Showing papers by "Ole Wichmann published in 2022"
TL;DR: Under the Omicron variant, the effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection is low and only short-lasting after full primary immunization, but can be improved by booster vaccination.
Abstract: Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is currently the dominant variant globally. This third interim analysis of a living systematic review summarizes evidence on the effectiveness of the coronavirus disease 2019 (COVID-19) vaccine (vaccine effectiveness, VE) and duration of protection against Omicron. Methods We systematically searched literature on COVID-19 for controlled studies, evaluating the effectiveness of COVID-19 vaccines approved in the European Union up to 14/01/2022, complemented by hand searches of websites and metasearch engines up to 11/02/2022. We considered the following comparisons: full primary immunization vs. no vaccination, booster immunization vs. no vaccination, and booster vs. full primary immunization. VE against any confirmed SARS-CoV-2 infection, symptomatic, and severe COVID-19 (i.e., COVID-19-related hospitalization, ICU admission, or death) was indicated, providing estimate ranges. Meta-analysis was not performed due to high study heterogeneity. The risk of bias was assessed with ROBINS-I, and the certainty of the evidence was evaluated using GRADE. Results We identified 26 studies, including 430 to 2.2 million participants, which evaluated VE estimates against infections with the SARS-CoV-2 Omicron variant. VE against any confirmed SARS-CoV-2 infection ranged between 0–62% after full primary immunization and between 34–66% after a booster dose compared to no vaccination. VE range for booster vs. full primary immunization was 34–54.6%. After full primary immunization VE against symptomatic COVID-19 ranged between 6-76%. After booster immunization VE ranged between 3-84% compared to no vaccination and between 56-69% compared to full primary immunization. VE against severe COVID-19 ranged between 3-84% after full primary immunization and between 12-100% after booster immunization compared to no vaccination, and 100% (95% CI 71.4-100) compared to full primary immunization (data from only one study). VE was characterized by a moderate to strong decline within 3–6 months for SARS-CoV-2 infections and symptomatic COVID-19. Against severe COVID-19, protection remained robust for at least up to 6 months. Waning immunity was more profound after primary than booster immunization. The risk of bias was moderate to critical across studies and outcomes. GRADE certainty was very low for all outcomes. Conclusions Under the Omicron variant, the effectiveness of EU-licensed COVID-19 vaccines in preventing any SARS-CoV-2 infection is low and only short-lasting after full primary immunization, but can be improved by booster vaccination. VE against severe COVID-19 remains high and is long-lasting, especially after receiving the booster vaccination.
23 citations
TL;DR: Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years and for immunodeficient persons, data indicate relevant waning.
Abstract: Background. The duration of protection after a single dose of yellow fever vaccine is a matter of debate. To summarize the current knowledge, we performed a systematic literature review and meta-analysis. Methods. Studies on the duration of protection after 1 and [≥]2 vaccine doses were reviewed. Data were stratified by time since vaccination. In our meta-analysis, we used random-effects models. Results. We identified 36 studies from 20 countries, comprising over 17,000 participants aged 6 months to 85 years. Among healthy adults and children, pooled seroprotection rates after single vaccination dose were close to 100% by 3 months and remained high in adults for 5 to 10 years. In children vaccinated before age 2, the seroprotection rate was 52% within 5 years after primary vaccination. For immunodeficient persons, data indicate relevant waning. Conclusions. The extent of waning of seroprotection after yellow fever vaccination depends on age at vaccination and immune status.
15 citations
TL;DR: In this article , a case-control study (2018-2020) aimed to examine reasons for low vaccine uptake, vaccine effectiveness (VE), and vaccine breakthrough infections (VBIs). Telephone interviews (581 cases, 975 matched controls) covered vaccinations, vaccination barriers, and confounders identified with directed acyclic graphs.
