No evidence of hemoglobin damage by SARS-CoV-2 infection

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) has affected over 22 million patients worldwide as of August 2020. As the medical community seeks better understanding of the underlying pathophysiology of COVID-19, several theories have been proposed. One widely shared theory suggests that SARS-CoV-2 proteins directly interact with human hemoglobin (Hb) and facilitate removal of iron from the heme prosthetic group, leading to the loss of functional hemoglobin and accumulation of iron. Herein, we refute this theory. We compared clinical data from 21 critically ill COVID-19 patients to 21 non-COVID-19 acute respiratory distress syndrome (ARDS) patient controls, generating hemoglobin-oxygen dissociation curves from venous blood gases. This curve generated from the COVID-19 cohort matched the idealized oxygen-hemoglobin dissociation curve well (Pearson correlation R2=0.97, P<0.0001; a coefficient of variation of the root-mean-square deviation [CV(RMSD)] =7.3%). We further analyzed hemoglobin, total bilirubin, lactate dehydrogenase, iron, ferritin, and haptoglobin levels. For all analyzed parameters, patients with COVID-19 had similar levels compared to patients with ARDS without COVID-19. These results indicate that patients with COVID-19 do not exhibit any hemolytic anemia or a shift in the normal hemoglobin-oxygen dissociation curve. We therefore conclude that COVID-19 does not impact oxygen delivery through a mechanism involving red cell hemolysis and subsequent removal of iron from the heme prosthetic group in hemoglobin.