Correction: Nygren et al. Tick-Borne Encephalitis Risk Increases with Dog Ownership, Frequent Walks, and Gardening: A Case-Control Study in Germany 2018-2020. Microorganisms 2022, 10, 690.

In the original publication [...].

Barriers and drivers to COVID-19 vaccination among the migrant and non-migrant population in Germany, 2021.

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, immunization programmes struggled to reach all population groups equally. While migrant groups face multiple barriers to health systems, including vaccination, little is known about their vaccine uptake. METHODS: We conducted a cross-sectional telephone survey on adults with and without migration history in Germany to investigate barriers and drivers to COVID-19 vaccination (11 April 2021 to 18 December 2021). Interviews were conducted in six languages. We used logistic regression models and a mediation model to analyze the association between migration history and vaccine uptake. Furthermore, we determined the effect of psychological determinants (5C model) on vaccine uptake. RESULTS: The survey comprised 2039 individuals, including 1015 with migration history. Of these, 448 were interviews conducted in languages other than German. Individuals with migration history had a significantly lower vaccine uptake but, while still unvaccinated, had a higher intention to get vaccinated (P = 0.015) compared with those without migration history. The association between migration history and vaccine uptake was no longer significant when other factors were included in the regression model (odds ratio = 0.9; 95% confidence interval: 0.57-1.47). Socio-economic index, language skills and discrimination experience fully mediated this association. Among the psychological determinants, 'higher confidence' and 'higher collective responsibility' increased the chance of individuals with migration history to be vaccinated. CONCLUSION: Migration history alone cannot explain vaccine uptake; socio-economic index, language skills and discrimination experiences need to be considered. To achieve vaccine equity, future public health policy should aim to reduce relevant barriers through tailored interventions.

Application of the screening method for estimating COVID-19 vaccine effectiveness using routine surveillance data: Germany's experience during the COVID-19 pandemic, July 2021 to March 2023.

The screening method represents a simple, quick, and practical tool for estimating vaccine effectiveness (VE) using routine disease surveillance and vaccine coverage data, even if these data cannot be linked. In Germany, where notification data, laboratory testing data, and vaccine coverage data cannot be linked due to strict data protection requirements, the screening method was used to assess COVID-19 VE continuously between July 2021 and March 2023. During this period, when Delta and Omicron variants circulated, VE estimates were produced in real-time for different age groups and clinical outcomes. Here we describe the country's overall positive experience using the screening method, including its strengths and limitations, and provide practical guidance regarding a few issues, such as case definition stringency, testing behaviour, and data stratification, that require careful consideration during data analysis and the interpretation of the results.

Prices of paediatric vaccines in European vaccination programmes.

Objective: To compare the vaccine prices per vaccinated child under 18 and vaccine funding and procurement systems in the national vaccination programmes (NVPs) in Europe. Methods: The on-line survey targeted to NVP managers collected data referred to the information available on 31 December 2016. The prices of vaccines were categorised into three groups. The price per child 1) fully vaccinated comprised all vaccines and doses offered in the NVP; 2) vaccinated with standard vaccines comprised the vaccines included in the NVP in all countries; 3) vaccinated with recent vaccines comprised the pneumococcal conjugate, human papillomavirus and rotavirus vaccines. Results: In the 23 out of 32 countries that answered the survey, 17 funded the vaccines by taxes and six by social insurance. 18 countries procured the vaccines through public tenders or negotiations. Five countries purchased the vaccines by healthcare providers and reimbursed from the health insurance system.In the countries with vaccine procurement through public tenders the price per child vaccinated with standard vaccines ranged from €59 to €117 when using pentavalent and from €98 to €220 when using hexavalent vaccines. The mean price per child vaccinated with recent vaccines was €130 for the countries that offered pneumococcal conjugate and human papillomavirus vaccines and €142 for the countries that in addition included rotavirus vaccine.In the countries that purchased the vaccines by healthcare providers and reimbursed from the health insurance system the price per child vaccinated with standard vaccines ranged from €136 to €427. Conclusions: The vaccine prices differ notably in Europe. Prices were lower in countries where vaccines in the NVP were tax-funded and nationally or regionally procured. Improved procurement systems could lead to substantial savings or possibilities to introduce more vaccines into the NVP.