Abstract: Tick-borne encephalitis (TBE) vaccination coverage remains low in Germany. Our case-control study (2018-2020) aimed to examine reasons for low vaccine uptake, vaccine effectiveness (VE), and vaccine breakthrough infections (VBIs). Telephone interviews (581 cases, 975 matched controls) covered vaccinations, vaccination barriers, and confounders identified with directed acyclic graphs. Multivariable logistic regression determined VE as 1-odds ratio with 95% confidence intervals (CI). We additionally calculated VE with the Screening method using routine surveillance and vaccination coverage data. Main vaccination barriers were poor risk perception and fear of adverse events. VE was 96.6% (95% CI 93.7-98.2) for ≥ 3 doses and manufacturer-recommended dosing intervals. Without boosters, VE after ≥ 3 doses at ≤ 10 years was 91.2% (95% CI 82.7-95.6). VE was similar for homologous/heterologous vaccination. Utilising routine surveillance data, VE was comparable (≥ 3 doses: 92.8%). VBIs (n = 17, 2.9% of cases) were older, had more comorbidities and higher severity than unvaccinated cases. However, only few VBIs were diagnostically confirmed; 57% of re-tested vaccinated cases (≥ 1 dose, n = 54) proved false positive. To increase TBE vaccine uptake, communication efforts should address complacency and increase confidence in the vaccines' safety. The observed duration of high VE may inform decision-makers to consider extending booster intervals to 10 years.
12 citations
TL;DR: In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than 'no vaccination' and based on limited data, there was no significant difference comparing the effectiveness of MF59®, adjUVanted vaccines with their non-adjuvanted counterparts.
Abstract: The most effective means of preventing seasonal influenza is through vaccination. In this systematic review, we investigated the efficacy, effectiveness and safety of MF59® adjuvanted trivalent and quadrivalent 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 (NRSIs) were eligible for inclusion. The search returned 28,846 records, of which 48 studies on MF59® adjuvanted vaccines met our inclusion criteria. No efficacy trials were identified. In terms of vaccine effectiveness (VE), MF59® adjuvanted trivalent influenza vaccines were effective in preventing laboratory‐confirmed influenza in older adults (aged ≥65 years) compared with no vaccination (VE = 45%, 95% confidence interval (CI) 23%–61%, 5 NRSIs across 3 influenza seasons). By subtype, significant effect was found for influenza A(H1N1) (VE = 61%, 95% CI 44%–73%) and B (VE = 29%, 95% CI 5%–46%), but not for A(H3N2). In terms of relative VE, there was no significant difference comparing MF59® adjuvanted trivalent vaccines with either non‐adjuvanted trivalent or quadrivalent vaccines. Compared with traditional trivalent influenza vaccines, MF59® adjuvanted trivalent influenza vaccines were associated with a greater number of local adverse events (RR = 1.90, 95% CI 1.50–2.39) and systemic reactions (RR = 1.18, 95% CI 1.02–1.38). In conclusion, MF59® adjuvanted trivalent influenza vaccines were found to be more effective than ‘no vaccination’. Based on limited data, there was no significant difference comparing the effectiveness of MF59® adjuvanted vaccines with their non‐adjuvanted counterparts.
8 citations
TL;DR: From limited data, 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.
Abstract: 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.
8 citations
TL;DR: The evidence base for the efficacy and effectiveness of recombinant haemagglutinin seasonal influenza vaccines is limited at present, although 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.
Abstract: 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.
7 citations
TL;DR:
Abstract: In Germany, tick-borne encephalitis (TBE) infections mainly occur in southern regions. Despite recent increases in incidence, TBE vaccination coverage remains low, necessitating additional preventive strategies against TBE. Our case-control study in Southern Germany from 2018 to 2020 mapped knowledge/application of tick-protective strategies and identified TBE risk factors. We calculated odds ratios (OR), with 95% confidence intervals (CI). We interviewed 581 cases and 975 matched controls. Most participants recalled lifetime tick bites, mainly while walking, gardening, or hiking. However, only 45% of cases noticed ticks during exposure time; another 12% reported unpasteurized milk intake. While tick-protection knowledge was satisfactory, application lagged behind. Risk factors included dog ownership (OR = 2.45, 95% CI: 1.85–3.24), walks ≥ 4×/week (OR = 2.11, 95% CI: 1.42–3.12), gardening ≥ 4×/week (OR = 1.83, 95% CI: 1.11–3.02), and garden proximity < 250 m of forests (OR = 2.54, 95% CI: 1.82–3.56). Applying ≥2 tick-protective strategies (OR = 0.52, 95% CI: 0.40–0.68) and keeping lawns mowed (OR = 0.63, 95% CI: 0.43–0.91) were inversely associated with TBE. In 2020 (likely pandemic-related), cases reported significantly more walks than previously, potentially explaining the record high case numbers. Our findings provide guidance on targets for TBE prevention. Persons with gardens near forests, frequent outdoor activities, or dogs could particularly benefit from targeted information, including on vaccination and preventing tick bites.
