Estimates of mortality attributable to COVID-19: a statistical model for monitoring COVID-19 and seasonal influenza,Denmark, spring 2020

BackgroundTimely monitoring of COVID-19 impact on mortality is critical for rapid risk assessment and public health action.AimBuilding upon well-established models to estimate influenza-related mortality, we propose a new statistical Attributable Mortality Model (AttMOMO), which estimates mortality attributable to one or more pathogens simultaneously (e.g. SARS-CoV-2 and seasonal influenza viruses), while adjusting for seasonality and excess temperatures.MethodsData from Nationwide Danish registers from 2014-week(W)W27 to 2020-W22 were used to exemplify utilities of the model, and to estimate COVID-19 and influenza attributable mortality from 2019-W40 to 2020-W20.ResultsSARS-CoV-2 was registered in Denmark from 2020-W09. Mortality attributable to COVID-19 in Denmark increased steeply, and peaked in 2020-W14. As preventive measures and national lockdown were implemented from 2020-W12, the attributable mortality started declining within a few weeks. Mortality attributable to COVID-19 from 2020-W09 to 2020-W20 was estimated to 16.2 (95% confidence interval (CI): 12.0 to 20.4) per 100,000 person-years. The 2019/20 influenza season was mild with few deaths attributable to influenza, 3.2 (95% CI: 1.1 to 5.4) per 100,000 person-years.ConclusionAttMOMO estimates mortality attributable to several pathogens simultaneously, providing a fuller picture of mortality by COVID-19 during the pandemic in the context of other seasonal diseases and mortality patterns. Using Danish data, we show that the model accurately estimates mortality attributable to COVID-19 and influenza, respectively. We propose using standardised indicators for pathogen circulation in the population, to make estimates comparable between countries and applicable for timely monitoring.     

Incidence,circulation, and spatiotemporal analysis of seasonal influenza in Shandong,China, 2008–2019: A retrospective study

BackgroundUnderstanding the influenza‐like illness (ILI) incidence, circulation pattern of virus strains and spatiotemporal pattern of influenza transmission are important for designing control interventions. Based on the 10 years'' surveillance data, we aimed to provide a baseline characterization and the epidemiology and dynamics of influenza virus in Shandong.MethodsWe extracted surveillance and laboratory testing data. We estimated the ILI incidence and analyzed the predominant virus. A wavelet power analysis was used to illustrate the periodicity. In addition, we applied a linear regression model to characterize the correlation of influenza seasonality with longitude.ResultsThe average ILI incidence was estimated to be 3744.79 per 1 million (95% confidence interval [CI]: 2558.09–4931.45) during 2009–2018. Influenza A/H1N1 and A/H3N2 strains predominated in the most influenza seasons in Shandong. The annual amplitude of influenza epidemics decreased with longitude (P < 0.05). In contrast, the epidemic peak of influenza emerged earlier in the western region and increased with longitude in influenza A (P < 0.05). The annual peak of the influenza B epidemic lagged a median of 4.2 weeks compared with that of influenza A.ConclusionsThe development or modification of seasonal influenza vaccination strategies requires the recognition that the incidence is higher in preschool‐ and school‐aged children. Although seasonal influenza circulates annually in Shandong, the predominant virus strain circulation pattern is extremely unpredictable and strengthening surveillance for the predominant virus strain is necessary. Lower longitude inland regions need to take nonpharmaceutical or pharmaceutical interventions in advance during influenza high‐occurrence seasons.     

