Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021-January 2022.

BACKGROUND: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. METHODS: National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin. RESULTS: VE against COVID-19 mortality was > 90 % for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80 % at 7-8 months post-primary series for most groups, and around 60 % for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to > 85 % in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups. CONCLUSION: At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.

Vaccine effectiveness against SARS-CoV-2 Delta and Omicron infection and infectiousness within households in the Netherlands between July 2021 and August 2022.

INTRODUCTION: We aimed to estimate vaccine effectiveness against infection (VE-infection) and against further transmission (VE-infectiousness) in a household setting during Delta and Omicron. Knowing these effects can aid policy makers in deciding which groups to prioritize for vaccination. METHODS: Participants with a positive SARS-CoV-2 test were asked about COVID-19 vaccination status and SARS-CoV-2 testing of their household members one month later. VE-infection and VE-infectiousness was estimated using GEE logistic regression adjusting for age, vaccination status, calendar week and household size. RESULTS: 3,399 questionnaires concerning 4,105 household members were included. During the Delta-period, VE-infection of primary series was 47% (95% CI: -27%; 78%) and VE-infectiousness of primary series was 70% (95% CI: 28%; 87%). During the Omicron-period, VE-infection was -36% (95% CI: -88%; 1%) for primary series and -28% (95% CI: -77%; 7%) for booster vaccination. The VE-infectiousness was 45% (95% CI: -14%; 74%) for primary series and 64% (95% CI: 31%; 82%) for booster vaccination. DISCUSSION: Our study shows that COVID-19 vaccination is effective against infection with SARS-CoV-2 Delta and against infectiousness of SARS-CoV-2 Delta and Omicron. Estimation of VE against infection with SARS-CoV-2 Omicron was limited by several factors. Our results support booster vaccination for those in close contact with vulnerable people to prevent transmission.

Number of COVID-19 hospitalisations averted by vaccination: Estimates for the Netherlands, January 6, 2021 through August 30, 2022.

BACKGROUND: Vaccines against COVID-19 have proven effective in preventing COVID-19 hospitalisation. In this study, we aimed to quantify part of the public health impact of COVID-19 vaccination by estimating the number of averted hospitalisations. We present results from the beginning of the vaccination campaign ('entire period', January 6, 2021) and a subperiod starting at August 2, 2021 ('subperiod') when all adults had the opportunity to complete their primary series, both until August 30, 2022. METHODS: Using calendar-time specific vaccine effectiveness (VE) estimates and vaccine coverage (VC) by round (primary series, first booster and second booster) and the observed number of COVID-19 associated hospitalisations, we estimated the number of averted hospitalisations per age group for the two study periods. From January 25, 2022, when registration of the indication of hospitalisation started, hospitalisations not causally related to COVID-19 were excluded. RESULTS: In the entire period, an estimated 98,170 (95 % confidence interval (CI) 96,123-99,928) hospitalisations were averted, of which 90,753 (95 % CI 88,790-92,531) were in the subperiod, representing 57.0 % and 67.9 % of all estimated hospital admissions. Estimated averted hospitalisations were lowest for 12-49-year-olds and highest for 70-79-year-olds. More admissions were averted in the Delta period (72.3 %) than in the Omicron period (63.4 %). CONCLUSION: COVID-19 vaccination prevented a large number of hospitalisations. Although the counterfactual of having had no vaccinations while maintaining the same public health measures is unrealistic, these findings underline the public health importance of the vaccination campaign to policy makers and the public.

Vaccine effectiveness of primary and booster COVID-19 vaccinations against SARS-CoV-2 infection in the Netherlands from July 12, 2021 to June 6, 2022: A prospective cohort study.

OBJECTIVES: We estimated vaccine effectiveness (VE) of primary and booster vaccinations against SARS-CoV-2 infection overall and in four risk groups defined by age and medical risk condition during the Delta and Omicron BA.1/BA.2 periods. METHODS: VAccine Study COvid-19 is an ongoing prospective cohort study among Dutch adults. The primary end point was a self-reported positive SARS-CoV-2 test from July 12, 2021 to June 06, 2022. The analyses included only participants without a previous SARS-CoV-2 infection based on a positive test or serology. We used Cox proportional hazard models with vaccination status as the time-varying exposure and adjustment for age, sex, educational level, and medical risk condition. RESULTS: A total of 37,170 participants (mean age 57 years) were included. In the Delta period, VE <6 weeks after the primary vaccination was 80% (95% confidence interval 69-87) and decreased to 71% (65-77) after 6 months. VE increased to 96% (86-99) shortly after the first booster vaccination. In the Omicron period, these estimates were 46% (22-63), 25% (8-39), and 57% (52-62), respectively. For the Omicron period, an interaction term between vaccination status and risk group significantly improved the model (P <0.001), with generally lower VEs for those with a medical risk condition. CONCLUSION: Our results show the benefit of booster vaccinations against infection, also in risk groups; although, the additional protection wanes quite rapidly.

Elevated risk of infection with SARS-CoV-2 Beta, Gamma, and Delta variant compared to Alpha variant in vaccinated individuals.