The Role of Vaccination Centers in a National Mass Immunization Campaign-Policymaker Insights from the German COVID-19 Pandemic Vaccine Roll-Out.

During the COVID-19 vaccination campaign, Germany, like other high-income countries, introduced mass vaccination centers for administering vaccinations. This qualitative study aimed to examine the role that these novel, temporary government healthcare structures played in a mass immunization roll-out and how they can be optimally deployed. In addition, learnings for general emergency preparedness were explored. A total of 27 high-level policymakers responsible for planning and implementing the COVID vaccination campaign at the national and state level in Germany were interviewed in May and June 2022. The semi-structured interviews were analyzed using thematic analysis. Interviewees indicated that mass vaccination structures played an essential role with respect to controllability, throughput, accessibility and openness in line with the key success criteria vaccination coverage, speed and accessibility. In contrast to the regular vaccination structures (private medical practices and occupational health services), public administration has direct authority over mass vaccination centers, allowing for reliable vaccine access prioritization and documentation. The deployment of vaccination centers should be guided by vaccine availability and demand, and vaccine requirements related to logistics, as well as local capacities, i.e., public-health-service strength and the physician density, to ensure effective, timely and equitable access. Improvements to the capacity use, scalability and flexibility of governmental vaccination structures are warranted for future pandemics.

Human papillomavirus prevalence and vaccine effectiveness in young women in Germany, 2017/2018: results from a nationwide study.

Background: Infections with human papillomaviruses (HPV) are sexually transmitted and can cause cancer. In Germany, vaccination against HPV is recommended for girls and boys aged 9-17 years. We aimed to investigate HPV DNA prevalence, genotype distribution and vaccine effectiveness (VE) in women aged 20-25 years 10 years after the introduction of HPV vaccination in Germany (2018-2019), and compared these data to an equally designed study from 2010-2012. Methods: Seventy six geographical clusters were randomly selected, followed by random selection of 61 women aged 20-25 years per cluster. Participants performed cervicovaginal self-sampling and answered questions on demographics, sexual behaviour and HPV vaccination. Samples were tested for 18 high risk and nine low risk HPV genotypes. We performed chi-square tests, Fisher's exact test, unpaired Student's t-test and proportion t-test, and calculated crude and adjusted prevalence ratios (PR) and 95% CIs. Results: Of 7,858 contacted women a total of 1,226 agreed to participate. Of these, 94 women were positive for HPV types 16 and/or 18. HPV16 prevalence was 7.0% (95% CI 5.6-8.6) and HPV18 prevalence was 0.8% (95% CI 0.4-1.5). HPV6 and HPV11 were rare with only five (0.4%; 0.1-0.9) and one (0%; 95% CI 0.0-0.5) positive tests. Seven hundred fifty-seven women (62%) had received at least one HPV vaccine dose and 348 (28%) were vaccinated as currently recommended. Confounder-adjusted VE was 46.4% (95% CI 4.2-70.1) against HPV16/18 infection and 49.1% (95% CI 8.2-71.8) against infection with at least one HPV genotype covered by the quadrivalent HPV vaccine. Compared with the 2010-2012 study results, HPV16/18 prevalence dropped from 22.5% (95% CI 19.0-26.3) to 10.3% (95% CI 7.5-13.9; p < 0.0001) in unvaccinated participants. Conclusion: Vaccine-covered HPV genotypes were rare among 20-25 years old women in Germany and decreased compared to the time point shortly after the start of the HPV vaccination program. HPV prevalence of almost all vaccine-covered genotypes was strongly reduced in vaccinated participants. A decrease of HPV16 and HPV18 was even observed in unvaccinated participants, compared to 2010-2012 data, suggesting indirect protection of unvaccinated women. Low VE against HPV16/18 and HPV6/11/16/18 in our study might be attributable to study design in combination with the endpoint selection of (mainly transient) HPV DNA positivity.

