This study investigates sex differences in immune responses to SARS-CoV-2 infection, which may explain the observed sex biases in COVID-19 disease outcomes. The researchers examined viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines, and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. They found that male patients had higher levels of innate immune cytokines like IL-8 and IL-18 and more robust induction of non-classical monocytes, while female patients had more robust T cell activation. Notably, poor T cell response negatively correlated with age and was associated with worse disease outcomes in male patients, whereas higher levels of innate immune cytokines were associated with worse disease progression in female patients. These findings suggest that sex-based approaches to treatment and care for male and female patients with COVID-19 may be necessary.This study investigates sex differences in immune responses to SARS-CoV-2 infection, which may explain the observed sex biases in COVID-19 disease outcomes. The researchers examined viral loads, SARS-CoV-2-specific antibody titres, plasma cytokines, and blood-cell phenotyping in patients with moderate COVID-19 who had not received immunomodulatory medications. They found that male patients had higher levels of innate immune cytokines like IL-8 and IL-18 and more robust induction of non-classical monocytes, while female patients had more robust T cell activation. Notably, poor T cell response negatively correlated with age and was associated with worse disease outcomes in male patients, whereas higher levels of innate immune cytokines were associated with worse disease progression in female patients. These findings suggest that sex-based approaches to treatment and care for male and female patients with COVID-19 may be necessary.