Atypical age distribution and high disease severity in children with RSV infections during two irregular epidemic seasons throughout the COVID-19 pandemic, Germany, 2021 to 2023.

BackgroundNon-pharmaceutical interventions (NPIs) during the COVID-19 pandemic affected respiratory syncytial virus (RSV) circulation worldwide.AimTo describe, for children aged < 5 years, the 2021 and 2022/23 RSV seasons in Germany.MethodsThrough data and 16,754 specimens from outpatient sentinel surveillance, we investigated RSV seasonality, circulating lineages, and affected children's age distributions in 2021 and 2022/23. Available information about disease severity from hospital surveillance was analysed for patients with RSV-specific diagnosis codes (n = 13,104). Differences between RSV seasons were assessed by chi-squared test and age distributions trends by Mann-Kendall test.ResultsRSV seasonality was irregular in 2021 (weeks 35-50) and 2022/23 (weeks 41-3) compared to pre-COVID-19 2011/12-2019/20 seasons (median weeks 51-12). RSV positivity rates (RSV-PR) were higher in 2021 (40% (522/1,291); p < 0.001) and 2022/23 (30% (299/990); p = 0.005) than in prior seasons (26% (1,430/5,511)). Known globally circulating RSV-A (lineages GA2.3.5 and GA2.3.6b) and RSV-B (lineage GB5.0.5a) strains, respectively, dominated in 2021 and 2022/23. In 2021, RSV-PRs were similar in 1 - < 2, 2 - < 3, 3 - < 4, and 4 - < 5-year-olds. RSV hospitalisation incidence in 2021 (1,114/100,000, p < 0.001) and in 2022/23 (1,034/100,000, p < 0.001) was approximately double that of previous seasons' average (2014/15-2019/20: 584/100,000). In 2022/23, proportions of RSV patients admitted to intensive care units rose (8.5% (206/2,413)) relative to pre-COVID-19 seasons (6.8% (551/8,114); p = 0.004), as did those needing ventilator support (6.1% (146/2,413) vs 3.8% (310/8,114); p < 0.001).ConclusionsHigh RSV-infection risk in 2-4-year-olds in 2021 and increased disease severity in 2022/23 possibly result from lower baseline population immunity, after NPIs diminished exposure to RSV.

COVID-19 vaccine effectiveness against symptomatic infection with SARS-CoV-2 BA.1/BA.2 lineages among adults and adolescents in a multicentre primary care study, Europe, December 2021 to June 2022.

BackgroundScarce European data in early 2021 suggested lower vaccine effectiveness (VE) against SARS-CoV-2 Omicron lineages than previous variants.AimWe aimed to estimate primary series (PS) and first booster VE against symptomatic BA.1/BA.2 infection and investigate potential biases.MethodsThis European test-negative multicentre study tested primary care patients with acute respiratory symptoms for SARS-CoV-2 in the BA.1/BA.2-dominant period. We estimated PS and booster VE among adults and adolescents (PS only) for all products combined and for Comirnaty alone, by time since vaccination, age and chronic condition. We investigated potential bias due to correlation between COVID-19 and influenza vaccination and explored effect modification and confounding by prior SARS-CoV-2 infection.ResultsAmong adults, PS VE was 37% (95% CI: 24-47%) overall and 60% (95% CI: 44-72%), 43% (95% CI: 26-55%) and 29% (95% CI: 13-43%) < 90, 90-179 and ≥ 180 days post vaccination, respectively. Booster VE was 42% (95% CI: 32-51%) overall and 56% (95% CI: 47-64%), 22% (95% CI: 2-38%) and 3% (95% CI: -78% to 48%), respectively. Primary series VE was similar among adolescents. Restricting analyses to Comirnaty had little impact. Vaccine effectiveness was higher among older adults. There was no signal of bias due to correlation between COVID-19 and influenza vaccination. Confounding by previous infection was low, but sample size precluded definite assessment of effect modification.ConclusionPrimary series and booster VE against symptomatic infection with BA.1/BA.2 ranged from 37% to 42%, with similar waning post vaccination. Comprehensive data on previous SARS-CoV-2 infection would help disentangle vaccine- and infection-induced immunity.

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024.

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.

Unmasking a silent killer: Prevalence of diagnosed and undiagnosed diabetes mellitus among people living with HIV in rural South Africa.

