Genes and Blood Type Determine Risk of COVID-19 Severity

A team of researchers have found gene variants for severe course of COVID-19, indicating that blood group might have an influence on the severity of the disease’s symptoms.

The world's first large-scale genome-wide study conducted by scientists at the University Medical Center Schleswig-Holstein (UKSH Kiel, Germany) and the Kiel University (CAU Kiel, Germany), in cooperation with a research group from Norway, has found gene variants that significantly influence the course of the disease-one of them concerns the gene for the blood group trait. This suggests that different blood groups may be responsible for why some people become severely ill with COVID-19 while others show hardly any symptoms.

Doctors from several hospitals of the corona epicenters in Northern Italy and Spain, sent blood samples of a total of 1,980 intensive care COVID-19 patients who had to be treated with oxygen or connected to a ventilator. For the control group, 2,205 randomly selected women and men from the population of these countries were obtained. Within only three weeks, DNA was isolated from the blood samples and 8.5 million positions of the genetic material from each individual were measured with so-called biochips (SNP arrays). The study showed that people with blood group A had an approximately 50% higher risk of severe COVID-19 progression than people with other blood groups. In contrast, people with type 0 blood groups were almost 50% better protected against serious COVID-19 disease. Thus, the study confirmed for the first time by means of a comprehensive genome-wide analysis two earlier studies by international researchers who had already described a possible correlation between blood group characteristics and the disease using the blood serum of COVID-19 patients.

In addition to the significant abnormality in the AB0 blood group locus, the gene locus by which the individual blood group is determined, the researchers found an even higher effect strength for a genetic variation on chromosome 3. Which of the several candidate genes located in this locus is responsible for this cannot be determined precisely at present, but the analysis was able to show that carriers of the gene are at a twofold higher risk of contracting severe COVID-19 than people who do not carry this variation. Among the Italian and Spanish patients who were so ill that they not only had to be supplied with oxygen but also connected to a ventilator, a particularly high number carried this genetic disposition. A result that was also evident in the distribution of blood groups: Among the particularly seriously ill, there were also a particularly large number of people with blood group A.

“The results were very exciting and surprising for us. The region on chromosome 3 in particular had not previously been associated with COVID-19 by scientists. In other regions of the genome for which an effect on the disease had been suspected, no statistically significant differences were found between the healthy volunteers and the patients; neither in the chromosome section 6p21, which is associated with the immune system and many infectious diseases, nor in the gene IFITM3, which is associated with influenza,” said Prof. Dr. Andre Franke, Director of the Institute of Clinical Molecular Biology (IKMB) and member of the steering committee of the cluster of excellence "Precision Medicine in Chronic Inflammation" (PMI). “With chromosome 3 and the AB0 blood group locus we describe real causes for a severe course of COVID-19. Our results, therefore, create an excellent basis for the development of active substances that can target the candidate genes found. It has been proven that a clinical study in which a drug is tested has twice as much success if genetic evidence for the target is already available. The results could also contribute to an improved risk assessment for a severe course of COVID-19 in patients.”

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University Medical Center Schleswig-Holstein (UKSH)
UKSH Kiel