Archives of Medical Research - (2020) -

OPINION
Glucose-6-Phosphate Dehydrogenase Deficiency: An Actionable Risk Factor
for Patients with COVID-19?
Brenda D. Jamerson,a,b T. Ho Haryadi,c and Arline Bohannond
a
Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA
b
Center on Health and Society, Duke University, Durham, NC, USA
c
Community Success Initiative, Raleigh, NC, USA
d
Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, USA
Received for publication June 1, 2020; accepted June 4, 2020 (ARCMED_2020_855).

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked mutation

that is more prevalent in African, Asian, Latin American and Mediterranean populations.
Although most individuals are asymptomatic, exposure to certain food, drugs, or infec-
tions can trigger acute hemolytic anemia. Given the potential for coronavirus to trigger
oxidative stress, unrecognized G6PD deficiency in the presence of the COVID-19 viral
infection may cause hemolytic crisis and worse outcome in affected individuals. Further,
since certain drugs that may be used to treat COVID-19 infection may cause hemolytic
crisis in individuals with G6PD deficiency, it may be warranted to recommend adding
G6PD deficiency to the list of screening elements in a COVID-19 workup for those pa-
tients where there is a high suspicion for this genetic mutation. Ó 2020 IMSS. Published
by Elsevier Inc.
Key Words: Glucose-6-phosphate deydrogenase deficiency, COVID-19, Risk factor, Coronavirus.

COVID-19 presents as mild to moderate disease in the ma- (1). This presentation has overlapping features of individ-
jority of patients, but as severe acute respiratory syndrome uals with glucose-6-phosphate dehydrogenase (G6PD)
in hospitalized patients who progress to a severe form. Risk deficiency who experience hemolytic crisis after being
factors identified for susceptibility to worse outcomes for exposed to oxidative agents or viral infections and there-
COVID-19 include comorbidities such as hypertension, fore raises the specter that G6PD deficiency is a predis-
diabetes, cardiovascular disease, chronic lung disease, and posing factor that could lead to a more severe COVID-
older age (1). 19 illness.
Several factors are associated with more severe disease
and fatal outcomes in COVID-19 patients. In a cross
sectional analysis examining laboratory parameters of
COVID-19 cases associated with mortality, a significant Glucose-6-Phosphate Dehydrogenase Deficiency
elevation of d-dimer, a biomarker of fibrin formation Genetic Features and Prevalence
and degradation, was present in those patients who did
G6PD deficiency is a common X-linked disorder affecting
not survive. Other biomarkers that are present in those
approximately 350e400 million people worldwide (3).
with more severe disease are an increase in inflammatory
G6PD is found in all cells of the body and catalyzes the
biomarkers of IL6, increase in liver transaminases, lower
initial step in the pentose phosphate pathway (4,5). This
platelets and increase ferritin (2). Venous thromboembo-
pathway functions to protect red blood cells against oxida-
lism has been reported in those who die from the disease
tive stress through the production of nicotinamide adenine
dinucleotide phosphate which is generated by G6PD to sup-
ply glutathione.4 G6PD deficiency is categorized as class
Address reprint requests to: Brenda D. Jamerson, Center on Health and
Society, Duke University, Erwin Mill Building, 2024 W Main Street, IeIV corresponding to G6PD enzyme activity. The major-
Durham, NC 27705, USA; Phone: 9198691468; FAX: 9198691468; ity of persons are defined class IIeIII (associated with
E-mail: [email protected] 10e60% enzyme activity) with fewer persons having a

0188-4409/$ - see front matter. Copyright Ó 2020 IMSS. Published by Elsevier Inc.
https://doi.org/10.1016/j.arcmed.2020.06.006
2 Jamerson et al./ Archives of Medical Research - (2020) -

more severe class I form (associated with less than 10% a) Unrecognized G6PD deficiency in the presence of the
G6PD activity) (5). Classical events which trigger red cell viral infection itself may cause hemolytic crisis and
hemolysis are the ingestion of fava beans, certain drugs worse outcome.
and infection (4). Hydroxychloroquine, a drug that is under b) Unrecognized G6PD deficiency is a risk factor for
investigation to treat COVID-19, has been reported to complications -not associated with hemolytic crisis
trigger hemolytic crisis in patients with G6PD deficiency but associated with venous thrombosis and cascade
(6,7). Therefore, when an unexpected drop in hemoglobin of CV complications.
occurs in a patient with COVID-19, it may also alert the c) Administration of hydroxycholorquine for treatment
clinician to the need to further evaluate for the possibility of COVID-19 in patients with unrecognized G6PD
of G6PD deficiency. deficiency could lead to worse outcomes associated
G6PD deficiency has a higher prevalence across African, with hemolytic crisis.
Asian, Latin America, and Mediterranean populations (3).
Based on this evidence, it may be warranted to recom-
The prevalence of G6PD deficiency commonly maps to
mend adding G6PD deficiency to the list of screening ele-
populations where historically malaria was prevalent and
ments in a COVID-19 workup for those patients where
is likely to have been a protective adaptation since cells
there is a high suspicion for this genetic mutation.
deficient in G6PD inhibit the growth of specific types of
malaria (4). In the United States, estimated prevalence of
G6PD deficiency based on estimates from the military pop-
ulation is 12% in African American males, 4% in African References
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