Fabyan Esberard de Lima Beltrão, Daniele Carvalhal de Almeida Beltrão, Giulia Carvalhal, Fabricia Elizabeth de Lima Beltrão, Jair de Souza Braga Filho, Jocyel de Brito Oliveira, Joice dos Santos de Jesus, Gabriel Jeferson Rodríguez Machado, Hatilla dos Santos Silva, Helena Mariana Pitangueira Teixeira, Juliana Lopes Rodrigues, Camila Alexandrina Viana de Figueiredo, Ryan dos Santos Costa, Fabio Hecht, Antonio C Bianco, Maria da Conceição Rodrigues Gonçalves, Helton Estrela Ramos
The Journal of Clinical Endocrinology & Metabolism, Volume 107, Issue 6, June 2022, Pages e2488–e2501
https://doi.org/10.1210/clinem/dgac075
The type 2 deiodinase and its Thr92Ala-DIO2 polymorphism have been linked to clinical outcomes in acute lung injury and pulmonary fibrosis.
Our objectives were to evaluate were cumulative mortality during admission according to Thr92Ala-DIO2 polymorphism.
Here we conducted an observational, longitudinal, and prospective cohort study to investigate a possible association between the Thr92Ala-DIO2 polymorphism and intrahospital mortality from COVID-19 in adult patients admitted between June and August 2020. Blood biochemistry, thyroid function tests, length of stay, comorbidities, complications, and severity scores were also studied according to Thr92Ala-DIO2 polymorphism.
In total, 220 consecutive patients (median age 62; 48-74 years) were stratified into 3 subgroups: Thr/Thr (n = 79), Thr/Ala (n = 119), and Ala/Ala (n = 23). While the overall mortality was 17.3%, the lethality was lower in Ala/Thr patients (12.6%) than in Thr/Thr patients (21.7%) or Ala/Ala patients (23%). The heterozygous genotype (Thr/Ala) was associated with a 47% reduced risk of intrahospital mortality whereas univariate and multivariate logistic regression adjusted for multiple covariates revealed a reduction that ranged from 51% to 66%. The association of the Thr/Ala genotype with better clinical outcomes was confirmed in a metanalysis of 5 studies, including the present one.
Here we provide evidence for a protective role played by Thr92Ala-DIO2 heterozygosity in patients with COVID-19. This protective effect follows an inheritance model known as overdominance, in which the phenotype of the heterozygote lies outside the phenotypical range of both homozygous.
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