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The distinctive pathogenesis of COVID-19 versus pandemic influenza (#37) reflects that (in humans at least) the growth of flu viruses is normally limited to the respiratory tract, while it is very clear that SARS-CoV-2 can cause viremia, with the virus being distributed via the blood to other organs. The difference is thus between a localised and a systemic (blood-borne) infection. In both cases we do, though, see systemic effects. This can reflect the release of cytokines and chemokines from cells like neutrophils, monocytes and macrophages (#7) as part of the innate immune response. While limiting the growth of the pathogen to some extent before the more specific ‘adaptive’ immune effectors (antibodies and T cells) become available, these ‘innate’ chemical defenders commonly spill-over into the blood where they can, for instance, influence brain function and promote excessive vascular leakage into the infected lung.