Excess mortality in Europe coincides with peaks of COVID-19, influenza and respiratory syncytial virus (RSV), November 2023 to February 2024.

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI:  91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

Why are different estimates of the effective reproductive number so different? A case study on COVID-19 in Germany.

The effective reproductive number Rt has taken a central role in the scientific, political, and public discussion during the COVID-19 pandemic, with numerous real-time estimates of this quantity routinely published. Disagreement between estimates can be substantial and may lead to confusion among decision-makers and the general public. In this work, we compare different estimates of the national-level effective reproductive number of COVID-19 in Germany in 2020 and 2021. We consider the agreement between estimates from the same method but published at different time points (within-method agreement) as well as retrospective agreement across eight different approaches (between-method agreement). Concerning the former, estimates from some methods are very stable over time and hardly subject to revisions, while others display considerable fluctuations. To evaluate between-method agreement, we reproduce the estimates generated by different groups using a variety of statistical approaches, standardizing analytical choices to assess how they contribute to the observed disagreement. These analytical choices include the data source, data pre-processing, assumed generation time distribution, statistical tuning parameters, and various delay distributions. We find that in practice, these auxiliary choices in the estimation of Rt may affect results at least as strongly as the selection of the statistical approach. They should thus be communicated transparently along with the estimates.

The Burden of Disease due to COVID-19 (BoCO-19): A study protocol for a secondary analysis of surveillance data in Southern and Eastern Europe, and Central Asia.

INTRODUCTION: The COVID-19 pandemic has had an extensive impact on public health worldwide. However, in many countries burden of disease indicators for COVID-19 have not yet been calculated or used for monitoring. The present study protocol describes an approach developed in the project "The Burden of Disease due to COVID-19. Towards a harmonization of population health metrics for the surveillance of dynamic outbreaks" (BoCO-19). The process of data collection and aggregation across 14 different countries and sub-national regions in Southern and Eastern Europe and Central Asia is described, as well as the methodological approaches used. MATERIALS AND METHODS: The study implemented in BoCO-19 is a secondary data analysis, using information from national surveillance systems as part of mandatory reporting on notifiable diseases. A customized data collection template is used to gather aggregated data on population size as well as COVID-19 cases and deaths. Years of life lost (YLL), as one component of the number of Disability Adjusted Life Years (DALY), are calculated as described in a recently proposed COVID-19 disease model (the 'Burden-EU' model) for the calculation of DALY. All-cause mortality data are collected for excess mortality sensitivity analyses. For the calculation of Years lived with disability (YLD), the Burden-EU model is adapted based on recent evidence. Because Covid-19 cases vary in terms of disease severity, the possibility and suitability of applying a uniform severity distribution of cases across all countries and sub-national regions will be explored. An approach recently developed for the Global Burden of Disease Study, that considers post-acute consequences of COVID-19, is likely to be adopted. Findings will be compared to explore the quality and usability of the existing data, to identify trends across age-groups and sexes and to formulate recommendations concerning potential improvements in data availability and quality. DISCUSSION: BoCO-19 serves as a collaborative platform in order to build international capacity for the calculation of burden of disease indicators, and to support national experts in the analysis and interpretation of country-specific data, including their strengths and weaknesses. Challenges include inherent differences in data collection and reporting systems between countries, as well as assumptions that have to be made during the calculation process.

Heat in Germany: Health risks and preventive measures.

Background: Climate change has already led to a significant temperature increase in Germany. The average temperature in the past decade was approximately 2°C above the pre-industrial level and eight of the ten hottest summers since the beginning of systematic weather records in 1881 were recorded in the last 30 years. Methods: Based on a selective literature search and authors' own results, the article summarises the current state of knowledge on heat and its health impacts for Germany, addresses adaptation measures, and gives an outlook on implementation and research questions. Results: Heat can aggravate pre-existing conditions such as diseases of the cardiovascular system, the respiratory tract, or the kidneys and trigger potentially harmful side effects for numerous medications. A significant increase in mortality is regularly observed during heat events. Previous approaches to mitigate the health impact of high temperatures include, for example, the heat alerts of the German Meteorological Service and recommendations for the preparation of heat-health action plans. Conclusions: Evidence on health impacts of heat and awareness of the need for heat-related health protection have grown in recent years, but there is still a need for further action and research.

Collaborative nowcasting of COVID-19 hospitalization incidences in Germany.

