New research suggests a causal link between blood group and severe
COVID-19

Date:
March 4, 2022
Source:
King's College London
Summary:
A new study has analysed over 3000 proteins to identify which are
causally linked to the development of severe COVID-19. This is the
first study to assess such a large number of proteins for their
connection to COVID-19. The findings provide insight into potential
new targets for approaches to treat and prevent severe COVID-19.



FULL STORY ==========================================================================
A new study has analysed over 3000 proteins to identify which are
causally linked to the development of severe COVID-19. This is the first
study to assess such a large number of proteins for their connection to COVID-19. The findings provide insight into potential new targets for approaches to treat and prevent severe COVID-19.


========================================================================== Published in PLOS Genetics and part-funded by the National Institute for
Health Research (NIHR) Maudsley Biomedical Research Centre, the study
used a genetic tool to screen over 3000 proteins. Researchers identified
six proteins that could underlie an increased risk of severe COVID-19
and eight that could contribute to protection from severe COVID-19.

One of the proteins (ABO) that was identified as having a causal
connection to the risk of developing severe COVID-19 determines blood
groups, suggesting that blood groups play an instrumental role in whether people develop severe forms of the disease.

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." Assessing how blood proteins are linked to disease can help understand the underlying mechanisms and identify potential new targets
for developing or repurposing drugs. Protein levels can be measured
directly from blood samples but conducting this type of research for
large numbers of proteins is costly and cannot establish causal direction.

This is where genetics can play a role. Mendelian randomisation, a
method of comparing causal relations between risk factors and health
outcomes, using large genetic datasets can assess the relationship between genetic variants connected with an exposure (in this case high levels of individual blood proteins) and genetic variants connected with disease
outcome (in this case severe COVID-19).



========================================================================== Co-first author Dr Vincent Millischerfrom the Medical University
of Vienna explained: "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."
The study considered two incremental levels of severity of COVID-19: hospitalisation and respiratory support or death. Using data from a number
of genome-wide association studies the researchers found six proteins
that were causally linked to an increased risk of hospitalisation or respiratory support/ death due to COVID-19 and eight causally linked to protection against hospitalisation or respiratory support/death.

Analysis showed some distinction in types of proteins linked to
hospitalisation and those linked to respiratory support/death, indicating different mechanisms may be at work in these two stages of disease.

The analysis identified that an enzyme (ABO) that determines blood group
was causally associated with both an increased risk of hospitalisation
and a requirement for respiratory support. This supports previous
findings around the association of blood group with higher likelihood of
death. Taken together with previous research showing that the proportion
of group A is higher in COVID-19 positive individuals, this suggests
blood group A is candidate for follow-up studies.

Co-last author Dr Christopher Hu"belfrom the IoPPN, King's College London
said: "The enzyme helps determine the blood group of an individual and
our study has linked it with both risk of hospitalisation and the need
of 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." Researchers also identified three
adhesion molecules as being causally linked to a decreased risk of hospitalisation and requirement of respiratory support.

As these adhesion molecules mediate interaction between immune cells and
blood vessels this chimes with previous research suggesting that late
stage COVID-19 is also a disease involving the linings of blood vessels.



==========================================================================
By identifying this suite of proteins, the research has highlighted
a number possible targets for drugs that could be used to help treat
severe COVID-19.

These will need further clinical investigation which can be undertaken
as part of the wider COVID-Clinical Neuroscience Study (COVID-CNS)
which is investigating the causes behind different aspects of COVID-19.

Gerome Breen, Professor of Genetics at the IoPPN, and co-last author on
the paper said: "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." The research was supported by NIHR Maudsley Biomedical Research Centre, Medical Research Council, UK Research and Innovation, Wellcome Trust and the Lundbeck Foundation.

The paper 'Proteome-wide Mendelian randomization identifies causal
links between blood proteins and severe COVID-19' was published in
PLOS Genetics.

========================================================================== Story Source: Materials provided by King's_College_London. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Alish B. Palmos, Vincent Millischer, David K. Menon, Timothy R.

Nicholson, Leonie S. Taams, Benedict Michael, Geraint
Sunderland, Michael J. Griffiths, Christopher Hu"bel, Gerome
Breen. Proteome-wide Mendelian randomization identifies causal
links between blood proteins and severe COVID-19. PLOS Genetics,
2022; 18 (3): e1010042 DOI: 10.1371/ journal.pgen.1010042 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220303141238.htm

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