【Latest News】HKUMed in alliance with international research collaboration discovers inborn errors of immunity in patients with life-threatening COVID-19
Researchers of the COVID Human Genetic Effort (COVID HGE), including scientists from the Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong (HKUMed), discover that more than 10% of people who developed severe COVID-19, regardless of age and pre-existing medical conditions, had misguided auto-antibodies that attack the immune system itself, weakening the immune response. Another 3.5%, at least, had specific mutations in the immune system, causing genetic diseases called inborn errors of immunity. The novel findings explain for the first time why some COVID-19 sufferers have a more severe disease than other patients their age, paving the way for invention of possible personalized treatment for these patients. The results also provide the first molecular answer why COVID-19 mortality is higher for men than women.
The way SARS-CoV-2 affects people differently has been puzzling. The virus can cause a symptom-free infection and go away quietly, or it can kill in a few days. Research in the field has shown that unusual susceptibility to certain infectious diseases, such as lethal seasonal influenza or invasive pneumococcal disease, can be traced to single-gene mutations that affect an individual’s immune response. Similarly, multisystem inflammatory syndrome in children (MIS-C) may also be due to single-gene errors.
Since February this year, investigators around the world in the COVID Human Genetic Effort have been enrolling thousands of COVID-19 patients to find out whether something in their genetic make-up drives the disparate clinical outcomes the disease produces. Researchers hypothesised that patients with life-threatening COVID-19 might, for different reasons, lack type I interferons (IFN-I), which are vital to the body's defence against viral infections.
In one study, the researchers genetically analysed blood samples from more than 650 patients with severe COVID-19. They may include the rare young patients which require intensive care, or older patients with good past health but life-threatening COVID-19. Genetic studies revealed that a significant number of people with severe disease carried rare variants in 13 genes related to IFN-I, and about 3.5% of them were in fact missing a functioning gene, meaning they had inborn errors of immunity. Examining 987 patients with life-threatening COVID-19 pneumonia, they found that more than 10% had auto-antibodies against IFN-I at the onset of their infection, impairing the IFN-I pathway and causing immunodeficiency. The majority of them, 95%, were men. Scientists may develop personalized treatment approaches for these two kinds of patients, for example, supplementation of IFN-I or plasmapheresis, for a higher chance of recovery.
The results have been published in two papers in Science, a pre-eminent science journal:
1.
https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
2.
https://science.sciencemag.org/content/early/2020/09/23/science.abd4585
#HKUMed #COVID19 #COVIDHumanGeneticEffort