OBJECTIVES: To document the prevalence of impaired glucose tolerance (IGT) and undiagnosed diabetes mellitus (DM) and to identify factors associated with undiagnosed DM in people living with HIV (PLWH). METHODS: Cross-sectional study performed at Ndlovu Medical Center, Limpopo, South Africa including PLWH aged ≥18 years. Between August and November 2017, 356 HIV-positive participants were included. Information was collected on socio-demographics, DM symptoms and risk factors for DM. IGT and DM were diagnosed using random plasma glucose and/or HbA1c. Factors associated with undiagnosed DM were assessed by comparing participants with newly diagnosed DM to participants without DM. RESULTS: IGT was diagnosed in 172 (48.3%) participants. Twenty-nine (8.1%) participants met the definition of DM, of whom 17 (58.6%) were newly diagnosed. Compared to participants without DM, participants with DM were on average 5 years older, were more likely to have a positive family history for DM, were less physically active and had higher systolic blood pressure, body mass index and waist circumference. Factors associated with undiagnosed DM included age ≥45 years (odds ratio [OR] = 3.59) and physical inactivity (OR = 3.17). CONCLUSIONS: The prevalence of IGT and DM among PLWH is high and more than half of DM cases were undiagnosed. Regular screening for DM in PLWH is recommended, especially in an ageing population with additional cardiovascular disease risk factors.

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

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

Exploring the effect of clinical case definitions on influenza vaccine effectiveness estimation at primary care level: Results from the end-of-season 2022-23 VEBIS multicentre study in Europe.

BACKGROUND: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. METHODS: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). RESULTS: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. DISCUSSION: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons.

Influenza vaccine effectiveness in Europe: Results from the 2022-2023 VEBIS (Vaccine Effectiveness, Burden and Impact Studies) primary care multicentre study.

Background: Influenza A(H3N2) viruses dominated early in the 2022-2023 influenza season in Europe, followed by higher circulation of influenza A(H1N1)pdm09 and B viruses. The VEBIS primary care network estimated the influenza vaccine effectiveness (VE) using a multicentre test-negative study. Materials and Methods: Primary care practitioners collected information and specimens from patients consulting with acute respiratory infection. We measured VE against any influenza, influenza (sub)type and clade, by age group, by influenza vaccine target group and by time since vaccination, using logistic regression. Results: We included 38 058 patients, of which 3786 were influenza A(H3N2), 1548 influenza A(H1N1)pdm09 and 3275 influenza B cases. Against influenza A(H3N2), VE was 36% (95% CI: 25-45) among all ages and ranged between 30% and 52% by age group and target group. VE against influenza A(H3N2) clade 2b was 38% (95% CI: 25-49). Overall, VE against influenza A(H1N1)pdm09 was 46% (95% CI: 35-56) and ranged between 29% and 59% by age group and target group. VE against influenza A(H1N1)pdm09 clade 5a.2a was 56% (95% CI: 46-65) and 79% (95% CI: 64-88) against clade 5a.2a.1. VE against influenza B was 76% (95% CI: 70-81); overall, 84%, 72% and 71% were among 0-14-year-olds, 15-64-year-olds and those in the influenza vaccination target group, respectively. VE against influenza B with a position 197 mutation of the hemagglutinin (HA) gene was 79% (95% CI: 73-85) and 90% (95% CI: 85-94) without this mutation. Conclusion: The 2022-2023 end-of-season results from the VEBIS network at primary care level showed high VE among children and against influenza B, with lower VE against influenza A(H1N1)pdm09 and A(H3N2).

COVID-19 Vaccine Effectiveness in Autumn and Winter 2022 to 2023 Among Older Europeans.

Importance: In the context of emerging SARS-CoV-2 variants or lineages and new vaccines, it is key to accurately monitor COVID-19 vaccine effectiveness (CVE) to inform vaccination campaigns. Objective: To estimate the effectiveness of COVID-19 vaccines administered in autumn and winter 2022 to 2023 against symptomatic SARS-CoV-2 infection (with all circulating viruses and XBB lineage in particular) among people aged 60 years or older in Europe, and to compare different CVE approaches across the exposed and reference groups used. Design, Setting, and Participants: This case-control study obtained data from VEBIS (Vaccine Effectiveness, Burden and Impact Studies), a multicenter study that collects COVID-19 and influenza data from 11 European sites: Croatia; France; Germany; Hungary; Ireland; Portugal; the Netherlands; Romania; Spain, national; Spain, Navarre region; and Sweden. Participants were primary care patients aged 60 years or older with acute respiratory infection symptoms who were recruited at the 11 sites after the start of the COVID-19 vaccination campaign from September 2022 to August 2023. Cases and controls were defined as patients with positive and negative, respectively, reverse transcription-polymerase chain reaction (RT-PCR) test results. Exposures: The exposure was COVID-19 vaccination. The exposure group consisted of patients who received a COVID-19 vaccine during the autumn and winter 2022 to 2023 vaccination campaign and 14 days or more before symptom onset. Reference group included patients who were not vaccinated during or in the 6 months before the 2022 to 2023 campaign (seasonal CVE), those who were never vaccinated (absolute CVE), and those who were vaccinated with at least the primary series 6 months or more before the campaign (relative CVE). For relative CVE of second boosters, patients receiving their second booster during the campaign were compared with those receiving 1 booster 6 months or more before the campaign. Main Outcomes and Measures: The outcome was RT-PCR-confirmed, medically attended, symptomatic SARS-CoV-2 infection. Four CVE estimates were generated: seasonal, absolute, relative, and relative of second boosters. CVE was estimated using logistic regression, adjusting for study site, symptom onset date, age, chronic condition, and sex. Results: A total of 9308 primary care patients were included, with 1687 cases (1035 females; median [IQR] age, 71 [65-79] years) and 7621 controls (4619 females [61%]; median [IQR] age, 71 [65-78] years). Within 14 to 89 days after vaccination, seasonal CVE was 29% (95% CI, 14%-42%), absolute CVE was 39% (95% CI, 6%-60%), relative CVE was 31% (95% CI, 15% to 44%), and relative CVE of second boosters was 34% (95% CI, 18%-47%) against all SARS-CoV-2 variants. In the same interval, seasonal CVE was 44% (95% CI, -10% to 75%), absolute CVE was 52% (95% CI, -23% to 82%), relative CVE was 47% (95% CI, -8% to 77%), and relative CVE of second boosters was 46% (95% CI, -13% to 77%) during a period of high XBB circulation. Estimates decreased with time since vaccination, with no protection from 180 days after vaccination. Conclusions and Relevance: In this case-control study among older Europeans, all CVE approaches suggested that COVID-19 vaccines administered in autumn and winter 2022 to 2023 offered at least 3 months of protection against symptomatic, medically attended, laboratory-confirmed SARS-CoV-2 infection. The effectiveness of new COVID-19 vaccines against emerging SARS-CoV-2 variants should be continually monitored using CVE seasonal approaches.

