Estimated number of lives directly saved by COVID-19 vaccination programs in the WHO European Region, December 2020 to March 2023 (preprint)

BackgroundBy March 2023, 54 countries, areas and territories (thereafter "CAT") reported over 2.2 million coronavirus disease 2019 (COVID-19) deaths to the World Health Organization (WHO) Regional Office for Europe (1). Here, we estimate how many lives were directly saved by vaccinating adults in the Region, from December 2020 through March 2023. MethodsWe estimated the number of lives directly saved by age-group, vaccine dose and circulating Variant of Concern (VOC) period, both regionally and nationally, using weekly data on COVID-19 mortality and COVID-19 vaccine uptake reported by 34 CAT, and vaccine effectiveness (VE) data from the literature. We calculated the percentage reduction in the number of expected and reported deaths. FindingsWe found that vaccines reduced deaths by 57% overall (CAT range: 15% to 75%), representing [~]1.4 million lives saved in those aged [≥]25 years (range: 0.7 million to 2.6 million): 96% of lives saved were aged [≥]60 years and 52% were aged [≥]80 years; first boosters saved 51%, and 67% were saved during the Omicron period. InterpretationOver nearly 2.5 years, most lives saved by COVID-19 vaccinationwere in older adults by first booster dose and during the Omicron period, reinforcing the importance of up-to-date vaccination among these most at-risk individuals. Further modelling work should evaluate indirect effects of vaccination and public health and social measures. FundingThis work was supported by a US Centers for Disease Control cooperative agreement (Grant number 6 NU511P000936-02-020), who had no role in data analysis or interpretation. DisclaimerThe authors affiliated with the World Health Organization (WHO) are alone responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of the WHO. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSSince first identified in late 2019, COVID-19 has caused disproportionately high mortality rates in older adults. With the rapid development and licensing of novel COVID-19 vaccines, immunization campaigns across the WHO European Region started in late 2020 and early 2021, initially targeting the most vulnerable and exposed populations, including older adults, people with comorbidities and healthcare professionals. Several studies have estimated the number of lives saved by COVID-19 vaccination, both at national and multi-country level in the earlier stages of the pandemic. However, only one multi-country study has assessed the number of lives saved beyond the first year of the pandemic, particularly when the Omicron variant of concern (VOC) circulated, a period when vaccination coverage was high in many countries, areas and territories (CAT), but COVID-19 transmission was at its highest. Added value of this studyHere we quantified the impact of COVID-19 vaccination in adults by age-group, vaccine dose and period of circulation of VOC, across diverse settings, using real world data reported by 34 CAT in the WHO European Region for the period December 2020 to April 2023. We estimated that COVID-19 vaccination programs were associated with a 57% reduction (CAT range: 15% to 75%) in the number of deaths among the [≥]25 years old, representing over 1.5 million lives saved (range: 0.7 million to 2.6 million) in 34 European CAT during the first 2.5 years following vaccine introduction. The first booster savedthe most lives (721,122 / 1,408,967, (57%) of all lives saved). The [≥]60 years old age group accounted for 96% of the total lives saved (1,349,617 / 1,408,967) whereas the [≥]80 years old age group represented 52% of the total lives saved (728,858 / 1,408,967 lives saved) and 67% of all lives were saved during the Omicron period (942,571 / 1,408,967). Implications of all the available evidenceOur results reinforce the importance of up-to-date COVID-19 vaccination, particularly among older age-groups. Communication campaigns supporting COVID-19 vaccination should stress the value of COVID-19 vaccination in saving lives to ensure vulnerable groups are up-to-date with vaccination ahead of periods of potential increased transmission.

A standardised protocol for assessment of relative SARS-CoV-2 variant severity, with application to severity risk for COVID-19 cases infected with Omicron BA.1 compared to Delta variants in six European countries (preprint)

Several SARS-CoV-2 variants that evolved during the COVID-19 pandemic have appeared to differ in severity, based on analyses of single-country datasets. With decreased SARS-CoV-2 testing and sequencing, international collaborative studies will become increasingly important for timely assessment of the severity of newly emerged variants. The Joint WHO Regional Office for Europe and ECDC Infection Severity Working Group was formed to produce and pilot a standardised study protocol to estimate relative variant case-severity in settings with individual-level SARS-CoV-2 testing and COVID-19 outcome data during periods when two variants were co-circulating. To assess feasibility, the study protocol and its associated statistical analysis code was applied by local investigators in Denmark, England, Luxembourg, Norway, Portugal and Scotland to assess the case-severity of Omicron BA.1 relative to Delta cases. After pooling estimates using meta-analysis methods (random effects estimates), the risk of hospital admission (adjusted hazard ratio [aHR]=0.41, 95% CI 0.31-0.54), ICU admission (aHR=0.12, 95% CI 0.05-0.27), and death (aHR=0.31, 95% CI 0.28-0.35) was lower for Omicron BA.1 compared to Delta cases. The aHRs varied by age group and vaccination status. In conclusion, this study has demonstrated the feasibility of conducting variant severity analyses in a multinational collaborative framework. The results add further evidence for the reduced severity of the Omicron BA.1 variant.