6 citations
01 Nov 2022
TL;DR: From July 2022, cases of imported Diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany as discussed by the authors , and up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n= 17).
Abstract: From July 2022, cases of imported diphtheria with toxigenic Corynebacterium diphtheriae remarkably increased among migrants arriving in Germany. Up to 30 September 2022, 44 cases have been reported to the national public health institute, all laboratory-confirmed, male, and mainly coming from Syria (n = 21) and Afghanistan (n = 17). Phylogeny and available journey information indicate that most cases (n = 19) were infected along the Balkan route. Active case finding, increased laboratory preparedness and epicentre localisation in countries along this route are important.
5 citations
TL;DR: In this article , 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.
4 citations
TL;DR: 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.
Abstract: 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.
3 citations
TL;DR: A large cumulative number of infections with the VOC Omicron in Germany with ICU occupancy likely remaining below capacity nevertheless, even without additional non-pharmaceutical interventions is expected, in line with the retrospectively observed waves.
Abstract: Background In November 2021, the first case of SARS-CoV-2 "variant of concern" (VOC) B.1.1.529 ("Omicron") was reported in Germany, alongside global reports of reduced vaccine efficacy against infections with this variant. The potential threat posed by the rapid spread of this variant in Germany remained, at the time, elusive. Methods We developed a variant-dependent population-averaged susceptible-exposed-infected-recovered (SEIR) infectious disease model. The model was calibrated on the observed fixation dynamics of the Omicron variant in December 2021, and allowed us to estimate potential courses of upcoming infection waves in Germany, focusing on the corresponding burden on intensive care units (ICUs) and the efficacy of contact reduction strategies. Results A maximum median incidence of approximately 300,000 (50% PI in 1000: [181,454], 95% PI in 1000: [55,804]) reported cases per day was expected with the median peak occurring in the mid of February 2022, reaching a cumulative Omicron case count of 16.5 million (50% PI in mio: [11.4, 21.3], 95% PI in mio: [4.1, 27.9]) until Apr 1, 2022. These figures were in line with the actual Omicron waves that were subsequently observed in Germany with respective peaks occurring in mid February (peak: 191k daily new cases) and mid March (peak: 230k daily new cases), cumulatively infecting 14.8 million individuals during the study period. The model peak incidence was observed to be highly sensitive to variations in the assumed generation time and decreased with shorter generation time. Low contact reductions were expected to lead to containment. Early, strict, and short contact reductions could have led to a strong "rebound" effect with high incidences after the end of the respective non-pharmaceutical interventions. Higher vaccine uptake would have led to a lower outbreak size. To ensure that ICU occupancy remained below maximum capacity, a relative risk of requiring ICU care of 10%-20% was necessary (after infection with Omicron vs. infection with Delta). Conclusions 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 non-pharmaceutical interventions. Our estimates were in line with the retrospectively observed waves. 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.
TL;DR: A mathematical model of RSV transmission is developed, which simulates the sequential re-infection and uses a flexible Von Mises function to model the seasonal forcing, which estimates that RSV dynamics in NSW can be best explained by a high effective baseline transmission rate.
