Interestingly, while elevated COHb levels seem to be correlated with COVID-19 severity, intensive care mortality from other causes was found to be associated with too low [12,77] and both too low or too high COHb values [11], indicating the existence of an optimal COHb level for optimal physiological functioning [12]. HO-1 upregulation, associated with elevations of COHb, has immunomodulatory and anti-inflammatory effects [78]. Inflammation changes COHb levels in the blood in a complex time-dependent manner as demonstrated by experimental endotoxemia in humans [79], highlighting the non-linear relationship between inflammation, disease severity and COHb levels.