Direct comparison of clinical diagnostic sensitivity of saliva from buccal swabs versus combined oro-/nasopharyngeal swabs in the detection of SARS-CoV-2 B.1.1.529 Omicron.

BACKGROUND/PURPOSE: While current guidelines recommend the use of respiratory tract specimens for the direct detection of SARS-CoV-2 infection, saliva has recently been suggested as preferred sample type for the sensitive detection of SARS-CoV-2 B.1.1.529 (Omicron). By comparing saliva collected using buccal swabs and oro-/nasopharyngeal swabs from patients hospitalized due to COVID-19, we aimed at identifying potential differences in virus detection sensitivity between these sample types. METHODS: We compare the clinical diagnostic sensitivity of paired buccal swabs and combined oro-/nasopharyngeal swabs from hospitalized, symptomatic COVID-19 patients collected at median six days after symptom onset by real-time polymerase chain reaction (PCR) and antigen test. RESULTS: Of the tested SARS-CoV-2 positive sample pairs, 55.8% were identified as SARS-CoV-2 Omicron BA.1 and 44.2% as Omicron BA.2. Real-time PCR from buccal swabs generated significantly higher quantification cycle (Cq) values compared to those from matched combined oro-/nasopharyngeal swabs and resulted in an increased number of false-negative PCR results. Reduced diagnostic sensitivity of buccal swabs by real-time PCR was observed already at day one after symptom onset. Similarly, antigen test detection rates were reduced in buccal swabs compared to combined oro-/nasopharyngeal swabs. CONCLUSION: Our results suggest reduced clinical diagnostic sensitivity of saliva collected using buccal swabs when compared to combined oro-/nasopharyngeal swabs in the detection of SARS-CoV-2 Omicron in symptomatic individuals.

Modeling the impact of the Omicron infection wave in Germany.

In November 2021, the first infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VOC) B.1.1.529 ('Omicron') was reported in Germany, alongside global reports of reduced vaccine efficacy (VE) against infections with this variant. The potential threat posed by its rapid spread in Germany was, at the time, difficult to predict. We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered infectious-disease model that included information about variant-specific and waning VEs based on empirical data available at the time. Compared to other approaches, our method aimed for minimal structural and computational complexity and therefore enabled us to respond to changes in the situation in a more agile manner while still being able to analyze the potential influence of (non-)pharmaceutical interventions (NPIs) on the emerging crisis. Thus, the model allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs), the efficacy of contact reduction strategies, and the success of the booster vaccine rollout campaign. We expected a large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity, nevertheless, even without additional NPIs. The projected figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid-February and mid-March. Most surprisingly, our model showed that early, strict, and short contact reductions could have led to a strong 'rebound' effect with high incidences after the end of the respective NPIs, despite a potentially successful booster campaign. The results presented here informed legislation in Germany. The methodology developed in this study might be used to estimate the impact of future waves of COVID-19 or other infectious diseases.

Recovery and sequelae in 523 adults and children with tick-borne encephalitis in Germany.

PURPOSE: Despite being vaccine-preventable, tick-borne encephalitis (TBE) continues to cause considerable morbidity in Germany. Limited insight into potentially debilitating consequences of TBE may partially underly low (~ 20%) TBE vaccine uptake. We aimed to systematically assess TBE sequelae and other consequences. METHODS: Routinely notified TBE patients from 2018 to 2020 from Southern Germany were invited to telephone interviews acutely and again after 18 months. Duration of acute symptoms was prospectively assessed. Recovery was defined as score 0 on the modified RANKIN scale. Determinants of time to recovery were analysed with cox regression, adjusted for covariates identified using directed acyclic graphs, yielding hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: Of 558 cases, 523 (93.7%) completed follow-up. Full recovery was reported by 67.3% (children: 94.9%, adults: 63.8%). Sequelae included fatigue (17.0%), weakness (13.4%), concentration deficit (13.0%), and impaired balance (12.0%). Compared with 18-39-year-olds, recovery rates were 44% lower in ≥ 50-year-olds (HR: 0.56, 95%CI 0.42-0.75) and 79% higher in children (HR: 1.79, 95%CI 1.25-2.56). The recovery rate was 64% lower after severe TBE (compared to mild; HR: 0.36, 95%CI 0.25-0.52) and 22% lower with comorbidities (HR: 0.78, 95%CI 0.62-0.99). Substantial health-care use was reported (90.1% hospitalisation, 39.8% rehabilitation). Of employed cases, 88.4% required sick leave; 10.3% planned/reported premature retirement due to sequelae. CONCLUSION: Half the adult and 5% of paediatric patients reported persisting sequelae after 18 months. Improved prevention could alleviate both individual (morbidity) and societal TBE burden (health-care costs, productivity losses). Insights into sequelae can help guide at-risk populations towards tick-avoidant strategies and encourage TBE vaccination.

