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Background: Estimates of the severity of the SARS-CoV-2 omicron variant (B.1.1.529) are crucial to assess the public health impact associated with its rapid global dissemination. We estimated the risk of SARS-CoV-2-related hospitalisations after infection with omicron compared with the delta variant (B.1.617.2) in Denmark, a country with high mRNA vaccination coverage and extensive free-of-charge PCR testing capacity. Methods: In this observational cohort study, we included all RT-PCR-confirmed cases of SARS-CoV-2 infection in Denmark, with samples taken between Nov 21 (date of first omicron-positive sample) and Dec 19, 2021. Individuals were identified in the national COVID-19 surveillance system database, which included results of a variant-specific RT-PCR that detected omicron cases, and data on SARS-CoV-2-related hospitalisations (primary outcome of the study). We calculated the risk ratio (RR) of hospitalisation after infection with omicron compared with delta, overall and stratified by vaccination status, in a Poisson regression model with robust SEs, adjusted a priori for reinfection status, sex, age, region, comorbidities, and time period. Findings: Between Nov 21 and Dec 19, 2021, among the 188 980 individuals with SARS-CoV-2 infection, 38 669 (20·5%) had the omicron variant. SARS-CoV-2-related hospitalisations and omicron cases increased during the study period. Overall, 124 313 (65·8%) of 188 980 individuals were vaccinated, and vaccination was associated with a lower risk of hospitalisation (adjusted RR 0·24, 95% CI 0·22–0·26) compared with cases with no doses or only one dose of vaccine. Compared with delta infection, omicron infection was associated with an adjusted RR of hospitalisation of 0·64 (95% CI 0·56–0·75; 222 [0·6%] of 38 669 omicron cases admitted to hospital vs 2213 [1·5%] of 150 311 delta cases). For a similar comparison by vaccination status, the RR of hospitalisation was 0·57 (0·44–0·75) among cases with no or only one dose of vaccine, 0·71 (0·60–0·86) among those who received two doses, and 0·50 (0·32–0·76) among those who received three doses. Interpretation: We found a significantly lower risk of hospitalisation with omicron infection compared with delta infection among both vaccinated and unvaccinated individuals, suggesting an inherent reduced severity of omicron. Our results could guide modelling of the effect of the ongoing global omicron wave and thus health-care system preparedness. Funding: None.

Summary Background The degree to which infection with SARS-CoV-2 confers protection towards subsequent reinfection is not well described. In 2020, as part of Denmark's extensive, free-of-charge PCR-testing strategy, approximately 4 million individuals (69% of the population) underwent 10·6 million tests. Using these national PCR-test data from 2020, we estimated protection towards repeat infection with SARS-CoV-2. Methods In this population-level observational study, we collected individual-level data on patients who had been tested in Denmark in 2020 from the Danish Microbiology Database and analysed infection rates during the second surge of the COVID-19 epidemic, from Sept 1 to Dec 31, 2020, by comparison of infection rates between individuals with positive and negative PCR tests during the first surge (March to May, 2020). For the main analysis, we excluded people who tested positive for the first time between the two surges and those who died before the second surge. We did an alternative cohort analysis, in which we compared infection rates throughout the year between those with and without a previous confirmed infection at least 3 months earlier, irrespective of date. We also investigated whether differences were found by age group, sex, and time since infection in the alternative cohort analysis. We calculated rate ratios (RRs) adjusted for potential confounders and estimated protection against repeat infection as 1 – RR. Findings During the first surge (ie, before June, 2020), 533 381 people were tested, of whom 11 727 (2·20%) were PCR positive, and 525 339 were eligible for follow-up in the second surge, of whom 11 068 (2·11%) had tested positive during the first surge. Among eligible PCR-positive individuals from the first surge of the epidemic, 72 (0·65% [95% CI 0·51–0·82]) tested positive again during the second surge compared with 16 819 (3·27% [3·22–3·32]) of 514 271 who tested negative during the first surge (adjusted RR 0·195 [95% CI 0·155–0·246]). Protection against repeat infection was 80·5% (95% CI 75·4–84·5). The alternative cohort analysis gave similar estimates (adjusted RR 0·212 [0·179–0·251], estimated protection 78·8% [74·9–82·1]). In the alternative cohort analysis, among those aged 65 years and older, observed protection against repeat infection was 47·1% (95% CI 24·7–62·8). We found no difference in estimated protection against repeat infection by sex (male 78·4% [72·1–83·2] vs female 79·1% [73·9–83·3]) or evidence of waning protection over time (3–6 months of follow-up 79·3% [74·4–83·3] vs ≥7 months of follow-up 77·7% [70·9–82·9]). Interpretation Our findings could inform decisions on which groups should be vaccinated and advocate for vaccination of previously infected individuals because natural protection, especially among older people, cannot be relied on. Funding None.

