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Functional immunity against SARS-CoV-2 in the general population after a booster campaign and the Delta and Omicron waves, Switzerland, March 2022
Functional immunity (defined here as serum neutralising capacity) critically contributes to conferring protection against SARS-CoV-2 infection and severe COVID-19. This cross-sectional analysis of a prospective, population-based cohort study included 1,894 randomly-selected 16 to 99-year-old participants from two Swiss cantons in March 2022. Of these, 97.6% (95% CI: 96.8–98.2%) had anti-spike IgG antibodies, and neutralising capacity was respectively observed for 94%, 92% and 88% against wild-type SARS-CoV-2, Delta and Omicron variants. Studying functional immunity to inform and monitor vaccination campaigns is crucial.
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COVID-19 vaccination and BA.1 breakthrough infection induce neutralising antibodies which are less efficient against BA.4 and BA.5 Omicron variants, Israel, March to June 2022
This work evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.4 and BA.5) in healthcare workers who had breakthrough BA.1 infection. Omicron breakthrough infection in individuals vaccinated three or four times before infection resulted in increased neutralising antibodies against the WT virus. The fourth vaccine dose did not further improve the neutralising efficiency over the third dose against all Omicron variants, especially BA.4 and BA.5. An Omicron-specific vaccine may be indicated.
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Estimation of COVID-19 vaccine effectiveness against hospitalisation in individuals aged ≥ 65 years using electronic health registries; a pilot study in four EU/EEA countries, October 2021 to March 2022
Alexis Sentís , Irina Kislaya , Nathalie Nicolay , Hinta Meijerink , Jostein Starrfelt , Iván Martínez-Baz , Jesús Castilla , Katrine Finderup Nielsen , Christian Holm Hansen , Hanne-Dorthe Emborg , Anthony Nardone , Tarik Derrough , Marta Valenciano , Baltazar Nunes , Susana Monge and the VEBIS-Lot4 working groupBy employing a common protocol and data from electronic health registries in Denmark, Navarre (Spain), Norway and Portugal, we estimated vaccine effectiveness (VE) against hospitalisation due to COVID-19 in individuals aged ≥ 65 years old, without previous documented infection, between October 2021 and March 2022. VE was higher in 65–79-year-olds compared with ≥ 80-year-olds and in those who received a booster compared with those who were primary vaccinated. VE remained high (ca 80%) between ≥ 12 and < 24 weeks after the first booster administration, and after Omicron became dominant.
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Effectiveness of complete primary vaccination against COVID-19 at primary care and community level during predominant Delta circulation in Europe: multicentre analysis, I-MOVE-COVID-19 and ECDC networks, July to August 2021
Esther Kissling , Mariëtte Hooiveld , Iván Martínez-Baz , Clara Mazagatos , Naoma William , Ana-Maria Vilcu , Marjolein N Kooijman , Maja Ilić , Lisa Domegan , Ausenda Machado , Simon de Lusignan , Mihaela Lazar , Adam Meijer , Mia Brytting , Itziar Casado , Amparo Larrauri , Josephine-L K Murray , Sylvie Behillil , Brechje de Gier , Ivan Mlinarić , Joan O’Donnell , Ana Paula Rodrigues , Ruby Tsang , Olivia Timnea , Marit de Lange , Maximilian Riess , Jesús Castilla , Francisco Pozo , Mark Hamilton , Alessandra Falchi , Mirjam J Knol , Sanja Kurečić Filipović , Linda Dunford , Raquel Guiomar , Jade Cogdale , Carmen Cherciu , Tessa Jansen , Theresa Enkirch , Luca Basile , Jeff Connell , Verónica Gomez , Virginia Sandonis Martín , Sabrina Bacci , Angela MC Rose , Lucia Pastore Celentano , Marta Valenciano and I-MOVE-COVID-19 and ECDC primary care study teamsIntroductionIn July and August 2021, the SARS-CoV-2 Delta variant dominated in Europe.
AimUsing a multicentre test-negative study, we measured COVID-19 vaccine effectiveness (VE) against symptomatic infection.
MethodsIndividuals with COVID-19 or acute respiratory symptoms at primary care/community level in 10 European countries were tested for SARS-CoV-2. We measured complete primary course overall VE by vaccine brand and by time since vaccination.
