The gut microbiome, resistome, and mycobiome in preterm newborn infants and mouse pups: lack of lasting effects by antimicrobial therapy or probiotic prophylaxis.

BACKGROUND: Enhancing our understanding of the underlying influences of medical interventions on the microbiome, resistome and mycobiome of preterm born infants holds significant potential for advancing infection prevention and treatment strategies. We conducted a prospective quasi-intervention study to better understand how antibiotics, and probiotics, and other medical factors influence the gut development of preterm infants. A controlled neonatal mice model was conducted in parallel, designed to closely reflect and predict exposures. Preterm infants and neonatal mice were stratified into four groups: antibiotics only, probiotics only, antibiotics followed by probiotics, and none of these interventions. Stool samples from both preterm infants and neonatal mice were collected at varying time points and analyzed by 16 S rRNA amplicon sequencing, ITS amplicon sequencing and whole genome shotgun sequencing. RESULTS: The human infant microbiomes showed an unexpectedly high degree of heterogeneity. Little impact from medical exposure (antibiotics/probiotics) was observed on the strain patterns, however, Bifidobacterium bifidum was found more abundant after exposure to probiotics, regardless of prior antibiotic administration. Twenty-seven antibiotic resistant genes were identified in the resistome. High intra-variability was evident within the different treatment groups. Lastly, we found significant effects of antibiotics and probiotics on the mycobiome but not on the microbiome and resistome of preterm infants. CONCLUSIONS: Although our analyses showed transient effects, these results provide positive motivation to continue the research on the effects of medical interventions on the microbiome, resistome and mycobiome of preterm infants.

Education and pandemic SARS-CoV-2 infections in the German working population - the mediating role of working from home.

OBJECTIVES: SARS-CoV-2 infections were unequally distributed during the pandemic, with those in disadvantaged socioeconomic positions being at higher risk. Little is known about the underlying mechanism of this association. This study assessed to what extent educational differences in SARS-CoV-2 infections were mediated by working from home. METHODS: We used data of the German working population derived from the seroepidemiological study "Corona Monitoring Nationwide - Wave 2 (RKI-SOEP-2)" (N=6826). Infections were assessed by seropositivity against SARS-CoV-2 antigens and self-reports of previous PCR-confirmed infections from the beginning of the pandemic until study participation (November 2021 - February 2022). The frequency of working from home was assessed between May 2021 and January 2022.We used the Karlson-Holm-Breen (KHB) method to decompose the effect of education on SARS-CoV-2 infections. RESULTS: Individuals with lower educational attainment had a higher risk for SARS-CoV-2 infection (adjusted prevalence ratio of low versus very high = 1.76, 95% confidence interval 1.08-2.88; P=0.023). Depending on the level of education, between 27% (high education) and 58% (low education) of the differences in infection were mediated by the frequency of working from home. CONCLUSIONS: Working from home could prevent SARS-CoV-2 infections and contribute to the explanation of socioeconomic inequalities in infection risks. Wherever possible, additional capacities to work remotely, particularly for occupations that require lower educational attainment, should be considered as an important measure of pandemic preparedness. Limitations of this study are the observational cross-sectional design and that the temporal order between infection and working from home remained unclear.

The Increase in Invasive Bacterial Infections With Respiratory Transmission in Germany, 2022/2023.

BACKGROUND: In late 2022, health care institutions in Germany reported an unusual number of severe, invasive bacterial infections in association with a high incidence of viral respiratory infections. METHODS: We analyzed routine data on invasive infections due to Haemophilus influenzae, Neisseria meningitidis, Staphylococcus aureus, Streptococcus pneumoniae, and Streptococcus pyogenes (2017-2023) from a voluntary, laboratory-based surveillance system involving continuously participating facilities providing diagnostic routine data that cover approximately one-third of the German population. RESULTS: In the first quarter (Q1) of 2023, the number of invasive S. pyogenes isolates rose by 142% (n = 837 vs. mean Q1/2017-2019 = 346, 95% CI [258; 434]), while the number of H. influenzae isolates rose by 90% (n = 209 in Q1/2023 vs. mean Q1/2017-2019 = 110, 95% CI [79; 142]), compared to pre-pandemic seasonal peak values. The number of invasive S. pneumoniae isolates was high in two quarters (n = 1732 in Q4/2022 und Q1/2023). Adults aged 55 and older and children younger than 5 years were most affected by invasive H. influenzae, S. pneumoniae, and S. pyogenes infections. N. meningitidis was most commonly found in children under age 5. CONCLUSION: The reason for the marked rise in invasive bacterial infections may be an increased circulation of respiratory pathogens and elevated susceptibility in the population after relaxation of the measures taken to prevent COVID-19 infection. Coinfections with respiratory viruses may have reinforced this effect. We recommend continuous surveillance, preventive measures such as raising awareness about invasive bacterial diseases, and vaccination as recommended by the German Standing Committee on Vaccinations (STIKO).