Denmark hosted four games during the 2020 UEFA European championships (EC2020). After declining positive SARS-CoV-2 test rates in Denmark, a rise occurred during and after the tournament, concomitant with the replacement of the dominant Alpha lineage (B.1.1.7) by the Delta lineage (B.1.617.2), increasing vaccination rates and cessation of several restrictions. A cohort study including 33 227 cases was conducted from 30 May to 25 July 2021, 14 days before and after the EC2020. Included was a nested cohort with event information from big-screen events and matches at the Danish national stadium, Parken (DNSP) in Copenhagen, held from 12 June to 28 June 2021. Information from whole-genome sequencing, contact tracing and Danish registries was collected. Case–case connections were used to establish transmission trees. Cases infected on match days were compared to cases not infected on match days as a reference. The crude incidence rate ratio (IRR) of transmissions was 1.55, corresponding to 584 (1.76%) cases attributable to EC2020 celebrations. The IRR adjusted for covariates was lower (IRR 1.41) but still significant, and also pointed to a reduced number of transmissions from fully vaccinated cases (IRR 0.59). These data support the hypothesis that the EC2020 celebrations contributed to the rise of cases in Denmark in the early summer of 2021.

Background: The more infectious SARS-CoV-2 lineage B.1.1.7 rapidly spread in Europe after December, 2020, and a concern that B.1.1.7 could cause more severe disease has been raised. Taking advantage of Denmark's high RT-PCR testing and whole genome sequencing capacities, we used national health register data to assess the risk of COVID-19 hospitalisation in individuals infected with B.1.1.7 compared with those with other SARS-CoV-2 lineages. Methods: We did an observational cohort study of all SARS-CoV-2-positive cases confirmed by RT-PCR in Denmark, sampled between Jan 1 and March 24, 2021, with 14 days of follow-up for COVID-19 hospitalisation. Cases were identified in the national COVID-19 surveillance system database, which includes data from the Danish Microbiology Database (RT-PCR test results), the Danish COVID-19 Genome Consortium, the National Patient Registry, the Civil Registration System, as well as other nationwide registers. Among all cases, COVID-19 hospitalisation was defined as first admission lasting longer than 12 h within 14 days of a sample with a positive RT-PCR result. The study population and main analysis were restricted to the proportion of cases with viral genome data. We calculated the risk ratio (RR) of admission according to infection with B.1.1.7 versus other co-existing lineages with a Poisson regression model with robust SEs, adjusted a priori for sex, age, calendar time, region, and comorbidities. The contribution of each covariate to confounding of the crude RR was evaluated afterwards by a stepwise forward inclusion. Findings: Between Jan 1 and March 24, 2021, 50 958 individuals with a positive SARS-CoV-2 test and at least 14 days of follow-up for hospitalisation were identified; 30 572 (60·0%) had genome data, of whom 10 544 (34·5%) were infected with B.1.1.7. 1944 (6·4%) individuals had a COVID-19 hospitalisation and of these, 571 (29·4%) had a B.1.1.7 infection and 1373 (70·6%) had an infection with other SARS-CoV-2 lineages. Although the overall number of hospitalisations decreased during the study period, the proportion of individuals infected with B.1.1.7 increased from 3·5% to 92·1% per week. B.1.1.7 was associated with a crude RR of hospital admission of 0·79 (95% CI 0·72–0·87; p

