Gene variant linked to asymptomatic COVID-19

A protective gene variant that enables the immune system to respond rapidly to COVID-19 has been uncovered by scientists.

Researchers have previously shown that people with asymptomatic COVID-19 mount a rapid immune response before symptoms can begin, often due to previous exposure to other coronaviruses. The new study provides the strongest evidence to date of a link between a person's genetics and the severity of their symptoms.

'We know that SARS-CoV-2 [the virus that causes COVID-19] has a lot of similarities with some seasonal coronaviruses,' Professor Jill Hollenbach from the University of California, San Francisco (UCSF), and joint senior author of the research, explained to Time. 'It's like having soldiers that are prepared for battle and already know what to look for,' she added.

The study, published in the journal Nature, investigated the genetics of close to 30,000 unvaccinated people to find patterns among those who tested positive for COVID-19 but experienced no symptoms. Of the participants, 1428 tested positive before April 2021, and of these around ten percent were asymptomatic.

Researchers from UCSF and La Trobe University in Melbourne, Australia, hypothesised that asymptomatic infections might be due to variation in human leukocyte antigen (HLA) genes. They found that even when adjusting for sex and age differences, people with a copy of the HLA-B*15:01 variant were roughly twice as likely to be asymptomatic despite being infected. This rose to eight times more likely for those with two copies of the variant (one inherited from each parent).

HLA proteins are found on nearly every cell in the body, and display fragments of proteins which can signal danger to T cells in the case of infection. They are among the most variable genes in humans. The researchers discovered that the variant HLA-B*15:01 could present nearly identical fragments from the spike proteins of COVID-19 and related, seasonal coronaviruses. Because of this, most participants with this HLA variant who had previously been exposed to seasonal coronaviruses already harboured highly potent memory T-cells, that could rapidly recognise and fight SARS-CoV-2-infected cells.

'In these cases, the seasonal coronaviruses sort of vaccinated the individuals,' Professor Stuart Tangye, of the Garvan Institute of Medical Research in Sydney, Australia, who was not involved in the study told ABC News.

Nevertheless, only one in five asymptomatic people had the HLA-B*15:01 variant, and so the question remains how the people without the variant avoided symptoms. Understanding these mechanisms could result in novel treatment and vaccination approaches for COVID-19.

Professor Stephanie Gras, joint senior author at La Trobe University commented: 'It may be possible to develop vaccines and treatments against SARS-CoV-2 that mimic the immune [system's] shield seen in the asymptomatic people with HLA-B15.'