Real-time surveillance is a crucial element in the response to infectious disease outbreaks. However, the interpretation of incidence data is often hampered by delays occurring at various stages of data gathering and reporting. As a result, recent values are biased downward, which obscures current trends. Statistical nowcasting techniques can be employed to correct these biases, allowing for accurate characterization of recent developments and thus enhancing situational awareness. In this paper, we present a preregistered real-time assessment of eight nowcasting approaches, applied by independent research teams to German 7-day hospitalization incidences during the COVID-19 pandemic. This indicator played an important role in the management of the outbreak in Germany and was linked to levels of non-pharmaceutical interventions via certain thresholds. Due to its definition, in which hospitalization counts are aggregated by the date of case report rather than admission, German hospitalization incidences are particularly affected by delays and can take several weeks or months to fully stabilize. For this study, all methods were applied from 22 November 2021 to 29 April 2022, with probabilistic nowcasts produced each day for the current and 28 preceding days. Nowcasts at the national, state, and age-group levels were collected in the form of quantiles in a public repository and displayed in a dashboard. Moreover, a mean and a median ensemble nowcast were generated. We find that overall, the compared methods were able to remove a large part of the biases introduced by delays. Most participating teams underestimated the importance of very long delays, though, resulting in nowcasts with a slight downward bias. The accompanying prediction intervals were also too narrow for almost all methods. Averaged over all nowcast horizons, the best performance was achieved by a model using case incidences as a covariate and taking into account longer delays than the other approaches. For the most recent days, which are often considered the most relevant in practice, a mean ensemble of the submitted nowcasts performed best. We conclude by providing some lessons learned on the definition of nowcasting targets and practical challenges.

[Evaluating the introduction of HIV pre-exposure prophylaxis as a benefit of statutory health insurance (EvE-PrEP) : Highly effective protection against HIV without an increase in sexually transmitted infections]. / Evaluation der Einführung der HIV-Präexpositionsprophylaxe als Leistung der gesetzlichen Krankenversicherung (EvE­PrEP) : Hocheffektiver Schutz vor HIV und keine Zunahme von sexuell übertragbaren Infektionen.

BACKGROUND: We investigated the impact of HIV pre-exposure prophylaxis (PrEP) as a new service of the statutory health insurance (SHI) on the incidence of HIV and other sexually transmitted infections (STIs) in Germany. In addition, PrEP needs and access barriers were analyzed. METHODS: The following data were evaluated as part of the evaluation project: HIV and syphilis notification data and extended surveillance by the Robert Koch Institute (RKI), pharmacy prescription data, SHI routine data, PrEP use in HIV-specialty care centers, Checkpoint, the BRAHMS and PrApp studies, as well as a community board. RESULTS: The majority of PrEP users were male (98-99%), primarily aged between 25-45 years, and predominantly of German nationality or origin (67-82%). The majority were men who have sex with men (99%). With regard to HIV infections, PrEP proved to be highly effective. There were only isolated cases of HIV infections (HIV incidence rate 0.08/100 person years); in most cases the suspected reason was low adherence. The incidences of chlamydia, gonorrhea, and syphilis did not increase but remained almost the same or even decreased. A need for information on PrEP for people in trans*/non-binary communities, sex workers, migrants, and drug users emerged. Needs-based services for target groups at increased risk of HIV are necessary. DISCUSSION: PrEP proved to be a very effective HIV prevention method. The partly feared indirect negative influences on STI rates were not confirmed in this study. Due to the temporal overlap with the containment measures during the COVID-19 pandemic, a longer observation period would be desirable for a conclusive assessment.

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.

Analysis of two choir outbreaks acting in concert to characterize long- range transmission risks through SARS-CoV-2, Berlin, Germany, 2020.

