Association of Glucose-6-Phosphate Dehydrogenase Deficiency With Outcomes in US Veterans With COVID-19

Abstract

Importance: The underlying biological risk factors for severe outcome due to SAR-CoV-2 infection are not well defined.

Objective: To determine the association between glucose-6-phosphate dehydrogenase (G6PD) deficiency and severity of COVID-19.

Design, setting, and participants: This retrospective cohort study included analysis of 24 700 veterans with G6PD enzyme testing prior to January 1, 2020, obtained through the US Veterans Health Administration national databases. These veterans were cross-referenced with the Veterans Administration COVID-19 Shared Data Resource for SARS-CoV-2 testing from February 15, 2020, to January 1, 2021. The final study population consisted of 4811 veterans who tested positive for SARS-CoV-2. Statistical analysis was performed from June to December 2021.

Exposures: G6PD deficiency.

Main outcomes and measures: COVID-19 severe illness, as defined by the Centers for Disease Control and Prevention: hospitalization, need for mechanical ventilation and/or intensive care unit admission, or in-hospital mortality after a positive SARS-CoV-2 test.

Results: Among 4811 veterans in the Veterans Health Administration who had historical G6PD enzyme activity test results and SARS-CoV-2 positivity included in this study, 3868 (80.4%) were male, 1553 (32.3%) were Black, and 1855 (39%) were White; 1228 (25.5%) were 65 years or older and 3583 (74.5%) were younger than 65 years. There were no significant differences in age, body mass index, or Charlson Comorbidity Index were present between the veterans with G6PD deficiency and without G6PD deficiency. Among these veterans with SARS-CoV-2 infection, G6PD deficiency was more prevalent in Black male veterans (309 of 454 [68.1%]) compared with other racial and ethnic groups. Black male veterans less than 65 years of age with G6PD deficiency had approximately 1.5-fold increased likelihood of developing severe outcomes from SARS-CoV-2 infection compared with Black male veterans without G6PD deficiency (OR, 1.47; 95% CI, 1.03-2.09). In the small subset of White male veterans with G6PD deficiency, we observed an approximately 3.6-fold increased likelihood of developing severe outcomes from SARS-CoV-2 infection compared with White male veterans aged 65 years or older without G6PD deficiency (OR, 3.58; 95% CI, 1.64-7.80). This difference between veterans with and without G6PD deficiency was not observed in younger White male veterans or older Black male veterans, nor in smaller subsets of other male veterans or in female veterans of any age.

Conclusions and relevance: In this cohort study of COVID-19-positive veterans, Black male veterans less than 65 years of age and White male veterans 65 years of age or older with G6PD deficiency had an increased likelihood of developing severe COVID-19 compared with veterans without G6PD deficiency. These data indicate a need to consider the potential for G6PD deficiency prior to treatment of patients with SARS-CoV-2 infection as part of clinical strategies to mitigate severe outcomes.

Figure 1.. Study Population of SARS-CoV-2–Positive US Veterans With or Without G6PD Deficiency

US veterans with both a prior medical record for G6PD deficiency testing and SARS-CoV-2 testing between February 15, 2020, to January 1, 2021, are shown (n = 24 700). The SARS-CoV-2–positive subgroup (n = 4811) was stratified by sex (male, female) and self-identified race (Black, White, other [self-identified as neither Black nor White or self-identified as Asian, Pacific Islander, or American Indian or Alaska Native]) for further study assessment.

Figure 2.. Prevalence of G6PD Deficiency in US Veteran Population That Tested Positive for SARS-CoV-2 Infection

Of the total male veterans (n = 3868) in this SARS-CoV-2–positive cohort (n = 4811), 10.8% (n = 418) had G6PD deficiency with the following distribution across racial ancestries: Black male veterans: 19.9% (309 of 1553), White male veterans: 3.7% (68 of 1855), and other male veterans (self-identified as neither Black nor White or self-identified as Asian, Pacific Islander, or American Indian or Alaska Native): 8.9% (41 of 460). Of the total female veterans of all racial ancestries (n = 907) in this SARS-CoV-2 positive cohort, 3.8% (36) had G6PD deficiency. These data show that the prevalence of G6PD deficiency in veterans positive for SARS-CoV-2 was higher than expected in the military population. All SARS-CoV-2 testing performed between February 15, 2020, to January 1, 2021. The percentages of US veterans with G6PD deficiency are presented as reported by the US Department of Defense.

Figure 3.. Clinical Characteristics of US Veterans Testing Positive for SARS-CoV-2 With or Without G6PD Deficiency

Heatmap illustrates the prevalence of comorbidities commonly associated with risk for severe outcomes due to SARS-CoV-2 infection (n = 4811). Veterans were grouped by age (<65 y and ≥65 y) and self-reported sex and race. Percentages for each comorbidity indicated are represented by the heatmap scale shown on the right. BMI indicates body mass index (calculated as weight in kilograms divided by height in meters squared); CAHD, coronary atherosclerosis and other heart disease; CCI, Charlson Comorbidity Index; CHF, congestive heart failure; CKD, chronic kidney disease; CLD, chronic liver disease; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease including hypertension; HIV, human immunodeficiency virus; Other, male veterans with other race (did not self-identify as White or Black, or self-identified as Asian, Pacific Islander, or American Indian or Alaska Native). ^aSevere outcomes include (1) in-hospital mortality, (2) hospitalization, (3) intensive care unit admission, or (4) mechanical ventilation. All data were extracted as indicated by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes. See eTable 1 in Supplement 1 for detailed information and raw data and eFigure 1 in Supplement 1 for representation of total cohort data.