Methemoglobinemia and AKI in patients with COVID-19: Don't forget G6PD deficiency

ABSTRACT

Introduction: Patients with COVID-19 can be asymptomatic or have severe illness. Oxidative stress may be a cause of increased severity and mortality in COVID-19 patients. Methaemoglobinaemia (MetHb) and haemolysis can occur as a result of oxidative stress. MetHb is associated with sepsis, exposure to drugs and inborn errors of metabolism. Glucose-6-phosphate dehydrogenase (G6PD) deficiency may also manifest with MetHb and severe haemolysis. Case Description A 31-year old man, originally from West Africa, with no comorbidities, presented with dyspnoea, cough, anosmia and oligo-anuria. He had type 1 respiratory failure and stage 3 AKI, which led to critical care admission for intubation, ventilation and haemofiltration. COVID-19 pneumonia was confirmed by nasopharyngeal swab and radiological imaging. He developed haemolytic anaemia. The MetHb was 3.5% (normal <1.5%). It rose to a peak of 10.7% with persisting anaemia and further investigations showed G6PD deficiency. He had no exposure to medications known to trigger haemolytic crises, such as Hydroxychloroquine. He was treated with supportive management including red cell transfusions and also with Tocilizumab for COVID-19. He was extubated after 15 days and recovered renal function. Data on 9 other patients admitted during this period to the ITU with COVID-19 and AKI showed 7 had normal MetHb levels and 2 had modest elevations (<3%). Discussion: Triggers of G6PD deficiency include stress from infections, fava beans, or drugs e.g Hydroxychloroquine. It typically presents as haemolytic anaemia, jaundice and AKI. Although MetHb is linked to severe illness including sepsis, little is known about a possible association with COVID-19. Our report highlights the importance of considering alternative diagnoses of very high MetHb levels such as G6PD deficiency in COVID-19 patients. This is of particular relevance as Hydroxychloroquine has been used as experimental treatment for COVID-19 and in the current climate, G6PD deficiency should be suspected in COVID-19 patients with AKI, acute haemolytic anaemia and signikficantly elevated MetHb, particularly in those from regions of high prevalence and those treated with known triggers such as Hydroxychloroquine.