Although coronavirus disease 2019 (COVID-19) predominantly causes acute respiratory syndrome, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, multiorgan dysfunctions are not uncommon and should be taken into consideration.

Researchers from King’s College Hospital National Health Service Foundation Trust in the United Kingdom described a case of a major complication in a patient with a common enzymatic disorder in a letter published in Emerging Infectious Diseases.1

A 62-year-old Afro-Caribbean man with an undiagnosed glucose-6-phosphate dehydrogenase (G6PD) deficiency presented to the hospital after 5 days of fever, dyspnea, vomiting, and diarrhea.

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Upon examination, the patient was dehydrated and had tachycardia, hypotension, a prolonged capillary refill time, dry mucous membranes, and bilateral crackling following auscultation of his chest. Laboratory testing revealed an acute kidney injury and SARS-CoV-2 infection, and treatment was initiated for both.

At 7 days postadmission, the patient’s peripheral oxygen saturations decreased and repeated laboratory results revealed hemolytic anemia. Major immune-mediated hemolysis was excluded following a direct antiglobulin test, and blood film resulted in normochromic and normocytic erythrocytes with some hemighost cells. Ultimately a 2-stage G6DP assay confirmed a G6DP deficiency.

G6DP deficiency, an X-linked disorder, affects nearly 400 million people globally. G6DP is the rate-limiting enzyme in the pentose phosphate pathway and catalyzes the formation of nicotinamide adenine dinucleotide phosphate (NADPH), a reducing agent that maintains hemoglobin in the ferrous state.1,2 Because intracellular reduced NADPH is depleted during oxidative stress, patients with G6DP deficiency will have more oxidative damaged proteins and lipids in red blood cells, resulting in the hemolysis of these cells.3

Oxidative agents, such as hydroxychloroquine, increase the risk for intravascular hemolysis in patients with G6DP deficiency, and is currently being studied in clinical trials for individuals with SARS-CoV-2.1

In addition, G6DP deficiency can lead to methemoglobinemia, and ultimately tissue hypoxia, because NADPH-flavin reductase is inhibited, therefore, methemoglobin, which is unable to bind to oxygen, cannot be reduced.

The patient in the case study was given 2 blood transfusions and oxygen therapy. His methemoglobinemia gradually resolved, oxygen therapy was no longer required, and he recovered dialysis-independent renal function. After 22 days, the patient was discharged from the hospital.

“Oxidative stress might contribute to the pathogenesis of severe SARS-CoV-2 infection,” the researchers noted. “Evaluation of parameters of oxidative stress in SARS-CoV-2 are currently underway (ClinicalTrials.gov Identifier: NCT04375137) and might determine whether there is an increased risk for drug-induced hemolysis in patients with G6PD deficiency.”

“During the SARS-CoV-2 pandemic, clinicians must be aware of the possible increased susceptibility of patients with G6DP deficiency to severe hemolytic crises and the consequences for investigation and treatment,” the authors concluded.

References

  1. Palmer K, Dick J, French W, Floro L, Ford M. Methemoglobinemia in patient with G6PD deficiency and SARS-CoV-2 infection [published online June 24, 2020]. Emerg Infect Dis. doi: 10.3201/eid2609.202353
  2. Aydemir D, Ulusu NN. Is glucose-6-phosphate dehydrogenase enzyme deficiency a factor in coronavirus-19 (COVID-19) infections and deaths? Pathog Glob Health. 2020;114(3):109-110.
  3. Kuipers MT, van Zwieten R, Heijmans J, et al. Glucose-6-phosphate dehydrogenase deficiency-associated hemolysis and methemoglobinemia in a COVID-19 patient treated with chloroquine. Am J Hematol. 2020;95(8):E194-E196.

Topics:

COVID19 General Hematology