Last week, the COVID Human Genetic Effort consortium published two Science reports on common genetic and immunological causes of the life-threatening disease. The first Science paper entitled “Auto-antibodies against type I IFNs in patients with life-threatening COVID-19” is co-authored by our co-director and neurologist at Amsterdam UMC Diederik van de Beek; over 60 Amsterdam UMC investigators are acknowledged because of their efforts in setting the Amsterdam UMC COVID-19 Biobank.

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. Since the COVID Human Genetic Effort consortium 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.

The researchers genetically analyzed blood samples from more than 650 patients who had been hospitalized for life-threatening pneumonia due to SARS-CoV-2, 14 percent of whom had died. They also included samples from another group of over 530 people with asymptomatic or benign infection.

More than 10 percent of young and healthy people who develop severe COVID-19 have misguided antibodies that attack not the virus, but the immune system itself, new research shows. Another 3.5 percent, at least, carry a specific kind of genetic mutation.

In both groups, the upshot is basically the same: The patients lack type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether the proteins have been neutralized by so-called auto-antibodies, or were not produced in sufficient amounts in the first place due to a faulty gene, their missing-in-action appears to be a common theme among a subgroup of COVID-19 sufferers whose disease has thus far been a mystery.

Published in two papers in Science, the findings help explain why some people develop a disease much more severe than others in their age group—including, for example, individuals who required admission to the ICU despite being in their 20s and free of underlying conditions. They may also provide the first molecular explanation for why more men than women die from the disease.

Read the two Science papers here: