A study by Kusakabe et al. reports increased antibody responses to specific fungi in individuals with severe COVID-19, particularly to Candida albicans, and shows that intestinal expansion of C. albicans correlates with disease severity and neutrophil frequency in these individuals. Unlike healthy individuals or individuals with mild or moderate COVID-19, those with severe COVID-19 retained antifungal antibodies and higher levels of neutrophils for up to a year after SARS-CoV-2 infection. In mice, colonization with patient-derived C. albicans enhanced IL-6 receptor (IL-6R)-dependent activation of granulocyte myeloid progenitors (GMPs) and induced lasting changes in antifungal transcriptional pathways in these cells, which could be reversed with an anti-IL-6R antibody or the antifungal drug fluconazole. In a mouse model of COVID-19, colonization with C. albicans increased neutrophilia and lung NETosis. Notably, patients who received the IL-6R-targeted monoclonal antibody tocilizumab (which showed mixed results in COVID-19) during acute severe COVID-19 infection had lower levels of antifungal antibodies and antifungal transcriptional signatures in GMPs compared with matched patients who did not receive tocilizumab. The authors hypothesize that gut-colonizing C. albicans induce or amplify emergency haematopoiesis, reprogram GMPs and amplify the production of activated neutrophils, which infiltrate the lungs. This enhances COVID-19 severity and may also contribute to the persistent immune alterations that are observed in long COVID.