Abstract: 1 Reduction in risk of death among patients admitted with COVID-19 between first and 2 second epidemic waves in New York City 3 26 Running Title: Epidemic wave impacts COVID-19 mortality 1 M A N Corresponding Author: Anthony Bowen, MD, PhD 622 West 168th Street 8th Floor, New York, NY, USA Ab5046@cumc.columbia.edu 260-403-6964 EP TE D Alternate Jason Zucker, MD, MS 622 West 168th Street 8th Floor, New York, NY, USA Jz2700@cumc.columbia.edu 201-723-6637 CC Keywords: COVID-19, Mortality, Cox regression, Epidemics A 29 U Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, USA. 2 Gertrude H. Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, USA. * Contributed equally 27 28 SC RI PT Anthony Bowen1,*, Jason Zucker1,*, Yanhan Shen2, Simian Huang1, Qiheng Yan2, Medini K. Annavajhala1, Anne-Catrin Uhlemann1, Louise Kuhn2, Magdalena Sobieszczyk1,*, Delivette Castor1,* © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercialNoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 1 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 1 Abstract 2 4 the emergence of SARS-CoV-2 with heterogeneous differences in mortality. Elucidating factors 5 differentially associated with mortality between epidemic waves may inform clinical and public 6 health strategies. 7 Methods: We examined clinical and demographic data among patients admitted with COVID-19 8 during the first (March-August 2020) and second (August 2020-March 2021) epidemic waves at 9 an academic medical center in New York City. 10 Results: Hospitalized patients (N=4631) had lower overall and 30-day in-hospital mortality, 11 defined as death or discharge to hospice, during the second wave (14% and 11%) than the first 12 (22% and 21%). The wave 2 in-hospital mortality decrease persisted after adjusting for several 13 potential confounders. Adjusting for the volume of COVID-19 admissions, a measure of health 14 system strain, accounted for the mortality difference between waves. Several demographic and 15 clinical patient factors were associated with an increased risk of mortality independent of wave; 16 SARS-CoV-2 cycle threshold, Do-Not-Intubate status, oxygen requirement, and intensive care 17 unit admission. 18 Conclusions: This work suggests that increased in-hospital mortality rates observed during the U N A M D TE EP CC 19 SC RI PT Background: Many regions have experienced successive epidemic waves of COVID-19 since first epidemic wave were partly due to strain on hospital resources. Preparations for future epidemics should prioritize evidence-based patient risks, treatment paradigms, and approaches to 21 augment hospital capacity. A 20 2