High influenza vaccination coverage among healthcare workers in acute care hospitals in Finland,seasons 2017/18, 2018/19 and 2019/20

BackgroundInfluenza vaccination is widely recommended for healthcare workers (HCWs) in European countries, but the coverage is not always satisfactory. In Finland, a new act was introduced in March 2017, according to which it is the employer’s responsibility to appoint only vaccinated HCWs for servicing vulnerable patients.AimWe determined the influenza vaccination coverage among HCWs in Finnish acute care hospitals in three influenza seasons after introduction of the act.MethodsWe analysed data collected by an internet-based survey sent annually to all Finnish acute care hospitals and described the influenza vaccination coverage among HCWs during seasons 2017/18, 2018/19 and 2019/20. We calculated mean coverage per healthcare district and season.ResultsIn season 2017/18, 38 of 39 hospitals, in 2018/19, 35 of 36 hospitals and in 2018/19 31 of 33 hospitals provided data. The mean influenza vaccination coverage was 83.7% (SD: 12.3) in season 2017/18, 90.8% (SD: 8.7) in 2018/19 and 87.6% (SD: 10.9) in season 2019/20. There was no significant increase or decrease in the mean coverage across the three seasons. The differences between districts were only significant in 2018/19 (p < 0.005).ConclusionsThe coverage of influenza-vaccinated HCWs in Finnish hospitals was high in all three seasons and the current legal situation (semi-mandatory system) in Finland seems to provide a good background for this. Data collection should be maintained and improved for further monitoring.     

Meta-analysis of the clinical performance of commercial SARS-CoV-2 nucleic acid and antibody tests up to 22 August 2020

BackgroundReliable testing for SARS-CoV-2 is key for the management of the COVID-19 pandemic.AimWe estimate diagnostic accuracy for nucleic acid and antibody tests 5 months into the COVID-19 pandemic, and compare with manufacturer-reported accuracy.MethodsWe reviewed the clinical performance of SARS-CoV-2 nucleic acid and antibody tests based on 93,757 test results from 151 published studies and 20,205 new test results from 12 countries in the European Union and European Economic Area (EU/EEA).ResultsPooling the results and considering only results with 95% confidence interval width ≤ 5%, we found four nucleic acid tests, including one point-of-care test and three antibody tests, with a clinical sensitivity ≥ 95% for at least one target population (hospitalised, mild or asymptomatic, or unknown). Nine nucleic acid tests and 25 antibody tests, 12 of them point-of-care tests, had a clinical specificity of ≥ 98%. Three antibody tests achieved both thresholds. Evidence for nucleic acid point-of-care tests remains scarce at present, and sensitivity varied substantially. Study heterogeneity was low for eight of 14 sensitivity and 68 of 84 specificity results with confidence interval width ≤ 5%, and lower for nucleic acid tests than antibody tests. Manufacturer-reported clinical performance was significantly higher than independently assessed in 11 of 32 and four of 34 cases, respectively, for sensitivity and specificity, indicating a need for improvement in this area.ConclusionContinuous monitoring of clinical performance within more clearly defined target populations is needed.     

Using routine emergency department data for syndromic surveillance of acute respiratory illness,Germany, week 10 2017 until week 10 2021

BackgroundThe COVID-19 pandemic expanded the need for timely information on acute respiratory illness at population level.AimWe explored the potential of routine emergency department data for syndromic surveillance of acute respiratory illness in Germany.MethodsWe used routine attendance data from emergency departments, which continuously transferred data between week 10 2017 and 10 2021, with ICD-10 codes available for > 75% of attendances. Case definitions for acute respiratory infection (ARI), severe acute respiratory infection (SARI), influenza-like illness (ILI), respiratory syncytial virus infection (RSV) and COVID-19 were based on a combination of ICD-10 codes, and/or chief complaints, sometimes combined with information on hospitalisation and age.ResultsWe included 1,372,958 attendances from eight emergency departments. The number of attendances dropped in March 2020 during the first COVID-19 pandemic wave, increased during summer, and declined again during the resurge of COVID-19 cases in autumn and winter of 2020/21. A pattern of seasonality of respiratory infections could be observed. By using different case definitions (i.e. for ARI, SARI, ILI, RSV) both the annual influenza seasons in the years 2017–2020 and the dynamics of the COVID-19 pandemic in 2020/21 were apparent. The absence of the 2020/21 influenza season was visible, parallel to the resurge of COVID-19 cases. SARI among ARI cases peaked in April–May 2020 (17%) and November 2020–January 2021 (14%).ConclusionSyndromic surveillance using routine emergency department data can potentially be used to monitor the trends, timing, duration, magnitude and severity of illness caused by respiratory viruses, including both influenza viruses and SARS-CoV-2.     

