Impact of Sex on Viral Shedding and Symptom Severity During Acute COVID-19

To evaluate the impact of sex on acute SARS-CoV-2 infection, 668 participants from the ACTIV-2/A5401 study were followed over a 28-day period.

A primary analysis was performed on 469 participants with quantifiable viral loads at baseline.

Male and female participants had comparable nasal SARS-CoV-2 RNA levels at study entry and throughout follow-up. However, sex-specific differences in viral shedding emerged when stratified by symptom duration. In the first 3 days after symptom onset, female participants exhibited higher nasal SARS-CoV-2 RNA levels than males, but lower viral RNA levels thereafter. The higher viral RNA levels in females during the earliest phase of acute COVID-19 were observed even after adjusting for age, race, and region of enrollment. Female participants also tended to have higher symptom scores across days since symptom onset, but no significant correlation was observed between nasal SARS-CoV-2 RNA levels and symptom score regardless of sex.

These findings highlight the impact of sex on both viral shedding and symptom dynamics and underscore the importance of considering time since symptom onset when evaluating antiviral therapies for respiratory viruses in clinical trials.