Sex differences in immune responses underlie COVID-19 disease outcomes. Men experience more severe symptoms and higher mortality from COVID-19 than women, but the mechanisms behind these differences are not well understood. A study analyzed immune responses in 98 patients with moderate COVID-19, finding that men had higher levels of innate immune cytokines like IL-8 and IL-18, along with more robust induction of non-classical monocytes. Women, on the other hand, showed more robust T cell activation. However, poor T cell responses in men were associated with worse disease outcomes, while higher innate immune cytokines in women were linked to worse outcomes. These findings suggest that sex differences in immune responses may explain the observed sex bias in COVID-19. The study also found that male patients had lower T cell activation and higher levels of innate immune cytokines compared to female patients. These differences were linked to disease progression, with male patients showing worse outcomes when T cell responses were poor, while female patients had worse outcomes with higher innate immune cytokines. The study highlights the importance of considering sex differences in immune responses when developing treatments for COVID-19. The research provides a basis for sex-based approaches to the treatment and care of male and female patients with COVID-19.Sex differences in immune responses underlie COVID-19 disease outcomes. Men experience more severe symptoms and higher mortality from COVID-19 than women, but the mechanisms behind these differences are not well understood. A study analyzed immune responses in 98 patients with moderate COVID-19, finding that men had higher levels of innate immune cytokines like IL-8 and IL-18, along with more robust induction of non-classical monocytes. Women, on the other hand, showed more robust T cell activation. However, poor T cell responses in men were associated with worse disease outcomes, while higher innate immune cytokines in women were linked to worse outcomes. These findings suggest that sex differences in immune responses may explain the observed sex bias in COVID-19. The study also found that male patients had lower T cell activation and higher levels of innate immune cytokines compared to female patients. These differences were linked to disease progression, with male patients showing worse outcomes when T cell responses were poor, while female patients had worse outcomes with higher innate immune cytokines. The study highlights the importance of considering sex differences in immune responses when developing treatments for COVID-19. The research provides a basis for sex-based approaches to the treatment and care of male and female patients with COVID-19.