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The abundance of a specific intestinal bacteria known to suppresses the binding of the coronavirus to human cell receptors is likely to play a role in the low COVID-19 mortality rates seen in Asia and Northern Europe, according to a study led by a team of researchers at Nagoya University.

Many scientists have speculated there may be an X-factor when it comes to the low death rates from COVID-19 in Asia, including Japan, and some countries in Northern Europe such as Finland. Genetic and immunological differences, as well as the taking of the BCG vaccine in early childhood to protect against tuberculosis, have often been cited as possible reasons. An in-vitro study by the Kyoto Prefectural University of Medicine has also shown that compounds in green tea known as catechins significantly reduced the infectiousness of the coronavirus.

The highly contagious omicron variant is known to lead to less serious cases than the delta variant, and the mortality rate has been lowered to be more or less comparable to that of influenza.

But the death rate from COVID-19 tends to go up with age. Other risk factors include obesity, diabetes, smoking and a history of respiratory infections, though COVID-19 vaccination curbs the possibility of severe illness and death.

To shed light on what the mysterious factor may be behind the low death rates in some countries, Nagoya University scientists analyzed raw sequencing data of gut micro-organisms in 953 healthy subjects in 10 countries from a public database.

The team analyzed the relationship between the composition of intestinal bacteria and the mortality rates of COVID-19, applying an advanced machine learning model in February 2021, when vaccines were not yet commonly available. It analyzed 30 important intestinal bacteria and found that having the lowest amount of one called collinsella was the highest predictive factor behind high COVID-19 mortality rates, with a markedly high statistical significance.

The scientists then categorized the data into five types of gut bacteriological ecosystems, called enterotypes, based on the compositional similarity of their micro-organisms. They compared them with the mortality rates of the 10 countries and found that the level of collinsella was negatively correlated with the mortality.

Where COVID-19 mortality rates are low, such as in South Korea, Japan and Finland, the enterotype with the highest amount of collinsella was dominant, accounting for 34% to 61% of the total, the study said. In Belgium, Britain, Italy and the U.S., where mortality rates were high, the enterotypes with the two of the lowest levels of collinsella were predominant, and only 4% to 18% of subjects had the enterotype with the largest amount. The other countries examined were Canada, Germany and Mexico.

“I’m not saying that intestinal bacteria alone can cure COVID-19,” said the study’s lead researcher, Masaaki Hirayama, an associate professor at the university’s Graduate School of Medicine. “The purpose of this study was to see if we could make a breakthrough in treatment if we could find at least one thing related to factor X.”

Hirayama said that collinsella transforms the gut’s bile acids into ursodeoxycholic acid, which has been known to suppress the binding of the coronavirus to its receptor and inhibit the potentially deadly immune response called a cytokine storm.

The study has undergone a full peer review and was published in the U.S. open access science and medicine journal Plos One in late November. Diverse factors, such as age and stress, can influence gut micro-organisms, but enterotypes are thought to be affected by intake of foods and are not strongly associated with race or gender, the Nagoya University researchers said.

Hirayama says it remains unclear whether mortality rates are higher for vaccinated individuals whose collinsella levels are lower. But based on results of the study, he has already begun work on joint research with respiratory medicine doctors to see if substances produced by this intestinal bacteria play a role in whether some patients become seriously ill while others do not.

“Serious cases of the disease have rapidly declined due to vaccination, so I don’t think we need to worry too much about low collinsella levels in some Japanese people,” he said. “In fact, most Japanese and other Asians have high levels of bifidobacteria and collinsella.”

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