Methemoglobinemia in Patient with G6PD Deficiency and SARS-CoV-2 Infection

Abstract

C oronavirus disease is a novel infectious disease that primarily manifests as an acute respiratory syndrome but can also cause multiorgan dysfunction. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been documented to cause vasoocclusive crisis and acute chest syndrome in patients with sickle cell anemia (1). We report another potentially major complication of infection in a patient with a common enzymatic disorder. Glucose 6-phosphate dehydrogenase (G6DP) deficiency is an X-linked enzymatic disorder that affects 400 million persons worldwide and has a high prevalence (5%-20%) in African and Asian populations (2). G6DP catalyzes the formation of nicotinamide adenine dinucleotide phosphate (NADPH) (3). NADPH maintains hemoglobin in the ferrous state by forming reduced glutathione, which prevents oxidative damage (3). G6DP deficiency increases the risk for intravascular hemolysis upon exposure to oxidative agents, such as fava beans, sulfonamides, and hydroxychloroquine, the subject of clinical trials for persons with SARS-CoV-2 infection. G6PD deficiency can induce methemoglobinemia by inhibiting NADPH-flavine reductase, which prevents the reduction of methemoglobin. Methemoglobin is unable to bind to oxygen, and the remaining oxyhemoglobin develops heightened oxygen affinity and diminished delivery, leading to tissue hypoxia (4). Viral infections, including HIV, hepatitis viruses (A, B, and E), and cytomegalovirus, can precipitate intravascular hemolysis in patients with G6PD deficiency (5,6). Concurrent methemoglobinemia has also been reported in the context of viral-induced hemolysis (5). RESEARCH LETTERS During the coronavirus disease pandemic in Spain, from April 10-24, 2020, a total of 5,869 persons were screened for severe acute respiratory syndrome coronavirus 2 at nursing homes. Among residents, 768 (23.9%) tested positive; among staff, 403 (15.2%). Of those testing positive, 69.7% of residents and 55.8% of staff were asymptomatic.

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

“…An anticorrelated development of tHb levels and MetHb levels in a COVID-19 patient has been reported [22], in line with the pathway described by Hare et al [51] of an NO-induced MetHb increase caused by anemia. The role of MetHb as a marker of anemic stress has been also been validated in a study investigating MetHb changes in patients undergoing heart surgery [57].…”

“…Based on the inclusion and exclusion criteria, seven duplicates were removed and 187 articles were excluded after abstract review. After the full set of remaining articles was screened, seven reports were finally included in the present study [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. The study selection process is shown in Figure 1 a.…”

“…From the seven studies included in this review for the case of MetHb and COVID-19, two were cross-sectional studies [ 19 , 21 ] and five case reports [ 17 , 18 , 20 , 22 , 23 ]. The case descriptions reported findings of one single patient [ 17 , 20 , 22 , 23 ] or three patients [ 18 ]. Five studies were published in journals [ 17 , 18 , 20 , 21 , 22 ] and two on the preprint server medRxiv (medrxiv.org) [ 19 , 23 ].…”

“…The case descriptions reported findings of one single patient [ 17 , 20 , 22 , 23 ] or three patients [ 18 ]. Five studies were published in journals [ 17 , 18 , 20 , 21 , 22 ] and two on the preprint server medRxiv (medrxiv.org) [ 19 , 23 ].…”

COVID-19/SARS-CoV-2 Infection: Lysosomes and Lysosomotropism Implicate New Treatment Strategies and Personal Risks

“…Oxidative stress (e.g., enhanced ROS levels and disturbance of antioxidant defense) has been demonstrated in experimental animal models of SARS [ 155 ]. Thus, intravascular hemolysis and methemoglobinemia has been observed in SARS-CoV-2 patients with Glucose-6-phosphate dehydrogenase (G6PD) deficiency [ 156 ], probably induced by oxidative stress in SARS-CoV-2 infection/COVID-19. Moreover, TMPRSS2 and cathepsin L, chloroquine and hydroxychloroquine are supposed to trigger severe drug-induced haemolytic anaemia in G6PD-deficient patients [ 157 , 158 , 159 ].…”