Safety and effectiveness of vaccines against COVID-19 in children aged 5-11 years: a systematic review and meta-analysis.

BACKGROUND: To date, more than 761 million confirmed SARS-CoV-2 infections have been recorded globally, and more than half of all children are estimated to be seropositive. Despite high SARS-CoV-2 infection incidences, the rate of severe COVID-19 in children is low. We aimed to assess the safety and efficacy or effectiveness of COVID-19 vaccines approved in the EU for children aged 5-11 years. METHODS: In this systematic review and meta-analysis, we included studies of any design identified through searching the COVID-19 L·OVE (living overview of evidence) platform up to Jan 23, 2023. We included studies with participants aged 5-11 years, with any COVID-19 vaccine approved by the European Medicines Agency-ie, mRNA vaccines BNT162b2 (Pfizer-BioNTech), BNT162b2 Bivalent (against original strain and omicron [BA.4 or BA.5]), mRNA-1273 (Moderna), or mRNA-1273.214 (against original strain and omicron BA.1). Efficacy and effectiveness outcomes were SARS-CoV-2 infection (PCR-confirmed or antigen-test confirmed), symptomatic COVID-19, hospital admission due to COVID-19, COVID-19-related mortality, multisystem inflammatory syndrome in children (MIS-C), and long-term effects of COVID-19 (long COVID or post-COVID-19 condition as defined by study investigators or per WHO definition). Safety outcomes of interest were serious adverse events, adverse events of special interest (eg, myocarditis), solicited local and systemic events, and unsolicited adverse events. We assessed risk of bias and rated the certainty of evidence (CoE) using the Grading of Recommendations Assessment, Development and Evaluation approach. This study was prospectively registered with PROSPERO, CRD42022306822. FINDINGS: Of 5272 screened records, we included 51 (1·0%) studies (n=17 [33%] in quantitative synthesis). Vaccine effectiveness after two doses against omicron infections was 41·6% (95% CI 28·1-52·6; eight non-randomised studies of interventions [NRSIs]; CoE low), 36·2% (21·5-48·2; six NRSIs; CoE low) against symptomatic COVID-19, 75·3% (68·0-81·0; six NRSIs; CoE moderate) against COVID-19-related hospitalisations, and 78% (48-90, one NRSI; CoE very low) against MIS-C. Vaccine effectiveness against COVID-19-related mortality was not estimable. Crude event rates for deaths in unvaccinated children were less than one case per 100 000 children, and no events were reported for vaccinated children (four NRSIs; CoE low). No study on vaccine effectiveness against long-term effects was identified. Vaccine effectiveness after three doses was 55% (50-60; one NRSI; CoE moderate) against omicron infections, and 61% (55-67; one NRSI; CoE moderate) against symptomatic COVID-19. No study reported vaccine efficacy or effectiveness against hospitalisation following a third dose. Safety data suggested no increased risk of serious adverse events (risk ratio [RR] 0·83 [95% CI 0·21-3·33]; two randomised controlled trials; CoE low), with approximately 0·23-1·2 events per 100 000 administered vaccines reported in real-life observations. Evidence on the risk of myocarditis was uncertain (RR 4·6 [0·1-156·1]; one NRSI; CoE low), with 0·13-1·04 observed events per 100 000 administered vaccines. The risk of solicited local reactions was 2·07 (1·80-2·39; two RCTs; CoE moderate) after one dose and 2·06 (1·70-2·49; two RCTs; CoE moderate) after two doses. The risk of solicited systemic reactions was 1·09 (1·04-1·16; two RCTs; CoE moderate) after one dose and 1·49 (1·34-1·65; two RCTs; CoE moderate) after two doses. The risk of unsolicited adverse events after two doses (RR 1·21 [1·07-1·38]; CoE moderate) was higher among mRNA-vaccinated compared with unvaccinated children. INTERPRETATION: In children aged 5-11 years, mRNA vaccines are moderately effective against infections with the omicron variant, but probably protect well against COVID-19 hospitalisations. Vaccines were reactogenic but probably safe. Findings of this systematic review can serve as a basis for public health policy and individual decision making on COVID-19 vaccination in children aged 5-11 years. FUNDING: German Federal Joint Committee.

