The Affinity of Hemoglobin for Oxygen Is Not Altered During COVID-19

Abstract

Background: A computational proteomic analysis suggested that SARS-CoV-2 might bind to hemoglobin (Hb). The authors hypothesized that this phenomenon could result in a decreased oxygen (O₂) binding and lead to hemolytic anemia as well. The aim of this work was to investigate whether the affinity of Hb for O₂ was altered during COVID-19. Methods: In this retrospective, observational, single-center study, the blood gas analyses of 100 COVID-19 patients were compared to those of 100 non-COVID-19 patients. Fifty-five patients with carboxyhemoglobin (HbCO) ≥8% and 30 with sickle cell disease (SCD) were also included ("positive controls" with abnormal Hb affinity). P₅₀ was corrected for body temperature, pH, and PCO₂. Results: Patients did not differ statistically for age or sex ratio in COVID-19 and non-COVID-19 groups. Median P₅₀ at baseline was 26 mmHg [25.2-26.8] vs. 25.9 mmHg [24-27.3], respectively (p = 0.42). As expected, P₅₀ was 22.5 mmHg [21.6-23.8] in the high HbCO group and 29.3 mmHg [27-31.5] in the SCD group (p < 0.0001). Whatever the disease severity, samples from COVID-19 to non-COVID-19 groups were distributed on the standard O₂-Hb dissociation curve. When considering the time-course of P₅₀ between days 1 and 18 in both groups, no significant difference was observed. Median Hb concentration at baseline was 14 g.dl^-1 [12.6-15.2] in the COVID-19 group vs. 13.2 g.dl^-1 [11.4-14.7] in the non-COVID-19 group (p = 0.006). Among the 24 COVID-19 patients displaying anemia, none of them exhibited obvious biological hemolysis. Conclusion: There was no biological argument to support the hypothesis that SARS-CoV-2 could alter O₂ binding to Hb.

Keywords: COVID-19; P50; SARS-CoV-2; anemia; gas exchange; gas transport; hemoglobin-oxygen affinity; hemolysis.

FIGURE 1

(A) Raw oxyhemoglobin (HbO₂) in relation to PO₂ in the COVID-19 group (red dots, 100 patients, 253 samples) and the non-COVID-19 group (blue dots, 100 patients, 221 samples). (B) Standardized HbO₂ (Std-HbO₂) in relation to PO₂ in the COVID-19 group, according to the level of oxygen therapy (light red triangles: ambient air; medium red dots: O₂ between 1 and 6 l.min^{− 1}; dark red triangles: O₂ ≥ 7 l.min^{− 1} or ventilation). Measured HbO₂ was standardized for normal conditions (temperature = 37°C; pH = 7.4; PCO₂ = 40 mmHg) in order to compare it to the predicted HbO₂ given by the standard O₂-Hb dissociation curve, represented in black. (C) Std-HbO₂ for normal conditions in relation to PO₂ in the non-COVID-19 group, according to the level of oxygen therapy (light blue triangles: ambient air; medium blue dots: O₂ between 1 and 6 l.min^{− 1}; dark blue triangles: O₂ ≥ 7 l.min^{− 1} or ventilation).

FIGURE 2

Time-course of mean P₅₀ in the COVID-19 group (red circles) and the non-COVID-19 group (blue squares). Some days were regrouped to have sufficient number of samples (D_8–10: n = 15 in the COVID-19 group and n = 10 in the non-COVID-19 group; D_11–15: n = 11 in both groups; D_16–18: n = 4 and n = 6, respectively). Data are presented as means and SE.