In this preprint, Takahashi et al. elucidate differences in the immune response to COVID-19 in 45 male and 48 female patients. Through both single time-point samples (collected before immunomodulatory therapy) and longitudinal analyses, they found that plasma CXCL8 and CCL5 levels were higher in male than in female patients, although other cytokines, such as TNFSF10 and IL-15, correlated with worse outcome in female but not male patients. Of note, female patients had more CD14+CD16+ monocytes, activated T cells and terminally differentiated CD8+ T cells; whereas male patients had a greater subset of CD14lowCD16+ monocytes but a poor CD8+ T cell response in disease progression. Collectively, these results, in association with clinical parameters, suggest less robust T cell-mediated immunity in male patients with worsening outcome and higher innate cytokine activity in declining female patients.