[Reading Science] Found the Reason Behind the Lucky 'Asymptomatic' COVID-19

University of California Research Team
Confirms Association with HLA Gene Variants
Identifies Similarities to Seasonal Colds for Early Eradication

About 20% of people infected with the COVID-19 virus showed no symptoms. While many simply considered it a matter of luck(?), a genetic cause has been identified.

A research team from the University of California announced on the 19th (local time) that they had discovered a genetic mutation related to asymptomatic COVID-19 infection. In a paper published that day in the international journal Nature, the team explained that this genetic mutation strengthens the immune cells of people who had previously been exposed to seasonal cold viruses. As a result, these patients’ immune systems can quickly track and destroy the virus before triggering various immune responses against the COVID-19 pathogen. Therefore, even if infected with COVID-19, they show no symptoms. Jean-Laurent Casanova, a professor of immunology at Rockefeller University who was not involved in the study, praised the findings as "worthy of applause" and said, "The correlation is stronger than any previously published research."

Until now, many scientists have focused on the causes of death and severe symptoms by studying the relationship between COVID-19 risks and genetics. However, in reality, most people infected with the COVID-19 virus experience mild symptoms, so it was necessary to uncover the reasons behind this.

The research team conducted a follow-up study on about 30,000 volunteers to track COVID-19 infection and asymptomatic status. Among them, approximately 1,400 were infected over 15 months, with about 10%, or 136 people, being asymptomatic. Based on this, the team analyzed the participants’ genes and found a correlation with the HLA gene. The HLA gene encodes proteins found on the surface of all human cells. These proteins play a role in triggering T-cells, which perform immune functions by detecting traces of external invaders. The team demonstrated that the asymptomatic phenomenon is linked to a mutation in the HLA gene possessed by about 10% of the participants. In other words, individuals with one copy of this gene mutation were twice as likely to be asymptomatic compared to those without it, and those with two copies were as much as eight times more likely to be asymptomatic.

The researchers also investigated how this gene mutation interacts with T-cells to cause asymptomatic infection. They obtained T-cells collected from individuals with the mutation before the COVID-19 pandemic and exposed them to the COVID-19 virus. These T-cells had never been exposed to the COVID-19 virus before, meaning they had no prior information about the "enemy." However, when the HLA protein detected the spike protein of the COVID-19 virus, it immediately initiated an attack. Because the spike protein structure was similar to that of seasonal cold coronaviruses previously encountered, the T-cells could instantly recognize it as an enemy.

Based on this, the team hypothesized that the mutation in the HLA protein allows better recognition of the similarity between the spike proteins of the COVID-19 virus and seasonal cold viruses, thereby triggering a stronger anti-coronavirus response from T-cells.

Mary Carrington, a researcher at the Frederick National Laboratory for Cancer Research, said, "This study provides a key clue in understanding the cause of asymptomatic infection," adding, "It will help develop a new generation of COVID-19 vaccines that can induce not only protection against severe disease but also complete asymptomatic infection."