Viral shedding and symptom severity across populations during acute COVID in the ACTIV-2 study

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 the 469 participants who had 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 duration of symptoms. In the first three days from 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 was seen 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 respiratory virus antiviral therapies in clinical trials.