The COVID-19 pandemic has led to an unprecedented demand for real-time surveillance data in order to inform critical decision makers regarding the management of the pandemic. The aim of this review was to describe how the Danish national microbiology database, MiBa, served as a cornerstone for providing data to the real-time surveillance system by linkage to other nationwide health registries. The surveillance system was established on an existing IT health infrastructure and a close network between clinical microbiologists, information technology experts, and public health officials. In 2020, testing capacity for SARS-CoV-2 was ramped up from none to over 10,000 weekly PCR tests per 100,000 population. The crude incidence data mirrored this increase in testing. Real-time access to denominator data and patient registries enabled adjustments for fluctuations testing activity, providing robust data on crude SARS-CoV-2 incidence during the changing diagnostic and management strategies. The use of the same data for different purposes, for example, final laboratory reports, information to the public, contact tracing, public health, and science, has been a critical asset for the pandemic response. It has also raised issues concerning data protection and critical capacity of the underlying technical systems and key resources. However, even with these limitations, the setup has enabled decision makers to adopt timely interventions. The experiences from COVID-19 may motivate a transformation from traditional indicator-based public health surveillance to an all-encompassing information system based on access to a comprehensive set of data sources, including diagnostic and reference microbiology.

Background: The degree to which infection with SARS-CoV-2 confers immunity towards subsequent infection is not yet known. In 2020, as part of Denmark’s extensive, free-of-charge PCR-testing strategy, 4 million individuals (69% of the population) underwent 10.6 million tests. Using these national PCR-test data from 2020, we estimated the natural immunity towards SARS-CoV-2 after infection and investigated differences by age, sex and time since infection. Methods: Analysing the second surge of the epidemic (September–December, 2020) we compared infection rates between those with and without a previous positive test from the first surge (March–May). In an alternative time-to-event analysis, we compared infection rates throughout the year between those with and without a previous confirmed infection three or more months earlier. Rate ratios were adjusted for potential cofounders and natural immunity was estimated as one minus the rate ratio. Findings: Among PCR positive individuals from the first surge, 0·65% tested positive again during the second surge compared with 3·3% without a previous infection. The natural immunity was 80·5% (95% CI 75·4–84·5). The time-to-event analysis gave a similar estimate, as did the use of two and four months’ separation between repeat positive tests, and limiting the cohort to frequently tested health staff only. Among those aged 65+ years, observed immunity was 47% (95% CI 24·7–62·8). There was no difference in immunity by sex or evidence of waning immunity over time. Interpretation: Person-identifiable test results from large scale national PCR-testing in Denmark suggest that the within-season immunity following symptomatic or non-symptomatic infection is around 80%, although significantly lower in the elderly. These findings may inform decisions of which groups to vaccinate and advocate for vaccination of previously infected individuals as natural protection among elderly citizens cannot be relied upon. Funding: No designated funding was received for this study. DM was funded by the European Centers for Disease Control and Prevention programme EUPHEM. Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: The present study was based on existing administrative data and did not require ethical approval.

Background: The more infectious SARS-CoV-2 virus lineage B.1.1.7, rapidly spread in Europe after December 2020, and a concern of B.1.1.7 causing more severe disease has been raised. Denmark has one of Europe´s highest capacities per capita of SARS-CoV-2 reverse transcription polymerase chain reaction (RT PCR) test and whole genome sequencing (WGS). We used national health register-data to explore whether B.1.1.7 increases the risk of COVID-19 hospitalisation. Methods and Findings: In an observational cohort study we included all SARS-CoV-2 RT PCR test-positive individuals in Denmark sampled between the 1st January and until the 9th February, 2021, identified in the national COVID-19 surveillance system. The surveillance system includes national individual RT PCR test results and viral WGS analyses and data from national health registers including COVID-19 related hospital admissions defined as first admission within 14 days of the test-positive swab. The odds ratio (OR) of admission according to infection with B.1.1.7, vs other co-existing lineages, was calculated in a logistic regression model adjusted for sex, age, period, follow-up time less than 14 days, region, and comorbidities. A total of 35,887 test-positive individuals were identified, 23,057 (64%) had WGS performed, of whom 18,499 (80%) resulted in a viral genome and a total of 2,155 of these were lineage B.1.1.7. The proportion of individuals with B.1.1.7 increased from 4% in early January to 45% in early February. Among the individuals with viral genome data, B.1.1.7 was associated with a crude OR of admission of 0.87 (95%CI, 0.72-1.05) and an adjusted OR of 1.64 (95%CI, 1.32-2.04) based on 128 admissions after B.1.1.7 infection and 1,107 admissions after infection with other lineages. The adjusted OR was increased in all strata of age and calendar time - the two most important confounders of the crude OR. Conclusions: Infection with lineage B.1.1.7 was associated with an increased risk of hospitalisation compared with other lineages. This finding may have serious public health impact in countries with spread of B.1.1.7 and can support hospital preparedness and modelling of projected impact of the epidemic. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: The authors declare that they have no competing interest. Ethics Approval Statement: This study was conducted on administrative register data. According to Danish law, ethics approval is not needed for such research.