Epidemiological and microbiological investigation of a large increase in vibriosis,northern Europe, 2018

BackgroundVibriosis cases in Northern European countries and countries bordering the Baltic Sea increased during heatwaves in 2014 and 2018.AimWe describe the epidemiology of vibriosis and the genetic diversity of Vibrio spp. isolates from Norway, Sweden, Denmark, Finland, Poland and Estonia in 2018, a year with an exceptionally warm summer.MethodsIn a retrospective study, we analysed demographics, geographical distribution, seasonality, causative species and severity of non-travel-related vibriosis cases in 2018. Data sources included surveillance systems, national laboratory notification databases and/or nationwide surveys to public health microbiology laboratories. Moreover, we performed whole genome sequencing and multilocus sequence typing of available isolates from 2014 to 2018 to map their genetic diversity.ResultsIn 2018, we identified 445 non-travel-related vibriosis cases in the study countries, considerably more than the median of 126 cases between 2014 and 2017 (range: 87–272). The main reported mode of transmission was exposure to seawater. We observed a species-specific geographical disparity of vibriosis cases across the Nordic-Baltic region. Severe vibriosis was associated with infections caused by Vibrio vulnificus (adjOR: 17.2; 95% CI: 3.3–90.5) or Vibrio parahaemolyticus (adjOR: 2.1; 95% CI: 1.0–4.5), age ≥ 65 years (65–79 years: adjOR: 3.9; 95% CI: 1.7–8.7; ≥ 80 years: adjOR: 15.5; 95% CI: 4.4–54.3) or acquiring infections during summer (adjOR: 5.1; 95% CI: 2.4–10.9). Although phylogenetic analysis revealed diversity between Vibrio spp. isolates, two V. vulnificus clusters were identified.ConclusionShared sentinel surveillance for vibriosis during summer may be valuable to monitor this emerging public health issue.     

A prospective multicentre screening study on multidrug-resistant organisms in intensive care units in the Dutch–German cross-border region, 2017 to 2018: the importance of healthcare structures

BackgroundAntimicrobial resistance poses a risk for healthcare, both in the community and hospitals. The spread of multidrug-resistant organisms (MDROs) occurs mostly on a local and regional level, following movement of patients, but also occurs across national borders.AimThe aim of this observational study was to determine the prevalence of MDROs in a European cross-border region to understand differences and improve infection prevention based on real-time routine data and workflows.MethodsBetween September 2017 and June 2018, 23 hospitals in the Dutch (NL)–German (DE) cross-border region (BR) participated in the study. During 8 consecutive weeks, patients were screened upon admission to intensive care units (ICUs) for nasal carriage of meticillin-resistant Staphylococcus aureus (MRSA) and rectal carriage of vancomycin-resistant Enterococcus faecium/E. faecalis (VRE), third-generation cephalosporin-resistant Enterobacteriaceae (3GCRE) and carbapenem-resistant Enterobacteriaceae (CRE). All samples were processed in the associated laboratories.ResultsA total of 3,365 patients were screened (median age: 68 years (IQR: 57–77); male/female ratio: 59.7/40.3; NL-BR: n = 1,202; DE-BR: n = 2,163). Median screening compliance was 60.4% (NL-BR: 56.9%; DE-BR: 62.9%). MDRO prevalence was higher in DE-BR than in NL-BR, namely 1.7% vs 0.6% for MRSA (p = 0.006), 2.7% vs 0.1% for VRE (p < 0.001) and 6.6% vs 3.6% for 3GCRE (p < 0.001), whereas CRE prevalence was comparable (0.2% in DE-BR vs 0.0% in NL-BR ICUs).ConclusionsThis first prospective multicentre screening study in a European cross-border region shows high heterogenicity in MDRO carriage prevalence in NL-BR and DE-BR ICUs. This indicates that the prevalence is probably influenced by the different healthcare structures.     

