PT - JOURNAL ARTICLE AU - Richard Kallet AU - Richard D Branson AU - Michael S Lipnick TI - Respiratory Drive, Dyspnea and Silent Hypoxemia: A Physiological Review in the Context of Coronavirus Disease 2019 AID - 10.4187/respcare.10075 DP - 2022 May 02 TA - Respiratory Care PG - respcare.10075 4099 - http://rc.rcjournal.com/content/early/2022/05/02/respcare.10075.short 4100 - http://rc.rcjournal.com/content/early/2022/05/02/respcare.10075.full AB - Infection with the severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) in select individuals results in viral sepsis, pneumonia and hypoxemic respiratory failure, collectively known as coronavirus disease 2019 (COVID-19). In the early months of the pandemic the combination of novel disease presentation, enormous surges of critically ill patients and severity of illness lent to early observations and pronouncements regarding COVID-19 that could not be scientifically validated owing to crisis circumstances. One of these was a phenomenon referred to as “happy hypoxia”. Widely discussed in the lay press, it was thought to represent a novel and perplexing phenomenon: severe hypoxemia coupled with the absence of respiratory distress and dyspnea. Silent hypoxemia is the preferred term describing an apparent lack of distress in the presence of hypoxemia. However, the phenomenon is well-known among respiratory physiologists as “hypoxic ventilatory decline”. Silent hypoxemia can be explained by physiologic mechanisms governing the control of breathing, breathing perception and cardiovascular compensation. This narrative review examines silent hypoxemia during COVID-19, as well as hypotheses that viral infection of the central and peripheral nervous system may be implicated. Moreover, the credulous embrace of “happy hypoxia” and the novel hypotheses proposed to explain it, has exposed significant misunderstandings among clinicians regarding the physiologic mechanisms governing both the control of breathing and the modulation of breathing sensations. Therefore, a substantial focus of this paper is to provide an in-depth review of these topics.