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 (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