Influenza clinical testing and oseltamivir treatment in hospitalized children with acute respiratory illness, 2015–2016

BackgroundAntiviral treatment is recommended for all hospitalized children with suspected or confirmed influenza, regardless of their risk profile. Few data exist on adherence to these recommendations, so we sought to determine factors associated with influenza testing and antiviral treatment in children.MethodsHospitalized children <18 years of age with acute respiratory illness (ARI) were enrolled through active surveillance at pediatric medical centers in seven cities between 11/1/2015 and 6/30/2016; clinical information was obtained from parent interview and chart review. We used generalized linear mixed‐effects models to identify factors associated with influenza testing and antiviral treatment.ResultsOf the 2299 hospitalized children with ARI enrolled during one influenza season, 51% (n = 1183) were tested clinically for influenza. Clinicians provided antiviral treatment for 61 of 117 (52%) patients with a positive influenza test versus 66 of 1066 (6%) with a negative or unknown test result. In multivariable analyses, factors associated with testing included neuromuscular disease (aOR = 5.35, 95% CI [3.58–8.01]), immunocompromised status (aOR = 2.88, 95% CI [1.66–5.01]), age (aOR = 0.93, 95% CI [0.91–0.96]), private only versus public only insurance (aOR = 0.78, 95% CI [0.63–0.98]), and chronic lung disease (aOR = 0.64, 95% CI [0.51–0.81]). Factors associated with antiviral treatment included neuromuscular disease (aOR = 1.86, 95% CI [1.04, 3.31]), immunocompromised state (aOR = 2.63, 95% CI [1.38, 4.99]), duration of illness (aOR = 0.92, 95% CI [0.84, 0.99]), and chronic lung disease (aOR = 0.60, 95% CI [0.38, 0.95]).ConclusionApproximately half of children hospitalized with influenza during the 2015–2016 influenza season were treated with antivirals. Because antiviral treatment for influenza is associated with better health outcomes, further studies of subsequent seasons would help evaluate current use of antivirals among children and better understand barriers for treatment.     

Use of High-Dose Influenza and Live Attenuated Influenza Vaccines by US Primary Care Physicians

BackgroundSeveral different types of influenza vaccine are licensed for use in adults in the USA including high-dose inactivated influenza vaccine (HD-IIV) and live attenuated influenza vaccine (LAIV). HD-IIV is licensed for use in adults ≥ 65 years, and recommendations for use of LAIV have changed several times in recent years.ObjectiveWe sought to examine family physicians’ (FPs) and general internal medicine physicians’ (GIMs) perceptions, knowledge, and practices for use of HD-IIV and LAIV during the 2016–2017 and 2018–2019 influenza seasons.DesignE-mail and mail surveys conducted February–March 2017, January–February 2019.ParticipantsNationally representative samples of FPs and GIMs.Main MeasuresSurveys assessed HD-IIV practices (2017), knowledge and perceptions (2019), and LAIV knowledge and practices (2017, 2019).Key ResultsResponse rates were 67% (620/930) in 2017 and 69% (642/926) in 2019. Many physicians believed HD-IIV is more effective than standard dose IIV in patients ≥ 65 years (76%) and reported their patients ≥ 65 years believe they need HD-IIV (67%). Most respondents incorrectly thought ACIP preferentially recommends HD-IIV for adults ≥ 65 years (88%); 65% “almost always/always” recommended HD-IIV for adults ≥ 65 years. Some physicians incorrectly thought ACIP preferentially recommends HD-IIV for adults < 65 years with cardiopulmonary disease (38%) or immunosuppression (48%); some respondents recommended HD-IIV for these groups (25% and 28% respectively). In 2017, 88% of respondents knew that ACIP recommended against using LAIV during the 2016–2017 influenza season, and 4% recommended LAIV to patients. In 2019, 63% knew that ACIP recommended that LAIV could be used during the 2018–2019 influenza season, and 8% recommended LAIV.ConclusionsMany physicians incorrectly thought ACIP had preferential recommendations for HD-IIV. Physicians should be encouraged to use any available age-appropriate influenza vaccine to optimize influenza vaccination particularly among older adults and patients with chronic conditions who are more vulnerable to severe influenza disease.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-020-06397-7.KEY WORDS: influenza vaccine, immunization, vaccination, influenza     