PRAISE network: Maaike S. M. van Mourik, Stephanie M.van Rooden, Mohamed Abbas, Olov Aspevall, Pascal Astagneau, Marc J. M. Bonten, Elena Carrara, Aina Gomila-Grange, Sabine C. de Greeff , Sophie Gubbels, Wendy Harrison, Hilary Humphreys, Anders Johansson, Mayke B. G. Koek, Brian Kristensen, Alain Lepape, Jean-Christophe Lucet, Siddharth Mookerjee, Pontus Naucler, Zaira R. Palacios-Baena, Elisabeth Presterl, Miquel Pujol, Jacqui Reilly, Christopher Roberts, Evelina Tacconelli, Daniel Teixeira, Thomas Tängdén, John Karlsson Valik, Michael Behnke, PetraGastmeier., [Introduction] Healthcare-associated infections (HAI) are a major public health concern. Monitoring of HAI rates, with feedback, is a core component of infection prevention and control programmes. Digitalization of healthcare data has created novel opportunities for automating the HAI surveillance process to varying degrees. However, methods are not standardized and vary widely between different healthcare facilities. Most current automated surveillance (AS) systems have been confined to local settings, and practical guidance on how to implement large-scale AS is needed., [Methods] This document was written by a task force formed in March 2019 within the PRAISE network (Providing a Roadmap for Automated Infection Surveillance in Europe), gathering experts in HAI surveillance from ten European countries., [Results] The document provides an overview of the key e-health aspects of implementing an AS system of HAI in a clinical environment to support both the infection prevention and control team and information technology (IT) departments. The focus is on understanding the basic principles of storage and structure of healthcare data, as well as the general organization of IT infrastructure in surveillance networks and participating healthcare facilities. The fundamentals of data standardization, interoperability and algorithms in relation to HAI surveillance are covered. Finally, technical aspects and practical examples of accessing, storing and sharing healthcare data within a HAI surveillance network, as well as maintenance and quality control of such a system, are discussed., [Conclusions] With the guidance given in this document, along with the PRAISE roadmap and governance documents, readers will find comprehensive support to implement large-scale AS in a surveillance network., This network has been supported under the 7th transnational call within the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), Network Call on Surveillance (2018) and was thereby funded by ZonMw (grant 549007001). This project also received support from the COMBACTE MAGNET EPI-Net project funded by the Innovative Medicines Initiative Joint Undertaking under grant agreement 115523 | 115620 | 115737 | 777362, resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. J.K.V. was supported by grants from Region Stockholm and Vinnova.

