The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

Scholkmann, Felix; Restin, Tanja; Ferrari, Marco; Quaresima, Valentina

doi:10.3390/jcm10010050

Cited by 32 publications

(34 citation statements)

References 93 publications

(163 reference statements)

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“…Aside of these structural damages, the function of Hb is influenced by formation of methemoglobin and CO-Hb (eventually more than 20%), which cannot bind oxygen reversibly ( 33 ). The consequences are described in the oxygen dissociation curve in covid-19 .…”

Section: Intraerythrocytic Changes In Covid-19mentioning

confidence: 99%

“…According to Hrinczenko et al ( 60 ), P 50 is reduced by 0.2 mmHg/%methemoglobin (MetHb). During COVID-19, COHb remains rather constant, but the change of MetHb is variable [reviewed by Scholkmann et al ( 33 )]; in a group of 25 patients, it rose to 16.4 ± 9.1% on day 6 of the hospital stay. Thus, 3.3 mmHg decrease in P 50 might be expected corresponding to the effect of a pH increase by 0.15 U or a 2,3-BPG reduction by 1 mmol/L red cells or 5 µmol/g Hb, respectively.…”

Section: The Effect Of Anemia In Covid-19mentioning

confidence: 99%

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The oxygen dissociation curve of blood in COVID-19

Böning

Kuebler

Bloch

2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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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.

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Section: Intraerythrocytic Changes In Covid-19mentioning

confidence: 99%

Section: The Effect Of Anemia In Covid-19mentioning

confidence: 99%

The oxygen dissociation curve of blood in COVID-19

Böning

Kuebler

Bloch

2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…While there are few reports to date on elevated COHb levels in COVID-19 patients [ 10 , 11 ] at our institute, we observed high COHb levels in critically ill COVID-19 patients, which our physician checked due to discrepancies between oxygen saturation measured by pulse oximetry and arterial blood gases. Therefore, we hypothesize that raised levels of both endogenous carbonmonoxide and elevated COHb levels may continue to increase to toxic levels in critically ill COVID-19 patients as overwhelmed and failed organs and systems lose their ability to absorb, metabolize, and excrete toxins.…”

Section: Introductionmentioning

confidence: 64%

“…Carboxyhemoglobinemia is a common and serious disorder. However, most published data have been limited to case reports and small case series [ 11 ], making the assessment of prevalence and risk factors difficult. Due to the scarcity of these data on a potentially life-threatening disorder and in light of the current pandemic, our study aimed to determine whether the novel coronavirus has any significant role in the pathogenesis of carboxyhemoglobinemia in COVID-19 disease.…”

Section: Discussionmentioning

confidence: 99%

Carboxyhemoglobinemia in Critically Ill Coronavirus Disease 2019 Patients

Faisal

Ali

et al. 2021

JCM

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Carboxyhemoglobinemia is a common but a serious disorder, defined as an increase in carboxyhemoglobin level. Unfortunately, there are few data on carboxyhemoglobinemia in coronavirus disease 2019 (COVID-19) patients. Therefore, our study aimed to evaluate the incidence and etiologies of carboxyhemoglobinemia in COVID-19 patients and determine any association between carboxyhemoglobinemia and novel coronavirus infection. A retrospective chart review was performed at an academic medical center for all inpatient COVID-19 cases with either single or serial carboxyhemoglobin (COHb) levels from March 2020 through August 2020.Our study demonstrates that carboxyhemoglobinemia in COVID-19 patients is due to sepsis, hemolysis, and cytokine storm, triggered by the novel coronavirus infection sequela and is not directly from the virulence of novel coronavirus. Given the coexisting illnesses in critically ill COVID-19 patients, it is impossible to establish if coronavirus virulence was the culprit of elevated COHb levels. Moreover, our study found a high incidence of carboxyhemoglobinemia in critically ill COVID-19 patients. The oxygen saturation measured by pulse oximetry can be inaccurate and unreliable; however, our study could not demonstrate any uniform results on the discrepancy between oxygen saturation measured by pulse oximetry and arterial blood gas. In this study, COHb levels were measured using a CO-oximeter. Therefore, we recommend monitoring the COHb level routinely in critically ill COVID-19 patients to allow more effective and prompt treatment.

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“…This condition, known as Methemoglobinemia, can be induced by drugs (chloroquine/hydroxychloroquine), inherited defects in Cytochrome b5 (or its reductase), or inheritance of an Hb variant characterized by an increase in the stability of oxidized (Ferric, Fe 3+ ) or a decrease in the stability of the (ferrous, Fe 2+ ) states. [5][6][7][8][9][10] Methemoglobinemia has been reported in many COVID-19 patients, [11][12][13] thus potentially complicating the assessment of blood O2 saturation levels in respiratory distress. Incidence of COVID-19 in patients with sickle cell disease (characterized by Hb S) was found to be 85 %, but prevalence of other Hb variants in COVID-19 patients remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

Electron transfer parameters for Methemoglobin formation in mutant Hemoglobin α-chains

Dixit

Blumberger

Vyas

2021

Preprint

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Hemoglobin mediated transport of dioxygen (O2) critically depends on the stability of the reduced (Fe2+) form of the Heme cofactors. Some protein mutations stabilize oxidized (Fe3+) state (Methemoglobin, Hb M) causing methemoglobinemia and can be lethal above 30 %. The majority of the analyses of factors influencing Hb oxidation are retrospective and give insights only for inner sphere mutations of Heme (His58, His87). Herein, we report the first all-atom MD simulations on redox states and calculations of the Marcus ET parameters for the alpha-chain Hb oxidation and reduction rates for Hb M. The Hb (wild type), and most of the studied α-chain variants maintain globin structure except the Hb M Iwate (H87Y). Using linear response approximation we calculated average energy gaps (<DeltaE>), total (lambda), protein (lambda-prot), solvent (lambda-solv) reorganization energies, and redox potentials (Eo), and oxidation free energies (DeltaGo). The total lambda ranges from 0.685 to 0.730 eV in agreement with literature on Hb and similar Heme proteins. The mutants forming Hb M tend to lower the Eo and thus stabilize the oxidized (Fe3+) state (e.g. the Hb Miyagi variant with K61E mutation). Solvent reorganization (lambda-solv 73 to 96 %) makes major contributions to lambda, while protein reorganization (lambda-prot) accounts for 27 to 30 % except for the Miyagi and J-Buda variants (lambda-prot ~ 4 %). Analysis of Heme-solvent H-bonding interactions among variants provide insights into the role of Lys61 residue in stabilizing Fe2+ state and ET parameters. The ET parameters provide valuable insights into the Hb oxidation to Hb M in agreement with the experimental data. Thus our methodology explains the effect of mutations on the structure, stability and Hb oxidation, and has the potential for the prediction of methemoglobinemia.

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The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

Cited by 32 publications

References 93 publications

The oxygen dissociation curve of blood in COVID-19

The oxygen dissociation curve of blood in COVID-19

Carboxyhemoglobinemia in Critically Ill Coronavirus Disease 2019 Patients

Electron transfer parameters for Methemoglobin formation in mutant Hemoglobin α-chains

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