Clinical and socioeconomic burden of rhinoviruses/enteroviruses in the community

BackgroundThe epidemiology, clinical features, and socioeconomic burden associated with detection of rhinoviruses (RV)/enteroviruses (EV) from individuals in the community with acute respiratory infections (ARIs) are not fully understood.MethodsTo assess the clinical and socioeconomic burden associated with RV/EV, a secondary analysis of data collected during a prospective, community‐based ARI surveillance study was performed. From December 2012 to September 2017, adult and pediatric participants with ARIs had nasopharyngeal specimens obtained and tested by multiplex polymerase chain reaction assay. Characteristics and socioeconomic burden including missed school or work and/or antibiotic use among participants who did and did not seek medical care and among participants with and without co‐detection of another respiratory pathogen with RV/EV were compared.ResultsThroughout the study period, RV/EV was detected in 54.7% (885/1617) of ARIs with a respiratory pathogen detected. Most ARI episodes associated with RV/EV occurred in females (59.1%) and children ≤17 years old (64.2%). Those ≤17 years were more likely to seek medical care. Compared to those not seeking medical care (n = 686), those seeking medical care (n = 199) had a longer duration of illness (5 vs. 7 days) and were more likely to miss work/school (16.4% vs. 47.7%) and/or use antibiotics (3.6% vs. 34.2%). Co‐detection occurred in 8% of ARIs of which 81% occurred in children. Co‐detection was not associated with longer illness, more missed work/or school, or antibiotic use.ConclusionNon‐medically attended and medically attended ARIs associated with RV/EV resulted in clinical and socioeconomic burden, regardless of co‐detection of other respiratory pathogens.     

Rapid influenza molecular testing in secondary care and influenza surveillance in England: Any impact?

IntroductionThe use of rapid molecular testing for influenza diagnosis is becoming increasingly popular. Used at the point of care or in a clinical laboratory, these tests detect influenza A and B viruses, though many do not distinguish between influenza A subtypes. The UK Severe Influenza Surveillance System (USISS) collects surveillance data on laboratory‐confirmed influenza admissions to secondary care in England.This study set out to understand how rapid influenza molecular testing was being used and how it might influence the availability of subtyping data collected on influenza cases admitted to secondary care in England.MethodsAt the end of the 2017/2018 and 2018/2019 influenza seasons, a questionnaire was sent to all National Health Service Hospital Trusts in England to evaluate the use of rapid influenza testing. Surveillance data collected through USISS was analysed from 2011/2012 to 2020/2021.ResultsOf responding trusts, 42% (13/31) in 2017/2018 and 55% (9/17) in 2018/2019 used rapid influenza molecular tests, either alone or in combination with other testing. The majority of rapid tests used did not subtype the influenza A result, and limited follow‐up testing occurred.Surveillance data showed significant proportions of influenza A hospital and intensive care unit/high dependency unit admissions without subtyping information, increasing by approximately 35% between 2012/2013 and 2020/2021.ConclusionsThe use of rapid influenza molecular tests is a likely contributing factor to the large proportion of influenza A hospitalisations in England that were unsubtyped. Given their clear clinical advantages, further work must be done to reinforce these data for public health through integrated genomic surveillance.     

