For the first time, a team of researchers from King’s College London and the Medical University of Vienna analysed over 3000 proteins to identify which ones may be connected to cases of severe COVID-19, according to a study published in PLOS Genetics. The study identified six proteins associated with an increased risk of severe COVID-19 and eight that can protect patients.
Understanding how blood proteins are linked to the severity of the disease can go a long way for researchers to unveil the mechanisms behind it and identify new targets for developing a treatment. For example, one of the proteins linked with severe COVID is involved in determining blood groups, which suggests that the patient’s blood type could play a role in deciding whether it’s a severe case or not.
“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,” said Co-first author Dr. Alish Palmos from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London.
Measuring blood proteins is relatively easy for one patient, but performing this type of analysis in hundreds of patients is expensive and time-consuming. This is where genetics is essential. The team used large genetic datasets to determine the relationship between genetic variants linked with an exposure —in this case, high levels of specific proteins — and genetic variants linked with disease outcome — in this case, the severity of 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,” said Co-first author Dr. Vincent Millischer from the Medical University of Vienna.
Out of the six proteins identified with severe COVID-19, one enzyme that determines blood type was linked with a higher risk of hospitalisation and respiratory support for patients. “The enzyme helps determine the blood group of an individual, and our study has linked it with both risks of hospitalisation and the need for 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 from the IoPPN, King’s College London.
In addition, out of the eight proteins that give some protection, three mediate interactions between immune cells and blood vessels, confirming that COVID-19 progression involves the lining of the blood vessels.
“What we have done in our study is provide a shortlist for the next stage of research. 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,” said Gerome Breen, Professor of Genetics at the IoPPN, and co-last author on the paper.
(1) Palmos A, Millischer V, Menon D, Nicholson T, Taams L, et al (2022) Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19. PLOS genetics, https://doi.org/10.1371/journal.pgen.1010042