ResultsOverall VE was 74% (95% CI: 69–79), 76% (95% CI: 71–80), 63% (95% CI: 48–75) and 63% (95% CI: 16–83) among those aged 30–44, 45–59, 60–74 and ≥ 75 years, respectively. VE among those aged 30–59 years was 78% (95% CI: 75–81), 66% (95% CI: 58–73), 91% (95% CI: 87–94) and 52% (95% CI: 40–61), for Comirnaty, Vaxzevria, Spikevax and COVID-19 Vaccine Janssen, respectively. VE among people 60 years and older was 67% (95% CI: 52–77), 65% (95% CI: 48–76) and 83% (95% CI: 64–92) for Comirnaty, Vaxzevria and Spikevax, respectively. Comirnaty VE among those aged 30–59 years was 87% (95% CI: 83–89) at 14–29 days and 65% (95% CI: 56–71%) at ≥ 90 days between vaccination and onset of symptoms.
ConclusionsVE against symptomatic infection with the SARS-CoV-2 Delta variant varied among brands, ranging from 52% to 91%. While some waning of the vaccine effect may be present (sample size limited this analysis to only Comirnaty), protection was 65% at 90 days or more between vaccination and onset.
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Hospitalised patients with breakthrough COVID-19 following vaccination during two distinct waves in Israel, January to August 2021: a multicentre comparative cohort study
Tal Brosh-Nissimov , Yasmin Maor , Meital Elbaz , Shelly Lipman-Arens , Yonit Wiener-Well , Khetam Hussein , Efrat Orenbuch-Harroch , Regev Cohen , Oren Zimhony , Bibiana Chazan , Lior Nesher , Galia Rahav , Hiba Zayyad , Mirit Hershman-Sarafov , Miriam Weinberger , Ronza Najjar-Debbiny and Michal ChowersBackgroundChanging patterns of vaccine breakthrough can clarify vaccine effectiveness.
AimTo compare breakthrough infections during a SARS-CoV-2 Delta wave vs unvaccinated inpatients, and an earlier Alpha wave.
MethodsIn an observational multicentre cohort study in Israel, hospitalised COVID-19 patients were divided into three cohorts: breakthrough infections in Comirnaty-vaccinated patients (VD; Jun–Aug 2021) and unvaccinated cases during the Delta wave (ND) and breakthrough infections during an earlier Alpha wave (VA; Jan–Apr 2021). Primary outcome was death or ventilation.
ResultsWe included 343 VD, 162 ND and 172 VA patients. VD were more likely older (OR: 1.06; 95% CI: 1.05–1.08), men (OR: 1.6; 95% CI: 1.0–2.5) and immunosuppressed (OR: 2.5; 95% CI: 1.1–5.5) vs ND. Median time between second vaccine dose and admission was 179 days (IQR: 166–187) in VD vs 41 days (IQR: 28–57.5) in VA. VD patients were less likely to be men (OR: 0.6; 95% CI: 0.4–0.9), immunosuppressed (OR: 0.3; 95% CI: 0.2–0.5) or have congestive heart failure (OR: 0.6; 95% CI: 0.3–0.9) vs VA. The outcome was similar between all cohorts and affected by age and immunosuppression and not by vaccination, variant or time from vaccination.
ConclusionsVaccination was protective during the Delta variant wave, as suggested by older age and greater immunosuppression in vaccinated breakthrough vs unvaccinated inpatients. Nevertheless, compared with an earlier post-vaccination period, breakthrough infections 6 months post-vaccination occurred in healthier patients. Thus, waning immunity increased vulnerability during the Delta wave, which suggests boosters as a countermeasure.
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mRNA vaccine effectiveness against hospitalisation due to severe acute respiratory infection (SARI) COVID-19 during Omicron variant predominance estimated from real-world surveillance data, Slovenia, February to March 2022
For the period of predominance of SARS-CoV-2 Omicron variant in Slovenia, February to March 2022, we estimated mRNA vaccine effectiveness (VE) against severe acute respiratory infection (SARI) COVID-19 using surveillance data. In the most vulnerable age group comprising individuals aged 65 years and more, VE against SARI COVID-19 was 95% (95% CI: 95–96%) for those vaccinated with three doses, in comparison to 82% (95% CI: 79–84%) for those vaccinated with two doses. Such levels of protection were maintained for at least 6 months.