Vaccine effectiveness against severe COVID-19 during the Omicron wave in Germany: results from the COViK study.

PURPOSE: COViK, a prospective hospital-based multicenter case-control study in Germany, aims to assess the effectiveness of COVID-19 vaccines against severe disease. Here, we report vaccine effectiveness (VE) against COVID-19-caused hospitalization and intensive care treatment during the Omicron wave. METHODS: We analyzed data from 276 cases with COVID-19 and 494 control patients recruited in 13 hospitals from 1 December 2021 to 5 September 2022. We calculated crude and confounder-adjusted VE estimates. RESULTS: 21% of cases (57/276) were not vaccinated, compared to 5% of controls (26/494; p < 0.001). Confounder-adjusted VE against COVID-19-caused hospitalization was 55.4% (95% CI: 12-78%), 81.5% (95% CI: 68-90%) and 95.6% (95%CI: 88-99%) after two, three and four vaccine doses, respectively. VE against hospitalization due to COVID-19 remained stable up to one year after three vaccine doses. CONCLUSION: Three vaccine doses remained highly effective in preventing severe disease and this protection was sustained; a fourth dose further increased protection.

Use of existing systematic reviews for the development of evidence-based vaccination recommendations: Guidance from the SYSVAC expert panel.

National immunization technical advisory groups (NITAGs) develop immunization-related recommendations and assist policy-makers in making evidence informed decisions. Systematic reviews (SRs) that summarize the available evidence on a specific topic are a valuable source of evidence in the development of such recommendations. However, conducting SRs requires significant human, time, and financial resources, which many NITAGs lack. Given that SRs already exist for many immunization-related topics, and to prevent duplication and overlap of reviews, a more practical approach may be for NITAGs to use existing SRs. Nevertheless, it can be challenging to identify relevant SRs, to select one SR from among multiple SRs, or to critically assess and effectively use them. To support NITAGs, the London School of Hygiene and Tropical Medicine, Robert Koch Institute and collaborators developed the SYSVAC project, which consists of an online registry of systematic reviews on immunization-related topics and an e-learning course, that supports the use of them (both freely accessible at https://www.nitag-resource.org/sysvac-systematic-reviews). Drawing from the e-learning course and recommendations from an expert panel, this paper outlines methods for using existing systematic reviews when making immunization-related recommendations. With specific examples and reference to the SYSVAC registry and other resources, it offers guidance on locating existing systematic reviews; assessing their relevance to a research question, up-to-dateness, and methodological quality and/or risk of bias; and considering the transferability and applicability of their findings to other populations or settings.

Estimating the share of SARS-CoV-2-immunologically naïve individuals in Germany up to June 2022.