ObjectiveTo provide population-level knowledge on individuals at high risk of severe and fatal coronavirus disease 2019 (COVID-19) in order to inform targeted protection strategies in the general population and appropriate triage of hospital contacts.Design, Setting, and ParticipantsNationwide population-based cohort of all 228.677 consecutive Danish individuals tested (positive or negative) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from the identification of the first COVID-19 case on February 27th, 2020 until April 30th, 2020.Main Outcomes and MeasuresWe examined characteristics and predictors of inpatient hospitalization versus community-management, and death versus survival, adjusted for age-, sex- and number of comorbidities.ResultsWe identified 9,519 SARS-CoV-2 PCR-positive cases of whom 78% were community-managed, 22% were hospitalized (3.2% at an intensive care unit) and 5.5% had died within 30 days. Median age varied from 45 years (interquartile range (IQR) 31-57) among community-managed cases to 82 years (IQR 7589) among those who died. Age was a strong predictor of fatal disease (odds ratio (OR) 14 for 70-79-year old, OR 26 for 80-89-year old, and OR 82 for cases older than 90 years, when compared to 50-59-year old and adjusted for sex and number of comorbidities). Similarly, the number of comorbidities was strongly associated with fatal disease (OR 5.2, for cases with ≥4 comorbidities versus no comorbidities), and 82% of fatal cases had at least 2 comorbidities. A wide range of major chronic diseases were associated with hospitalization with ORs ranging from 1.3-1.4 (e.g. stroke, ischemic heart disease) to 2.2-2.7 (e.g. heart failure, hospital-diagnosed kidney disease, chronic liver disease). Similarly, chronic diseases were associated with mortality with ORs ranging from 1.2-1.3 (e.g. ischemic heart disease, hypertension) to 2.4-2.7 (e.g. major psychiatric disorder, organ transplantation). In the absence of comorbidities, mortality was relatively low (5% or less) in persons aged up to 80 years.Conclusions and RelevanceIn this first nationwide population-based study, increasing age and number of comorbidities were strongly associated with hospitalization requirement and death in COVID-19. In the absence of comorbidities, the mortality was, however, lowest until the age of 80 years. These results may help in accurate identification, triage and protection of high-risk groups in general populations, i.e. when reopening societies.

SUMMARYThe surveillance of Clostridium difficile (CD) in Denmark consists of laboratory based data from Departments of Clinical Microbiology (DCMs) sent to the National Registry of Enteric Pathogens (NREP). We validated a new surveillance system for CD based on the Danish Microbiology Database (MiBa). MiBa automatically collects microbiological test results from all Danish DCMs. We built an algorithm to identify positive test results for CD recorded in MiBa. A CD case was defined as a person with a positive culture for CD or PCR detection of toxin A and/or B and/or binary toxin. We compared CD cases identified through the MiBa-based surveillance with those reported to NREP and locally in five DCMs representing different Danish regions. During 2010–2014, NREP reported 13 896 CD cases, and the MiBa-based surveillance 21 252 CD cases. There was a 99·9% concordance between the local datasets and the MiBa-based surveillance. Surveillance based on MiBa was superior to the current surveillance system, and the findings show that the number of CD cases in Denmark hitherto has been under-reported. There were only minor differences between local data and the MiBa-based surveillance, showing the completeness and validity of CD data in MiBa. This nationwide electronic system can greatly strengthen surveillance and research in various applications.

BACKGROUNDIn 2015, Denmark launched an automated surveillance system for hospital-acquired infections, the Hospital-Acquired Infections Database (HAIBA).OBJECTIVETo describe the algorithm used in HAIBA, to determine its concordance with point prevalence surveys (PPSs), and to present trends for hospital-acquired bacteremiaSETTINGPrivate and public hospitals in DenmarkMETHODSA hospital-acquired bacteremia case was defined as at least 1 positive blood culture with at least 1 pathogen (bacterium or fungus) taken between 48 hours after admission and 48 hours after discharge, using the Danish Microbiology Database and the Danish National Patient Registry. PPSs performed in 2012 and 2013 were used for comparison.RESULTSNational trends showed an increase in HA bacteremia cases between 2010 and 2014. Incidence was higher for men than women (9.6 vs 5.4 per 10,000 risk days) and was highest for those aged 61–80 years (9.5 per 10,000 risk days). The median daily prevalence was 3.1% (range, 2.1%–4.7%). Regional incidence varied from 6.1 to 8.1 per 10,000 risk days. The microorganisms identified were typical for HA bacteremia. Comparison of HAIBA with PPS showed a sensitivity of 36% and a specificity of 99%. HAIBA was less sensitive for patients in hematology departments and intensive care units. Excluding these departments improved the sensitivity of HAIBA to 44%.CONCLUSIONSAlthough the estimated sensitivity of HAIBA compared with PPS is low, a PPS is not a gold standard. Given the many advantages of automated surveillance, HAIBA allows monitoring of HA bacteremia across the healthcare system, supports prioritizing preventive measures, and holds promise for evaluating interventions.Infect Control Hosp Epidemiol 2017;38:559–566