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COVID-19 vaccine effectiveness against severe disease from SARS-CoV-2 Omicron BA.1 and BA.2 subvariants – surveillance results from southern Sweden, December 2021 to March 2022
We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.
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SARS-CoV-2 Omicron variant BA.2 neutralisation in sera of people with Comirnaty or CoronaVac vaccination, infection or breakthrough infection, Hong Kong, 2020 to 2022
Samuel MS Cheng , Chris Ka Pun Mok , Karl CK Chan , Susanna S Ng , Bosco HS Lam , Leo LH Luk , Fanny W Ko , Chunke Chen , Karen Yiu , John KC Li , Ken KP Chan , Leo CH Tsang , Leo LM Poon , David SC Hui and Malik PeirisBackgroundOmicron subvariant BA.2 circulation is rapidly increasing globally.
AimWe evaluated the neutralising antibody response from vaccination or prior SARS-CoV-2 infection against symptomatic infection by BA.2 or other variants.
MethodsUsing 50% plaque reduction neutralisation tests (PRNT50), we assessed neutralising antibody titres to BA.2, wild type (WT) SARS-CoV-2 and other variants in Comirnaty or CoronaVac vaccinees, with or without prior WT-SARS-CoV-2 infection. Titres were also measured for non-vaccinees convalescing from a WT-SARS-CoV-2 infection. Neutralising antibodies in BA.2 and BA.1 breakthrough infections and in BA.2 infections affecting non-vaccinees were additionally studied.
ResultsIn vaccinees or prior WT-SARS-CoV-2-infected people, BA.2 and BA.1 PRNT50 titres were comparable but significantly (p < 10 − 5) lower than WT. In each group of 20 vaccinees with (i) three-doses of Comirnaty, (ii) two CoronaVac followed by one Comirnaty dose, or (iii) one dose of either vaccine after a WT-SARS-CoV-2 infection, ≥ 19 individuals developed detectable (PRNT50 titre ≥ 10) antibodies to BA.2, while only 15 of 20 vaccinated with three doses of CoronaVac did. Comirnaty vaccination elicited higher titres to BA.2 than CoronaVac. In people convalescing from a WT-SARS-CoV-2 infection, a single vaccine dose induced higher BA.2 titres than three Comirnaty (p = 0.02) or CoronaVac (p = 0.00001) doses in infection-naïve individuals. BA.2 infections in previously uninfected and unvaccinated individuals elicited low (PRNT50 titre ≤ 80) responses with little cross-neutralisation of other variants. However, vaccinees with BA.1 or BA.2 breakthrough infections had broad cross-neutralising antibodies to WT viruses, and BA.1, BA.2, Beta and Delta variants.
ConclusionsExisting vaccines can be of help against the BA.2 subvariant.
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A 5-year look-back at the notification and management of vaccine supply shortages in Germany
BackgroundUnavailability of vaccines endangers the overall goal to protect individuals and whole populations against infections.
MethodsThe German notification system includes the publication of vaccine supply shortages reported by marketing authorisation holders (MAH), information on the availability of alternative vaccine products, guidance for physicians providing vaccinations and an unavailability reporting tool to monitor regional distribution issues.
AimThis study provides a retrospective analysis of supply issues and measures in the context of European and global vaccine supply constraints.
Resultsbetween October 2015 and December 2020, the 250 notifications concerned all types of vaccines (54 products). Most shortages were caused by increased demand associated with immigration in Germany in 2015 and 2016, new or extended vaccine recommendations, increased awareness, or changes in global immunisation programmes. Shortages of a duration up to 30 days were mitigated using existing storage capacities. Longer shortages, triggered by high demand on a national level, were mitigated using alternative products and re-allocation; in a few cases, vaccines were imported. However, for long lasting supply shortages associated with increased global demand, often occurring in combination with manufacturing issues, few compensatory mechanisms were available. Nevertheless, only few critical incidents were identified: (i) shortage of hexavalent vaccines endangering neonatal immunisation programmes in 2015;(ii) distribution issues with influenza vaccines in 2018; and (iii) unmet demand for pneumococcal and influenza vaccines during the coronavirus disease (COVID)-19 pandemic.
