Protein levels can be measured directly from blood samples, but conducting this type of study on large amounts of protein is expensive and cannot establish a causal direction.
This is where the genetic method known as Mendelian randomization, which compares causal relationships between risk factors and health outcomes, using large genetic data sets is used.
It can assess the relationship between genetic variants associated with exposure (in this case, high levels of individual blood proteins) and outcome-related genetic variants. illness (in this case, severe COVID-19).
Causality between exposure and disease can be established because genetic variants inherited from parent to child are randomly assigned at conception similar to how a randomized controlled trial divides. people into groups.
In this study, groups were identified according to their genetic predisposition to different blood protein levels, allowing an assessment of the causal direction from high blood protein levels to COVID-19 severity while avoid the influence of environmental impacts.
The analysis determined that an enzyme (ABO) that determines blood type is causally associated with both an increased risk of hospitalization and the need for respiratory support.
This supports previous findings around the association of blood types with a higher likelihood of death. Combined with previous research showing a higher proportion of group A in COVID-19-positive individuals, this suggests that blood type A is a candidate for further studies.
The researchers also identified three adhesion molecules that were causally linked with a reduced risk of hospitalization and the need for respiratory support.
As these adhesion molecules mediate interactions between immune cells and blood vessels, previous research suggests that late-stage COVID-19 is also a disease involving the lining of blood vessels.
These findings will require further clinical investigation that can be performed as part of a broader study aimed at investigating the causes behind various aspects of COVID-19.