Abstract Background Prior outpatient studies often lacked structured longitudinal symptom assessments and serial virological measurements, limiting evaluation of sex-specific trajectories.Sex-specific differences in clinical manifestations and antiviral response of mild-to-moderate Coronavirus disease 2019 (COVID-19) remain incompletely understood. Method We analyzed otherwise healthy patients with mild-to-moderate COVID-19 enrolled in a randomized, placebo-controlled trial, incorporating daily symptom diaries and serial viral load measurements to capture both the natural course and antiviral treatment response. The outcomes included time to sustained resolution of 11 prespecified symptoms, symptom profiles, time to resolution of individual symptoms and changes in viral loads. Sex-specific differences were analyzed using Kaplan-Meier curves and accelerated failure time models. Results From August 19, 2022, to December 16, 2022, 1,106 otherwise healthy patients were included, with the median age of 35.0 years and 649 58.7% males (Fig. A). Females exhibited higher baseline symptom severity (6.30 ± 3.23 VS. 5.88 ± 3.16; P = 0.03) and more high proportions of cough (77.0% VS. 68.9%, P = 0.004), stuffy nose (60.0% VS. 51.9%, P = 0.010) and sore throat (77.9% VS. 70.7%, P = 0.009) than males. Without antiviral treatment, females showed greater viral reduction of 0.41±0.24 log10 copies/ml than males on day 5. In antiviral group, more obvious viral loads reduction was observed in males (0.49±0.34 log10 copies/ml) than females on day 5 (Fig. B-C). Kaplan-Meier curve indicated that men experienced shorter symptom recovery times than women in both antiviral and placebo groups (Fig. D). After the proportional hazards assumption testing, Cox proportional hazards model was not appropriate. Multivariable accelerated failure time modeling confirmed female sex was independently associated with prolonged time recovery (time ratio 1.14; 95% CI: 1.02-1.26)(Fig. E). Conlusion Our findings refine the understanding of sex differences in COVID-19 by demonstrating that, in mild-to-moderate disease, females experience longer symptom duration despite faster viral clearance, contrasting with prior studies that emphasized worse outcomes in males. Our findings highlight the importance of integrating sex as a biological variable in COVID-19 management and trials. This abstract is funded by: None
Liu et al. (Fri,) studied this question.