In this brief communication we are showing original research results with early estimates from Danish nationwide databases of vaccine effectiveness (VE) against the novel SARS-CoV-2 Omicron variant (B.1.1.529) up to five months after a primary vaccination series with the BNT162b2 or mRNA-1273 -19 vaccines. Our study provides evidence of protection against infection with the Omicron variant after completion of a primary vaccination series with the BNT162b2 or mRNA-1273 vaccines; in particular, we found a VE against the Omicron variant of 55.2% (95% confidence interval (CI): 23.5 to 73.7%) and 36.7% (95% CI: 69.9 to 76.4%) for the BNT162b2 and mRNA-1273 vaccines, respectively, in the first month after primary vaccination. However, the VE is significantly lower than that against Delta infection and declines rapidly over just a few months. The VE is re-established upon revaccination with the BNT162b2 vaccine (54.6%, 95% CI: 30.4 to 70.4%).

Background At the end of 2020, Denmark launched an immunization program against SARS-CoV-2. The Danish health authorities prioritized persons currently living in long-term care facilities (LTCF residents) and frontline healthcare workers (HCW) as the first receivers of vaccination. Here we present preliminary population based vaccine effectiveness (VE) estimates in these two target groups. Methods The study was designed as a retrospective registry- and population-based observational cohort study including all LTCF residents and all HWC. The outcome was a polymerase chain reaction confirmed SARS-CoV-2, and VE was estimated for different periods following first and second dose. We used Poisson and Cox regressions to estimate respectively crude and calendar time-adjusted VE for the BNT162b2 mRNA Covid-19 Vaccine from Pfizer/BioNTech with 95% confidence intervals (CI) for vaccinated versus unvaccinated. Results A total of 39,040 LTCF residents (median age at first dose; 84 years, Interquartile range (IQR): 77-90) and 331,039 HCW (median age at first dose; 47 years, IQR: 36-57) were included. Among LTCF residents, 95.2% and 86.0% received first and second dose from 27 December 2020 until 18 February 2021, for HWC the proportion was 27.8% and 24.4%. During a median follow-up of 53 days , there were 488 and 5,663 confirmed SARS-CoV-2 cases in the unvaccinated groups, whereas there were 57 and 52 in LTCF residents and HCW within the first 7 days after the second dose and 27 and 10 cases beyond seven days of second dose. No protective effect was observed for LTCF residents after first dose. In HCW, VE was 17% (95% CI; 4-28) in the > 14 days after first dose (before second dose). Furthermore, the VE in LTCF residents at day 0-7 of second dose was 52% (95% CI; 27-69) and 46% (95% CI; 28-59) in HCW. Beyond seven days of second dose, VE increased to 64% (95% CI; 14-84) and 90% (95% CI; 82-95) in the two groups, respectively. Conclusion The results were promising regarding the VE both within and beyond seven days of second vaccination with the BNT162b2 mRNA Covid-19 Vaccine currently used in many countries to help mitigate the global SARS-CoV-2 pandemic. Impact of the research: So far, observational studies of the real-word effectiveness of the mRNA Vaccine BNT162b2 has been limited to the period after the administration of the first dose. This is the first report to date to present vaccine effectiveness (VE) estimates after the second BNT162b2 mRNA Covid-19 Vaccine. We estimated a VE of 52% and 46% in LTCF residents and HCW within seven days, which increased to 64% and 90% in the two groups respectively beyond seven days of immunization. These findings supports maintaining a two-dose schedule of the BNT162b2 mRNA Covid-19 Vaccine.

Background The continued occurrence of more contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants and waning immunity over time require ongoing reevaluation of the vaccine effectiveness (VE). This study aimed to estimate the effectiveness in 2 age groups (12 to 59 and 60 years or above) of 2 or 3 vaccine doses (BNT162b2 mRNA or mRNA-1273) by time since vaccination against SARS-CoV-2 infection and Coronavirus Disease 2019 (COVID-19) hospitalization in an Alpha-, Delta-, or Omicron-dominated period. Methods and findings A Danish nationwide cohort study design was used to estimate VE against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha, Delta, or Omicron variant. Information was obtained from nationwide registries and linked using a unique personal identification number. The study included all previously uninfected residents in Denmark aged 12 years or above (18 years or above for the analysis of 3 doses) in the Alpha (February 20 to June 15, 2021), Delta (July 4 to November 20, 2021), and Omicron (December 21, 2021 to January 31, 2022) dominated periods. VE estimates including 95% confidence intervals (CIs) were calculated (1-hazard ratio∙100) using Cox proportional hazard regression models with underlying calendar time and adjustments for age, sex, comorbidity, and geographical region. Vaccination status was included as a time-varying exposure. In the oldest age group, VE against infection after 2 doses was 90.7% (95% CI: 88.2; 92.7) for the Alpha variant, 82.3% (95% CI: 75.5; 87.2) for the Delta variant, and 39.9% (95% CI: 26.3; 50.9) for the Omicron variant 14 to 30 days since vaccination. The VE waned over time and was 73.2% (Alpha, 95% CI: 57.1; 83.3), 50.0% (Delta, 95% CI: 46.7; 53.0), and 4.4% (Omicron, 95% CI: −0.1; 8.7) >120 days since vaccination. Higher estimates were observed after the third dose with VE estimates against infection of 86.1% (Delta, 95% CI: 83.3; 88.4) and 57.7% (Omicron, 95% CI: 55.9; 59.5) 14 to 30 days since vaccination. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 98.1% or above for the Alpha and Delta variants. Among both age groups, VE against COVID-19 hospitalization 14 to 30 days since vaccination with 2 or 3 doses was 95.5% or above for the Omicron variant. The main limitation of this study is the nonrandomized study design including potential differences between the unvaccinated (reference group) and vaccinated individuals. Conclusions Two vaccine doses provided high protection against SARS-CoV-2 infection and COVID-19 hospitalization with the Alpha and Delta variants with protection, notably against infection, waning over time. Two vaccine doses provided only limited and short-lived protection against SARS-CoV-2 infection with Omicron. However, the protection against COVID-19 hospitalization following Omicron SARS-CoV-2 infection was higher. The third vaccine dose substantially increased the level and duration of protection against infection with the Omicron variant and provided a high level of sustained protection against COVID-19 hospitalization among the +60-year-olds.

