A recent study looked at over 3000 proteins to see which ones were connected to the onset of severe COVID-19. This is the first research to look at so many proteins to see if they’re linked to COVID-19. The findings point to possible 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 versions of the illness.
Co-first author Dr Alish Palmos from Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London said: “We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19. Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.”
Understanding how blood proteins are connected to illness might 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 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).
Dr. Vincent Millischer, a co-first author from the Medical University of Vienna, 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 various blood protein levels, which allowed us to analyse the causative direction from high blood protein levels to COVID-19 severity while excluding the influence of external factors.”
The researchers looked at two degrees of COVID-19 severity: hospitalisation and respiratory support, or death. The researchers discovered six proteins that were causally connected to an elevated risk of hospitalisation or respiratory support/death owing to COVID-19 using data from a variety of genome-wide association studies.
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 phases of sickness.
An enzyme (ABO) that determines blood type was shown to be causally linked to an increased likelihood of hospitalisation and the need for respiratory assistance in the study. This backs up earlier research that show a link between blood type and a higher risk of mortality. When combined with earlier data indicating that the proportion of COVID-19 positive patients who have blood group A is greater, blood group A appears to be a possibility for further investigation.
“The enzyme helps define an individual’s blood type, and our study has associated it with both danger of hospitalisation and the requirement for respiratory assistance or mortality,” said co-last author Dr Christopher Hübel of the IoPPN at King’s College London.
Although our study did not find a relationship 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 greater 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 assistance. Due to the fact that these adhesion molecules mediate contact between immune cells and blood vessels, earlier research has shown 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 might be done as part of the larger COVID-Clinical Neuroscience Study (COVID-CNS), which is looking into the reasons of various COVID-19 symptoms.
“What we have done in our study is present a shortlist for the next stage of research,” said Gerome Breen, Professor of Genetics at the IoPPN and co-last author on the publication.
We whittled it down to about 14 blood proteins 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 the ultimate goal of developing new treatments, as well as 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.
PLOS Genetics released a research titled “Proteome-wide Mendelian randomization finds causal linkages between blood proteins and severe COVID-19.”
