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.

Differences in Mortality in Critically Ill Elderly Patients During the Second COVID-19 Surge in Europe (preprint)

Purpose: The primary aim of this study was to assess the outcome of elderly ICU patients treated during the spring and autumn COVID-19 surges in Europe.Methods: A prospective European observation study (The COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020. An electronic Case Record Form was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, comorbidities, usual ICU procedures including pharmacotherapy, limitation of care, ICU length of stay and survival at 30 days. The study was registered at ClinicalTrials.gov (ID: NCT04321265).Results: In total 2711 patients were included, 1325 from the first and 1291 from the second surge and 94 in between. Median age was 74 and 75 years in surge 1 and surge 2 respectively. SOFA score was higher in the first surge (median 6 versus 5, p<0.0001). The PaO2/FiO2 ratio at admission was higher during surge 1 and more patients received mechanical ventilation (78% versus 68%, p<0.0001). More patients were given corticosteroids in surge 2 (93 vs 38%, p<0.0001). 30 days survival was lower in the second surge (57.4% vs 49.3%) with adjusted HR of 1.43 (1.18-1.74).Conclusion: An unexpected, but significant, increase in 30-day mortality was observed during the second surge in our cohort of elderly ICU patients. The reason for this is unknown, however, practice changed and this might not be supported by sufficient evidence in this elderly population with COVID-19.Trial Registration: NCT04321265Funding Statement: The support of the study in France by a grant from Fondation Assistance Publique-Hôpitaux de Paris pour la recherche is greatly appreciated. In Norway, the study was supported by a grant from the Health Region West. In addition, the study was supported by a grant from the European Open Science Cloud (EOSC). EOSCsecretariat.eu has received funding from the European Union's Horizon Programme call H2020-INFRAEOSC-05-2018-2019, grant agreement number 831644.Declaration of Interests: The authors declare that they have no competing interests. JCS reports grants (full departmental disclosure) from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer , Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Dräger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Philips Medical, Phagenesis Ltd, Prolong Pharmaceuticals and Nycomed outside the submitted work. The money went into departmental funds. No personal financial gain applied.Ethics Approval Statement: The study was organised by the Very old Intensive care Patients (VIP) project 10,11 within the European Society of Intensive Care Medicine (ESICM) who also endorsed the study (www.vipstudy.org). Due to variations in requirement for ethical consent, some countries could recruit patients without upfront informed consent while others had to obtain it. The study deliberately allowed for coenrolment of study patients to other COVID-19 studies. The study adhered to the European Union General Data Privacy Regulation (GDPR) directive.