Effectiveness of COVID-19 vaccines administered in the 2023 autumnal campaigns in Europe: Results from the VEBIS primary care test-negative design study, September 2023-January 2024.

In autumn 2023, European vaccination campaigns predominantly administered XBB.1.5 vaccine. In a European multicentre study, we estimated 2023 COVID-19 vaccine effectiveness (VE) against laboratory-confirmed symptomatic infection at primary care level between September 2023 and January 2024. Using a test-negative case-control design, we estimated VE in the target group for COVID-19 vaccination overall and by time since vaccination. We included 1057 cases and 4397 controls. Vaccine effectiveness was 40 % (95 % CI: 26-53 %) overall, 48 % (95 % CI: 31-61 %) among those vaccinated < 6 weeks of onset and 29 % (95 % CI: 3-49 %) at 6-14 weeks. Our results suggest that COVID-19 vaccines administered to target groups during the autumn 2023 campaigns showed clinically significant effectiveness against laboratory-confirmed, medically attended symptomatic SARS-CoV-2 infection in the 3 months following vaccination. A longer study period will allow for further variant-specific COVID-19 VE estimates, better understanding decline in VE and informing booster administration policies.

Influenza vaccine effectiveness against influenza A subtypes in Europe: Results from the 2021-2022 I-MOVE primary care multicentre study.

BACKGROUND: In 2021-2022, influenza A viruses dominated in Europe. The I-MOVE primary care network conducted a multicentre test-negative study to measure influenza vaccine effectiveness (VE). METHODS: Primary care practitioners collected information on patients presenting with acute respiratory infection. Cases were influenza A(H3N2) or A(H1N1)pdm09 RT-PCR positive, and controls were influenza virus negative. We calculated VE using logistic regression, adjusting for study site, age, sex, onset date, and presence of chronic conditions. RESULTS: Between week 40 2021 and week 20 2022, we included over 11 000 patients of whom 253 and 1595 were positive for influenza A(H1N1)pdm09 and A(H3N2), respectively. Overall VE against influenza A(H1N1)pdm09 was 75% (95% CI: 43-89) and 81% (95% CI: 45-93) among those aged 15-64 years. Overall VE against influenza A(H3N2) was 29% (95% CI: 12-42) and 25% (95% CI: -41 to 61), 33% (95% CI: 14-49), and 26% (95% CI: -22 to 55) among those aged 0-14, 15-64, and over 65 years, respectively. The A(H3N2) VE among the influenza vaccination target group was 20% (95% CI: -6 to 39). All 53 sequenced A(H1N1)pdm09 viruses belonged to clade 6B.1A.5a.1. Among 410 sequenced influenza A(H3N2) viruses, all but eight belonged to clade 3C.2a1b.2a.2. DISCUSSION: Despite antigenic mismatch between vaccine and circulating strains for influenza A(H3N2) and A(H1N1)pdm09, 2021-2022 VE estimates against circulating influenza A(H1N1)pdm09 were the highest within the I-MOVE network since the 2009 influenza pandemic. VE against A(H3N2) was lower than A(H1N1)pdm09, but at least one in five individuals vaccinated against influenza were protected against presentation to primary care with laboratory-confirmed influenza.