Whether an individual experiences severe illness from COVID-19 is influenced by genetic factors, according to a recent study. Researchers examined a large group of COVID-19 patients and confirmed the significant role of the TLR7 gene in severe cases of the disease in men. They also found evidence suggesting that this gene may contribute to severe outcomes in women. Furthermore, the study highlighted genetic variations in three other genes related to the innate immune system that are linked to severe COVID-19.
Researchers from the University Hospital Bonn and the University of Bonn, along with other international teams, conducted a study involving a substantial number of COVID-19 patients. The results, published in the journal Human Genetics and Genomics Advances, shed light on the genetic factors influencing severe COVID-19 cases.
Despite the decrease in severe COVID-19 cases, understanding why the infection was more severe in some individuals during the peak of the pandemic remains crucial. Identifying these factors could enhance our understanding of the immune system’s response to pathogens and aid in identifying at-risk individuals for better protection or targeted therapies. These findings may also have implications for future pandemics,” stated corresponding author Prof. Kerstin Ludwig.
Besides age and pre-existing conditions, an individual’s genetic makeup can contribute to the severity of COVID-19. Initial studies during the pandemic had identified genes involved in the innate immune response, with TLR7 standing out as a significant gene associated with severe cases. However, it was unclear how genetic changes in TLR7 independently influenced disease severity and if other genes played a role.
Role of Three Additional Genes in Severe COVID-19 Risk Besides TLR7
The study by Prof. Ludwig and her team involved analyzing gene sequences from 52 candidate genes, including TLR7, in a large sample of COVID-19 patients. The research included DNA material from severely affected individuals and control subjects from Spain and Italy without SARS-CoV-2 status, providing valuable insights.
The study revealed a higher frequency of non-functional mutations in the TLR7 gene among severely affected COVID-19 patients compared to the control group. Additionally, mutations in three other genes, TBK1, INFAR1, and IFIH1, were identified in severely affected individuals, adding to the understanding of genetic factors influencing COVID-19 severity.
Gender-Specific Variations in Genetic Impact on COVID-19 Severity
Further investigation into the TLR7 gene revealed intriguing findings related to gender differences. TLR7 is located on the X chromosome, meaning men have one copy while women have two. Surprisingly, mutations in TLR7 were observed more frequently in women with severe COVID-19 cases. The study also suggested different genetic changes in women compared to men and highlighted potential implications on immune function.
The collaborative study involved several institutions, including the University Hospital Schleswig-Holstein, Humanitas University Milan, and University Hospital Radboudumc, in addition to the University of Bonn and University Hospital Bonn. Support for the study was provided by various research facilities and programs.
