According to a new study, blood types play a vital impact in whether or not patients acquire severe COVID-19.

Over 3000 proteins were evaluated in a new study to see which were causally associated to the development of severe COVID-19. This is the first study to look at so many proteins to see if they're linked to COVID-19. The findings point to potential new targets for COVID-19 treatment and prevention strategies.

The study, which was supported in part by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, employed a genetic technique to screen over 3000 proteins and was published in PLOS Genetics. Researchers discovered six proteins linked to an elevated risk of severe COVID-19 and eight proteins linked to protection against severe COVID-19.

Blood types are determined by one of the proteins (ABO) that has been linked to the likelihood of acquiring severe COVID-19, implying that blood groups play an important role in whether people get severe forms of the illness.

Dr. Alish Palmos of King's College London's Institute of Psychiatry, Psychology, and Neuroscience (IoPPN) said: "We investigated a huge number of blood proteins using a purely genetic method and discovered that just a few have causal ties to the development of severe COVID-19. Identifying this set of proteins is a critical first step toward identifying potentially useful targets for the development of novel therapeutics."

Understanding how blood proteins are linked to disease can help researchers better understand the underlying mechanisms and find new targets for medication 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 randomization, 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).

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Dr. Vincent Millischer of the Medical University of Vienna, a co-first author, explained: "Because genetic variants inherited from parents to offspring are randomly assigned at conception, similar to how people are randomly assigned to groups in a randomised controlled trial, causality between exposure and disease can be established. The groups in our study were identified by their genetic susceptibility to different blood protein levels, which allowed us to analyse the causal direction from high blood protein levels to COVID-19 severity while excluding the influence of external factors."

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

The types of proteins connected to hospitalisation and those linked to respiratory support/death were found to be unique, indicating that separate processes may be at action in these two stages of sickness.

An enzyme (ABO) that determines blood group was found to be causally linked to an increased likelihood of hospitalisation and the need for respiratory support in the study. This backs up previous research that show a link between blood group and a higher risk of death. When combined with earlier data indicating that the proportion of COVID-19 positive patients who have blood group A is higher, blood group A appears to be a possibility for further investigation.

Dr. Christopher Hübel, co-last author from King's College London's IoPPN, said: "The enzyme is used to determine a person's blood group, and our research has connected it to the likelihood of hospitalisation as well as the requirement for respiratory support or death. Although our study did not find a link between specific blood groups and the likelihood of severe COVID-19, earlier research has revealed that the proportion of persons who are group A is higher in COVID-19 positive people, suggesting that blood group A is a better option for follow-up investigations."

Three adhesion molecules were also shown to be causally connected to a lower incidence of hospitalisation 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 clinical examination, 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.

Professor of Genetics at the IoPPN and co-last author on the publication, Gerome Breen, said: "Our research has resulted in a shortlist for the next step of investigation. We've narrowed it down to about 14 blood proteins that have some sort of causal link to the risk of severe COVID-19, and they represent a potentially important avenue for further research to better understand the mechanisms behind COVID-19, with the ultimate goal of developing new treatments but also potentially preventative therapies."

The NIHR Maudsley Biomedical Research Centre, Medical Research Council, UK Research and Innovation, Wellcome Trust, and Lundbeck Foundation all contributed to the study.