Large genetic study on severe COVID-19

Bonn researchers confirm three other genes for increased risk in addition to the known TLR7 gene

Whether or not a person becomes seriously ill with COVID-19 depends, among other things, on genetic factors. With this in mind, researchers from the University Hospital Bonn (UKB) and the University of Bonn, in cooperation with other research teams from Germany, the Netherlands, Spain and Italy, investigated a particularly large group of affected individuals. They confirmed the central and already known role of the TLR7 gene in severe courses of the disease in men, but were also able to find evidence for a contribution of the gene in women. In addition, they were able to show that genetic changes in three other genes of the innate immune system contribute to severe COVID-19. The results have now been published in the journal “Human Genetics and Genomics Advances”.

Even though the number of severe cases following infection with the SARS-CoV-2 virus has decreased, there is still great interest in understanding why, at the height of the coronavirus pandemic, the infection was severe in some people but not in others. “This is important because it gives us information about the function and reaction of the immune system when it first comes into contact with a pathogen. If we have a better understanding of how severe courses of the disease develop, we can identify people at risk and protect them better or develop targeted therapies. We assume that the findings can be transferred at least in part to future pandemics,” says corresponding author Prof. Kerstin Ludwig from the Institute of Human Genetics at the UKB, who is also a member of the Cluster of Excellence ImmunoSensation2 and the Transdisciplinary Research Area TRA “Life and Health” at the University of Bonn.

In addition to many possible reasons such as increased age or pre-existing conditions, some people’s own genetic make-up can cause a severe course of the disease. Early work in the pandemic had already identified affected genes, most of which are involved in the innate immune response. The gene with the strongest evidence to date is the TLR7 gene, which was identified as the cause of the disease in two pairs of Dutch brothers with severe cases back in summer 2020. However, it was not yet known to what extent the effect of genetic changes in TLR7 is independent of other non-genetic risk factors, such as increased age or previous illnesses, and whether there are other genes in which so-called mutations significantly increase the risk of severe COVID. […]

Participating Core Facilities: The authors acknowledge the support from the Next Generation Sequencing Core Facility.

Participating institutions and funding:

In addition to the University Hospital Bonn and the University of Bonn, the University Hospital Schleswig-Holstein, the Humanitas University Milan (Italy) and the University Hospital Radboudumc (Netherlands) were also centrally involved.

The study was supported by the NGS Core Facility of the UKB and the BONFOR program of the Faculty of Medicine.

Publication: J. Boos et al: Stratified analyses refine association between TLR7 rare variants and severe COVID-19; HGG Advances; DOI: 10.1016/j.xhgg.2024.100323