The extent to which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOC) break through infection- or vaccine-induced immunity is not well understood. We analyzed 28,578 sequenced SARS-CoV-2 samples from individuals with known immune status obtained through national community testing in the Netherlands from March to August 2021. We found evidence of an increased risk of infection by the Beta (B.1.351), Gamma (P.1), or Delta (B.1.617.2) variants compared to the Alpha (B.1.1.7) variant after vaccination. No clear differences were found between vaccines. However, the effect was larger in the first 14-59 days after complete vaccination compared to ≥60 days. In contrast to vaccine-induced immunity, there was no increased risk for re-infection with Beta, Gamma or Delta variants relative to Alpha variant in individuals with infection-induced immunity.

Vaccine Impact and Effectiveness of Meningococcal Serogroup ACWY Conjugate Vaccine Implementation in the Netherlands: A Nationwide Surveillance Study.

BACKGROUND: In response to the recent serogroup W invasive meningococcal disease (IMD-W) epidemic in the Netherlands, meningococcal serogroup C (MenC) conjugate vaccination for children aged 14 months was replaced with a MenACWY conjugate vaccination, and a mass campaign targeting individuals aged 14-18 years was executed. We investigated the impact of MenACWY vaccination implementation in 2018-2020 on incidence rates and estimated vaccine effectiveness (VE). METHODS: We extracted IMD cases diagnosed between July 2014 and December 2020 from the national surveillance system. We calculated age group-specific incidence rate ratios by comparing incidence rates before (July 2017-March 2018) and after (July 2019-March 2020) MenACWY vaccination implementation. We estimated VE in vaccine-eligible cases using the screening method. RESULTS: Overall, the IMD-W incidence rate declined by 61% (95% confidence interval [CI], 40 to 74). It declined by 82% (95% CI, 18 to 96) in the vaccine-eligible age group (individuals aged 15-36 months and 14-18 years) and by 57% (95% CI, 34 to 72) in vaccine-noneligible age groups. VE was 92% (95% CI, -20 to 99.5) in vaccine-eligible toddlers (aged 15-36 months). No IMD-W cases were reported in vaccine-eligible teenagers after the campaign. CONCLUSIONS: The MenACWY vaccination program was effective in preventing IMD-W in the target population. The IMD-W incidence reduction in vaccine-noneligible age groups may be caused by indirect effects of the vaccination program. However, disentangling natural fluctuation from vaccine effect was not possible. Our findings encourage the use of toddler and teenager MenACWY vaccination in national immunization programs.

COVID-19 outbreak in an elderly care home: Very low vaccine effectiveness and late impact of booster vaccination campaign.

BACKGROUND: Elderly people in long-term care facilities (LTCF) are at higher risk for (severe) COVID-19, yet evidence of vaccine effectiveness (VE) in this population is scarce. In November 2021 (Delta period), a COVID-19 outbreak occurred at a LTCF in the Netherlands, continuing despite measures and booster vaccination campaign. We investigated the outbreak to assess VE of primary COVID-19 vaccination against SARS-CoV-2 infection and mortality, and to describe the impact of the booster vaccination. METHODS: We calculated attack rate (AR) and case fatality (CF) per vaccination status (unvaccinated, primarily vaccinated and boostered). We calculated VE - at on average 6 months after vaccination - as 1- risk ratio (RR) using the crude risk ratio (RR) with 95% confidence intervals (CI) for the association between vaccination status (primary vaccination versus unvaccinated) and outcomes (SARS-CoV-2 infection and mortality < 30 days after testing positive for SARS-CoV-2). RESULTS: The overall AR was 67% (70/105). CF was 33% (2/6) among unvaccinated cases, 12% among primarily vaccinated (7/58) and 0% (0/5) among boostered. The VE of primary vaccination was 17% (95% CI -28%; 46%) against SARS-CoV-2 infection and 70% (95% CI -44%; 96%) against mortality. Among boostered residents (N = 55), there were 25 cases in the first week after receiving the booster dose, declining to 5 in the second and none in the third week. CONCLUSION: VE of primary vaccination in residents of LTCF was very low against SARS-CoV-2 infection and moderate against mortality. There were few cases at 2 weeks after the booster dose and no deaths, despite the presence of susceptible residents. These data are consistent with the positive impact of the booster vaccination in curbing transmission. Timely booster vaccination in residents of LTCF is therefore important.

Protection of COVID-19 vaccination and previous infection against Omicron BA.1, BA.2 and Delta SARS-CoV-2 infections.

Given the emergence of the SARS-CoV-2 Omicron BA.1 and BA.2 variants and the roll-out of booster COVID-19 vaccination, evidence is needed on protection conferred by primary vaccination, booster vaccination and previous SARS-CoV-2 infection by variant. We employed a test-negative design on S-gene target failure data from community PCR testing in the Netherlands from 22 November 2021 to 31 March 2022 (n = 671,763). Previous infection, primary vaccination or both protected well against Delta infection. Protection against Omicron BA.1 infection was much lower compared to Delta. Protection was similar against Omicron BA.1 compared to BA.2 infection after previous infection, primary and booster vaccination. Higher protection was observed against all variants in individuals with both vaccination and previous infection compared with either one. Protection against all variants decreased over time since last vaccination or infection. We found that primary vaccination with current COVID-19 vaccines and previous SARS-CoV-2 infections offered low protection against Omicron BA.1 and BA.2 infection. Booster vaccination considerably increased protection against Omicron infection, but decreased rapidly after vaccination.