To the editor: We thank Wim van der Hoek and colleagues for their interest in our work [1] and for sharing the preliminary data on influenza vaccine effectiveness (VE) for the 2012/13 season in the Netherlands. When we wrote our article, we emphasised that the findings were based on analysis of data from elderly people mainly admitted to hospital. We cannot make any inference as regards VE among younger, unselected individuals seen in primary healthcare. However, the main public health objective with the influenza vaccination campaign is to prevent morbidity and premature mortality among the frail and the elderly. With this in mind, our observations do have relevance.

Our aim was to determine the frequency of 12 common respiratory viruses in patients admitted to intensive care units with respiratory symptoms, evaluate the clinical characteristics and to compare the results to routine microbiological diagnostics. Throat swabs from 122 intensive care-patients >18 years with acute respiratory symptoms were collected upon admission and analysed with multiplex real-time polymerase chain reaction, for 12 community respiratory viruses. Blood and respiratory tract specimens were analysed for bacteria and fungi upon clinicians' request. Clinical and paraclinical data were collected. Viruses were detected in 19 (16%) of the 122 study patients. Five virus-positive patients (26%) had possible clinically relevant bacteria or fungi co-detected. Patients with exacerbation in COPD were associated with a viral infection (p = 0.02). Other comorbidities, clinical and paraclinical parameters, and death were independent of a viral infection or co-detection of bacteria/fungi. In conclusion, respiratory viruses were frequently detected in the patients. The investigated clinical and paraclinical parameters were not different in viral infections compared to other agents, thus respiratory viruses likely have similar impact on the clinical course as other agents. In 25% of the virus-positive patients, polymicrobial aetiology was identified. Comprehensive and sensitive diagnostic methods should be emphasized to enhance respiratory diagnostics.

Based on Kuhn et al. (2012), this chapter describes the course and investigation of a large Danish foodborne outbreak in 2010, caused by a rare Salmonella Typhimurium phage type with the majority of patients residing in the eastern and southern parts of Denmark. It describes the interview studies conducted and the changes in the Salmonella subtypes and human demography during the outbreak. It also suggests interpretations of these changes. Comprehensive Danish register data on herds, slaughterhouses and Salmonella surveillance were utilized for the tracing of products and herds and for assessing the risks of herds, slaughterhouses and meat production plants being the source of infection in the outbreak.

Objective: The objective of this study was to describe the clinical course of severe and complicated pandemic (H1N1)v infection treated with oral oseltamivir and inhaled zanamivir in a series of intensive care patients. Methods: We investigated a case series of patients with respiratory failure and a positive (H1N1)v real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Treatment consisted of oseltamivir tablets 75 mg × 4 daily in a nasogastric tube plus zanamivir intravenous (i.v.) solution 25 mg × 4 daily as inhalation. Ventilator inspiratory plateau airway pressure in the ventilator was kept below 30 cmH(2)O, PaO(2) above 8 kPa and pH above 7.30. If this could not be achieved, inhalational nitric oxide (NO) was added or extracorporeal membrane oxygenation (ECMO) was initiated. Results: Twenty-one patients were admitted, with a median age of 50 y (range 6-69 y). Five patients (23.8%) died in the intensive care unit (ICU) and 1 patient died 2 weeks after ICU discharge. Nine patients received ECMO treatment, of whom 3 died during ECMO (33.3%; 3/9) and 1 at 2 weeks after. The mortality in patients not receiving ECMO treatment was 16.6% (2/12). Sixteen patients (76%) were influenza PCR-positive on day 7 after the start of antiviral treatment. Irreversible presumed lung fibrosis complicated with pneumothorax was common. A high Murray score at admission was significantly associated with a fatal outcome. Conclusions: The mortality in these patients was high despite combined antiviral treatment with oseltamivir and zanamivir. Patients shed virus for a long time despite intensive therapy. Optimal management of patients with bilateral pneumonia and respiratory failure caused by (H1N1)v still needs to be determined.

