BackgroundThe role of diet on COVID-19 is emerging.MethodsWe included 42,935 participants aged 55 to 99 years in two ongoing cohort studies, Nurses’ Health Study II and Health Professionals Follow-up Study, who completed a series of COVID-19 surveys in 2020 and 2021. Using data from food frequency questionnaires prior to COVID-19, we assessed diet quality using the Alternative Healthy Eating Index (AHEI)-2010, the alternative Mediterranean Diet (AMED) score, an Empirical Dietary Index for Hyperinsulinemia (EDIH), and an Empirical Dietary Inflammatory Pattern (EDIP). We calculated multivariable adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for SARS-CoV-2 infection and severity of COVID-19 after controlling for demographic, medical, and lifestyle factors.ResultsAmong 19,754 participants tested for SARS-CoV-2, 1,941 participants reported a positive result. Of these, 1,327 reported symptoms needing assistance and another 109 were hospitalized. Healthier diet, represented by higher AHEI-2010 and AMED scores and lower EDIH and EDIP scores, were associated with lower likelihood of SARS-CoV-2 infection (ORs Q (quartile) 4 vs. Q1 (95%CI) were 0.80 (0.69, 0.92) for AHEI-2010; 0.78 (0.67, 0.92) for AMED; 1.36 (1.16, 1.57) for EDIH; and 1.13 (0.99, 1.30) for EDIP; all p for trend ≤ 0.01). In the analysis of COVID-19 severity, participants with healthier diet had lower likelihood of severe infection and were less likely to be hospitalized due to COVID-19. However, associations were no longer significant after controlling for BMI and pre-existing medical conditions.ConclusionDiet may be an important modifiable risk factor for SARS-CoV-2 infection, as well as for severity of COVID-19. This association is partially mediated by BMI and pre-existing medical conditions.