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Clinical Laboratories and Pathology Groups

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European Study Links Genes Inherited from Neanderthals to Higher Risk for Severe COVID-19 Infections in Today’s Humans

About 50% of South Asians and 16% of Europeans carry gene cluster associated with respiratory failure after SARS-CoV-2 infection and hospitalization

Clinical pathology laboratories and medical laboratory scientists may be intrigued to learn that scientists from two research institutes in Germany and Sweden have determined that a strand of DNA associated with a higher risk of severe COVID-19 in humans is similar to the corresponding DNA sequences of a roughly 50,000-year-old Neanderthal from Croatia.

The researchers concluded that this gene cluster—passed down from Neanderthals to homo sapiens—triples the risk of developing severe COVID-19 respiratory symptoms for some modern day humans.

The study, published in the journal Nature, was authored by Svante Pääbo, PhD, Director of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, and Hugo Zeberg, MD, PhD, an Assistant Professor in the Department of Neuroscience at the Karolinska Institute, in Stockholm, Sweden, and research scientist at the Max Planck Institute for Evolutionary Anthropology.

In a press release, Pääbo said, “It is striking that the genetic heritage from the Neanderthals has such tragic consequences during the current pandemic. Why this is must now be investigated as quickly as possible.”

Might Useful Biomarkers for Clinical Laboratory Tests Be Identified?

Though it is not immediately clear how these findings may alter current approaches to developing treatments and a vaccine for the SARS-CoV-2 coronavirus, it is another example of how increased knowledge of human DNA leads to new understandings about genetic sequences that can spur development of useful biomarkers for clinical laboratory diagnostics tests.

Swedish geneticist Svante Pääbo, PhD

Swedish geneticist Svante Pääbo, PhD (above right), Director of the Max Planck Institute for Evolutionary Anthropology in Germany, is co-author of a recent study that traced a gene cluster linked to a higher risk of severe COVID-19 to 50,000-year-old Neanderthals from Croatia. “It is striking that the genetic heritage from the Neanderthals has such tragic consequences during the current pandemic,” he said. Nevertheless, such discoveries sometimes lead to new biomarkers for clinical laboratory tests and diagnostics. (Photo copyright: Max Planck Institute for Evolutionary Anthropology.)

This latest research reveals that people who inherit a specific six-gene combination on chromosome 3—called a haplotype—are three times more likely to need artificial ventilation if they are infected by the SARS-CoV-2 coronavirus. Yet, the researchers can only speculate as to why the gene cluster confers a higher risk.

“The genes in this region may well have protected the Neanderthals against some other infectious diseases that are not around today. And now, when we are faced with the [SARS-CoV-2] coronavirus, these Neanderthal genes have these tragic consequences,” Pääbo told the Guardian.

According to the study, the gene risk variant is most common in South Asia where about half of the population carries the Neanderthal risk variant. In comparison, one in six Europeans have inherited the gene sequence and the trait is almost nonexistent in Africa and East Asia.

“About 63% of people in Bangladesh have at least one copy of the disease-associated haplotype, and 13% have two copies (one from their mother and one from their father). For them, the Neandertal DNA might be partially responsible for increased mortality from a coronavirus infection. People of Bangladeshi origin living in the United Kingdom, for instance, are twice as likely to die of COVID-19 as the general population,” Science News reported.

Other Research Connecting Genes to Severe COVID-19 Symptoms

The haplotype on chromosome 3 first made headlines in June when the New England Journal of Medicine (NEJM) published the “Genomewide Association Study of Severe COVID-19 with Respiratory Failure,” which analyzed COVID-19 patients in seven hospitals in Italy and Spain. The researchers found an association between the gene cluster on chromosome 3 and severe symptoms of SARS-CoV-2 after infection and hospitalization. The study also pointed to the potential involvement of chromosome 9, which contains the ABO blood-group system gene, indicating that humans with type A blood may have a 45% higher risk of developing severe COVID-19 infections.

However, Mark Maslin, PhD, Professor of Climatology at University College London, cautions against drawing strong conclusions from the initial research tying disease risk to the genetic legacy of Neanderthals, the Guardian reported. He suggested that, while the Neanderthal-derived variant may contribute to COVID-19 risk in certain populations, genes are more likely to be just one of multiple risk factors for COVID-19 that include age, gender, and pre-existing conditions.

“COVID-19 is a complex disease, the severity of which has been linked to age, gender, ethnicity, obesity, health, virus load among other things,” Maslin told the Guardian. “This paper links genes inherited from Neanderthals with a higher risk of COVID-19 hospitalization and severe complications. But as COVID-19 spreads around the world it is clear that lots of different populations are being severely affected, many of which do not have any Neanderthal genes.

“We must avoid simplifying the causes and impact of COVID-19, as ultimately a person’s response to the disease is about contact and then the body’s immunity response, which is influenced by many environmental, health and genetic factors.”

Andre Franke, PhD, Director of the Institute of Clinical Molecular Biology, Kiel University in Germany, agrees with Maslin, the Associated Press reported. In a statement “ahead of the study’s final publication,” he said these latest findings have no immediate impact on the treatment of COVID-19, and he questioned “why that haplotype—unlike most Neanderthal genes—survived until today,” AP reported.

