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.

COVID-19 trends and severity among symptomatic children aged 0 to 17 years in ten EU countries, 3 August 2020 to 3 October 2021 (preprint)

To guide evidence-based prevention of COVID-19 in children, we estimated risks of severe outcomes in 820,404 symptomatic paediatric cases reported by 10 EU Member States between August 2020 and October 2021. Case and hospitalisation rates rose as overall transmission increased but severe outcomes were rare: 9,611 (1.2%) were hospitalised, 640 (0.08%) required intensive care and 84 (0.01%) died. Despite increased individual risk (aOR; 95% CI for hospitalisation: 7.3; 3.3 - 16.2, ICU: 8.7; 6.2 - 12.3) in cases with comorbidities such as cancer, diabetes, cardiac or lung disease, most (83.7%) hospitalised children had no reported comorbidity.

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.

The role of children in the transmission chain of SARS-CoV-2: a systematic review and update of current evidence (preprint)

Decisions on school closures and on safe schooling during the COVID-19 pandemic should be evidence-based. We conducted a systematic literature review to assess child-to-child and child-to-adult SARS-CoV-2 transmission and to characterise the potential role of school closures on community transmission. 1337 peer-reviewed articles published through August 31, 2020 were screened; 22 were included in this review. The literature appraised provides sufficient evidence that children can both be infected by and transmit SARS-CoV-2 in community, household and school settings. Transmission by children was most frequently documented in household settings, while examples of children as index cases in school settings were rare. Included studies suggested that school closures may help to reduce SARS-CoV-2 transmission, but the societal, economic, and educational impacts of prolonged school closures must be considered. In-school mitigation measures, alongside continuous surveillance and assessment of emerging evidence, will promote the protection and educational attainment of students and support the educational workforce.