Prolonged carriage of OXA-244-carbapenemase-producing Escherichia coli complicates epidemiological investigations.

The rapid increase of OXA-244-producing Escherichia coli, predominantly driven by genetically clustered isolates of sequence type (ST)38, has been observed in at least nine European countries, including Germany. However, the reasons for the spread of OXA-244-producing E. coli remain unclear. Here, we aim to evaluate the possibility of prolonged carriage. We identified a total of six different patients with repeated detection of OXA-244-producing E. coli isolates, which were subjected to both short and long-read whole-genome sequencing (WGS). Besides allelic differences using core genome multilocus sequence typing (cgMLST) analyses, we obtained numbers of single-nucleotide polymorphisms (SNPs) to calculate individual base-pair substitution (BPS) rates. To assess possible re-exposure and risk factors for prolonged carriage, case interviews were conducted. The time between detections ranged from eleven months to more than three years. Initial isolates originated in three+ out of six cases from clinical samples, whereas remaining samples were from screening, mostly in the inpatient setting. As expected, cgMLST analyses showed low numbers of allelic differences between isolates of each case ranging from 1 to 4, whereas numbers of SNPs were between 2 and 99 (mean = 36), thus clearly highlighting the discrepancy between these different bacterial typing approaches. For five out of six cases, observed BPS rates suggest that patients can be colonized with OXA-244-producing E. coli, including ST38 cluster isolates, for extensively long times. Thus, we may have previously missed the epidemiological link between cases because exposure to OXA-244-producing E. coli could have occurred in a time frame, which has not been evaluated in previous investigations. Our results may help to guide future epidemiological investigations as well as to support the interpretation of genetic diversity of OXA-244-producing E. coli, particularly among ST38 cluster isolates.

Antimicrobial resistance in Germany and Europe - A systematic review on the increasing threat accelerated by climate change.

Background: Antimicrobial Resistance (AMR) is one of the top ten global public health threats facing humanity, alongside climate change. Here, we aim to summarise the effects of climate change (i.e. raise of temperature, change in humidity or precipitation) on spread of antibiotic resistance and on infections with antibiotic-resistant bacteria in Germany. Methods: We conducted a literature search with articles published between January 2012 and July 2022. Two authors screened titles, abstracts and full texts and extracted the data systematically. Results: From originally 2,389 titles, we identified six studies, which met our inclusion criteria. These studies show that an increase in temperature may lead to higher antibiotic resistance rates and an increased risk of colonisation as well as spread of pathogens. Furthermore, the number of healthcare-associated infections increases with increased temperature. Data indicate that higher antibiotic use is present in areas with warmer mean temperature. Conclusions: European data are scarce, but all studies identified point towards an increasing AMR burden due to climate change. However, further studies are needed to draw attention to the links between climatic factors and AMR and develop targeted preventive measures.

Catering of high-risk foods and potential of stored food menu data for timely outbreak investigations in healthcare facilities, Italy and Germany.

