Table 1.
Purported mechanistic explanations for silent hypoxemia and associated reported findings in COVID-19 lung injury and non–COVID-19 ARDS
| COVID-19 Lung Injury | Non–COVID-19 ARDS | |
|---|---|---|
| Vascular regulation | ||
| Proposed | Vasoplegia and HPV impaired | Intact vascular responsiveness |
| Observed | • Vascular imaging demonstrates vascular engorgement and increased perfusion in areas of diseased lung (21, 26) | • Hypoxemia in ARDS is responsive to almitrine, inhaled pulmonary vasodilators; worsened by systemic vasodilators (57, 58) |
| • Lung vasculature expresses angiotensin-converting enzyme 2 (52) | • Mildly elevated PA pressure and PVR, by PA catheterization (47, 48) | |
| • Benefit from almitrine and inhaled pulmonary vasodilators argues against global vasoplegia (59, 77) | • Direct evidence of HPV responsiveness (54) | |
| • Mildly elevated PA pressure, by echocardiography and PA catheterization (44–46) | ||
| • No direct evidence of HPV impairment | ||
| Conclusion | Very limited data with a need for more investigation because of angiotensin-converting enzyme 2 expression in the pulmonary endothelium and arterial smooth muscle |
|
| Lung compliance | ||
| Proposed | Compliance minimally reduced | Compliance greatly reduced |
| Observed | • Cst range, 20–90 ml/cmH2O in newly intubated patients (2, 4, 23, 24) | • Cst range, 10–78 ml/cmH2O (32, 33) |
| Conclusion | Minimal and clinically nonsignificant differences in observed values, especially given the wide range of compliance seen in non–COVID-19 ARDS |
|
| Neural oxygen sensing and dyspnea perception |
||
| Proposed | Impaired central and peripheral O2 sensing and dyspnea perception secondary to direct viral effects | Preserved O2 sensing at both peripheral and central chemoreceptors and intact dyspnea perception |
| Observed | • Viral access in brain stem and cortex in humans (68) | • 0–27% of patients with no reported dyspnea in SARS and H1N1 influenza ARDS (11–14) |
| • Viral brain stem access in animals (67) | • No direct HVR testing performed | |
| • Carotid body & brain express angiotensin-converting enzyme 2 (65, 66) | ||
| • 9–34% of patients with no reported dyspnea (1, 2, 4) | ||
| • No direct HVR testing performed | ||
| Conclusion | Very limited data, with a need for more investigation because of angiotensin-converting enzyme 2 expression in the brain and chemoreceptors and documented viral presence in these sites | |
Definition of abbreviations: ARDS = acute respiratory distress syndrome; COVID-19 = coronavirus disease; Cst = static total respiratory system compliance; HPV = hypoxic pulmonary vasoconstriction; HVR = hypoxic ventilatory response; PA = pulmonary artery; PVR = pulmonary vascular resistance; SARS = severe acute respiratory syndrome.