The oxygen dissociation curve of blood in COVID-19

Abstract

COVID-19 hinders oxygen transport to the consuming tissues by at least two mechanisms: In the injured lung, saturation of hemoglobin is compromised, and 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 second, 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-bisphosphoglycerate (2,3-BPG) concentration. In three 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 (MetHb), which increases the oxygen affinity and thus apparently compensates for the 2,3-BPG effect. However, 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.

Keywords: anemia; half-saturation pressure; hemoglobin oxygen affinity; in vivo oxygen dissociation curve; methemoglobin.

Figure 1.

Fragmentocytes in a lung capillary from a 58-yr-old patient with COVID-19 (unpublished results used with permission from Konrad Steinestel and Wilhelm Bloch). Lung tissue was immersion-fixed with 4% paraformaldehyde, Epon embedded following standard procedures. Thereafter 70- to 90-nm thick sections were cut with an Ultracut UCT ultramicrotome (Fa. Reichert). The sections were studied with a Zeiss EM 109 electron microscope (Fa. Zeiss). Original magnification: ×4,000, image width: 23.5 µm. (Courtesy of Prof. Dr. Konrad Steinestel, Institute of Pathology and Molecular Pathology, Bundeswehrkrankenhaus Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany.)

Figure 2.

Deviation of in vivo Po₂ (heparinized blood measured immediately after sampling) corrected to pH 7.4 from the corresponding individual in vitro standard ODC between 40% and 90% So₂ in 14 controls and 14 patients with cystic fibrosis. The in vivo left shift facilitates oxygen loading in the lungs. [From Böning et al. (23) with permission from PLoS One.]

Figure 3.

Half-saturation pressures (pH 7.4, Pco₂, 37°). Standard: in vitro standard according to Severinghaus (20); anemia: in vitro according to Böning and Enciso (43); Methemoglobin (MetHb): effect on anemia calculated according to Scholkmann et al. (33); and COVID-19 in vivo: untreated blood samples according to Vogel et al. (8).