The seasonal H1N1 flu virus may be a direct descendant of the strain of influenza that caused the Spanish flu in 1918. Researchers from the Robert Koch Institute (RKI) report this in the journal “Nature Communications”. They genetically analyzed tissue samples from patients from that time. However, they cannot yet say how the deadly pathogen became a milder flu virus.

The Spanish flu of 1918 and 1919 is considered the worst pandemic of the 20th century. Worldwide, 50 to 100 million people are said to have died from it. However, how the influenza A virus (IAV) evolved during the pandemic and what made it so deadly is still unclear.

This is also due to the fact that tissue samples from this period are extremely rare. In 2005, US researchers sequenced the first full genome of the virus strain from an Alaskan woman whose body was preserved in ice. The analysis at the time suggested that the virus jumped from birds to humans. A second complete genome sequencing followed in 2013.

A team led by epidemiologist Sébastien Calvignac-Spencer from the RKI examined 13 European lung tissue samples dating from the years 1900 to 1931 and preserved in formalin in the Berlin Medical History Museum and in the Vienna pathological-anatomical collection. Six of these samples were taken in 1918 and 1919. From these, the researchers were able to sequence two partial genomes and a complete genome of the influenza A virus. A comparison with the US samples showed genetic differences between the pathogens from different waves.

According to the study, the genetic diversity of the 1918 influenza A viruses is consistent with a combination of local transmission and transcontinental spread. Today it is assumed that the disease originated in the American Midwest and then came to Europe with soldiers during the First World War.

In a press conference on the study, co-author and virologist Thorsten Wolff explains that the observed genetic variations can probably be traced back to adaptations of the virus. While the genome of the samples from the early days of the pandemic was more similar to the original avian viruses, the later samples showed mutations that made it easier for the influenza virus to evade the human immune system. This would also explain why the first wave was milder than the two later ones.

The RKI researchers also used a genetic method known as the molecular clock, which can be used to estimate evolutionary time scales. Their modeling based on this suggested that all genomic segments of the seasonal H1N1 flu circulating today could descend directly from the 1918 pandemic strain. However, the development from there cannot yet be explained.

Wolff reports that although there were winters with increased mortality due to influenza and pneumonia after the Spanish flu, these have decreased: “It is a process in which it is difficult to determine whether this is due to a increase in the immunity of the population or a decreasing virulence of the pathogen.”

It is just as difficult to predict when and whether pathogens circulating today could become as deadly again, says Wolff. For example, there was another H1N1 pandemic in 2009 and 2010 with the swine flu. However, today’s circulation of H1N1 viruses and the available vaccinations against it also mean that the immune system of today’s people is not as naïve towards the pathogen from 1918 as it was 100 years ago.

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