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ObjectivesThis systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings.MethodsThis literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within household settings. The inclusion criteria were based on the PEO framework (P-Population, E-Exposure, O-Outcome) for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with pediatric index cases 1–17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either a SAR or the probability of onward infection (outcome).ResultsOf 1,819 studies originally identified, 25 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 23 studies, while there was no evidence of secondary transmission from children to other household members in two studies. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings.ConclusionsSARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary.

ObjectivesCOVID-19 poses a threat of loss of life, economic instability, and social disruption. We conducted a systematic review of published economic analyses to assess the direct and indirect costs of the SARS-CoV-2 pandemic, and to contrast these with the costs and the cost-benefit of public health surveillance, preparedness, and response measures in averting and/or responding to SARS-CoV-2 pandemic.SettingA systematic literature review was conducted to identify peer-reviewed articles estimating the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions in EU/EEA/UK and OECD countries, published from the 1st of January 2020 through 22nd April 2021 in Ovid Medline and EMBASE. The cost-effectiveness of interventions was assessed through a dominance ranking matrix approach. All cost data were adjusted to the 2021 Euro, with interventions compared with the null.Primary and secondary outcome measuresDirect and indirect costs for SARS-CoV-2 and preparedness and/or response or cost-benefit and cost-effectiveness were measured.ResultsWe included data from 41 economic studies. Ten studies evaluated the cost of COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness, and response measures. Overall, the economic burden of SARS-CoV-2 was found to be substantial for both the general population and within specific population subgroups. Community screening, bed provision policies, investing in personal protective equipment and vaccination strategies were cost-effective, in most cases due to the representative economic value of below acceptable cost-effectiveness thresholds. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented.ConclusionsSARS-CoV-2 is associated with substantial economic costs to healthcare systems, payers, and societies, both short term and long term, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.

BackgroundAs mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations.MethodsWe performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11th June 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients.FindingsWe included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease.InterpretationThe results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions.FundingEuropean Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.

ObjectivesThis systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings.MethodsThis literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of SARS-CoV-2 within household settings. The inclusion criteria were based on the Population, Exposure, Outcome framework for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with paediatric index cases 1–17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either an SAR or the probability of onward infection (outcome).ResultsOf 1819 studies originally identified, 19 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 15 studies, while there was no evidence of secondary transmission from children to other household members in one study. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings.ConclusionsSARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary.

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July−October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8–52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.

We assessed the impact of COVID-19 on healthcare workers (HCWs) from data on 2.9 million cases reported from nine countries in the EU/EEA. Compared to non-HCWs, HCWs had a higher adjusted risk of hospitalization (IRR 3.0 [95% CI 2.2-4.0]), but not death (IRR 0.9, 95% CI 0.4-2.0).Article Summary LineHealthcare workers are hospitalized more frequently than non-healthcare workers when adjusting for age, sex, and comorbidities.

Purpose To investigate whether herpes zoster vaccine (HZV) was associated with socioeconomic status in Stockholm, when the vaccine was reimbursed in Sweden. Methods This was an observational retrospective case-control study, using population-based health care registers. During the study period, September 2013 to November 2014, the HZV was reimbursed as part of the National Pharmaceutical Benefits Scheme in Sweden and recommended for individuals over 50 years. A case was any person, living in Stockholm County, who received HZV during the study period. For each case, 10 (unvaccinated) controls living in Stockholm County were selected and matched by age and sex. In total, 9099 cases and 89 736 controls were included. Socioeconomic variables investigated included education, income, immigration status, and marital status. We also investigated whether HZV was associated with the Charlson Comorbidity Index (CCI), and/or previous herpes zoster diagnosis. Results Mean age at vaccination was 69.8 years, and 65.8% of vaccinees were women. There was a positive association between vaccination and higher education (OR = 3.4 (95% CI 3.0-3.8) for men and OR = 2.8 (95% CI 2.6-3.0) for women, respectively) in comparison to primary education. Higher income and being married were positively associated with vaccination, particularly for men, whereas being an immigrant was negatively associated. There was a negative association between a higher CCI score and HZV, indicating that healthier individuals were more likely to have been vaccinated. Conclusions Despite the vaccine being part of the National Pharmaceutical Benefit Scheme, receipt of the HZV was significantly associated with socioeconomic factors.

