Patients with COVID-19 often present with life-threatening hypoxemia without dyspnea or signs of respiratory distress. Termed silent or happy hypoxia, it has puzzled clinicians and challenged and defied our understanding of normal respiratory physiology. A range of host- and pathogen-related factors appears to contribute to its development, including SARS-CoV-2’s ability to produce different COVID-19 phenotypes; induce endothelial damage and elicit a vascular distress response; invade cells of the central nervous system and disrupt normal interoception and response; and modulate transcription factors involved in hypoxic responses. Because hypoxemia in COVID-19 is associated with increased mortality risk and poorer survival, early detection and prompt treatment is essential to prevent potential complications. Interventions to prevent hypoxemia and improve oxygen delivery to the blood and the tissues include home pulse-oximetry monitoring, optimization of patient positioning, judicious use of supplemental oxygen, breathing control exercises, and timely and appropriate use of ventilatory modalities and adjuncts.
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