Age-specific severity of SARS-CoV-2 in February 2020 - June 2021 in the Netherlands (preprint)

Background: Severity of SARS-CoV-2 infection may vary over time. Here, we estimate age-specific risks of hospitalization, ICU admission and death given infection in the Netherlands from February 2020 - June 2021. Methods: A nationwide longitudinal serology study was used to estimate numbers of infections in three epidemic periods (February 2020 - June 2020, July 2020 - February 2021, March 2021 - June 2021). We accounted for reinfections and, as vaccination started in January 2021, breakthrough infections among vaccinated persons. Severity estimates were inferred by combining numbers of infections with aligned numbers of hospitalizations and ICU admissions from a national hospital-based registry, and aligned numbers of deaths based on national excess all-cause mortality estimates. Results: In each period there was a nearly consistent pattern of accelerating, almost exponential, increase in severity of infection with age. The rate of increase with age was highest for death and lowest for hospitalization. In the first period, the overall risk of hospitalization, ICU admission and death were 1.5% (95%-confidence interval [CI] 1.3-1.8%), 0.36% (95%-CI: 0.31-0.42%) and 1.2% (95%-CI: 1.0-1.4), respectively. The risk of hospitalization was higher in the following periods, while the risk of ICU admission remained stable. The risk of death decreased over time, with a substantial drop among [≥]70-years-olds in February 2021 - June 2021. Conclusion: The accelerating increase in severity of SARS-CoV-2 with age remained intact during the first three epidemic periods in the Netherlands. The substantial drop in risk of death among elderly in the third period coincided with the introduction of COVID-19 vaccination.

COVID-19 vaccine effectiveness against mortality and risk of death from other causes after COVID-19 vaccination, the Netherlands, January 2021- January 2022 (preprint)

Background: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk in non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. Methods: National registries of causes of death, COVID-19 vaccination and long-term care reimbursements were linked by a unique identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 8 weeks following a first, second or booster dose, adjusting for birth year, sex and country of origin. Results: VE against COVID-19 mortality was >90% for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80% at 7-8 months post-primary series for most groups, and around 60% for elderly receiving a high level of long-term care and for people aged 90+ years. The risk of non-COVID-19 mortality was lower or similar in the 8 weeks following a first booster dose compared to no vaccination, first or second dose, respectively, for all age and long-term care groups. Conclusion: COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was seen at the population level.