BACKGROUND: Superspreading events are important drivers of the SARS-CoV-2 pandemic and long-range (LR) transmission is believed to play a major role. We investigated two choir outbreaks with different attack rates (AR) to analyze the contribution of LR transmission and highlight important measures for prevention. METHODS: We conducted two retrospective cohort studies and obtained demographic, clinical, laboratory and contact data, performed SARS-CoV-2 serology, whole genome sequencing (WGS), calculated LR transmission probabilities, measured particle emissions of selected choir members, and calculated particle air concentrations and inhalation doses. RESULTS: We included 65 (84%) and 42 (100%) members of choirs 1 and 2, respectively, of whom 58 (89%) and 10 (24%) became cases. WGS confirmed strain identity in both choirs. Both primary cases transmitted presymptomatically. Particle emission rate when singing was 7 times higher compared to talking. In choir 1, the median concentration of primary cases' emitted particles in the room was estimated to be 8 times higher, exposure at least 30 minutes longer and room volume smaller than in choir 2, resulting in markedly different estimated probabilities for LR transmission (mode: 90% vs. 16%, 95% CI: 80-95% vs. 6-36%). According to a risk model, the first transmission in choir 1 occurred likely after 8 minutes of singing. CONCLUSIONS: The attack rate of the two choirs differed significantly reflecting the differences in LR transmission risks. The pooled proportion of cases due to LR transmission was substantial (81%; 55/68 cases) and was facilitated by likely highly infectious primary cases, high particle emission rates, and indoor rehearsing for an extended time. Even in large rooms, singing of an infectious person may lead to secondary infections through LR exposure within minutes. In the context of indoor gatherings without mask-wearing and waning or insufficient immunity, these results highlight the ongoing importance of non-pharmaceutical interventions wherever aerosols can accumulate.

SARS-CoV-2 Omicron variants BA.1 and BA.2 both show similarly reduced disease severity of COVID-19 compared to Delta, Germany, 2021 to 2022.

German national surveillance data analysis shows that hospitalisation odds associated with Omicron lineage BA.1 or BA.2 infections are up to 80% lower than with Delta infection, primarily in ≥ 35-year-olds. Hospitalised vaccinated Omicron cases' proportions (2.3% for both lineages) seemed lower than those of the unvaccinated (4.4% for both lineages). Independent of vaccination status, the hospitalisation frequency among cases with Delta seemed nearly threefold higher (8.3%) than with Omicron (3.0% for both lineages), suggesting that Omicron inherently causes less severe disease.

Corrigendum: Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008-2019.

[This corrects the article DOI: 10.3389/fpubh.2021.667253.].

The impact of regional socioeconomic deprivation on the timing of HIV diagnosis: a cross-sectional study in Germany.

BACKGROUND: HIV infections which are diagnosed at advanced stages are associated with significantly poorer health outcomes. In Germany, the proportion of persons living with HIV who are diagnosed at later stages has remained continuously high. This study examined the impact of regional socioeconomic deprivation on the timing of HIV diagnosis. METHODS: We used data from the national statutory notification of newly diagnosed HIV infections between 2011 and 2018 with further information on the timing of diagnosis determined by the BED-Capture-ELISA test (BED-CEIA) and diagnosing physicians. Data on regional socioeconomic deprivation were derived from the German Index of Socioeconomic Deprivation (GISD). Outcome measures were a non-recent infection based on the BED-CEIA result or an infection at the stage of AIDS. The effect of socioeconomic deprivation on the timing of diagnosis was analysed using multivariable Poisson regression models with cluster-robust error variance. RESULTS: Overall, 67.5% (n = 10,810) of the persons were diagnosed with a non-recent infection and 15.2% (n = 2746) with AIDS. The proportions were higher among persons with heterosexual contact compared to men who have sex with men (MSM) (76.8% non-recent and 14.9% AIDS vs. 61.7% non-recent and 11.4% AIDS). MSM living in highly deprived regions in the countryside (< 100 k residents) were more likely to have a non-recent infection (aPR: 1.16, 95% CI: 1.05-1.28) as well as AIDS (aPR: 1.41, 95% CI: 1.08-1.85) at the time of diagnosis compared to MSM in less deprived regions in the countryside. No differences were observed among MSM from towns (100 k ≤ 1 million residents) or major cities (≥ 1 million residents), and no differences overall in the heterosexual transmission group. CONCLUSIONS: An effect of socioeconomic deprivation on the timing of HIV diagnosis was found only in MSM from countryside regions. We suggest that efforts in promoting HIV awareness and regular HIV testing are increased for heterosexual persons irrespective of socioeconomic background, and for MSM with a focus on those living in deprived regions in the countryside.

Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008-2019.

Background: Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Methods: Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Results: Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1-5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Conclusion: Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.

SARS-CoV-2 variant B.1.1.7 susceptibility and infectiousness of children and adults deduced from investigations of childcare centre outbreaks, Germany, 2021.

