Each time I began to plan an Oxygenologist post for April 2020, some new information emerged about the pulmonary complexity of COVID-19. It’s going to take some time to sort out the details, so this month’s entry will be a brief one.
It seems COVID-19 is more complicated physiologically than previously imagined: atypical pneumonia, blood clots everywhere, bi-phasic pulmonary compliance patterns, atypical oxygen requirements.
One thing I have noted, though, is how baffled my “adult” doctor colleagues are by what they are seeing. Those of us who cared for “preemies” back before surfactant rescued most acute Respiratory Distress Syndrome (RDS) patients from chronic Brocho-Pulmonary Dysplasia (BPD), may recognize familiar patterns, though of a reverse nature.
Take hypoxic preconditioning. Newborns emerge from months in an “hypoxic” (14%) intrauterine environment acutely into atmospheric (21%) or supra-atmospheric (>21% up to 100%) conditions. This shift induces monumental changes in cardiac and pulmonary vessel physiology that underscore how transcriptional and translational events govern rapid decreases in pulmonary resistance, induce patent ductus (PDA) closure, and reverse the intra-cardiac shunts present under neonatal hypoxic conditions.
Perhaps there is a lesson here that is relevant to adults: gradual onset of hypoxia over a period of days, as is seen in some patients with COVID-19, may be permissive for levels of hypoxic tolerance development.
Unlike in acute respiratory arrest, where one goes from adequate to inadequate arterial oxygen saturation (SaO2) in no time, a gradual decrease in arterial oxygen partial pressure (PaO2) over days may give cells time to adapt through HIF-system governed transcriptional and translational events to tolerate greater degrees of hypoxia.
While plausible, it must be understood that not all cells function optimally at the same oxygen tensions–most notably stem cells. Oxygen tensions that are salutatory for some cell populations may be toxic to others, as is illustrated by the apparent hypoxic-hyperoxic tolerance differences of white and gray matter, GI track cells, and cells in different bone marrow compartments.
Speculation is not science, however. More information is needed to understand what is happening in COVID-19 hypoxic circumstances in select patients.
Is the virus interfering with oxidative phosphorylation and mitochondrial chemiosmotic gradients to decrease oxygen utilization efficiency? Are micro-clots producing ventilation/perfusion (V/Q) mismatches that combine with pneumonia-induced V/Q mismatches to produce a bizarre picture of tolerable hypoxia? Are inflammatory responses causing amplification of Reactive Oxygen Species (ROS) effects that will manifest in a stochastic fashion in the not too distant future?
These and other questions intrigue, remain to be answered, and may underscore some mysteries surrounding the atypical nature of COVID-19 pulmonary disease.