The influenza A(H1N1)pdm09 vaccination campaign from 2009 to 2010 was associated with a sudden increase in the incidence of narcolepsy in several countries. Narcolepsy with cataplexy is strongly associated with the human leukocyte antigen (HLA) class II DQB1*06:02 allele, and protective associations with the DQB1*06:03 allele have been reported. Several non-HLA gene loci are also associated, such as common variants of the T-cell receptor-α (TRA), the purinergic receptor P2RY11, cathepsin H (CTSH) and TNFSF4/OX40L/CD252. In this retrospective multicenter study, we investigated if these predisposing gene loci were also involved in vaccination-associated narcolepsy. We compared HLA− along with single-nucleotide polymorphism genotypes for non-HLA regions between 42 Pandemrix-vaccinated narcolepsy cases and 1990 population-based controls. The class II gene loci associations supported previous findings. Nominal association (P-value

Background Type 1 narcolepsy is a neurological disorder characterized by excessive daytime sleepiness and cataplexy associated with the HLA allele DQB1*06:02. Genetic predisposition along with external triggering factors may drive autoimmune responses, ultimately leading to the selective loss of hypocretin-positive neurons. Objective The aim of this study was to investigate potential aetiological factors in Swedish cases of postvaccination (Pandemrix) narcolepsy defined by interferon-gamma (IFNγ) production from immune cells in response to molecularly defined targets. Methods Cellular reactivity defined by IFNγ production was examined in blood from 38 (HLA-DQB1*06:02+) Pandemrix-vaccinated narcolepsy cases and 76 (23 HLA-DQB1*06:02+ and 53 HLA-DQB1*06:02−) control subjects, matched for age, sex and exposure, using a variety of different antigens: β-haemolytic group A streptococcal (GAS) antigens (M5, M6 and streptodornase B), influenza (the pandemic A/H1N1/California/7/09 NYMC X-179A and A/H1N1/California/7/09 NYMC X-181 vaccine antigens, previous Flu-A and -B vaccine targets, A/H1N1/Brisbane/59/2007, A/H1N1/Solomon Islands/3/2006, A/H3N2/Uruguay/716/2007, A/H3N2/Wisconsin/67/2005, A/H5N1/Vietnam/1203/2004 and B/Malaysia/2506/2004), noninfluenza viral targets (CMVpp65, EBNA-1 and EBNA-3) and auto-antigens (hypocretin peptide, Tribbles homolog 2 peptide cocktail and extract from rat hypothalamus tissue). Results IFN-γ production was significantly increased in whole blood from narcolepsy cases in response to streptococcus serotype M6 (P = 0.0065) and streptodornase B protein (P = 0.0050). T-cell recognition of M6 and streptodornase B was confirmed at the single-cell level by intracellular cytokine (IL-2, IFNγ, tumour necrosis factor-alpha and IL-17) production after stimulation with synthetic M6 or streptodornase B peptides. Significantly, higher (P = 0.02) titres of serum antistreptolysin O were observed in narcolepsy cases, compared to vaccinated controls. Conclusion β-haemolytic GAS may be involved in triggering autoimmune responses in patients who developed narcolepsy symptoms after vaccination with Pandemrix in Sweden, characterized by a Streptococcus pyogenes M-type-specific IFN-γ cellular immune response.

Increased narcolepsy incidence was observed in Sweden following the 2009 influenza vaccination with Pandemrix®. A substitution of the 2009 nucleoprotein for the 1934 variant has been impli...

