Associations between COVID-19 and Glucose-6-Phosphate Dehydrogenase Activity in Brazil

Maria Gabriela de Almeida Rodrigues Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Wuelton Marcelo Monteiro Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Gisely Cardoso de Melo Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Ádila Liliane Barros Dias Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Marco Aurélio Sartim Department of Postgraduate, Research and Innovation, Universidade Nilton Lins, Manaus, Brazil;
Institute of Biological Sciences, Universidade Federal do Amazonas, Manaus, Brazil;

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Mariana Simão Xavier Clinical Research Laboratory for Acute Febrile Illnesses, Instituto Nacional de Infectologia Carlos Chagas, Rio de Janeiro, Brazil;

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Rebeca Linhares Abreu Netto Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Fernando Fonseca Almeida Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Djane Clarys Baía-da-Silva Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;
Department of Postgraduate, Research and Innovation, Universidade Nilton Lins, Manaus, Brazil;
Institute of Biological Sciences, Universidade Federal do Amazonas, Manaus, Brazil;
Instituto Leônidas e Maria Deane/Fiocruz Amazônia, Instituto de Pesquisas Clínicas Carlos Borborema, Manaus, Brazil;

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José Diego Brito-Sousa Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;

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Marcus Vinicius Guimarães de Lacerda Universidade do Estado do Amazonas, Manaus, Brazil;
Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;
Instituto Leônidas e Maria Deane/Fiocruz Amazônia, Instituto de Pesquisas Clínicas Carlos Borborema, Manaus, Brazil;

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Vanderson de Souza Sampaio Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil;
Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil;
Instituto Todos pela Saúde, São Paulo, Brazil

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ABSTRACT.

Glucose-6 phosphate dehydrogenase deficiency (G6PDd) was suggested as a risk factor for severe disease in patients with COVID-19. We evaluated clinical outcomes and glucose-6 phosphate dehydrogenase (G6PD) activity during and after illness in patients with COVID-19. This prospective cohort study included adult participants (≥ 18 years old) who had clinical and/or radiological COVID-19 findings or positive reverse transcription–polymerase chain reaction results. Epidemiological and clinical data were extracted from electronic medical records. Glucose-6 phosphate dehydrogenase activity was measured using SD Biosensor STANDARD G6PD® equipment on admission and 1 year after discharge. Samples were genotyped for the three most common single nucleotide polymorphisms for G6PDd in the Brazilian Amazon. Seven hundred fifty-three patients were included, of whom 123 (16.3%) were G6PD deficient. There was no difference between groups regarding the risks of hospitalization (P = 0.740) or invasive mechanical ventilation (P = 0.31), but the risk of death was greater in patients with normal G6PD levels (P = 0.022). Only 29 of 116 participants (25%) carried the African G6PDd genotype. Of 30 participants tested as G6PD deficient during disease, only 11 (36.7%) results agreed 1 year after discharge. In conclusion, this study does not demonstrate an association of G6PDd with severity of COVID-19. Limitations of the test for detecting enzyme levels during COVID-19 illness were demonstrated by genotyping and retesting after the disease period. Care must be taken when screening for G6PDd in patients with acute COVID-19.

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Author Notes

Financial support: This work was supported by Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) (grant no. PCTI-EMERGESAÚDE/AM–Chamada II 006/2020 and Pró-Estado public calls); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES); Superintendência da Zona Franca de Manaus; Departamento de Ciência e Tecnologia/Ministério da Saúde; Ministério da Ciência, Tecnologia e Inovações; Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (grant no. 403253/2020-9); FAPEAM (grant no. PAPAC 005/2019 and Pró-Estado public calls); Fundação de Amparo à Pesquisa do Estado de São Paulo (grant no. 2020/05369-6); and Fundação de Amparo à Pesquisa do Estado do Amazonas (FAPEAM) (grant no. RESOLUÇÃO N. 002/2023-POSGRAD 2023-Coordenador/Auxílio Financeiro). Many members from the Metcovid and CloroCovid-19 team are funded by FAPEAM and CAPES. W. M. Monteiro, M. V. G. Lacerda, G. C. Melo, and V. S. Sampaio have fellowships from the CNPq. D. C. Baıa-da-Silva is the recipient of a national visiting researcher grant from FAPEAM. J. D. Brito-Sousa received a postgraduate scholarship from FAPEAM.

Disclosure: We used data from the medical records of patients included in clinical trials conducted by the research team. These trials were approved by the Brazilian Committee of Ethics in Human Research for their respective original objectives (CAAE: 30152620.1.0000.0005, 30504220.5.0000.0005, and 30615920.2.0000.0005). All participants signed an informed consent form at the time of inclusion in the primary studies or, when unable, a family member performed the consent process. Participants’ sensitive data were made not available to avoid identification. All measures were taken to ensure participants’ confidentiality in accordance with good clinical practice.

Authors’ addresses: Maria Gabriela de Almeida Rodrigues, Wuelton Marcelo Monteiro, Gisely Cardoso de Melo, Ádila Liliane Barros Dias, Rebeca Linhares Abreu Netto, Fernando Fonseca Almeida, and José Diego Brito-Sousa, Universidade do Estado do Amazonas, Manaus, Brazil, and Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil, E-mails: rodriguesgabriela016@gmail.com, wueltonmm@gmail.com, cardosogisely@gmail.com, adiladias@yahoo.com.br, rbk.netto@gmail.com, ffaval@gmail.com, and sousajdb@live.com. Marco Aurélio Sartim, Department of Postgraduate, Research and Innovation, Universidade Nilton Lins, Manaus, Brazil, and Institute of Biological Sciences, Universidade Federal do Amazonas, Manaus, Brazil, E-mail: marcosartim@hotmail.com. Mariana Simão Xavier, Clinical Research Laboratory for Acute Febrile Illnesses, Instituto Nacional de Infectologia Carlos Chagas, Rio de Janeiro, Brazil, E-mail: marianasimaoxavier@gmail.com. Djane Clarys Baía-da-Silva, Universidade do Estado do Amazonas, Manaus, Brazil, Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil, Department of Postgraduate, Research and Innovation, Universidade Nilton Lins, Manaus, Brazil, Institute of Biological Sciences, Universidade Federal do Amazonas, Manaus, Brazil, and Instituto Leônidas e Maria Deane/Fiocruz Amazônia, Manaus, Brazil, E-mail: djane.claryss@gmail.com. Marcus Vinicius Guimarães de Lacerda, Universidade do Estado do Amazonas, Manaus, Brazil, Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil, and Instituto Leônidas e Maria Deane/Fiocruz Amazônia, Manaus, Brazil, E-mail: marcuslacerda.br@gmail.com. Vanderson de Souza Sampaio, Department of Education and Research, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil, Fundação de Vigilância em Saúde do Amazonas, Manaus, Brazil, and Instituto Todos pela Saúde, São Paulo, Brazil, E-mail: vandersons@gmail.com.

Address correspondence to Vanderson de Souza Sampaio, Av. Pedro Teixeira, 25 Dom Pedro, Manaus, Amazonas 69040-000, Brazil. E-mail: vandersons@gmail.com
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