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King’s College London Researchers Discover Causal Link between Blood Type and COVID-19 Severity; May Provide Clinical Laboratories with a Useful Diagnostic Insight

Findings are ‘a vital first step in discovering potentially valuable targets for development of new [COVID-19] treatments,’ noted co-first author of the study

Researchers at King’s College London (KCL) have determined that levels of certain blood proteins specific to each person’s blood type can be “causally linked” to an increased risk of hospitalization and death from a COVID-19 infection. The scientists also found that a person’s genetics play a key role in establishing the levels of those proteins in the blood.

This is relevant for clinical laboratories—particularly hospital/health system laboratories—because testing for specific proteins in the blood by medical laboratories could help flag incoming patients at higher risk for an acute COVID-19 infection.

Also, “By identifying this suite of proteins, the research has highlighted a number [of] possible targets for drugs that could be used to help treat severe COVID-19,” noted a KCL news release.

Identifying certain drugs that would be more effective for specific individuals or healthcare groups is a core goal of precision medicine.

The KCL researchers published their findings in the journal PLOS Genetics, titled, “Proteome-wide Mendelian Randomization Identifies Causal Links between Blood Proteins and Severe COVID-19.”

Alish Palmos, PhD
“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,” said Alish Palmos, PhD (above), Postdoctoral Research Associate, King’s College London Social, Genetic and Developmental Psychiatry Center, and co-first author of the study. “Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.” Medical laboratories may soon be able to use this knowledge as a way to determine risk for severe COVID-19 hospitalization, as well as to guide decisions on how to use new precision medicine drugs for combating the infection. (Photo copyright: Twitter.)

Genetic Variants Linked to Causality

Since the COVID-19 pandemic began in late 2019, scientists and researchers have been vigorously trying to understand the SARS-CoV-2 coronavirus and determine why some patients have more severe symptoms than others.

To conduct their study, the KCL researchers screened more than 3,000 blood proteins to identify which proteins have a causal link to hospitalization risk, the need for respiratory support, and death from a severe COVID-19 infection.

“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 randomized controlled trial assigns people to groups,” said Vincent Millischer, MD, PhD, Medical University of Vienna and co-first author of the study in the KCL news release.

“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,” he added. 

The scientists selected genetic variants, known as single nucleotide polymorphisms, that were strongly associated with blood protein levels. They then performed their analysis using Mendelian randomization to test the causal associations of those blood proteins with the development of severe COVID-19 infections.

“Mendelian randomization uses genetic variants associated with a trait [e.g., protein level] and measures their causal effect on disease outcomes, [avoiding] environmental confounding factors, such as lifestyle, being physically ill, etc.,” Alish Palmos, PhD, told Medical News Today. Palmos is a Postdoctoral Research Associate at King’s College London’s Social, Genetic, and Developmental Psychiatry Center and co-first author of the study.

Blood Groups Linked to COVID-19 Hospitalization, Death

One of the most important findings of the KCL research is a causal association between COVID-19 severity and an enzyme called ABO, which determines blood type. This discovery suggests that blood groups perform an instrumental role in whether individuals develop severe forms of the illness. 

“The enzyme helps determine the blood group of an individual and our study has linked it with both risk of hospitalization and the need of respiratory support or death,” said Christopher Hübel, PhD, Postdoctoral Research Associate, King’s College and co-last author of the study in the press release. “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.” 

The KCL researchers uncovered several compelling findings regarding blood proteins and COVID-19, including:

  • The discovery of six blood markers that were significantly associated with an elevated risk of hospitalization.
  • The discovery of nine blood markers that were significantly associated with a decreased risk of hospitalization.
  • Consistent results indicating hospitalization being significantly associated with decreased levels of macrophage inflammatory protein.
  • Five blood markers associated with the need for respiratory support or death.
  • Eight blood markers causally associated with a statistically significantly decreased risk of need for respiratory support or death.
  • Consistent results with respiratory support or death being significantly causally associated with decreased levels of neprilysin.

Developing New COVID-19 Treatments and Preventative Therapies

“What we have done in our study is provide a shortlist for the next stage of research,” said Gerome Breen, PhD, in the KCL news release. Breen is Professor of Psychiatric Genetics at King’s College London’s Institute of Psychiatry, Psychology and Neuroscience, and co-last author of the study.

“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,” he added. 

Further research and clinical investigation are needed to validate the King’s College London researchers’ findings. However, their insights could result in new clinical laboratory tests and personalized treatments for COVID-19.

JP Schlingman

Related Information:

Genetic Study Reveals Causal Link Between Blood Type and COVID Severity

Proteome-wide Mendelian Randomization Identifies Causal Links Between Blood Proteins and Severe COVID-19

New Research Suggests a Causal Link Between Blood Group and Severe COVID-19

Researchers Identify Six Proteins Linked with Severe COVID-19

COVID: Risk of Severe Disease Could be in Your Blood, New Research Finds

COVID-19 Severity: Blood Group May Influence Risk

A Two Minute Primer on Mendelian Randomization