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A genetic study has identified six proteins that could be key in having a higher risk of severe Covid-19 and another eight that could contribute to protection against severe Covid-19. This is the first study to evaluate such a large amount of protein for its connection to Covid-19.
The work, Posted in
PLOS Geneticshas analyzed more than 3,000 proteins to identify which ones are causally related to the development of severe Covid-19. The findings provide information on potential new targets to treat and prevent severe Covid-19.
The researchers identified six proteins that could underlie an increased risk of severe Covid-19 and eight that could contribute to protection against severe Covid-19.
one of the proteins (ABO) identified as having a causal connection to the risk of developing severe Covid-19 determines blood groups, suggesting that blood groups play a critical role in people developing severe forms of the disease.
Co-author Alish Palmos of the
King’s College London (UK) explains that “a purely genetic approach has been used to investigate a large number of blood proteins and we established that some have causal links with the development of severe Covid-19. Refining this group of proteins is a vital first step in discovering potentially valuable targets for the development of new treatments.”
Assess how blood proteins are linked to disease can help understand underlying mechanisms and identify potential new targets for drug development or reuse. The protein levels can be measured directly from blood samplesbut performing this type of research for a large number of proteins is expensive and cannot establish a causal direction.
This is where genetics can play a role. The Mendelian randomizationa method for comparing causal relationships between risk factors and health outcomes, using large genetic data sets can assess the relationship between genetic variants related to an exposure (in this case, high levels of individual blood proteins) and Genetic variants related to disease outcome
(in this case severe Covid-19).
The first author, Vincent Millischerfrom
Medical University of Vienna (Austria)points out that “the causality between the exposure and disease it can be established because genetic variants inherited from parents to children are randomly assigned at conception similar to how a randomized controlled trial assigns people to groups.” In our study, groups are defined by their genetic propensity for different blood protein levels, allowing an assessment of the causal direction from high blood protein levels to Covid severity, while avoiding the influence of environmental effects.
The study considered two incremental severity levels of Covid-19: hospitalization and respiratory support or death. Using data from a series of genome-wide association studies, the researchers found six proteins that were causally related with an increased risk of hospitalization or ventilation/death due to Covid-19 and eight causally related to protection against hospitalization or ventilation/death.
The analysis showed some distinction in the types of proteins linked to hospitalization and those linked to respiratory support/death, indicating that different mechanisms may be at work in these two stages of the disease.
Furthermore, it shows that an enzyme (ABO) that determines blood group was causally associated with both higher risk of hospitalization as with the need for respiratory assistance. This supports previous findings on the association of blood group with a higher probability of death.
Together with some previous research showing that the proportion of group A is higher in individuals positive for Covid-19, this suggests that blood group A is a candidate for follow-up studies.
The researchers also identified three adhesion molecules as being causally related to a lower risk of hospitalization and need for respiratory support. As these adhesion molecules mediate the interaction between immune cells and blood vessels, this is consistent with previous research suggesting that late-stage COVID-19 is also a disease that affects the lining of blood vessels.
Gerome Breen, co-author of the article, adds that “the study is providing a short list for the next stage of research. From thousands of blood proteins, we have narrowed them down to about 14 that have some kind of causal connection to the risk of severe Covid-19 and present a potentially important pathway for future research to better understand the mechanisms behind Covid-19 with the aim of developing new treatments, but potentially also preventative therapies.”