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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/8218| Circulating ADAM17 is associated with COVID-19 severity | |
| Mengyu Pan Isabel Goncalves Andreas Edsfeldt Jiangming Sun | |
| Acceso Abierto | |
| Atribución-NoComercial-SinDerivadas | |
| https://doi.org/10.1101/2023.08.23.23294465 | |
| https://www.medrxiv.org/content/10.1101/2023.08.23.23294465v1 | |
| bstract Background ADAM17 are emerging as an important role in the severe outcomes of COVID-19. This study aims to characterize causal relationship between ADAM17 and COVID-19. Methods Using mendelian randomization analyses, we examined the causal effects for circulating ADAM17 on COVID-19 outcomes using summary statistics from large genome wide association studies of ADAM17 (up to 35 559 individuals) from the Icelandic Cancer Project and deCODE genetics, critical COVID-19 (cases:13 769; controls:1 072 442), hospitalized COVID-19 (cases:32 519; controls: 2 062 805) and SARS-CoV-2 infection (cases:122 616; controls:2 475 240) from the COVID-19 Host Genetics Initiative. Results Mendelian randomization analyses demonstrated that 1 standard deviation increase of genetically determined circulating ADAM17 at extracellular domain were associated with increasing risk of developing critical COVID-19 (odds ratio [OR]=1.26, 95% CI 1.03-1.55). Multivariable MR analysis suggested a direct causal role of circulating ADAM17 at extracellular domain on the risk of critical COVID-19 (OR=1.09; 95% CI 1.01-1.17), accounting for body mass index. Casual effects for the cytoplasmic domain of ADAM17 on COVID-19 were not observed. Conclusion Our results suggest that the increased circulating ADAM17 at extracellular domain are associated with a high risk of critical COVID-19 strengthening that of ADAM17 may contribute to the risk stratification and a therapeutic option for severe COVID-19. What is already known on this topic Various inflammatory stimuli, as well as the SARS-CoV-2 S-protein, elevate the activity of a disintegrin and metalloproteinase 17 (ADAM17). Inhibition of ADAM17 activity in vitro has illustrated the ability to effectively impede the infection caused by SARS-CoV-2. Nonetheless, the predictive capability of ADAM17 in predicting the severity of COVID-19 outcomes remains less certain within human populations. | |
| bioRxiv | |
| 24-08-2023 | |
| Preimpreso | |
| Inglés | |
| Público en general | |
| VIRUS RESPIRATORIOS | |
| Aparece en las colecciones: | Materiales de Consulta y Comunicados Técnicos |
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