After the winter of 2021/2022, the coronavirus disease 2019 (COVID-19) pandemic had reached a phase where a considerable number of people in Germany have been either infected with a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, vaccinated or both, the full extent of which was difficult to estimate, however, because infection counts suffer from under-reporting, and the overlap between the vaccinated and recovered subpopulations is unknown. Yet, reliable estimates regarding population-wide susceptibility were of considerable interest: Since both previous infection and vaccination reduce the risk of severe disease, a low share of immunologically naïve individuals lowers the probability of further severe outbreaks, given that emerging variants do not escape the acquired susceptibility reduction. Here, we estimate the share of immunologically naïve individuals by age group for each of the sixteen German federal states by integrating an infectious-disease model based on weekly incidences of SARS-CoV-2 infections in the national surveillance system and vaccine uptake, as well as assumptions regarding under-ascertainment. We estimate a median share of 5.6% of individuals in the German population have neither been in contact with vaccine nor any variant up to 31 May 2022 (quartile range [2.5%-8.5%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.8% [1.6%-5.9%] for ages 18-59 and 2.1% [1.0%-3.4%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.3% [14.1%-17.9%] of the population in Germany, across all ages, are estimated to be immunologically naïve, highlighting the large impact the first two Omicron waves had until the beginning of summer in 2022. The method developed here might be useful for similar estimations in other countries or future outbreaks of other infectious diseases.

Tick-borne encephalitis: Acute clinical manifestations and severity in 581 cases from Germany, 2018-2020.

OBJECTIVES: Tick-borne encephalitis (TBE) is a growing public health problem with an average of 361 cases notified annually to Germany's passive surveillance system since 2001. We aimed to assess clinical manifestations and identify covariates associated with severity. METHODS: We included cases notified 2018-2020 in a prospective cohort study and collected data with telephone interviews, questionnaires to general practitioners, and hospital discharge summaries. Covariates' causal associations with severity were evaluated with multivariable logistic regression, adjusted for variables identified via directed acyclic graphs. RESULTS: Of 1220 eligible cases, 581 (48%) participated. Of these, 97.1% were not (fully) vaccinated. TBE was severe in 20.3% of cases (children: 9.1%, ≥70-year-olds: 48.6%). Routine surveillance data underreported the proportion of cases with central nervous system involvement (56% vs. 84%). Ninety percent required hospitalization, 13.8% intensive care, and 33.4% rehabilitation. Severity was most notably associated with age (odds ratio (OR): 1.04, 95% confidence interval (CI): 1.02-1.05), hypertension (OR: 2.27, 95%CI: 1.37-3.75), and monophasic disease course (OR: 1.67, 95%CI: 1.08-2.58). CONCLUSIONS: We observed substantial TBE burden and health service utilization, suggesting that awareness of TBE severity and vaccine preventability should be increased. Knowledge of severity-associated factors may help inform patients' decision to get vaccinated.

Effectiveness of vaccines in preventing hospitalization due to COVID-19: A multicenter hospital-based case-control study, Germany, June 2021 to January 2022.

We included 852 patients in a prospectively recruiting multicenter matched case-control study in Germany to assess vaccine effectiveness (VE) in preventing COVID-19-associated hospitalization during the Delta-variant dominance. The two-dose VE was 89 % (95 % CI 84-93 %) overall, 79 % in patients with more than two comorbidities and 77 % in adults aged 60-75 years. A third dose increased the VE to more than 93 % in all patient-subgroups.

Systematic review of the efficacy, effectiveness and safety of recombinant haemagglutinin seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of recombinant haemagglutinin (HA) seasonal influenza vaccines to prevent laboratory-confirmed influenza. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials and non-randomised studies of interventions were eligible for inclusion. The search returned 28,846 records, of which 10 studies on recombinant HA influenza vaccine met our inclusion criteria. One study found that the quadrivalent recombinant HA influenza vaccine had higher relative vaccine efficacy (rVE) in preventing laboratory-confirmed influenza during the 2014-15 season compared with traditional quadrivalent vaccination in adults aged ≥50 years (rVE = 30%, 95% CI 10%-47%, moderate-certainty evidence). In a subgroup analysis, higher rVE was reported for influenza A (rVE = 36%, 95% CI 14% to 53%), but not for B (non-significant). Another study reported higher efficacy for the trivalent recombinant HA vaccine compared with placebo (VE = 45%, 95% CI 19-63, 1 RCT, low-certainty evidence) in adults aged 18-55 years. With the exception of a higher rate of chills (RR = 1.33, 95% CI 1.03-1.72), the safety profile of recombinant HA vaccines was comparable to that of traditional influenza vaccines. The evidence base for the efficacy and effectiveness of recombinant HA influenza vaccines is limited at present, although one study found that the quadrivalent recombinant HA influenza vaccine had higher rVE compared with traditional quadrivalent vaccination in adults aged ≥50 years.

