The pathophysiology of 'happy' hypoxemia in COVID-19

Respir Res. 2020 Jul 28;21(1):198. doi: 10.1186/s12931-020-01462-5.


The novel coronavirus disease 2019 (COVID-19) pandemic is a global crisis, challenging healthcare systems worldwide. 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's 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.

Keywords: COVID-19; Dyspnea; Gas exchange; Hypoxemia; Respiratory failure; SARS-CoV-2.

Publication types

  • Review

MeSH terms

  • Betacoronavirus*
  • COVID-19
  • Coronavirus Infections / complications*
  • Coronavirus Infections / epidemiology
  • Critical Illness
  • Humans
  • Hypoxia / etiology*
  • Hypoxia / metabolism
  • Hypoxia / physiopathology
  • Lung / physiopathology*
  • Oxygen Consumption / physiology*
  • Pandemics*
  • Pneumonia, Viral / complications*
  • Pneumonia, Viral / epidemiology
  • Respiratory Insufficiency / complications*
  • Respiratory Insufficiency / metabolism
  • Respiratory Insufficiency / physiopathology
  • SARS-CoV-2