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Many patients present with a remarkable disconnect in rest between profound hypoxemia yet without proportional signs of respiratory distress (i.e. happy hypoxemia) and rapid deterioration can occur. This particular clinical presentation in COVID-19 patients contrasts with the experience of physicians usually treating critically ill patients in respiratory failure and ensuring timely referral to the intensive care unit can, therefore, be challenging. A thorough understanding of the pathophysiological determinants of respiratory drive and hypoxemia may promote a more complete comprehension of a patient\u2019s clinical presentation and management. Preserved oxygen saturation despite low partial pressure of oxygen in arterial blood samples occur, due to leftward shift of the oxyhemoglobin dissociation curve induced by hypoxemia-driven hyperventilation as well as possible direct viral interactions with hemoglobin. Ventilation-perfusion mismatch, ranging from shunts to alveolar dead space ventilation, is the central hallmark and offers various therapeutic targets.<\/jats:p>","DOI":"10.1186\/s12931-020-01462-5","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T12:02:53Z","timestamp":1595937773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":428,"title":["The pathophysiology of \u2018happy\u2019 hypoxemia in COVID-19"],"prefix":"10.1186","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5615-3191","authenticated-orcid":false,"given":"Sebastiaan","family":"Dhont","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Derom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Van Braeckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Depuydt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart N.","family":"Lambrecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"1462_CR1","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1001\/jama.2020.2648","volume":"323","author":"Z Wu","year":"2020","unstructured":"Wu Z, McGoogan JM. 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