Surveillance of 2009 pandemic influenza A(H1N1) in Denmark was enhanced during the 2009–10 winter season with a system monitoring the burden of the pandemic on intensive care units (ICUs), in order to inform policymakers and detect shortages in ICUs in a timely manner. Between week 46 of 2009 and week 11 of 2010, all 36 relevant Danish ICUs reported in two ways: aggregate data were reported online and case-based data on paper. Cases to be reported were defined as patients admitted to an ICU with laboratory-confirmed 2009 pandemic influenza A(H1N1) infection or clinically suspected illness after close contact with a laboratory-confirmed case. Aggregate numbers of cases were reported weekly: during weeks 48-51 (the peak), reporting was daily. The case-based reports contained demographic and clinical information. The aggregate surveillance registered 93 new cases, the case-based surveillance 61, of whom 53 were laboratory confirmed. The proportion of beds used for influenza patients did not exceed 4.5% of the national capacity. Hospitals with cases used a median of 11% of bed capacity (range: 3–40%). Of the patients for whom information was available, 15 of 48 patients developed renal insufficiency, 19 of 50 developed septic shock and 17 of 53 died. The number of patients with pandemic influenza could be managed within the national bed capacity, although the impact on some ICUs was substantial. The combination of both reporting methods (collecting aggregate and case-based data) proved to be useful for monitoring the burden of the pandemic on ICUs.

We analysed Danish surveillance data to estimate influenza-associated morbidity and mortality in 2009. To obtain population-based estimates of the clinical attack rate, we combined data from two different primary health care surveillance systems, national numbers of the proportion of positive influenza tests, and data from a web-based interview on health care seeking behaviour during the pandemic. From a national registry, we obtained data on hospital admissions (ICD-10 codes) for influenza related conditions. Admission to intensive care was monitored by a dedicated surveillance scheme. Mortality was estimated among laboratory confirmed cases but was also expressed as excess all-cause mortality attributed to influenza-like illness in a multivariable time series analysis. In total, we estimated that 274,000 individuals (5%) in Denmark experienced clinical illness. The highest attack rate was found in children 5–14 years (15%). Compared with the expected number of hospital admissions, there was an 80% increase in number of influenza related hospital admissions in this age group. The numbers of patients admitted to intensive care approached 5% of the national capacity. Estimates of the number of deaths ranged from 30 to 312 (0.5–5.7 per 100,000 population) depending on the methodology. In conclusion, the pandemic was characterised by high morbidity and unprecedented high rates of admissions to hospitals for a range of influenza-related conditions affecting mainly children. Nonetheless, the burden of illness was lower than assumed in planning scenarios, and the present pandemic compares favourable with the 20th century pandemics.

The immune response against human adenovirus (HAdV) has gained interest because of the application of HAdV-based vectors in gene therapy and the high incidence of infections in pediatric recipients of allogeneic stem cell grafts. Because antiviral medication is frequently ineffective, the option of adoptive transfer of HAdV-specific donor-derived T cells in these immunocompromised patients is investigated. To generate good manufacturing practice-compatible reagents, a panel of 63 long, overlapping, peptides of the hexon protein was screened for recognition by T cells. Five conserved peptides of 30 amino acids were identified that were recognized by the majority of adult donors. CD4+ T cells from long-term cultures of PBMC, stimulated with this set of five peptides, recognized cells infected with HAdV serotypes belonging to different species. These data demonstrate that adult human T cells preferentially recognize conserved sequences of amino acid residues from a structural protein of HAdV. In the context of gene therapy, this observation may limit the beneficial effect of switching to HAdV-based vectors derived from less common serotypes of HAdV in an attempt to circumvent pre-existing immunity. However, this cross-reactivity benefits the application of HAdV-specific T cells for adoptive immunotherapy in immunocompromised transplant recipients.

National surveillance of Clostridium Difficile (CD) is currently performed in two ways in Denmark: by the Enteropathogen Registry (TBR) for all CD culture positive samples (reported from clinical microbiology laboratories), and since 2009 by a specific CD027 Registry with mandatory submission of CD strains for further characterization.