Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study
M T H M Henkens, AG Raafs, Job A.J. Verdonschot, Marijke Linschoten, Maarten van Smeden, Ping Wang, B. H. M. van der Hooft, R. G. Tieleman, Marcus L.F. Janssen, Rachel M.A. ter Bekke, Mark R. Hazebroek, Iwan C.C. van der Horst, Folkert W. Asselbergs, F. J. H. Magdelijns, Stéphane Heymans, A. K. Al-Ali, Fahd A Al-Muhanna, N. Y. Y. Al-Windy, Y. A. Almubarak, A. N. Alnafie, Mohammed Alshahrani, A. M. Alshehri, R. L. Anthonio, Folkert W. Asselbergs, Avinash Aujayeb, Jan Berg, A. J. M. van Boxem, Gaby Captur, Massimo Caputo, N. Charlotte, Paul Dark, Johan De Sutter, C. E. Delsing, H. G. R. Dorman, J. T. Drost, M E Emans, Janise Braga Barros Ferreira, Laurence Gabriël, Wiek H. van Gilst, B. E. Groenemeijer, H. E. Haerkens-Arends, Pim van der Harst, Behnam Hedayat, Dirk J. van der Heijden, Elias Hellou, R. S. Hermanides, J.F. Hermans-van Ast, M. W. J. van Hessen, Stéphane Heymans, Iwan C.C. van der Horst, Sabrina H. van Ierssel, L. S. D. Jewbali, MT Kearney, H. A. M. van Kesteren, Bas Kietselaer, Aafke M H Koning, P. Y. Kopylov, A. F. M. Kuijper, Johanna M. Kwakkel‐van Erp, M. M. J. M. van der Linden, Marijke Linschoten, G. C. M. Linssen, Rosa Macías‐Ruiz, F. J. H. Magdelijns, Fabrice M A C Martens, Gerry P McCann, Pim van der Meer, M. F. L. Meijs, Peter Messiaen, P. S. Monraats, Laura Montagna, A. Moriarty, Arend Mosterd, P.R. Nierop, Clara E E van Ofwegen-Hanekamp, Y M Pinto, Hamidreza Poorhosseini, SK Prasad, Josep Redón, A. C. Reidinga, M. I. A. Ribeiro, David P Ripley, Rehab Salah, E. Saneei, Manish Saxena, Jeroen Schaap, Dirk Schellings, Astrid Schut, Akbar Shafiee, Angela C. Shore, Hans‐Marc J. Siebelink, Maarten van Smeden, Peter Smits, Ron Pisters, Elena Tessitore, R. G. Tieleman, Philippe Timmermans, R. A. Tio, Fleur V.Y. Tjong, Corstiaan A. den Uil
Abstract
BACKGROUND: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. METHODS: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. RESULTS: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p< 0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. CONCLUSIONS: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. TRIAL REGISTRATION: CAPACITY-COVID ( NCT04325412 ).