Abstract: Background: Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections and bronchiolitis in young children. The seasonal pattern of RSV is shaped by short-lived immunity, seasonally varying contact rates and pathogen viability. The magnitude of each of these parameters is not fully clear. The disruption of the regular seasonality of RSV during the COVID pandemic in 2020 due to control measures, and the ensuing delayed surge in RSV cases provides an opportunity to disentangle these factors and to understand the implication for vaccination strategies. A better understanding of the drivers of RSV seasonality is key for developing future vaccination strategies. Methods: We developed a mathematical model of RSV transmission, which simulates the sequential re-infection (SEIRRS4) and uses a flexible Von Mises function to model the seasonal forcing. Using MCMC we fit the model to laboratory confirmed RSV data from 2010-2022 from NSW while accounting for the reduced contact rates during the pandemic with Google mobility data. We estimated the baseline transmission rate, its amplitude and shape during RSV season as well as the duration of immunity. The resulting parameter estimates were compared to a fit to pre-pandemic data only, and to a fit with a cosine forcing function. We then simulated the expected shifts in peak timing and amplitude under two vaccination strategies: continuous and seasonal vaccination. Results: We estimate that RSV dynamics in NSW can be best explained by a high effective baseline transmission rate (2.94/d, 95% CrI 2.72-3.19) and a narrow peak with a maximum 13% increase compared to the baseline transmission rate. We also estimate the duration of post infection temporary but sterilizing immunity to be 412 days (95% CrI 391-434). A cosine forcing resulted in a similar fit and posterior estimates. Excluding the data from the pandemic period in the fit increased parameter correlation and yielded less informative posterior distributions. The continuous vaccination strategy led to more extreme seasonal incidence with a delay in the peak timing and a higher amplitude whereas seasonal vaccination flattened the incidence curves. Conclusion: Quantifying the parameters that govern RSV seasonality is key in determining potential indirect effects from immunization strategies as those are being rolled out in the next few years.
TL;DR: In this article , the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1-17 years living in Germany in 2003-2005.
Abstract: In Germany, HPV vaccination of adolescent girls was introduced in 2007. Nationally representative data on the distribution of vaccine-relevant HPV types in the pre-vaccination era are, however, only available for the adult population. To obtain data in children and adolescents, we assessed the prevalence and determinants of serological response to 16 different HPV types in a representative sample of 12,257 boys and girls aged 1-17 years living in Germany in 2003-2005.Serum samples were tested for antibodies to nine mucosal and seven cutaneous HPV types. The samples had been collected during the nationally representative German Health Interview and Examination Survey for Children and Adolescents in 2003-2006. We calculated age- and gender-specific HPV seroprevalence. We used multivariable regression models to identify associations between demographic and behavioral characteristics and HPV seropositivity.We found low but non-zero seroprevalence for the majority of tested HPV types among children and adolescents in Germany. The overall seroprevalence of HPV-16 was 2.6%, with slightly higher values in adolescents. Seroprevalence of all mucosal types but HPV-6 ranged from 0.6% for HPV-33, to 6.4% for HPV-31 and did not differ by gender. We found high overall seroprevalence for HPV-6 with 24.8%. Cutaneous HPV type seroprevalence ranged from 4.0% for HPV-38 to 31.7% for HPV-1. In the majority of cutaneous types, seroprevalence did not differ between boys and girls, but increased sharply with age, (e.g., HPV-1 from 1.5% in 1-3-years-old to 45.1% in 10-11-years-old). Associations between behavioral factors and type-specific HPV prevalence were determined to be heterogeneous.We report the first nationally representative data of naturally acquired HPV antibody reactivity in the pre-HPV-vaccination era among children and adolescents living in Germany. These data can be used as baseline estimates for evaluating the impact of the current HPV vaccination strategy targeting 9-14-years-old boys and girls.
TL;DR: A high share of individuals with SARS-CoV-2 immunity lowers the probability of severe outbreaks that could potentially overburden the public health system once again, given that emerging variants do not escape this reduction in susceptibility.