Age Specific Associations Between Underlying Conditions and Hospitalisation, Death and In-Hospital Death Among Confirmed COVID-19 Cases: A Multi-Country Study Based on Surveillance Data (preprint)

Background: Underlying conditions have been found to be associated with severe COVID-19 outcomes, such as hospitalisation and death. This study aimed to estimate age-specific adjusted relative and absolute effects of individual underlying conditions on hospitalisation, death and in-hospital death among COVID-19 cases.Methods: We analysed case-based COVID-19 data submitted to The European Surveillance System (TESSy) between 2 June and 13 December 2020 by nine European countries. We individually assessed the association between 11 underlying conditions with hospitalisation, death and in-hospital death. Two additional categorical exposures were created: number of underlying conditions (1,2, ≥ 3) and the presence of any underlying condition (≥ 1). Adjusted ORs (aOR) for the association between each exposure condition and outcome were estimated using two multivariable logistic regression models: 1) an age-adjusted model and 2) an age-interaction model (exposure condition*age). All models were adjusted for sex, reporting period (June-September; October-December) and reporting country. From the age-interaction model we estimated the predicted probability of the three outcomes for each level of condition and age-group, marginalised over the levels of each covariable.Findings: After controlling for age, sex, reporting period and reporting country in the age-adjusted models, cases with cancer, cardiac disorder, diabetes, immune deficiency disorder, kidney disease, liver disease, lung disease, neurological disorders, obesity, any underlying condition or up to three or more conditions were between 1·5 and 5·6 times more likely to be hospitalised or die than cases with no underlying condition. Asthma was associated with increased overall risk of hospitalisation, not death. Age was an important modifier of these associations, with an age interaction present in the majority of models. For all outcomes, age-specific aOR in the age-interaction models tended to decrease with increasing age, whereas predicted probabilities of the outcome increased with age. For instance, individuals aged <20 years with any underlying condition were significantly more likely to be hospitalised (aOR: 5·16, 95%CI: 4·42 - 6·02) and die (aOR: 33·77, 95%CI: 12·57 - 90·75) compared to same-aged individuals without condition. The aOR fell to 1·77 (95%CI: 1·71 - 1·83) and 1·61 (95%CI: 1·55 - 1·68) respectively in individuals 80 years and older. Conversely, the predicted probabilities of hospitalisation and death among cases aged <20 years were 5·69% (95%CI: 4·97 - 6·51) and 0.15% (95%CI: 0·08 - 0·31), respectively, while they were 44·55% (95%CI: 43·68 - 45·43) and 16·31% (95%CI: 15·44 - 17·21), respectively for individuals aged 80 years and older. For some conditions, the probability of the outcome was at least as high in younger individuals with the condition as older cases without the condition.Interpretation: Several underlying conditions were found to have a significant independent effect on severe COVID-19 outcomes. Age is an important effect modifier in these associations. Interpretation of the results in this study is facilitated by considering together the estimates of relative (aOR) and absolute (predicted probabilities) effects that are presented. The presence of underlying conditions tended to have a larger relative effect in the young than the old, but the absolute probability of being hospitalised or dying increased with age. The finding that for some conditions, a younger person may have the same or even higher probability of severe outcome than an older person without it, has relevance for age and risk-factor based prioritisation of vaccination, particularly in the young.Funding Information: This study was funded through ECDC internal funding.Declaration of Interests: None to declare.

Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys (preprint)

Background Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. Funding This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Risk of hospitalization and risk of death for healthcare workers with COVID-19 in nine European Union/European Economic Area countries, January 2020 - January 2021 (preprint)

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.

SARS-CoV-2 Transmission in Educational Settings During an Early Summer Epidemic Wave in Luxembourg (preprint)

Background: The role of schools and children in the transmission of SARS-CoV-2 remains to be determined. Following a first wave in spring and gradual easing of lockdown, Luxembourg experienced an early second epidemic wave before the start of summer school holidays on 15th July. This provided the opportunity to study the role of school-age children and school settings in SARS-CoV-2 transmission. More specifically, we compared the incidence in school-age children, teachers and the general working population, and estimated the number of secondary transmissions occurring at schools using contact tracing data.Findings: While SARS-CoV-2 incidence was much higher in adults aged 20 and above than in children aged 0 to 19 during the first wave in spring, no significant difference was found during the second wave in early summer. The incidence during the second wave was similar for pupils, teachers and the general working population. Based on a total of 424 reported confirmed COVID-19 cases in school-age children and teachers, we estimate that 179 index cases caused 49 secondary transmissions in schools. While some small clusters of mainly student-to-student transmission within the same class were identified, we did not observe any large outbreaks with multiple generations of infection.Interpretation: Transmission of SARS-CoV-2 within Luxembourg schools was limited during the early summer epidemic wave in 2020. Precautionary measures including physical distancing as well as easy access to testing, systematic contact tracing appears to have been successful in mitigating transmission within educational settings.Funding Statement: LV is supported by the Luxembourg National Research Fund grant COVID-19/2020- 1/14701707/REBORN, LM is supported by Luxembourg National Research Fund grant COVID19/14863306/PREVID, PW is supported by the European Research Council (ERC-CoG 863664).Declaration of Interests: No competing interests.Ethics Approval Statement: The Health Directorate has the legal permission to process patient confidential information for national surveillance of communicable diseases in general and contact tracing for the COVID-19 pandemic and individual patient consent is not required.