Pertussis surveillance results from a French general practitioner network,France, 2017 to 2020

IntroductionIn France, three complementary surveillance networks involving hospitals and paediatrician practices currently allow pertussis surveillance among infants (<1 year old) and children (1–12 years old). Data on incidences among adolescents (13–17 years old) and adults (≥ 18 years) are scarce. In 2017, a sentinel surveillance system called Sentinelles network, was implemented among general practitioners (GPs).AimThe purpose of Sentinelles network is to assess pertussis incidence, monitor the cases’ age distribution and evaluate the impact of the country’s vaccination policy. We present the results from the first 4 years of this surveillance.MethodsGPs of the French Sentinelles network reported weekly numbers of epidemiologically or laboratory-confirmed cases and their characteristics.ResultsA total of 132 cases were reported over 2017–2020. Estimated national incidence rates per 100,000 inhabitants were 17 (95% confidence interval (CI): 12–22) in 2017, 10 (95% CI: 6–14) in 2018, 15 (95% CI: 10–20) in 2019 and three (95% CI: 1–5) in 2020. The incidence rate was significantly lower in 2020 than in 2017–2019. Women were significantly more affected than men (83/132; 63% of women, p = 0.004); 66% (87/132) of cases were aged 15 years or over (median age: 31.5 years; range: 2 months–87 years). Among 37 vaccinated cases with data, 33 had received the recommended number of doses for their age.ConclusionsThese results concur with incidences reported in other European countries, and with studies showing that the incidences of several respiratory diseases decreased in 2020 during the COVID-19 pandemic. The results also suggest a shift of morbidity towards older age groups, and a rapid waning of immunity after vaccination, justifying to continue this surveillance.     

Hospitalisation,morbidity and outcomes associated with respiratory syncytial virus compared with influenza in adults of all ages

BackgroundRespiratory syncytial virus (RSV) is understood to be a cause of significant disease in older adults and children. Further analysis of RSV in younger adults may reveal further insight into its role as an important pathogen in all age groups.MethodsWe identified, through laboratory data, adults who tested positive for either influenza or RSV between January 2017 and June 2019 at a single Australian hospital. We compared baseline demographics, testing patterns, hospitalisations and outcomes between these groups.ResultsOf 1128 influenza and 193 RSV patients, the RSV cohort was older (mean age 54.7 vs. 64.9, p < 0.001) and was more comorbid as determined by the Charlson Comorbidity Index (2.4 vs. 3.2, p < 0.001). For influenza hospitalisations, the majority admitted were aged under 65 which was not the case for RSV (61.8% vs. 45.6%, p < 0.001). Testing occurred later in RSV hospitalisations as measured by the proportion tested in the emergency department (ED) (80.3% vs. 69.2%, p < 0.001), and this was strongly associated with differences in presenting phenotype (the presence of fever). RSV was the biggest predictor of 6‐month representation, with age and comorbidities predicting this less strongly.ConclusionRSV is a significant contributor to morbidity and hospitalisation, sometimes outweighing that of influenza, and is not limited to elderly cohorts. Understanding key differences in the clinical syndrome and consequent testing paradigms may allow better detection and potentially treatment of RSV to reduce individual morbidity and health system burden. This growing area of research helps quantify the need for directed therapies for RSV.     