Abstract: After having affected the population for two years, the COVID-19 pandemic has reached a phase where a considerable number of people in Germany have been either infected with a SARS-CoV-2 variant, vaccinated, or both. Yet the full extent to which the population has been in contact with either virus or vaccine remains elusive, particularly on a regional level, because (a) infection counts suffer from under-reporting, and (b) the overlap between the vaccinated and recovered subpopulations is unknown. Since previous infection, vaccination, or especially a combination of both reduce the risk of severe disease, a high share of individuals with SARS-CoV-2 immunity lowers the probability of severe outbreaks that could potentially overburden the public health system once again, given that emerging variants do not escape this reduction in susceptibility. Here, we estimate the share of immunologically naive individuals by age group for each of the 16 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 7.0% of individuals in the German population have neither been in contact with vaccine nor any variant as of March 31, 2022 (quartile range [3.6%-9.8%]). For the adult population at higher risk of severe disease, this figure is reduced to 3.5% [1.3%-5.5%] for ages 18-59 and 4.3% [2.7%-5.8%] for ages 60 and above. However, estimates vary between German states mostly due to heterogeneous vaccine uptake. Excluding Omicron infections from the analysis, 16.1% [14.0%-17.8%] of the population in Germany, across all ages, are estimated to be immunologically naive, highlighting the large impact the Omicron wave had until the beginning of spring in 2022.
01 Jan 2022
TL;DR: The absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance, which is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.
Abstract: Background Guillain–Barré syndrome (GBS) is a rare autoimmune disease that can follow viral infections and has in a few cases been linked to vaccinations. Pre-licensure clinical trials did not observe an association between human papillomavirus (HPV) vaccination and GBS, a post-marketing study from 2017 reported an increased relative risk. Aim We assessed the risk of GBS after HPV vaccination through a systematic literature review and meta-analysis. Methods We searched Embase, MEDLINE and Cochrane for studies reporting on the risk of GBS after HPV vaccination in individuals aged ≥ 9 years, published between 1 January 2000 and 4 April 2020, excluding studies without a comparator group. Seven studies reporting relative effect sizes were pooled using random-effects meta-analysis. We assessed quality of evidence using the GRADE approach. Study protocol was registered (PROSPERO No. #CRD42019123533). Results Of 602 identified records, we included 25 studies. Based on over 10 million reports, cases of GBS were rare. In 22 studies no increased risk was observed, while in three studies a signal of increased risk of GBS after HPV vaccination was identified. Meta-analysis yielded a pooled random-effects ratio of 1.21 (95% CI: 0.60–2.43); I2 = 72% (95% CI: 36–88). This translates to a number needed to harm of one million to be vaccinated to generate one GBS case. Quality of evidence was very low. Conclusions The absolute and relative risk of GBS after HPV vaccination is very low and lacks statistical significance. This is reassuring for the already implemented vaccination programmes and should be used in respective communication activities.
TL;DR: In this paper , the authors investigated the acceptance and potential unintended consequences of the measles vaccine mandate in Germany and used mediation analysis to measure how trust in institutions had an impact on the attitude towards the mandate, mediated by level of reactance.
Abstract: Abstract Background In Germany, a measles vaccine mandate came into effect in March 2020, requiring proof of measles immunization for children attending kindergarten or school and for staff in a variety of facilities. Mandates can be successful if implemented with care and in a context-sensitive manner. They may, however, also lead to inequities and decreased uptake of other vaccines. The aim of this study was to investigate the acceptance and potential unintended consequences of the measles vaccine mandate in Germany. Methods As part of a larger evaluation project on the new mandate, we conducted an online survey among parents in August/September 2020. We assessed differences in knowledge about the mandate and the measles vaccine by socio-economic status. We used linear and logistic regression to estimate how reactance to the mandate was associated with vaccination status and vaccination intention against other diseases. We used mediation analysis to measure how trust in institutions had an impact on the attitude towards the mandate, mediated by level of reactance. Results In total, 4,863 parents participated in the study (64.2% female, mean age = 36.8 years). Of these, 74.1% endorsed a measles vaccine mandate for children. Parents with lower socio-economic status had less knowledge about the mandate and the measles vaccine. The higher parents’ levels of reactance, the lower the vaccination intentions and the likelihood for the child to be vaccinated against other diseases. Furthermore, higher institutional trust decreased the level of reactance and increased positive attitudes towards the mandate (partial mediation). Conclusions The new measles vaccine mandate in Germany, though well accepted by many, might have unintended consequences. Parents with lower socio-economic status, who know less about the mandate and vaccine, might be less likely to comply with it. The mandate may also lead to some parents omitting other childhood vaccines, as a way to restore their freedom. This could decrease vaccination coverage of other vaccines. Any potential loss of trust might provoke more reactance and lower acceptance of mandates. Policymakers should now expand communication activities on the mandate, monitor trends in vaccination coverage carefully and take measures to strengthen trust.
