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The inadequacy of the popular explanations of seasonality is discussed, and a simple hypothesis is proposed, called temperature dependent viral tropism (TDVT), that is compatible with the above features of respiratory illness. TDVT notes that viruses can spread more effectively if they<jats:italic>moderate<\/jats:italic>their pathogenicity (thereby maintaining host mobility) and suggests that endemic respiratory viruses accomplish this by developing thermal sensitivity within a range that supports organ\u2010specific viral tropism within the human body, whereby they replicate most rapidly at<jats:italic>temperatures below body temperature<\/jats:italic>. This can confine them to the upper respiratory tract and allow them to avoid infecting the lungs, heart, gut etc. Biochemical and tissue\u2010culture studies show that \u2018wild\u2019 respiratory viruses show such natural thermal sensitivity. The typical early autumn surge of colds and the occurrence of respiratory illness in the Tropics year\u2010round at intermediate levels are explained by the tendency for strains to adapt their thermal sensitivity to their local climate and season. TDVT has important practical implications for preventing and treating respiratory illness including Covid\u201019. It is testable with many options for experiments to increase our understanding of viral seasonality and pathogenicity.<\/jats:p>","DOI":"10.1002\/rmv.2241","type":"journal-article","created":{"date-parts":[[2021,5,4]],"date-time":"2021-05-04T04:22:30Z","timestamp":1620102150000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Temperature dependent viral tropism: understanding viral seasonality and pathogenicity as applied to the avoidance and treatment of endemic viral respiratory illnesses"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0184-4083","authenticated-orcid":false,"given":"Patrick D.","family":"Shaw Stewart","sequence":"first","affiliation":[{"name":"Douglas Instruments Ltd. Hungerford Berkshire UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia L.","family":"Bach","sequence":"additional","affiliation":[{"name":"Amgen Inc. 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