All of this deepens the mystery of the SARS-CoV-2 coronavirus. Genomics research continues to add new insights into what is known about COVID-19 and may ultimately provide answers on why some people contract the disease and remain asymptomatic—or have mild symptoms—while others become seriously ill or die. Understanding why and how certain genes increase the risk of severe COVID-19 could give rise to targeted clinical laboratory tests and therapies to fight the disease.

—Andrea Downing Peck

Related Information:

The Major Genetic Risk Factor for Severe COVID-19 Is Inherited from Neanderthals

Genomewide Association Study of Severe COVID-19 with Respiratory Failure

Neanderthal Genes Increase Risk of Serious COVID-19, Study Claims

Neandertal Gene Variant Increases Risk of Severe COVID-19

Study: Neanderthal Genes May Be a Liability for COVID Patients

Neanderthal Genes in People Today May Raise Risk of Severe COVID-19

COVID-19 Hospitalization and Death by Race/Ethnicity

Aalto University Researchers Develop Plasmonic Biosensor That Can Distinguish Differences in Exosomes, Giving Clinical Laboratories New Tool for Spotting Disease in Human Blood with Naked Eye

Analysis performed by this new biosensor could help identify inflammatory bowel diseases, cancer, and other chronic diseases, and contribute to influencing the best treatment options, a critical aspect of personalized medicine

Anatomic pathologists and clinical laboratories have long known that disease, as the saying goes, “is written in the blood.” How to spot the disease has been the challenge.

Now, researchers at Finland’s Aalto University have developed a cutting-edge plasmonic biosensor that uses the intense light absorption and reflective properties of plasmonic materials to discern refractive changes between healthy and diseased exosomes—even with the naked eye!

This opens the door to a plethora of non-invasive health tests similar to home pregnancy tests. Should such tests prove accurate and affordable, medical laboratories could have new tools in their fight to end chronic disease.

New Rules for Differentiating Healthy and Diseased Human Exosomes

The Aalto researchers produced the biosensor by depositing plasmonic metaparticles (hypothetical particles that always move faster than light, such as Tachyons) on a black metal surface capable of absorbing electromagnetic radiation. With it, abnormalities can be distinguished by the color generated when the plasmons impact the black surface.

“We exploited it as the basis of new design rules to differentiate diseased human serum exosomes from healthy ones in a simple manner with no need [for] any specialized equipment”, Dr. Abdou Elsharawy, PhD, Postdoctoral Researcher at Kiel University in Kiel, Germany, stated in an Aalto University news release.


Plasmonic Biosensor Aalto University

Researchers at Aalto University in Finland have developed a method for “visualizing the specular reflection color by a blackbody substrate. The carriers containing Ag nanoparticles [shown above] are covered with various dielectrics of AlN [aluminum nitride], SiO2 [silicon dioxide], and the composites thereof that are placed on a black background to enhance the reflectivity contrast of various colors at a normal angle of incidence.” This has resulted in a tool that medical laboratories could use to differentiate between healthy and diseased exosomes in human blood. (Photo and caption copyrights: Aalto University.)



Dr. Mady Elbahri, PhD, Professor, Nanochemistry and Nanoengineering, Department of Chemistry and Materials Science at Aalto University, indicated that there is no need to use sophisticated fabrication and patterning methods with the biosensor as bulk biodetection of samples can be seen with the naked eye.

“It is extraordinary that we can detect diseased exosomes by the naked eye. The conventional plasmonic biosensors are able to detect analytes solely at a molecular level. So far, the naked-eye detection of biosamples has been either rarely considered or unsuccessful,” Elbahri noted in the news release.

Exosomes Critical to Many Human Bodily Processes

Exosomes are cell-derived vesicles that are present in many and perhaps all eukaryotic fluids, including blood, urine, and cultured medium of cell cultures. These small bundles of material are released by the outer wall of a cell and contain everything from proteins to ribonucleic acid (RNA) and Messenger RNA (mRNA). They are important indicators of health conditions.

There is mounting evidence that exosomes have exclusive functions and perform a significant role in bodily processes like coagulation, intercellular signaling, and waste management.

Interest in the clinical applications of exosomes is increasing, along with their potential for use in prognosis, development of therapies, and as biomarkers for diseases. But, exosomes are rare and distinguishing them among all other elements located in bodily fluids has proven difficult.

Thus, the Aalto study has strong implications for clinical laboratories and anatomic pathology groups. More research and regulatory approval will be needed before use of this new tool comes to fruition. However, any method that accurately and inexpensively identifies chronic disease biomarkers will impact the medical laboratory and anatomic pathology professions and is worth watching

—JP Schlingman

Related Information:

Plasmonic Biosensors Enable Development of New Easy-to-use Health Tests

Plasmonic Biosensor to Detect Exosomes with Naked Eye

Plasmonic Metaparticles on a Blackbody Create Vivid Reflective Colors for Naked‐Eye Environmental and Clinical Biodetection

Plasmonic Biosensors