TL;DR: The vaccination campaign should be continued at high intensity until at least 85% of 12-59- year-olds or 90% of ≥ 60-year-olds are fully vaccinated against COVID-19, based on the population's willingness to be vaccinated.
Abstract: Abstract Background Control of the 2019 coronavirus disease (COVID-19) pandemic in Germany and return to pre-pandemic behaviour can only be achieved through natural or vaccine-induced immunity. Sufficient vaccine capacity promotes interest in the necessary and feasible target vaccination coverage. Methods An age and risk group stratified SEIR transmission model was used to assess the impact of vaccination coverage ranging 65%-95% for 12-59-year-olds and 90%-95% for ≥ 60-year-olds on COVID-19 incidence and intensive care unit (ICU) utilization between 01.07.2021-31.03.2022. Separate implementation of licensed vaccines allows to consider different efficacies, delivery rates and age-specific national vaccination recommendations. The analysis was conducted under different assumptions about contact behaviour during summer, reduction of daily contacts with increasing number of cases, daily vaccination uptake and the dominant variant. Data from the COVIMO study (N = 3004, data collection: 17.05.-09.06.2021) were used to define the population percentage willing to be vaccinated. Results The COVIMO study indicates an achievable vaccination compliance rate of 83.9% among 12-59-year-olds and 94.8% among those ≥ 60-year-olds. Maximum incidence or ICU utilization during observation period decreases from 385 to 61 and 6220 to 2800, respectively, with an increase in vaccination coverage from 65% to 95% of 12-59-year-olds, 90% vaccination rate among ≥ 60-year-olds, compared to pre-pandemic reduced contact behaviour in summer and reduction of contacts as case numbers increase. Conclusions The vaccination campaign should be continued at high intensity until at least 85% of 12-59-year-olds or 90% of ≥ 60-year-olds are fully vaccinated against COVID-19. Based on the population's willingness to be vaccinated, this goal seemed feasible. Key messages • Mathematical modeling was used to determine an evidence-based target vaccination coverage of ≥ 85%. • Expertise in modeling should be further strengthened.
TL;DR: In this article , a network of NITAGs in the European Union and Economic Area countries was established under the coordination of the European Centre for Disease Prevention and Control (ECDC).
Abstract: Abstract Issue/problem NITAGs are independent expert advisory committees that provide evidence-based recommendations to the Ministry of Health to guide the introduction of new vaccines and formulate national immunization plans. Description of the problem The evaluation of vaccines has become more and more complex. This is not only because the number of vaccines on the market and the diseases they target has increased, but also because a much wider range of population subgroups can be targeted, and for some diseases several vaccines are available and need to be compared. In addition, vaccines not only have an impact on individual well-being, but can also induce population-level effects and broader socioeconomic value. Results NITAGs consider to a large extent similar key factors in their evaluation processes. These can be divided into context-free and context-specific aspects. Context-free aspects include effectiveness and safety. Local disease epidemiology, potential vaccine impact at population-level, cost-effectiveness and societal or cultural values and preferences are context-specific aspects. Collaboration is possible when jointly assessing the evidence related to context-free aspects, since this is usually easily transferrable across countries. In 2019, a network of NITAGs in the European Union and Economic Area countries was established under the coordination of the European Centre for Disease Prevention and Control. Within this network, working groups have been established and either performed themselves or supported external contractors in conducting systematic reviews on vaccines effectiveness and safety. Lessons The increasing workload of NITAGs and the prospect of joint clinical assessments draw the attention to a number of practical issues to be solved, e.g., consensus on methodological guidelines for systematic reviews, processes to ensure that the products meet NITAGs expectations (content, quality, timing), and approaches how to consider unpublished data.
TL;DR: In this article , a living systematic review is presented to evaluate vaccine efficacy/effectiveness and safety of COVID-19 vaccines for children aged 5-11 years in the European Union for SARS-CoV-2 infections.