Incidence of medically attended influenza and influenza virus infections confirmed by serology in Ningbo City from 2017–2018 to 2019–2020

ObjectivesIn mainland China, the disease burden of influenza is not yet fully understood. Based on population‐based data, we aimed to estimate incidence rates of medically attended influenza and influenza virus infections in Ningbo City.MethodsWe used data for outpatient acute respiratory illness (OARI) from a platform covering all health and medical institutes in Yingzhou District, Ningbo City. We applied generalized additive regression models to estimate influenza‐associated excess incidence rate of OARI by age. We recruited local residents aged ≥60 years in the autumn of 2019 and conducted follow‐up nearly 9 months later. Every survey, the sera were collected for testing hemagglutination inhibition antibody.ResultsFrom 2017–2018 to 2019–2020, the annual average of influenza‐associated incidence rate of OARI in all ages was 10.9%. The influenza‐associated incidence rate of OARI was the highest in 2017–2018 (16.9%) and the lowest in 2019–2020 (4.8%). Regularly, influenza‐associated incidence rates of OARI were the highest in children aged 5–14 years (range: 44.1–77.6%) and 0–4 years (range: 8.3–46.6%). The annual average of excess OARI incidence rate in all ages was the highest for influenza B/Yamagata (3.9%). The overall incidence rate of influenza infections indicated by serology in elderly people was 21% during the winter season of 2019–2020.ConclusionsWe identified substantial outpatient influenza burden in all ages in Ningbo. Our cohort study limited in elderly people found that this age group had a high risk of seasonal influenza infections. Our study informs the importance of increasing influenza vaccine coverage in high‐risk population including elderly people.     

Global patterns of seasonal influenza activity,duration of activity and virus (sub)type circulation from 2010 to 2020

BackgroundSeasonal influenza viruses undergo unpredictable changes, which may lead to antigenic mismatch between circulating and vaccine strains and to a reduced vaccine effectiveness. A continuously updated knowledge of influenza strain circulation and seasonality is essential to optimize the effectiveness of influenza vaccination campaigns. We described the global epidemiology of influenza between the 2009 A(H1N1)p and the 2020 COVID‐19 pandemic.MethodsInfluenza virological surveillance data were obtained from the WHO‐FluNet database. We determined the median proportion of influenza cases caused by the different influenza virus types, subtypes, and lineages; the typical timing of the epidemic peak; and the median duration of influenza epidemics (applying the annual average percentage method with a 75% threshold).ResultsWe included over 4.6 million influenza cases from 149 countries. The median proportion of influenza cases caused by type A viruses was 75.5%, highest in the Southern hemisphere (81.6%) and lowest in the intertropical belt (73.0%), and ranged across seasons between 60.9% in 2017 and 88.7% in 2018. Epidemic peaks typically occurred during winter months in Northern and Southern hemisphere countries, while much more variability emerged in tropical countries. Influenza epidemics lasted a median of 25 weeks (range 8–42) in countries lying between 30°N and 26°S, and a median of 9 weeks (range 5–25) in countries outside this latitude range.ConclusionsThis work will establish an important baseline to better understand factors that influence seasonal influenza dynamics and how COVID‐19 may have affected seasonal activity and influenza virus types, subtypes, and lineages circulation patterns.     

All‐cause versus cause‐specific excess deaths for estimating influenza‐associated mortality in Denmark,Spain, and the United States

BackgroundSeasonal influenza‐associated excess mortality estimates can be timely and provide useful information on the severity of an epidemic. This methodology can be leveraged during an emergency response or pandemic.MethodFor Denmark, Spain, and the United States, we estimated age‐stratified excess mortality for (i) all‐cause, (ii) respiratory and circulatory, (iii) circulatory, (iv) respiratory, and (v) pneumonia, and influenza causes of death for the 2015/2016 and 2016/2017 influenza seasons. We quantified differences between the countries and seasonal excess mortality estimates and the death categories. We used a time‐series linear regression model accounting for time and seasonal trends using mortality data from 2010 through 2017.ResultsThe respective periods of weekly excess mortality for all‐cause and cause‐specific deaths were similar in their chronological patterns. Seasonal all‐cause excess mortality rates for the 2015/2016 and 2016/2017 influenza seasons were 4.7 (3.3–6.1) and 14.3 (13.0–15.6) per 100,000 population, for the United States; 20.3 (15.8–25.0) and 24.0 (19.3–28.7) per 100,000 population for Denmark; and 22.9 (18.9–26.9) and 52.9 (49.1–56.8) per 100,000 population for Spain. Seasonal respiratory and circulatory excess mortality estimates were two to three times lower than the all‐cause estimates.DiscussionWe observed fewer influenza‐associated deaths when we examined cause‐specific death categories compared with all‐cause deaths and observed the same trends in peaks in deaths with all death causes. Because all‐cause deaths are more available, these models can be used to monitor virus activity in near real time. This approach may contribute to the development of timely mortality monitoring systems during public health emergencies.     

