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A recent study examines links between blood proteins and the risk of developing severe COVID-19. Felix Cesare/Getty Images
  • Recent research has identified a causal link between specific blood proteins and the risk of hospitalization, the need for respiratory support, or the risk of death from severe COVID-19.
  • While certain blood proteins were associated with an increased risk of severe COVID-19, others were protective.
  • Confirming the findings and exploring their clinical applicability will require further research.

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In late 2019, scientists first identified SARS-CoV-2, the virus that causes COVID-19. Since then, in the United States alone, there have been more than 79 million cases and over 950,000 deaths from the disease.

Most people who develop COVID-19 have mild to moderate symptoms, such as a fever, chills, shortness of breath, a sore throat, and a runny nose, and these resolve without special treatment. However, others have an increased risk of severe illness and death from COVID-19.

Often, people with severe COVID-19 require hospitalization with intensive care and ventilation.

Although this has not been conclusively proven, scientists believe that an overactive and abnormal immune response to SARS-CoV-2 may be responsible for the damage seen in severe COVID-19.

The immune system fights viruses, bacteria, fungi, and other foreign substances through innate and adaptive responses. When pathogens enter the body, the innate immune system releases white blood cells called leukocytes, as well as enzymes and natural killer cells to target and kill the pathogens.

If the innate immune system cannot neutralize the pathogen, such as a virus, the adaptive immune system produces T lymphocytes, B lymphocytes, and antibodies, which specifically target the virus. They help the immune system’s “memory,” so it can respond quickly to future infections with the same virus.

Genetics influence the response of the innate immune system. And so, genetic differences may help explain why some people are more likely to develop severe COVID-19.

Previous research has identified relationships between different genetic factors, hospitalization, and the need for ventilation due to COVID-19.

Other studies have shown genetic variations between blood proteins modulating the immune response in healthy individuals.

This led the authors of the new study to turn to data from genome-wide association studies. They looked for blood proteins associated with the risk of hospitalization, the need for respiratory support, and death from severe COVID-19.

The team has published its results in the journalPLOS Genetics.

Study co-author Dr. Alish Palmos, from the Social, Genetic, and Developmental Psychiatry Research Centre at King’s College London, explained to Medical News Today that the researchers looked at thousands of proteins using Mendelian randomization.

“Mendelian randomization uses genetic variants associated with a trait, i.e., protein level, and measures their causal effect on disease outcomes, [avoiding] environmental confounding factors, such as lifestyle, being physically ill, etc.”

After examining more than 3,000 blood proteins using a genetic tool, they found 14 proteins with causal effects, including the:

  • blood group proteins ABO and KEL
  • antigen recognition proteins CD207 and SFTPD, structures on the surface of the virus identified by the immune system
  • adhesion molecules SELL, SELE, PECAM-1, and sICAM-1, which recruit virus-killing white blood cells called neutrophils to the site of inflammation
  • transporters RAB14 and ATP2A3, which are proteins that move materials across a cell membrane
  • enzymes GCNT4, C1GALT1C1, FAAH2, LCTL, which are proteins that speed up chemical reactions in a cell

The researchers found that increased levels of ABO, C1GALT1C1, CD207, GCNT4, and RAB14 were associated with a 1.12 to 1.35 times greater risk of hospitalization, need for respiratory support, or death from COVID-19.

Higher levels of FAAH2 indicated a 1.19 times increased risk of hospitalization only.

Higher levels of the adhesion molecules PECAM-1, SELE, and SELL decreased the risk of hospitalization, need for respiratory support, or death from COVID-19 by 9–20%.

Increased ATP2A3, KEL, LCTL, and SFTPD were linked to decreased hospitalization risk, while higher levels of sICAM-1 were associated with a reduced risk of death or need for respiratory support.

Dr. Fady Youssef, a pulmonologist, internist, and critical care specialist at Memorial Care Long Beach Medical Center, provided context for MNT:

“This study offers some [ideas] about ways that we can […] better predict which patients will have a worse […] course and which patients are […] protected based on their genetics.”

Dr. Palmos was surprised that the study did not show an association between “classic pro-inflammatory proteins,” such as C-reactive protein or interleukin-6, and severe COVID-19. “It was also surprising to see such a consistent protective effect of adhesion molecules with severe COVID-19.”

“Our findings causally support many observational studies that have suggested endocannabinoids to be protective against severe illness and blood groups to be associated with increased risk of severe illness.”

– Dr. Palmos

The strengths of the study included its design and use of Mendelian randomization. Weaknesses include the reliance on data from other studies, which could be subject to error despite quality control measures.

Dr. Palmos stated, “Clinical studies in patients would need to be carried out first to confirm our findings. One such study is the COVID-Clinical Neuroscience Study, which is investigating the causes behind different aspects of COVID-19.”

Dr. Youssef told MNT, “Once you start applying [the data] widely, then you understand the [true] impact.” He believes that this study “adds another piece in that puzzle […] that would inform which interventions would be offered to patients depending on their risk profile.”