Healthcare-associated foodborne outbreaks (HA-FBOs) can cause significant morbidity and mortality, affecting particularly vulnerable hospital populations. Electronic records of food served in healthcare facilities (HCFs) could be useful for timely investigations of HA-FBOs. We explored the availability and usability of electronic food menu data to support investigations of HA-FBOs through a survey among 35 HCFs in Germany (n = 13) and in Italy (n = 22). Large variability was reported in the storage time of menu data (from no storage up to 10 years) and their formats, including paper, electronic (PDF, Word, Excel), or fully searchable databases (15/22 in Italian HCFs, 3/13 in German HCFs). Food products that may present a risk to vulnerable persons - including deli salads, raw/fermented sausage products, soft cheese, smoked fish or frozen berries - were offered on the menu of all HCFs in Germany, and one-third of the Italian HCFs. The usability of electronic food menu data for the prevention or investigation of HA-FBOs may be suboptimal in a large number of HCFs in Germany, as well as in some HCFs in Italy. Standardised collection for use of electronic food menu data might help discover the association between illnesses and food eaten during outbreak investigations. Hospital hygienists, food safety and public health authorities should collaborate to increase implementation of food safety guidelines.

Monitoring the SARS-CoV-2 Pandemic: Prevalence of Antibodies in a Large, Repetitive Cross-Sectional Study of Blood Donors in Germany-Results from the SeBluCo Study 2020-2022.

SARS-CoV-2 serosurveillance is important to adapt infection control measures and estimate the degree of underreporting. Blood donor samples can be used as a proxy for the healthy adult population. In a repeated cross-sectional study from April 2020 to April 2021, September 2021, and April/May 2022, 13 blood establishments collected 134,510 anonymised specimens from blood donors in 28 study regions across Germany. These were tested for antibodies against the SARS-CoV-2 spike protein and nucleocapsid, including neutralising capacity. Seroprevalence was adjusted for test performance and sampling and weighted for demographic differences between the sample and the general population. Seroprevalence estimates were compared to notified COVID-19 cases. The overall adjusted SARS-CoV-2 seroprevalence remained below 2% until December 2020 and increased to 18.1% in April 2021, 89.4% in September 2021, and to 100% in April/May 2022. Neutralising capacity was found in 74% of all positive specimens until April 2021 and in 98% in April/May 2022. Our serosurveillance allowed for repeated estimations of underreporting from the early stage of the pandemic onwards. Underreporting ranged between factors 5.1 and 1.1 in the first two waves of the pandemic and remained well below 2 afterwards, indicating an adequate test strategy and notification system in Germany.

Molecular surveillance reveals the emergence and dissemination of NDM-5-producing Escherichia coli high-risk clones in Germany, 2013 to 2019.

BackgroundCarbapenemase-producing Enterobacterales (CPE) are rapidly increasing worldwide, also in Europe. Although prevalence of CPE in Germany is comparatively low, the National Reference Centre for Multidrug-resistant Gram-negative Bacteria noted annually increasing numbers of NDM-5-producing Escherichia coli isolates.AimAs part of our ongoing surveillance programme, we characterised NDM-5-producing E. coli isolates received between 2013 and 2019 using whole genome sequencing (WGS).MethodsFrom 329 identified NDM-5-producing E. coli, 224 isolates from known geographical locations were subjected to Illumina WGS. Analyses of 222 sequenced isolates included multilocus sequence typing (MLST), core genome (cg)MLST and single-nucleotide polymorphism (SNP)-based analyses.ResultsResults of cgMLST revealed genetically distinct clusters for many of the 43 detected sequence types (ST), of which ST167, ST410, ST405 and ST361 predominated. The SNP-based phylogenetic analyses combined with geographical information identified sporadic cases of nosocomial transmission on a small spatial scale. However, we identified large clusters corresponding to clonal dissemination of ST167, ST410, ST405 and ST361 strains in consecutive years in different regions in Germany.ConclusionOccurrence of NDM-5-producing E. coli rose in Germany, which was to a large extent due to the increased prevalence of isolates belonging to the international high-risk clones ST167, ST410, ST405 and ST361. Of particular concern is the supra-regional dissemination of these epidemic clones. Available information suggest community spread of NDM-5-producing E. coli in Germany, highlighting the importance of epidemiological investigation and an integrated surveillance system in the One Health framework.

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices.

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results.

Socioeconomic differences in the reduction of face-to-face contacts in the first wave of the COVID-19 pandemic in Germany.

