Neanderthal ancestry may give added protection from COVID

Inheritance of Neanderthal genes might explain why some people have stronger immunity to SARS-CoV-2

A new study has revealed key insights into the natural human antiviral defences against SARS-CoV-2, the virus that causes COVID-19.

Versions of a gene known as OAS1, inherited from Neanderthals on chromosome 12 protect cells from viral invasion. The key to the protective properties lies in the ability of the version of the gene to 'express' the addition of a lipid molecule to certain proteins, a process known as 'prenylation'. Prenylated lipo-proteins of this nature evolved to create an 'alarm system' that detect invaders and are involved in the process of activating our natural immune systems. The Neantherdal link means that these protective genes are more prevalent in people of European ancestry.

Dr Sam Wilson, University of GlasgowThe research, published in the journal Science and led by a team of scientists at the MRC-University of Glasgow, Centre for Virus Research, sheds new light on why some people are naturally more resistant to serious SARS-CoV-2 infection – and how, in the future, the coronavirus might overcome this resistance.

Understanding the natural anti-viral response

Although the method of transmission is still not clear, COVID-19 is spread from person to person after the virus, shed by an infected person, infects the cells of a new host. Once infected, our cells try to fight off the invading virus and scientists already know that this works better is some people, making their experience of the disease less severe. However, until now, that anti-viral response – and its effect on the virus SARS-CoV-2 has not been well-understood.

In the study, the scientists reveal that some people have a version of the gene, called OAS1, that potently inhibits SARS-CoV-2. The study showed that, while some people can express a more protective ‘prenylated’ version of the OAS1 gene, other people express a version of this gene which does not detect SARS-CoV-2.

NB OAS1 should not be confused with the other immunological concept of original antigenic sin (OAS). Although both types of OAS can have a profound impact on our responses to vaccines and disease.

Lipid coat alarm sensors

Inside cells, coronaviruses hide and replicate inside vesicles coated with lipid (fat). Prenylation is the addition of a single molecule of lipid (fat) to a protein – and it’s this technical difference that allows prenylated OAS1 to ‘seek and destroy’ the invading virus by first ‘sounding the alarm’.

The study found that, in hospitalised patients, expression of a prenylated version of this gene was associated with protection from severe COVID-19, which suggests this antiviral defence is a major component of a protective antiviral response; and is likely to have offered protection to many people during the course of the pandemic.

Bad OAS1 had worse outcomes

The study also found that hospitalized COVID-19 patients with the ‘bad’ form of OAS1 had worse clinical outcomes compared to those who expressed the protective prenylated version of OAS1. Severe disease was significantly more frequent with ICU admission or death being approximately 1.6 times more likely in these patients. 

Interestingly, the researchers also found that, approximately 55 million years ago, there was a removal of this protective gene in horseshoe bats (the presumed source of SARS-CoV-2), so SARS-CoV-2 never had to adapt to evade this defence.

As the protective prenylated OAS1 gene is widespread in animals, the billions of people that lack this protective gene could make humans particularly vulnerable to the spill over of coronaviruses from horseshoe bats.

Repertoire of natural anti-viral defences

Sam Wilson (pictured above) said: “We know viruses adapt, and even SARS-CoV-2 has likely adapted to replicate in the animal reservoir(s) in which it circulates. Cross-species transmission to humans exposed the virus SARS-CoV-2 to a new repertoire of antiviral defences, some of which SARS-CoV-2 may not know how to evade".

Concerning questions over the impact of Neanderthal ancestry on the nature of immune responses, Dr Wilson says, "The answer is that human ancestry is complicated and both [factors for risk and protection] are probably true. The Neanderthal haplotype from chromosome 3 is likely a risk factor whereas the allele of OAS1, inherited from Neanderthals (which is prenylated), on chromosome 12 is protective. Modern humans could have either, both or neither of these regions inherited from Neanderthals".

The study, ‘A Prenylated dsRNA Sensor Protects Against Severe COVID-19,’ is published in Science. The study was predominantly funded by the Medical Research Council, Wellcome, and UKRI.

See also - Neanderthal ancestry may provide greater protection

A substance that prompts the immune system to fight infection with antibodies. Full medical glossary
A substance that acts against viruses, for example and antiviral drug. Full medical glossary
The basic unit of all living organisms. Full medical glossary
Structures in the cell nucleus that carry genetic information. Full medical glossary
One of the three main food constituents (with carbohydrate and protein), and the main form in which energy is stored in the body. Full medical glossary
The basic unit of genetic material carried on chromosomes. Full medical glossary
An animal or plant that supports a parasite. Full medical glossary
intermittent claudication Full medical glossary
The organs specialised to fight infection. Full medical glossary
Relating to the structure and function of the immune system, the organs in the body that are specialised to fight infection. Full medical glossary
Invasion by organisms that may be harmful, for example bacteria or parasites. Full medical glossary
osteoarthritis Full medical glossary
An outbreak of infection that affects numerous people in different countries. Full medical glossary
Compounds that form the structure of muscles and other tissues in the body, as well as comprising enzymes and hormones. Full medical glossary
The ability of a microbe, such as a type of bacteria, to resist the effects of antibiotics or other drugs. Full medical glossary
A microbe, such as a type of bacteria, that is able to resist the effects of antibiotics or other drugs. Full medical glossary
septic arthritis Full medical glossary
A microbe that is only able to multiply within living cells. Full medical glossary
Microbes that are only able to multiply within living cells. Full medical glossary