Abstract: Long-term diet and risk of SARS -CoV-2 infection and Coronavirus Disease 2019 (COVID19) severity Yiyang Yue, MS1, Wenjie Ma, ScD 2,3, Emma K. Accorsi, PhD4, Ming Ding, ScD1, Frank Hu, ScD1,5,7, Janet Rich Edwards, ScD5,7, Stephanie A. Smith-Warner, PhD1,5, Shilpa N. PT Bhupathiraju, PhD1,6 Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA 2 Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard SC RI 1 Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, N 3 U Medical School, Boston, MA M Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA ED 4 A Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 6 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s ED IT 5 Division of Women’s Health, Department of Medicine, Brigham and Women’s Hospital and U 7 N Hospital and Harvard Medical School, Boston, MA L Harvard Medical School, Boston, MA IN A Corresponding author: Shilpa N Bhupathiraju (sbhupath@hsph.harvard.edu) Running head: Diet and risk of COVID-19 infection and severity G Word counts: O RI Abstract: 265 Main text: 3,699 © The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com MD, PhD1,5,6, Walter C. Willett, MD, PhD1,5,6, Andrew T. Chan, MD, MPH2,3,5,6, Qi Sun, MD, Abbreviations AHEI, Alternate Healthy Eating Index; AMED, alternative Mediterranean Diet; BMI, body mass index; COVID-19, Coronavirus Disease 2019; EDIH, Empirical Dietary Index for Follow-up Study; IPW, inverse probability weighting; MET, metabolic equivalent of tasks; NHS, O RI G IN A L U N ED IT ED M A N U SC RI PT Nurses’ Health Study; PPE, personal protective equipment; Q, quartile Hyperinsulinemia; EDIP, empirical dietary inflammatory pattern; HPFS, Health Professionals ABSTRACT Background The role of diet on COVID-19 is emerging. We included 42,935 participants aged 55 to 99 years in two ongoing cohort studies, Nurses’ PT Health Study II and Health Professionals Follow-up Study, who completed a series of COVID19 surveys in 2020 and 2021. Using data from food frequency questionnaires prior to COVID-19, RI we assessed diet quality using the Alternative Healthy Eating Index (AHEI)-2010, the alternative SC Mediterranean Diet (AMED) score, an Empirical Dietary Index for Hyperinsulinemia (EDIH), U and an Empirical Dietary Inflammatory Pattern (EDIP). We calculated multivariable adjusted N odds ratios (ORs) and 95% confidence intervals (95% CIs) for SARS-CoV-2 infection and M A severity of COVID-19 after controlling for demographic, medical, and lifestyle factors. Results ED Among 19,754 participants tested for SARS-CoV-2, 1,941 participants reported a positive result. IT Of these, 1,327 reported symptoms needing assistance and another 109 were hospitalized. ED Healthier diet, represented by higher AHEI-2010 and AMED scores and lower EDIH and EDIP N scores, were associated..