BACKGROUND: The COVID-19 pandemic has led to physical distancing measures to control the spread of SARS-CoV-2. Evidence on contact dynamics in different socioeconomic groups is still sparse. This study aimed to investigate the association of socioeconomic status with private and professional contact reductions in the first COVID-19 wave in Germany. METHODS: Data from two especially affected municipalities were derived from the population-based cross-sectional seroepidemiological CORONA-MONITORING lokal study (data collection May-July 2020). The study sample (n = 3,637) was restricted to working age (18-67 years). We calculated the association of educational and occupational status (low, medium, high) with self-reported private and professional contact reductions with respect to former contact levels in the first wave of the pandemic. Multivariate Poisson regressions were performed to estimate prevalence ratios (PR) adjusted for municipality, age, gender, country of birth, household size, contact levels before physical distancing measures, own infection status, contact to SARS-CoV-2 infected people and working remotely. RESULTS: The analyses showed significant differences in the initial level of private and professional contacts by educational and occupational status. Less private contact reductions with lower educational status (PR low vs. high = 0,79 [CI = 0.68-0.91], p = 0.002; PR medium vs. high = 0,93 [CI = 0.89-0.97], p = 0.001) and less professional contact reductions with lower educational status (PR low vs. high = 0,87 [CI = 0.70-1.07], p = 0.179; PR medium vs. high = 0,89 [CI = 0.83-0.95], p = 0.001) and lower occupational status (PR low vs. high = 0,62 [CI = 0.55-0.71], p < 0.001; PR medium vs. high = 0,82 [CI = 0.77-0.88], p < 0.001) were observed. CONCLUSIONS: Our results indicate disadvantages for groups with lower socioeconomic status in private and professional contact reductions in the first wave of the pandemic. This may be associated with the higher risk of infection among individuals in lower socioeconomic groups. Preventive measures that a) adequately explain the importance of contact restrictions with respect to varying living and working conditions and b) facilitate the implementation of these reductions especially in the occupational setting seem necessary to better protect structurally disadvantaged groups during epidemics.

Germany's Burden of Disease of Bloodstream Infections Due to Vancomycin-Resistant Enterococcus faecium between 2015-2020.

In Germany, there is an increasing amount of vancomycin-resistant Enterococcus faecium (VREfm) isolates in bloodstream infections (BSIs); however, estimates on recent incidences and disease burden are missing. We aim to estimate the incidence and calculate the annual disease burden in disease-adjusted life years (DALYs) for BSIs due to VREfm in Germany between 2015 and 2020 to support informed decision-making in the field of antimicrobial resistance (AMR). We used the Antibiotic Resistance Surveillance (ARS) system data to obtain incidence estimates. The estimated incidences were used in the Burden of Communicable Disease in Europe (BCoDE) toolkit to calculate the attributable DALYs. A total of 3417 VREfm blood culture-positive isolates were observed within ARS. The estimated incidence of VREfm-BSIs per 100,000 inhabitants increased from 1.4 (95% Uncertainty Interval [UI]: 0.8−1.9) in 2015 to 2.9 (95% UI: 2.4−3.3) in 2020. The estimated burden, expressed in DALYs per 100,000 inhabitants, increased from 8.5 (95% UI: 7.3−9.7; YLD = 0.9, YLL = 7.6) in 2015 to 15.6 (95% UI: 14.6−16.6; YLD = 1.6, YLL = 14) in 2020. The most affected groups within the observed period are the 65−69-year-old males with 262.9 DALYs per 100,000 inhabitants, and in the younger age groups (<30 years), the under-one-year-old with 43.1 DALYs per 100,000 inhabitants and 34.5 DALYs for male and female, respectively. The increasing DALYs of BSIs due to VREfm require targeted prevention and control measures to address their unequal distribution across gender and age, especially for older hospitalized patients, neonates, and infants in Germany.

Nationally representative results on SARS-CoV-2 seroprevalence and testing in Germany at the end of 2020.