Abstract: Background: To date, more than 628 million confirmed SARS-CoV-2 infections were recorded globally. Highest incidences were usually observed in school-aged children. Methods: The aim of this living systematic review is to evaluate vaccine efficacy/effectiveness (VE) and safety of COVID-19 vaccines approved in the European Union for children aged 5-11 years. In this version, we included studies of any design identified through searching the COVID-19 L·OVE (Living OVerview of Evidence) platform up to 13 September 2022. We assessed risk of bias and rated the certainty of evidence (CoE) using GRADE. Findings: In total 4,651 records were screened and 30 studies were included. The studies assessed two mRNA vaccines (BNT162b2 or mRNA-1273), with pivotal randomized controlled trials (RCTs) being conducted before and all other studies during the Omicron era.VE against pre-Omicron variant SARS-CoV-2 infections was 73·0% (41%-87%, 1 RCT, CoE: moderate), while VE against Omicron variant SARS-CoV-2 infections was 41·9% (27·4%-53·5%, 6 non-randomized studies of interventions [NRSIs], CoE: moderate). Pre-Omicron VE against symptomatic COVID-19 was 86·7% (58·1-95·8%, 2 RCTs, CoE: moderate) and 38·7% (21·7%-52·1%, 5 NRSIs, CoE: moderate) after Omicron emergence. No cases of severe COVID-19 were reported in RCTs. VE against Omicron-associated COVID-19 hospitalisation was 75·3% (68·0%-81·0%, 6 NRSIs, CoE: moderate).Safety data suggests no increased risk of serious adverse events (RR 0·83 [0·21-3·33], 2 RCTs, CoE: low), with approximately 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], 1 NRSI, CoE: low), with 0·13-1·04 observed events per 100,000 administered vaccines. The risk of AEs (RR 1·21 [1·07-1·38], CoE: moderate) was higher among mRNA-vaccinated children. Interpretation: In 5-11-year-old children mRNA-vaccines are moderately effective against infections with the Omicron variant, but probably still protect well against COVID-19 hospitalisations. Vaccines were reactogenic but generally safe.
TL;DR: First estimates for effectiveness of mRNA booster vaccinations against Omicron-infections in adolescents are encouragingly high and can be a valid and resource-saving approach upon surge of novel SARS-CoV-2 variants.
Abstract: Background: mRNA-based COVID-19 booster vaccinations have been administered in Germany since mid-September 2021. We utilized Germany’s national COVID-19 surveillance data to assess effectiveness of three vaccination doses among adolescents and adults during Delta- and Omicron-predominance. Methods: We applied a quasi-Poisson regression model to estimate incidence rate ratios and 95% confidence intervals for symptomatic SARS-CoV-2 infection and COVID-19 associated hospitalization and severe illness by age group (12-17, 18-59, and ≥60 years). We further investigated waning of vaccine effectiveness (VE) over time during Omicron-predominance. Findings: VE against symptomatic infection was considerably lower during Omicron- versus Delta-predominance (70% vs. 95% among ≥18 year-olds). During Omicron-predominance, estimated 3-dose VE at <4 weeks post-vaccination was highest in 12-17 year-olds (89·7%), followed by ≥60 year-olds (87·8%) and 18-59 year-olds (77·4%), and declined to 84·4% at 4 to <8 weeks post-vaccination and 51·1% and 76·4% at 8 to <12 weeks post-vaccination, respectively. VE against hospitalization was high in all age groups and remained >90% among ≥60 year-olds and >75% among 18-59 year-olds at 8 to <12 weeks post-vaccination, while VE against severe illness among ≥60 year-olds was >95% at 8 to <12 weeks. Interpretation: First estimates for effectiveness of mRNA booster vaccinations against Omicron-infections in adolescents are encouragingly high. Waning of protection against mild illness over the first 15 weeks post-vaccination was marked among 18-59 year-olds;however, boosting offered excellent protection against hospitalization and severe illness. Utilizing routine surveillance data to monitor COVID-19 VE in real time can be a valid and resource-saving approach upon surge of novel SARS-CoV-2 variants.