Why some people are less naturally resistant to COVID-19

A large team of researchers affiliated with a multitude of institutions in the UK and Brazil have partially solved the mystery of why some people are less naturally resistant to COVID-19 than others. In their article published in the journal Science, the group describes their study of the interferon system and the role it plays in the fight against the SARS-CoV-2 virus.

As the global pandemic has unfolded, it has become clear that some people have much more severe symptoms when they contract COVID-19 than others. This is because some people have no symptoms, while others get so sick that they die. In this new effort, the researchers conducted an extensive screening of gene expression stimulated by interferon to isolate possible enzymes involved in alerting the immune system to infection. Interferons are signaling proteins that alert the body when invasive entities such as bacteria and viruses are detected.

The researchers’ work led them to OAS1, an enzyme that reacts to interferon signaling by calling for an immune response when the SARS-CoV-2 virus is detected. Previous research has shown that OAS1 binds to membranes using a prenyl group as part of the signaling process. Previous research has also shown that this signaling can inhibit the replication of the SARS-CoV-2 virus. Noting its value in protecting people from COVID-19, the researchers looked at the transcriptomes of 500 COVID-19 patients who had presented a wide range of symptoms and found that those who did not have prenylated OAS1 exhibited much more serious symptoms. Why some people are born without the enzyme is still a mystery, but the team’s work could help lead to new types of vaccines against COVID-19 and other types of infections.

Intrigued by their findings, the researchers turned their attention to another mammal possibly involved in the pandemic, the horseshoe bat. They found that it lacks the prenylated form of OAS1 that protects humans against the virus, helping to explain why the virus is so deadly to this species. The discovery could also help explain why bats are such prolific hosts for a variety of viruses.

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