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Blood group A may carry clues to treat and prevent severe COVID-19 – Scientists

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Six proteins were discovered as being associated with an increased risk of severe COVID-19 infection and eight were identified as being associated with protection from severe COVID-19 infection.

A new study looked at over 3000 proteins to see which ones were connected to the onset of severe COVID-19. The findings point to potential new targets for COVID-19 treatment and prevention strategies.

The study employed a genetic technique to screen over 3000 proteins. Researchers discovered six proteins linked to an elevated risk of severe COVID-19 and eight proteins linked to protection against severe COVID-19.

One of the proteins (ABO) associated with the risk of developing severe COVID-19 is responsible for determining blood groups, implying that blood groups have a significant role in determining whether people develop severe versions of the illness.

Understanding how blood proteins are linked to disease can help researchers better understand the underlying mechanisms and find new targets for drug development or repurposing. Protein levels can be determined directly from blood samples, however, doing so for a large number of proteins is expensive and ineffective in determining causality.

This is when genetics may come into play. Using large genetic datasets, Mendelian randomisation, a method of comparing causal relationships between risk factors and health outcomes, can assess the relationship between genetic variants linked to an exposure (in this case, high levels of individual blood proteins) and genetic variants linked to disease outcome (in this case severe COVID-19).

“Causality between exposure and disease can be established because genetic variants inherited from parent to offspring are randomly assigned at conception similar to how a randomised controlled trial assigns people to groups. In our study the groups are defined by their genetic propensity to different blood protein levels, allowing an assessment of causal direction from high blood protein levels to COVID-19 severity whilst avoiding influence of environmental effects,” explained Co-first author Dr. Vincent Millischer.

The researchers looked at two levels of COVID-19 severity: hospitalization and respiratory support, or death. Using data from several genome-wide association studies, the researchers discovered six proteins that were causally linked to an increased risk of hospitalization or respiratory support/death due to COVID-19, and eight proteins that were causally linked to protection against hospitalization or respiratory support/death.

The analysis revealed a differential between the types of proteins associated with hospitalization and those associated with respiratory support/death, implying that unique mechanisms may be at work during these two stages of sickness.

An enzyme (ABO) that determines blood group was found to be causally linked to an increased likelihood of hospitalization and the need for respiratory support in the study. This research backs up previous results that blood types are linked to a higher risk of death. When combined with earlier study demonstrating that the proportion of COVID-19 positive persons who have blood group A is higher, this suggests that blood group A should be investigated further.

“The enzyme helps determine the blood group of an individual and our study has linked it with both risk of hospitalisation and the need of respiratory support or death. Our study does not link precise blood group with risk of severe COVID-19 but since previous research has found that proportion of people who are group A is higher in COVID-19 positive individuals, this suggests that blood group A is more likely candidate for follow-up studies,” said Co-last author Dr Christopher Hübel.

Three adhesion molecules were also shown to be causally connected to a lower incidence of hospitalization and the need for respiratory support. Due to the fact that these adhesion molecules mediate interaction between immune cells and blood vessels, earlier research has suggested that late stage COVID-19 is also a disease affecting blood vessel linings.

The discovery of this group of proteins has led to the identification of a number of potential therapeutic targets for treating severe COVID-19. These will require further medical assessment, which could be done as part of the larger COVID-Clinical Neuroscience Study (COVID-CNS), which is looking into the reasons of various COVID-19 symptoms.

Gerome Breen, Professor of Genetics at the IoPPN, and co-last author on the paper said: “Out of 1000s of blood proteins we have whittled it down to about 14 that have some form of causal connection to the risk of severe COVID-19 and present a potentially important avenue for further research to better understand the mechanisms behind COVID-19 with an ultimate aim of developing new treatments but potentially also preventative therapies.”

Source: 10.1371/journal.pgen.1010042

Image Credit: Getty

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