The oxygen dissociation curve of blood in COVID-19

Abstract

COVID-19 hinders oxygen transport to the consuming tissues by at least 2 mechanisms: In the injured lung saturation of hemoglobin is compromised, in the tissues an associated anemia reduces the volume of delivered oxygen. For the first problem increased hemoglobin oxygen affinity (left shift of the oxygen dissociation curve ODC) is of advantage, for the 2nd, however, the contrary is the case. Indeed a right shift of the ODC has been found in former studies for anemia caused by reduced cell production or hemolysis. This resulted from increased 2,3-biphosphglycerate (2,3-BPG) concentration. In 3 investigations in COVID-19, however, no change of hemoglobin affinity was detected in spite of probably high [2,3-BPG]. The most plausible cause for this finding is formation of methemoglobin, which increases the oxygen affinity and thus apparently compensates for the 2,3-BPG effect. But this "useful effect" is cancelled by the concomitant reduction of functional hemoglobin. In the largest study on COVID-19 even a clear left shift of the ODC was detected when calculated from measurements in fresh blood rather than after equilibration with gases outside the body. This additional „in vivo" left shift possibly results from various factors (e. g. concentration changes of Cl-, 2,3-BPG, ATP, lactate, nitrocompounds, glutathione, glutamate, because of time delay between blood sampling and end of equilibration, or enlarged distribution space including interstitial fluid and is useful for O2 uptake in the lungs. Under discussion for therapy are the affinity-increasing 5-hydroxymethyl-2-furfural (5-HMF), erythropoiesis stimulating substances like erythropoietin, and methylene blue against MetHb formation.

The increased hemoglobin oxygen affinity in COVID-19

“…to the editor : In their review, “The oxygen dissociation curve of blood in COVID-19,” Böning et al ( 1 ) provide an excellent overview of the available literature, put the increased hemoglobin oxygen affinity ( 2 ) into the context of anemia, and present new, important hypotheses.…”

Reply to Vogel et al.

“…As the patients of Dr. Vogel were severely anemic, one would in fact even expect a right shift of the ODC due to an adaptive increase in the concentration of 2,3-bisphosphoglycerate ([2,3-BPG]). Anemia, a frequent complication in SARS-CoV-2 infection, usually causes an increase in [2, in most cases except those with acidosis (reviewed in our article). Astonishingly, we could detect only one publication where 2,3-BPG had been measured in patients with COVID-19 (6).…”

“…Since it was previously reported that methemoglobin (MetHb) formation may cause a left shift of the ODC ( 4 , 5 ), we had contacted Dr. Vogel in January 2021 regarding respective measurements in his patients and learned that these data at that time had not been evaluated yet. In our article finally submitted on April 26, 2021, we thus proposed increased levels of MetHb as a potential cause of the ODC left shift in COVID-19 ( 2 ). Dr. Vogel’s letter to the editor ( 1 ) now clarifies, however, that MetHb is not the underlying cause for the observed effect in the study by Vogel et al ( 3 ).…”

“…D'Alessandro), who communicated that because of methodological reasons the concentrations are only given in arbitrary units, while the actual absolute concentrations in mmol/L red cells remain unknown. That notwithstanding, it seems fair to conclude that [2, should be increased in patients with COVID-19 given that the concentration was higher relative to the non-COVID control group also suffering from slight anemia in the study by D'Alessandro and colleagues (6).…”

“…TO THE EDITOR: We thank Dr. Vogel and colleagues for their letter (1) in response to our recent review on the oxygen dissociation curve (ODC) in COVID-19 (2). Indeed, we initially became interested in this topic when reading the paper by Vogel et al (3), which showed a surprising left shift of the in vivo ODC in severe disease with marked anemia.…”