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Updated: Jul 4, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
[Genetic factors associated with long COVID]
E J Gamero-de-Luna1, M R Sánchez-Jaén2
1Medicina Familiar y Comunitaria, Centro de Salud El Juncal, Sevilla, España; GT Medicina Genómica Personalizada y Enfermedades Raras, SEMERGEN, España.
Introduction:
The variability in expression and evolution of COVID is not completely explained by clinical factors. In fact, genetic factors play an important role. Moreover, it is unknown whether the genetic factor that contribute to susceptibility and severity are also involved in the onset and evolution of long-COVID. The objective of this review is to gather information from literature to understand which genetic factors are involved in the onset of persistent COVID.
Material And Methods:
Systematic review in PubMed and bioRxiv and medRxiv repositories based on MeSH-descriptors and MeSH-terms related to COVID and genetic factors. Using these terms 2715 articles were pooled. An initial screening performed by authors independently, selected 205 articles of interest. A final deeper screening a total of 85 articles were chosen for complete reading and summarized in this review.
Results:
Although ACE2 and TMPSS6 are involved in COVID susceptibility, their involvement in long-COVID has not been found. On the other hand, the severity of the disease and the onset of long-COVID has been associated with different genes involved in the inflammatory and immune response. Particularly interesting has been the association found with the FOXP4 locus.
Conclusions:
Although studies on long-COVID are insufficient to fully comprehend the cause, it is clear that the current identified genetic factors do not fully explain the progression and onset of long-COVID. Other factors such as polygenic action, pleiotropic genes, the microbiota and epigenetic changes must be considered and studied.
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