Influenza hospitalizations in Australian children 2010–2019: The impact of medical comorbidities on outcomes,vaccine coverage,and effectiveness

BackgroundChildren with comorbidities are at greater risk of severe influenza outcomes compared with healthy children. In Australia, influenza vaccination was funded for those with comorbidities from 2010 and all children aged <5 years from 2018. Influenza vaccine coverage remains inadequate in children with and without comorbidities.MethodsChildren ≤16 years admitted with acute respiratory illness and tested for influenza at sentinel hospitals were evaluated (2010–2019). Multivariable regression was used to identify predictors of severe outcomes. Vaccine effectiveness was estimated using the modified incidence density test‐negative design.ResultsOverall, 6057 influenza‐confirmed hospitalized cases and 3974 test‐negative controls were included. Influenza A was the predominant type (68.7%). Comorbidities were present in 40.8% of cases. Children with comorbidities were at increased odds of ICU admission, respiratory support, longer hospitalizations, and mortality. Specific comorbidities including neurological and cardiac conditions increasingly predisposed children to severe outcomes. Influenza vaccine coverage in influenza negative children with and without comorbidities was low (33.5% and 17.9%, respectively). Coverage improved following introduction of universal influenza vaccine programs for children <5 years. Similar vaccine effectiveness was demonstrated in children with (55% [95% confidence interval (CI): 45; 63%]) and without comorbidities (57% [(95%CI: 44; 67%]).ConclusionsComorbidities were present in 40.8% of influenza‐confirmed admissions and were associated with more severe outcomes. Children with comorbidities were more likely experience severe influenza with ICU admission, mechanical ventilation, and in‐hospital morality. Despite demonstrated vaccine effectiveness in those with and without comorbidities, vaccine coverage was suboptimal. Interventions to increase vaccination are expected to reduce severe influenza outcomes.     

Comparative sensitivity evaluation for 122 CE-marked rapid diagnostic tests for SARS-CoV-2 antigen,Germany, September 2020 to April 2021

IntroductionNumerous CE-marked SARS-CoV-2 antigen rapid diagnostic tests (Ag RDT) are offered in Europe, several of them with unconfirmed quality claims.AimWe performed an independent head-to-head evaluation of the sensitivity of SARS-CoV-2 Ag RDT offered in Germany.MethodsWe addressed the sensitivity of 122 Ag RDT in direct comparison using a common evaluation panel comprised of 50 specimens. Minimum sensitivity of 75% for panel specimens with a PCR quantification cycle (Cq) ≤ 25 was used to identify Ag RDT eligible for reimbursement in the German healthcare system.ResultsThe sensitivity of different SARS-CoV-2 Ag RDT varied over a wide range. The sensitivity limit of 75% for panel members with Cq ≤ 25 was met by 96 of the 122 tests evaluated; 26 tests exhibited lower sensitivity, few of which failed completely. Some RDT exhibited high sensitivity, e.g. 97.5 % for Cq < 30.ConclusionsThis comparative evaluation succeeded in distinguishing less sensitive from better performing Ag RDT. Most of the evaluated Ag RDT appeared to be suitable for fast identification of acute infections associated with high viral loads. Market access of SARS-CoV-2 Ag RDT should be based on minimal requirements for sensitivity and specificity.