ConclusionVaccine product shortages in Germany resemble those present in neighbouring EU states and often reflect increased global demand not matched by manufacturing capacities.
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Social conformism and confidence in systems as additional psychological antecedents of vaccination: a survey to explain intention for COVID-19 vaccination among healthcare and welfare sector workers, France, December 2020 to February 2021
BackgroundThe start of the COVID-19 vaccination campaign among French healthcare and welfare sector workers in January 2021 offered an opportunity to study psychological antecedents of vaccination in this group.
AimWe explored whether knowledge and attitude items related to social conformism and confidence in systems contributed to explaining intention for COVID-19 vaccination.
MethodsWe developed a knowledge and attitude questionnaire with 30 items related to five established and two hypothetical psychological antecedents of vaccination (KA-7C). The online questionnaire was distributed from 18 December 2020 to 1 February 2021 through chain-referral via professional networks, yielding a convenience sample. We used multivariable logistic regression to explore the associations of individual and grouped KA-7C items with COVID-19 vaccine intention.
ResultsAmong 5,234 participants, the vaccine intention model fit (pseudo R-squared values) increased slightly but significantly from 0.62 to 0.65 when adding social conformism and confidence in systems items. Intention to vaccinate was associated with the majority opinion among family and friends (OR: 11.57; 95% confidence interval (CI): 4.51–29.67) and a positive perception of employer’s encouragement to get vaccinated (vs negative; OR: 6.41; 95% CI: 3.36–12.22). The strongest association of a knowledge item was identifying the statement ‘Some stages of vaccine development (testing) have been skipped because of the epidemic emergency.’ as false (OR: 2.36; 95% CI: 1.73–3.22).
ConclusionThe results suggest that social conformism and confidence in systems are distinct antecedents of vaccination among healthcare and welfare workers, which should be taken into account in vaccine promotion.
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Vaccine-induced and naturally-acquired protection against Omicron and Delta symptomatic infection and severe COVID-19 outcomes, France, December 2021 to January 2022
More LessWe assessed the protection conferred by naturally-acquired, vaccine-induced and hybrid immunity during the concomitant Omicron and Delta epidemic waves in France on symptomatic infection and severe COVID-19. The greatest levels of protection against both variants were provided by hybrid immunity. Protection against Omicron symptomatic infections was systematically lower and waned at higher speed than against Delta in those vaccinated. In contrast, there were little differences in variant-specific protection against severe inpatient outcomes in symptomatic individuals.
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Immediate side effects of Comirnaty COVID-19 vaccine: A nationwide survey of vaccinated people in Israel, December 2020 to March 2021
BackgroundCOVID-19 vaccine safety is of major interest worldwide, since there is no prior experience with it. Israel was one of the first countries to widely use the Comirnaty vaccine.
AimWe aimed to assess the vaccine's short-term side effects directly from a large population and to predict influencing factors for self-reporting side effects.
MethodsIn a retrospective cohort study, we investigated self-reported systemic vaccine side-effects using electronic surveys sent to vaccinated individuals between 20 December 2020 and 11 March 2021, within 3 days following administration of the first and second dose. We determined predictors for reporting systemic side effects by logistic regression.
ResultsA total of 1,213,693 patients received at least one vaccine dose and 301,537 (24.8%) answered at least one survey. Among them, 68,162 (30.4%) and 89,854 (59.9%) individuals filled the first and the second dose surveys, respectively, and reported one or more side effects. Most common side effects were fatigue, headache and myalgia. Several respondents reported facial paraesthesia after first and second dose, respectively (n = 1,675; 0.7% and n = 1,601; 1.1%). Individuals younger than 40 years and women reported side effects more frequently than others, but pregnant women reported less. Pregnancy was a weak predictor for reporting any side effect in general and in particular fatigue, myalgia, headache, chills and fever.
ConclusionsWe found further support for minor short-term side effects, within 3 days of receiving the Comirnaty vaccine. These findings from vaccine recipients in general and pregnant women in particular can improve vaccine acceptance.