Systematic review of the efficacy, effectiveness and safety of high-dose seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

This review sought to assess the efficacy, effectiveness and safety of high-dose inactivated influenza vaccines (HD-IIV) for the prevention of laboratory-confirmed influenza in individuals aged 18 years or older. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were included. The search returned 28,846 records, of which 36 studies were included. HD-IIV was shown to have higher relative vaccine efficacy in preventing influenza compared with standard-dose influenza vaccines (SD-IIV3) in older adults (Vaccine effectiveness (VE) = 24%, 95% CI 10-37, one RCT). One NRSI demonstrated significant effect for HD-IIV3 against influenza B (VE = 89%, 95% CI 47-100), but not for influenza A(H3N2) (VE = 22%, 95% CI -82 to 66) when compared with no vaccination in older adults. HD-IIV3 showed significant relative effect compared with SD-IIV3 for influenza-related hospitalisation (VE = 11.8%, 95% CI 6.4-17.0, two NRSIs), influenza- or pneumonia-related hospitalisation (VE = 13.7%, 95% CI 9.5-17.7, three NRSIs), influenza-related hospital encounters (VE = 13.1%, 95% CI 8.4-17.7, five NRSIs), and influenza-related office visits (VE = 3.5%, 95% CI 1.5-5.5, two NRSIs). For safety, HD-IIV were associated with significantly higher rates of local and systemic adverse events compared with SD-IIV (combined local reactions, pain at injection site, swelling, induration, headache, chills and malaise). From limited data, compared with SD-IIV, HD-IIV were found to be more effective in the prevention of laboratory-confirmed influenza, for a range of proxy outcome measures, and associated with more adverse events.

Systematic review of the efficacy, effectiveness and safety of cell-based seasonal influenza vaccines for the prevention of laboratory-confirmed influenza in individuals ≥18 years of age.

The most effective means of preventing seasonal influenza is through strain-specific vaccination. In this study, we investigated the efficacy, effectiveness and safety of cell-based trivalent and quadrivalent influenza vaccines. A systematic literature search was conducted in electronic databases and grey literature sources up to 7 February 2020. Randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) were eligible for inclusion. Two reviewers independently screened, extracted data and assessed the risk of bias of included studies. Certainty of evidence for key outcomes was assessed using the GRADE methodology. The search returned 28,846 records, of which 868 full-text articles were assessed for relevance. Of these, 19 studies met the inclusion criteria. No relative efficacy data were identified for the direct comparison of cell-based vaccines compared with traditional vaccines (egg-based). Efficacy data were available comparing cell-based trivalent influenza vaccines with placebo in adults (aged 18-49 years). Overall vaccine efficacy was 70% against any influenza subtype (95% CI 61%-77%, two RCTS), 82% against influenza A(H1N1) (95% CI 71%-89%, 2 RCTs), 72% against influenza A(H3N2) (95% CI 39%-87%, 2 RCTs) and 52% against influenza B (95% CI 30%-68%, 2 RCTs). Limited and heterogeneous data were presented for effectiveness when compared with no vaccination. One NRSI compared cell-based trivalent and quadrivalent vaccination with traditional trivalent and quadrivalent vaccination, finding a small but significant difference in favour of cell-based vaccines for influenza-related hospitalisation, hospital encounters and physician office visits. The safety profile of cell-based trivalent vaccines was comparable to traditional trivalent influenza vaccines. Compared with placebo, cell-based trivalent influenza vaccines have demonstrated greater efficacy in adults aged 18-49 years. Overall cell-based vaccines are well-tolerated in adults, however, evidence regarding the effectiveness of these vaccines compared with traditional seasonal influenza vaccines is limited.