Objective To assess incidence of condyloma after two doses of quadrivalent human papillomavirus (qHPV) vaccine, by time since first vaccine dose, in girls and women initiating vaccination before age 20 years. Design Register-based nationwide open cohort study. Setting Sweden. Participants Girls and women initiating qHPV vaccination before age 20 years between 2006 and 2012. The study cohort included 264 498 girls, of whom 72 042 had received two doses of qHPV vaccine and 185 456 had received all three doses. Main outcome measure Incidence rate ratios (IRRs) of condyloma estimated by time between first and second doses of qHPV in months (m) and age at vaccination, adjusted for attained age. Results For girls first vaccinated with two doses before the age of 17 years, the IRR of condyloma for 0–3 months between the first and second doses was 1.96 (95% CI 1.43 to 2.68) as compared with the standard three-dose schedule. The IRRs were 1.27 (95% CI 0.63 to 2.58) and 4.36 (95% CI 2.05 to 9.28) after receipt of two doses with 4–7 months and 8+ months between doses, respectively. For women first vaccinated after the age of 17 years, vaccination with two doses of qHPV vaccine and 0–3 months between doses was associated with an IRR of 2.12 (95% CI 1.62 to 2.77). For an interval of 4–7 months between doses, the IRR did not statistically significantly differ to the standard three-dose schedule (IRR=0.81, 95% CI 0.36 to 1.84). For women with 8+ months between dose 1 and dose 2 the IRR was 3.16 (95% CI 1.40 to 7.14). Conclusion A two-dose schedule for qHPV vaccine with 4–7 months between the first and second doses may be as effective against condyloma in girls and women initiating vaccination under 20 years as a three-dose schedule. Results from this nationwide study support immunogenicity data from clinical trials.

Objectives To investigate disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy. Methods Case-control study in Sweden. Cases included persons referred for a Multiple Sleep Latency Test between 2009 and 2010, identified through diagnostic sleep centres and confirmed through independent review of medical charts. Controls, selected from the total population register, were matched to cases on age, gender, MSLT-referral date and county of residence. Disease history (prescriptions and diagnoses) and vaccination history was collected through telephone interviews and population-based healthcare registers. Conditional logistic regression was used to investigate disease history before A(H1N1)pdm09 vaccination as a risk-factor for narcolepsy. Results In total, 72 narcolepsy cases and 251 controls were included (range 3–69 years mean19-years). Risk of narcolepsy was increased in individuals with a disease history of nervous system disorders (OR range = 3.6–8.8) and mental and behavioural disorders (OR = 3.8, 95% CI 1.6–8.8) before referral. In a second analysis of vaccinated individuals only, nearly all initial associations were no longer statistically significant and effect sizes were smaller (OR range = 1.3–2.6). A significant effect for antibiotics (OR = 0.4, 95% CI 0.2–0.8) and a marginally significant effect for nervous system disorders was observed. In a third case-only analysis, comparing cases referred before vaccination to those referred after; prescriptions for nervous system disorders (OR = 26.0 95% CI 4.0–170.2) and ADHD (OR = 35.3 95% CI 3.4–369.9) were statistically significant during the vaccination period, suggesting initial associations were due to confounding by indication. Conclusion The findings of this study do not support disease history before A(H1N1)pdm09 vaccination as a risk factor for narcolepsy.

Narcolepsy is a lifelong sleep disorder related to hypocretin deficiency resulting from a specific loss of hypocretin-producing neurons in the lateral hypothalamic area. The disease is thought to be autoimmune due to a strong association with HLA-DQB1*06:02. In 2009 the World Health Organization (WHO) declared the H1N1 2009 flu pandemic (A/H1N1PDM09). In response to this, the Swedish vaccination campaign began in October of the same year, using the influenza vaccine Pandemrix(®). A few months later an excess of narcolepsy cases was observed. It is still unclear to what extent the vaccination campaign affected humoral autoimmunity associated with narcolepsy. We studied 47 patients with narcolepsy (6-69 years of age) and 80 healthy controls (3-61 years of age) selected after the Pandemrix vaccination campaign. The first aim was to determine antibodies against A/H1N1 and autoantibodies to Tribbles homolog 2 (TRIB2), a narcolepsy autoantigen candidate as well as to GAD65 and IA-2 as disease specificity controls. The second aim was to test if levels and frequencies of these antibodies and autoantibodies were associated with HLA-DQB1*06:02. In vitro transcribed and translated [(35)S]-methionine and -cysteine-labeled influenza A virus (A/California/04/2009/(H1N1)) segment 4 hemagglutinin was used to detect antibodies in a radiobinding assay. Autoantibodies to TRIB2, GAD65 and IA-2 were similarly detected in standard radiobinding assays. The narcolepsy patients had higher median levels of A/H1N1 antibodies than the controls (p = 0.006). A/H1N1 antibody levels were higher among the