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Risk reduction of severe outcomes in vaccinated COVID-19 cases: an analysis of surveillance data from Estonia, Ireland, Luxembourg and Slovakia, January to November 2021
Despite high COVID-19 vaccine coverage in the EU/EEA, there are increasing reports of SARS-CoV-2 infections and hospitalisations in vaccinated individuals. Using surveillance data from Estonia, Ireland, Luxembourg and Slovakia (January–November 2021), we estimated risk reduction of severe outcomes in vaccinated cases. Increasing age remains the most important driver of severity, and vaccination significantly reduces risk in all ages for hospitalisation (adjusted relative risk (aRR): 0.32; 95% confidence interval (CI): 0.26–0.39) and death (aRR: 0.20; 95% CI: 0.13–0.29).
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Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population, Normandy, France, November to December 2021
Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.
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Waning antibody levels after COVID-19 vaccination with mRNA Comirnaty and inactivated CoronaVac vaccines in blood donors, Hong Kong, April 2020 to October 2021
The mRNA vaccine Comirnaty and the inactivated vaccine CoronaVac are both available in Hong Kong’s COVID-19 vaccination programme. We observed waning antibody levels in 850 fully vaccinated (at least 14 days passed after second dose) blood donors using ELISA and surrogate virus neutralisation test. The Comirnaty-vaccinated group’s (n = 593) antibody levels remained over the ELISA and sVNT positive cut-offs within the first 6 months. The CoronaVac-vaccinated group’s (n = 257) median antibody levels began to fall below the cut-offs 4 months after vaccination.
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Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22
Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.
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Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021
Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2–4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2–4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.
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Vaccine effectiveness against severe acute respiratory infections (SARI) COVID-19 hospitalisations estimated from real-world surveillance data, Slovenia, October 2021
We estimated vaccine effectiveness (VE) against severe COVID-19 during October 2021, using Slovenian surveillance data. For people fully vaccinated with any vaccine in age groups 18–49, 50–64, ≥ 65 years, VE was 86% (95% CI: 79–90), 89% (85–91), and 77% (74–81). Among ≥ 65 year-olds fully vaccinated with mRNA vaccines, VE decreased from 93% (95% CI: 88–96) in those vaccinated ≤ 3 months ago to 43% (95% CI: 30–54) in those vaccinated ≥ 6 months ago, suggesting the need for early boosters.
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Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021
Carl Suetens , Pete Kinross , Pilar Gallego Berciano , Virginia Arroyo Nebreda , Eline Hassan , Clémentine Calba , Eugenia Fernandes , Andre Peralta-Santos , Pedro Casaca , Nathalie Shodu , Sara Dequeker , Flora Kontopidou , Lamprini Pappa , Oliver Kacelnik , Anita Wang Børseth , Lois O’Connor , Patricia Garvey , Rasa Liausedienė , Rolanda Valintelienė , Corinna Ernst , Joël Mossong , Mária Štefkovičová , Zuzana Prostináková , Ann Caroline Danielsen , Aikaterini Mougkou , Favelle Lamb , Orlando Cenciarelli , Dominique L. Monnet and Diamantis PlachourasWe collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July−October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8–52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.
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Initial assessment of the COVID-19 vaccination’s impact on case numbers, hospitalisations and deaths in people aged 80 years and older, 15 EU/EEA countries, December 2020 to May 2021
Nathalie Nicolay , Francesco Innocenti , Julien Beauté , Veronika Učakar , Marta Grgič Vitek , Eero Poukka , Tuula Hannila-Handelberg , Charmaine Gauci , Tanya Melillo , Theano Georgakopoulou , Jiri Jarkovsky , Pavel Slezak , Concepción Delgado-Sanz , Carmen Olmedo-Lucerón , Heleene Suija , Rasa Liausediene , Piaras O’Lorcain , Niamh Murphy , André Peralta-Santos , Pedro Casaca , Ioanna Gregoriou , Nick Bundle , Gianfranco Spiteri and Giovanni RavasiPrioritisation of elderly people in COVID-19 vaccination campaigns aimed at reducing severe outcomes in this group. Using EU/EEA surveillance and vaccination uptake, we estimated the risk ratio of case, hospitalisation and death notifications in people 80 years and older compared with 25–59-year-olds. Highest impact was observed for full vaccination uptake 80% or higher with reductions in notification rates of cases up to 65% (IRR: 0.35; 95% CI: 0.13–0.99), hospitalisations up to 78% (IRR: 0.22; 95% CI: 0.13–0.37) and deaths up to 84% (IRR: 0.16; 95% CI: 0.13–0.20).
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