Pre-vaccine SARS-CoV-2 seroprevalence data from Germany are scarce outside hotspots, and socioeconomic disparities remained largely unexplored. The nationwide representative RKI-SOEP study (15,122 participants, 18-99 years, 54% women) investigated seroprevalence and testing in a supplementary wave of the Socio-Economic-Panel conducted predominantly in October-November 2020. Self-collected oral-nasal swabs were PCR-positive in 0.4% and Euroimmun anti-SARS-CoV-2-S1-IgG ELISA from dry-capillary-blood antibody-positive in 1.3% (95% CI 0.9-1.7%, population-weighted, corrected for sensitivity = 0.811, specificity = 0.997). Seroprevalence was 1.7% (95% CI 1.2-2.3%) when additionally correcting for antibody decay. Overall infection prevalence including self-reports was 2.1%. We estimate 45% (95% CI 21-60%) undetected cases and lower detection in socioeconomically deprived districts. Prior SARS-CoV-2 testing was reported by 18% from the lower educational group vs. 25% and 26% from the medium and high educational group (p < 0.001, global test over three categories). Symptom-triggered test frequency was similar across educational groups. Routine testing was more common in low-educated adults, whereas travel-related testing and testing after contact with infected persons was more common in highly educated groups. This countrywide very low pre-vaccine seroprevalence in Germany at the end of 2020 can serve to evaluate the containment strategy. Our findings on social disparities indicate improvement potential in pandemic planning for people in socially disadvantaged circumstances.

The Burden of Disease in Germany at the National and Regional Level.

BACKGROUND: .Summary measures such as disability-adjusted life years (DALY) are becoming increasingly important for the standardized assessment of the burden of disease due to death and disability. The BURDEN 2020 pilot project was designed as an independent burden-of-disease study for Germany, which was based on nationwide data, but which also yielded regional estimates. METHODS: DALY is defined as the sum of years of life lost due to death (YLL) and years lived with disability (YLD). YLL is the difference between the age at death due to disease and the remaining life expectancy at this age, while YLD quantifies the number of years individuals have spent with health impairments. Data are derived mainly from causes of death statistics, population health surveys, and claims data from health insurers. RESULTS: In 2017, there were approximately 12 million DALY in Germany, or 14 584 DALY per 100 000 inhabitants. Conditions which caused the greatest number of DALY were coronary heart disease (2321 DALY), low back pain (1735 DALY), and lung cancer (1197 DALY). Headache and dementia accounted for a greater disease burden in women than in men, while lung cancer and alcohol use disorders accounted for a greater disease burden in men than in women. Pain disorders and alcohol use disorders were the leading causes of DALY among young adults of both sexes. The disease burden rose with age for some diseases, including cardiovascular diseases, dementia, and diabetes mellitus. For some diseases and conditions, the disease burden varied by geographical region. CONCLUSION: The results indicate a need for age- and sex-specific prevention and for differing interventions according to geographic region. Burden of disease studies yield comprehensive population health surveillance data and are a useful aid to decision-making in health policy.

Temporal Dynamics of Socioeconomic Inequalities in COVID-19 Outcomes Over the Course of the Pandemic-A Scoping Review.

Objectives: International evidence of socioeconomic inequalities in COVID-19 outcomes is extensive and growing, but less is known about the temporal dynamics of these inequalities over the course of the pandemic. Methods: We systematically searched the Embase and Scopus databases. Additionally, several relevant journals and the reference lists of all included articles were hand-searched. This study follows the PRISMA guidelines for scoping reviews. Results: Forty-six studies were included. Of all analyses, 91.4% showed stable or increasing socioeconomic inequalities in COVID-19 outcomes over the course of the pandemic, with socioeconomically disadvantaged populations being most affected. Furthermore, the study results showed temporal dynamics in socioeconomic inequalities in COVID-19, frequently initiated through higher COVID-19 incidence and mortality rates in better-off populations and subsequent crossover dynamics to higher rates in socioeconomically disadvantaged populations (41.9% of all analyses). Conclusion: The identified temporal dynamics of socioeconomic inequalities in COVID-19 outcomes have relevant public health implications. Socioeconomic inequalities should be monitored over time to enable the adaption of prevention and interventions according to the social particularities of specific pandemic phases.

Controlling an Unprecedented Outbreak with Vancomycin-Resistant Enterococcus faecium in Germany, October 2015 to November 2019.