We investigated three SARS-CoV-2 variant B.1.1.7 childcare centre and related household outbreaks. Despite group cohorting, cases occurred in almost all groups, i.e. also among persons without close contact. Children's secondary attack rates (SAR) were similar to adults (childcare centres: 23% vs 30%; p = 0.15; households: 32% vs 39%; p = 0.27); child- and adult-induced household outbreaks also led to similar SAR. With the advent of B.1.1.7, susceptibility and infectiousness of children and adults seem to converge. Public health measures should be revisited accordingly.

[Monitoring of COVID-19 by extending existing surveillance for acute respiratory infections]. / Überwachung von COVID-19 durch Erweiterung der etablierten Surveillance für Atemwegsinfektionen.

As part of the national influenza pandemic preparedness, surveillance systems have been established in Germany in addition to the mandatory notifications according to the Protection Against Infection Act. The aim of these systems is the description, analysis, and evaluation of the epidemiology of acute respiratory infections (ARIs), the identification of the circulating viruses, and the trend. Since the beginning of the COVID-19 pandemic, the systems have been expanded to enable monitoring of infections with SARS-CoV­2.Three systems are presented: GrippeWeb, the primary care sentinel Arbeitsgemeinschaft Influenza with its electronic reporting module SEEDARE, and the ICD-10-based hospital sentinel ICOSARI. With these systems, ARIs can be monitored at the population, outpatient, and inpatient levels. In combination with the monitoring of mortality, these systems provide important information on the frequency of different stages of disease severity in the population. In order to expand the systems to SARS-CoV­2, only a few adjustments were needed.As the case definitions for ARIs were preserved, historical baselines of the systems can still be used for comparison. All systems are structured in such a way that stable and established reference values are available for calculating weekly proportions and rates.This is an important addition to the mandatory reporting system of infectious diseases in Germany, which depends on the particular testing strategy, the number of tests performed, and on specific case definitions, which are adapted as required.The surveillance systems have proven to be feasible and efficient in the COVID-19 pandemic, even when compared internationally.

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.

Heat-Related Mortality.

BACKGROUND: As a consequence of global warming, heat waves are expected to become more frequent, more intense, and longer. The elderly and persons with chronic diseases are especially vulnerable to health problems due to heat. This article is devoted to the question of the extent to which the effects of heat waves in Germany are changing over time, and whether preventive health measures are working. METHODS: We use a statistical model to quantify the effect of high mean temperatures on mortality. Within this model, different exposure-response curves for the three temporal intervals 1992-2000, 2001-2010, and 2011-2017 are estimated. Attention is also paid to the delayed effect on mortality of high mean temperatures in the preceding week. RESULTS: Our analysis reveals a clear, systematic association of the mean temperature in the current week, as well as the mean temperature in the preceding week, with weekly mortality. This association is more pronounced for higher age groups and decreases over the years under analysis, with the exception of a relatively weak effect of heat in southern Germany in 1992-2000. The strongest effects were related to the heat waves in 1994 and 2003, with approximately 10 200 and 9600 fatalities, respectively. Approximately 7800 fatalities were estimated for the summer of 2006, and 4700 and 5200 for 2010 and 2015, respectively. CONCLUSION: In Germany, as elsewhere, climate change has been causing more frequent, more intense, and longer periods of heat in the summer. The harmful effect of heat on health is reduced by adaptive processes, presumably including successful preventive measures. Such measures should be extended in the future, and perhaps complemented by other measures in order to further diminish the effect of heat on mortality .

Invasive Haemophilus influenzae Infections in Germany After the Introduction of Routine Childhood Immunization, 2001-2016.

BACKGROUND: Haemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001-2016, including serotype distribution and ampicillin resistance. METHODS: Nationwide data from statutory disease surveillance (2001-2016) were linked with laboratory surveillance data (2009-2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends. RESULTS: In 2001-2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups <1 year (15.2) and ≥80 years (15.5). Nontypeable Hi (NTHi) caused 81% (n = 1545) of cases in 2009-2016. Of capsulated cases, 69% were serotype f and 17% serotype b. Of Hib cases eligible for vaccination, 10% (3/29) were fully vaccinated. For 2009-2016, significant increasing trends were observed for NTHi and Hif infections in the age groups <5 years and ≥60 years and for ampicillin resistance in NTHi. CONCLUSIONS: This is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.