Objective: To estimate in a real life setting, the vaccine effectiveness of the BNT162b2 mRNA vaccine against confirmed SARS-CoV-2 infection, hospital admission, and death among five priority groups for vaccination Design: Cohort study Setting: Roll-out of the BNT162b2 mRNA vaccine in Denmark Participants: 864,096 individuals who were first inline to receive the BNT162b2 mRNA vaccine: 46,101 long-term care facility (LTCF) residents, 61,805 individuals 65 years and older living at home but requiring practical help and personal care (65PHC), 98,533 individuals ≥85 years of age (+85), 425,799 health-care workers (HCWs), and 231,858 individuals with comorbidities that predispose for severe COVID-19 disease (SCD). Intervention: vaccination with BNT162b2 mRNA vaccine Main outcome measures: RT-PCR confirmed SARS-CoV-2 infections, COVID-19 related admissions within 14 days after a confirmed SARS-CoV-2 infection, all-cause admission, COVID-19 related death within 30 days after confirmed SARS-CoV-2 infection, and all-cause death. Results: Beyond 7 days after the second dose, the VE against SARS-CoV-2 infection in all groups ranged from 53-86%. In 65PHC, HCW and SCD, we observed a substantial reduction in risk of infection 0-7 days after the second dose ranging from 46-71%. The VE against COVID-19 related admissions ranged from 75-87% in all groups except +85 and HCWs where no events occurred. For COVID-19 related deaths, a significant VE was observed in LTCF residents (VE of 89%) and 65PHC (VE of 97%), whereas no events were observed in the three remaining groups. VE against all-cause death ranged from 26-73% in all groups except HCW where an insignificant VE was estimated. For all-cause admission, the VE ranged from 37-50% in all groups except in SCD where a negative VE was observed. Conclusion: In a real-life setting and more than 7 days after the second dose of BNT162b2 mRNA was administered to the most vulnerable individuals, the vaccine was associated with a reduction of SARS-CoV-2 infection (53-86%) and COVID-19 related admissions (≥75%) or deaths (≥89%).

Background The recommendations in several countries to stop using the ChAdOx1 vaccine has led to vaccine programs combining different Coronavirus Disease 2019 (COVID-19) vaccine types, which necessitates knowledge on vaccine effectiveness (VE) of heterologous vaccine schedules. The aim of this Danish nationwide population-based cohort study was therefore to estimate the VE against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and COVID-19–related hospitalization and death following the first dose of the ChAdOx1 vaccine and the combination of the ChAdOx1/mRNA vaccines. Methods and findings All individuals alive in or immigrating to Denmark from 9 February 2021 to 23 June 2021 were identified in the Danish Civil Registration System. Information on exposure, outcomes, and covariates was obtained from Danish national registries. Poisson and Cox regression models were used to calculate crude and adjusted VE, respectively, along with 95% confidence intervals (CIs) against SARS-CoV-2 infection and COVID-19–related hospitalization or death comparing vaccinated versus unvaccinated individuals. The VE estimates were adjusted for calendar time as underlying time and for sex, age, comorbidity, country of origin, and hospital admission. The analyses included 5,542,079 individuals (97.6% of the total Danish population). A total of 144,360 individuals were vaccinated with the ChAdOx1 vaccine as the first dose, and of these, 136,551 individuals received an mRNA vaccine as the second dose. A total of 1,691,464 person-years and 83,034 SARS-CoV-2 infections were included. The individuals vaccinated with the first dose of the ChAdOx1 vaccine dose had a median age of 45 years. The study population was characterized by an equal distribution of males and females; 6.7% and 9.2% originated from high-income and other countries, respectively. The VE against SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine was 88% (95% CI: 83; 92) 14 days after the second dose and onwards. There were no COVID-19–related hospitalizations or deaths among the individuals vaccinated with the combined vaccine schedule during the study period. Study limitations including unmeasured confounders such as risk behavior and increasing overall vaccine coverage in the general population creating herd immunity are important to take into consideration when interpreting the results. Conclusions In this study, we observed a large reduction in the risk of SARS-CoV-2 infection when combining the ChAdOx1 and an mRNA vaccine, compared with unvaccinated individuals.