines change among US-based military personnel before and during the predominance of the SARS-CoV-2 Delta (B.1.617.2) variant? In this case-control study of 441?379 active US military personnel, overall COVID-19 vaccine effectiveness decreased by 19% from the pre-Delta to the Delta period. JNJ-78436735 had the lowest overall vaccine effectiveness in the pre-Delta (81.8%) and Delta (38.3%) periods.

The primary analysis included 182,122 matched pairs. Relative vaccine effectiveness in days 7 to 30 after the fourth dose was estimated to be 45% (95% confidence interval [CI], 44 to 47) against polymerase-chain-reaction–confirmed SARS-CoV-2 infection, 55% (95% CI, 53 to 58) against symptomatic Covid-19, 68% (95% CI, 59 to 74) against Covid-19–related hospitalization, 62% (95% CI, 50 to 74) against severe Covid-19, and 74% (95% CI, 50 to 90) against Covid-19–related death. The corresponding estimates in days 14 to 30 after the fourth dose were 52% (95% CI, 49 to 54), 61% (95% CI, 58 to 64), 72% (95% CI, 63 to 79), 64% (95% CI, 48 to 77), and 76% (95% CI, 48 to 91). In days 7 to 30 after a fourth vaccine dose, the difference in the absolute risk (three doses vs. four doses) was 180.1 cases per 100,000 persons (95% CI, 142.8 to 211.9) for Covid-19–related hospitalization and 68.8 cases per 100,000 persons (95% CI, 48.5 to 91.9) for severe Covid-19.

The cohort included 897932 individuals. Comirnaty (BioNTech/Pfizer) VE against Covid-19-related hospitalization was 93% (95% CI90%–95%) and 87% (95% CI 84%–89%) 14–90 and 91–180 days after the second dose; VE increased to 96% (95% CI 95%–97%) 14–60 days after the third dose. VE of other homologous and heterologous three dose series was similar. Protection against severe Covid-19 requiring ICU treatment was even better. Since January 1, 2022, Comirnaty VE was 91% (95% CI 79%–96%) and 76% (95% CI 56%–86%) 14–90 and 91–180 days after the second and 95% (95% CI 94%–97%) 14–60 days after the third dose.

Convalescent sera from unvaccinated individuals infected by the ancestral virus demonstrated reduced neutralization against beta and omicron VOCs. Sera from individuals that received three doses of the Pfizer or Moderna vaccines demonstrated reduced neutralization of the omicron variant relative to ancestral SARS-CoV-2. Sera from individuals that were naturally infected with ancestral SARS-CoV-2 and subsequently received two doses of the Pfizer vaccine induced significantly higher neutralizing antibody levels against ancestral virus and all VOCs. Infection alone, either with ancestral SARS-CoV-2 or the delta variant was not sufficient to induce high neutralizing antibody titers against omicron.

People with rare diseases had increased risk of COVID19-related deaths compared to the unaffected relatives (OR [95% CI] = 3.47 [1.21- 12.2]). Although, the effect was insignificant after adjusting for age and number of comorbidities (OR [95% CI] = 1.94 [0.65-5.80]). Neurology and neurodevelopmental diseases was significantly associated with COVID19-related death in both univariable (OR [95% CI] = 4.07 [1.61-10.38]) and multivariable analysis (OR [95% CI] = 4.22 [1.60-11.08]).

Measuring COVID-19 disease severity in a population has been important for understanding the public health impact of each variant of concern. It also impacts immunologists and virologists closely as it reflects population immunity and the mechanisms of viral infection. The Omicron variant of SARS-CoV-2 has been reported to cause milder disease in adults but lead to increased hospital admissions in children. How can we compare disease severity in Omicron and Delta infections, and how should differences be interpreted?

We developed a web-based bioinformatic pipeline ("COVID-Profiler") that inputs raw or assembled sequencing data, displays raw alignments for quality control, annotates mutations found and performs phylogenetic analysis. The pipeline software can be applied to other (re-) emerging pathogens.

Using data from the UK Biobank, which contains in-depth genotyping data and linked vaccination and health outcomes information, we generated a polygenic risk score (PRS) using 299 genetic variants identified from a previous large genome-wide association study. We prospectively assessed associations between PRS and incident VTE after first and the second-dose vaccination separately. The PRS was significantly associated with a higher risk of VTE (HR per 1 SD increase in PRS, 1.41 (95% CI 1.15 to 1.73) in 28 days and 1.36 (95% CI 1.22 to 1.52) in 90 days). Similar associations were found after stratification by vaccine type, in the two-dose cohort and across the historical unvaccinated cohorts.

COVID-19 can cause severe illness in children. Children aged 5–11 years became eligible for COVID-19 vaccination on November 2, 2021. During the period of Omicron predominance (December 19, 2021–February 28, 2022), COVID-19–associated hospitalization rates in children aged 5–11 years were approximately twice as high among unvaccinated as among vaccinated children. Non-Hispanic Black children represented the largest group of unvaccinated children. Thirty percent of hospitalized children had no underlying medical conditions, and 19% were admitted to an intensive care unit. Children with diabetes and obesity were more likely to experience severe COVID-19.

Did the effectiveness of the mRNA-1273, BNT162b2, and JNJ-78436735 COVID-19 vaccines change among US-based military personnel before and during the predominance of the SARS-CoV-2 Delta (B.1.617.2) variant? In this case-control study of 441?379 active US military personnel, overall COVID-19 vaccine effectiveness decreased by 19% from the pre-Delta to the Delta period. JNJ-78436735 had the lowest overall vaccine effectiveness in the pre-Delta (81.8%) and Delta (38.3%) periods.