Hospital outbreaks with vancomycin-resistant enterococci (VRE) pose a serious health threat and a challenge to infection prevention and control (IPC). We herein report on a VRE outbreak of unprecedented extent in Southern Germany (October 2015-November 2019). We used descriptive epidemiology and whole-genome sequencing (WGS) for a detailed outbreak investigation. Of the 2905 cases, 2776 (95.3%) were colonized, whereas from 127 (3.7%), VRE could be isolated from otherwise sterile body fluids or sites unlikely for enterococci colonization. Cases had a median age of 78 years (IQR 68-84) and 1339/2905 (46%) were female. The majority of isolates sequenced belonged to the clonal lineage ST80/CT1013 (212/397, 53%). Nosocomial transmission was observed as well as the constant import of VRE into the hospital. Extensive IPC measures were implemented and terminated the outbreak in late 2019, eventually. Our study shows that the combination of epidemiological and genomic analyses is indispensable for comprehensive outbreak investigations. The adaptation of IPC measures to these findings, their timely implementation, and strict execution also allow containment of large VRE outbreaks in hospital settings.

Combined Clinical, Epidemiological, and Genome-Based Analysis Identified a Nationwide Outbreak of Burkholderia cepacia Complex Infections Caused by Contaminated Mouthwash Solutions.

Background: In September 2018, Burkholderia cepacia complex (BCC) infections in 3 patients associated with exposure to a mouthwash solution (MWS) were reported to the Robert Koch Institute (RKI). As the product was still on the market and the scale of the outbreak was unclear, a nation-wide investigation was initiated. Methods: We aimed to investigate BCC infections/colonizations associated with MWS. Hospitals, laboratories, and public health services were informed that BCC isolates should be sent to the RKI. These isolates were typed by pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) including development of an ad hoc core genome MLST (cgMLST) scheme. Results: In total, 36 patients from 6 hospitals met the case definition, the last patient in November 2018. Twenty-nine isolates from 26 of these patients were available for typing. WGS analysis revealed 2 distinct cgMLST clusters. Cluster 1 (Burkholderia arboris) contained isolates from patients and MWS obtained from 4 hospitals and isolates provided by the manufacturer. Patient and MWS isolates from another hospital were assigned to cluster 2 (B. cepacia). Conclusions: The combined clinical, epidemiological, and microbiological investigation, including whole-genome analysis, allowed for uncovering a supraregional BCC outbreak in health care settings. Strains of B. arboris and B. cepacia were identified as contaminating species of MWS bottles and subsequent colonization and putative infection of patients in several hospitals. Despite a recall of the product by the manufacturer in August 2018, the outbreak lasted until December 2018. Reporting of contaminated medical products and recalls should be optimized to protect patients.

SARS-CoV-2 outbreaks in hospitals and long-term care facilities in Germany: a national observational study.

BACKGROUND: Outbreaks of coronavirus disease (COVID-19) in hospitals and long-term care facilities (LTCFs) pose serious public health threats. We analysed how frequency and size of SARS-CoV-2 outbreaks in hospitals and LTCFs have altered since the beginning of the pandemic, in particular since the start of the vaccination campaign. METHODS: We used mandatory notification data on SARS-CoV-2 cases in Germany and stratified by outbreak cases in hospitals and LTCFs. German vaccination coverage data were analysed. We studied the association of the occurrence of SARS-CoV-2 outbreaks and outbreak cases with SARS-CoV-2 cases in Germany throughout the four pandemic waves. We built also counterfactual scenarios with the first pandemic wave as the baseline. FINDINGS: By 21 September 2021, there were 4,147,387 SARS-CoV-2 notified cases since March 2020. About 20% of these cases were reported as being related to an outbreak, with 1% of the cases in hospitals and 4% in LTCFs. The median number of outbreak cases in the different phases was smaller (≤5) in hospitals than in LTCFs (>10). In the first and second pandemic waves, we observed strong associations in both facility types between SARS-CoV-2 outbreak cases and total number of notified SARS-CoV-2 cases. However, during the third pandemic wave we observed a decline in outbreak cases in both facility types and only a weak association between outbreak cases and all cases. INTERPRETATION: The vaccination campaign and non-pharmaceutical interventions have been able to protect vulnerable risk groups in hospitals and LTCFs. FUNDING: No specific funding.