Declaration of interests: The authors declare no competing interests. 28 Role of the funding sources: No funding was received for this work. The corresponding author 29 had full access to all the data in the study and had final responsibility for the decision to submit 30 for publication.
The pathophysiology of the acute respiratory syndrome in the setting of COVID-19 is not 34 yet fully understood. 1 Differences in severity and fatality outcomes according to patient's sex 35 have been noted across multiple early pandemic outbreak areas, such as China 2 and Italy. 3
Studies performed in the US have examined predictors of mortality and severity, however they 37 included a few hundred patients 4 , or were focused on time periods early in the COVID-19 38 outbreak and confounders were not properly addressed with multivariate analyses 5,6 . Here we 39 assess differences in COVID-19 severity between male and female patients while accounting for were downloaded from 02/29/2020 to 05/19/2020 and emergency department and inpatient 46 encounters were selected. The dataset contained patient demographics, comorbidities, vitals and outcomes. COVID-19 results were confirmed using RT-PCR on nasopharyngeal swabs. Ever-48 smokers were defined as current and former smokers. Hypoxemia was determined as a peripheral 49 SpO2 measurement at or below 92%. 7 Sepsis was determined using the Systemic Inflammatory 50 Response Syndrome criteria. 8 The main outcomes in this study were 1) mortality and 2) clinical 51 presentation at admission (peripheral O 2 saturation, sepsis). Chi-squared tests were performed for 52 univariate analyses, and multivariate stepwise logistic regression models were performed for 53 multivariate analyses. Demographic and clinical variables to be included in the model were 54 selected according to a priori knowledge of their association with COVID-19 mortality and severity, as well as according to results of univariate analyses (Supplementary Table 1 were significantly associated with decreased O 2 saturation upon presentation. A history of cancer 80 was significantly associated with higher odds of sepsis on initial presentation, and a significant 81 interaction between age and sex was observed (p<0.05). Males in each age category were more 82 likely to present with sepsis than female, although the association was significant for the age 83 groups < 40 years and 40-69 years. Here we also report that sepsis and hypoxemia at admission are early clinical indicators 99 of subsequent mortality from COVID-19, and that male, older patients, patients with 100 comorbidities were more likely to present with these clinical characteristics. These results add to the conversation about predictors of worse outcomes in COVID-19 patients, and point at male J o u r n a l P r e -p r o o f *Stepwise logistic regression model performed. Smoking status, hypertension, asthma, CKD, HIV were originally included in the model and were removed. The final model was Sex, age, race, history of COPD, history of cancer, and BMI. Hypoxemia was defined as patients with ≤ 92% peripheral O 2 saturation. #Stepwise logistic regression model performed. Smoking status, asthma, COPD, CKD, HIV, and obesity were originally included in the model and were removed. The final model was adjusted for sex*age, age, race, history of cancer, and history of hypertension. The age*sex interaction term (p<0.05) and the sex and age group interaction terms (40-69 vs <40 years p = 0.0182; ≥70 vs <40 years, p = 0.0018) were statistically significant J o u r n a l P r e -p r o o f