The reason that Japan has fared far better than the West when it comes to COVID-19 cases and deaths may come down to simple genetics, according to research by a leading Japanese institute.

Most Japanese have an inherited component of the immune system that can more effectively kill various coronaviruses, including the one that causes COVID-19, scientists with Riken research institute have said, adding that this could be one of the factors behind the low number of cases and deaths in Japan during the pandemic compared with the U.S. and Europe.

Many scientists have speculated there may be an X-factor when it comes to the mysteriously low COVID-19 infection and death rates in Japan and neighboring China, South Korea and Taiwan. Higher rates of mask-wearing, along with genetic and immunological characteristics, have often been cited as possible reasons. Riken's research, if proven, would point to the latter.

Humans have two types of adaptive immune systems that fend off pathogens based on memory from past infections with seasonal coronaviruses, a group of viruses that includes ones that cause the common cold, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). Natural antibodies work as a first line of defense against the pathogens. Then, when a virus enters the body, the other defense mechanism — a powerful immune response composed of T cells inside white blood cells that bind to and kill infected cells — kicks in.

The key to preventing serious COVID-19 cases is activated T cells, and that's where human leukocyte antigen (HLA) comes in. This complex set of genes helps T cells identify infected cells in order to destroy them.

A human body contains tens of thousands of HLAs and each individual has multiple HLA types, which are genetically inherited.

Until now, research into HLA types and their relationship with the COVID-19 virus had been conducted mainly on people in Europe and the U.S., and it had remained unclear whether the memory T cells from past cold infections would reawaken T cells and trigger a “cross immunity” to kill the virus that causes COVID-19 and its variants.

A nurse receives a third shot of the COVID-19 vaccine at Tokyo Medical University Hachioji Medical Center on Dec. 1. | KYODO
A nurse receives a third shot of the COVID-19 vaccine at Tokyo Medical University Hachioji Medical Center on Dec. 1. | KYODO

A team of scientists at Japan's government-backed Riken research institute studied the HLA-A24 molecule, which is found in around 60% of Japanese but only about 10% to 20% of people in Europe and the U.S. They then investigated the spike protein of the virus that causes COVID-19 and identified an antigen component, or epitope peptide, called QYI that binds to HLA-A24, activates the T cells and multiplies them. Basically, it signals to the body's immune system that there is an intruder that must be fought off.

The institute is calling their discovery a world first.

The team also found that a similar epitope exists in seasonal coronaviruses and binds to HLA-A24, which triggers and multiplies T cells to fight against them. Researchers say this proves the existence of cross immunity against the common coronaviruses and the virus that causes COVID-19 on a molecular level.

The discovery of the epitope that causes a strong immune response, which was published online in the scientific journal Communications Biology earlier this month, could lead to the development of a new COVID-19 vaccine and drugs that would be especially beneficial for people who do not see a rise in antibody levels despite getting vaccinated due to conditions such as blood disorders or cancer, says Shin-ichiro Fujii, team leader at Riken Center for Integrative Medical Sciences Laboratory for Immunotherapy.

“(Despite the vaccination), those people see a sharp decline in antibody levels and a very high share of them have died (after getting infected with COVID-19),” he said. “The analysis of people with cancer using the epitope that’s discovered showed that 60% to 70% of them can activate killer T cells. We believe that this method could be used as the next cure for those for whom the vaccine does not work.”

As of Saturday, Japan had reported under 18,500 COVID-19 deaths and about 1.73 million cases of the virus since the start of the pandemic, according to Our World in Data. That compares with about 797,000 deaths and nearly 50 million cases in the U.S. and approximately 147,000 deaths and 10.8 million cases in Britain.

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