The effects of IFNγ deficiency have been investigated in an experimental model of haemophagocytic lymphohistiocytosis, which develops when perforin deficient (Prf1−/−) mice are infected with the lymphocytic choriomeningitis virus. Surprisingly, mice lacking both IFNγ and perforin (IFNγ−/−Prf1−/−) still develop a severe MAS-like disease that requires the IL-33–ST2 axis and is downstream mediated by GM-CSF-producing CD8+ T cells. The inflammatory burden in infected IFNγ−/−Prf1−/− mice is even higher than in Prf1−/− mice, being characterised by a 10–15 times increase in neutrophils and stronger upregulation of IL-1β and IL-6.32 The same interplay between IL-33 and GM-CSF might occur in patients with COVID-19, which would initiate the cytokine storm syndrome. Thus, severe forms of COVID-19 might represent atypical MAS or MAS-like reactions with incorporated interferon deficiencies.