BACKGROUND: Severe Covid-19 is associated with a cytokine storm leading to the hyper-expression of cytokines such as IFN-gamma, TNF-alpha, and IL-6, which may be responsible for most severe symptoms and signs of the disease. The immune response of the atopic patient is mostly Th2-oriented, associated with the expression of cytokines such as IL-4, IL-5, and IL-13, and atopic patients express fewer ACE-2 receptors than non-atopic individuals do. We assessed whether atopic status may protect from the most severe consequences of Covid-19. METHODS: Atopic status along with co-factors such as diabetes, hypertension, coronary heart disease, and thrombosis was investigated in severe Covid-19 patients admitted to different Italian hospitals. Patients were classified as having a mild, severe, or very severe disease based on the need of respiratory assistance; severity was plotted against the different co-factors and underwent multivariate analysis. RESULTS: 531 adults aged 25 - 100 years were studied; 57 (11.7%) were atopic. Atopic status showed a significant association with a milder disease irrespective of all other co-factors considered (p <0.001); the protective effect of atopy was detectable throughout all age groups (p< 0.001). CONCLUSIONS: Atopic status appears to protect from the most severe consequences of Covid-19.