IntroductionTimely hospital presentation and treatment are critical for recovery from coronavirus disease (COVID-19). However, the relationship between symptom onset-to-door time and key clinical outcomes, such as inpatient mortality, has been poorly understood due to the difficulty of retrospectively measuring symptom onset in observational data. This study examines the association between patient-reported symptom onset-to-door time (ODT) and mortality among patients hospitalized and treated for COVID-19 disease. MethodsWe conducted a retrospective cohort study of emergency department (ED) encounters of patients with COVID-19 disease who were hospitalized and received remdesivir and/or dexamethasone between March 1, 2020, and March 1, 2022. The exposure was patient-reported ODT in days. The outcome of interest was inpatient mortality, including referral to hospice care. We used multivariable logistic regression to examine the association between ODT and mortality while adjusting for patient characteristics, hospital sites, and seasonality. We tested whether severe illness on hospital presentation modified the association between ODT and mortality. Severe illness was defined by Emergency Severity Index triage level 1 or 2 and hypoxia (SpO2 < 94%). ResultsOf the 3451 ED hospitalizations included, 439 (12.7%) resulted in mortality, and 1693 (49.1%) involved patients with severe illness on hospital presentation. Greater ODT was significantly associated with lower odds of inpatient mortality (adjusted odds ratio (AOR) = 0.96, 95% CI = 0.93–1.00, P = 0.023). There was a statistically significant interaction between ODT and severe illness at hospital arrival on mortality, suggesting the negative association between ODT and mortality specifically pertained to patients who were not severely ill upon ED presentation (AOR = 0.93, 95% CI = 0.87–1.00, P = 0.035). The adjusted probability of mortality was significantly lower for non-severely ill, hospitalized patients who presented on days 8–14 (5.2%–3.3%) versus days 0–3 (9.4%–7.5%) after symptom onset. ConclusionMore days between symptom onset and hospital arrival were associated with lower mortality among hospitalized patients treated for COVID-19 disease, particularly if they did not have severe illness at ED presentation. However, onset-to-door time was not associated with mortality among hospitalized patients with severe illness at ED presentation. Collectively, these results suggest that non-severely ill COVID-19 patients who require hospitalization are less likely to decompensate with each passing day without severe illness. These findings may continue to guide clinical care delivery for hospitalized COVID-19 patients.