Seasonal flu, possible direct descendant of the Spanish flu

The most devastating respiratory pandemic of the 20th century, the so-called Spanish flu of 1918-1919 – a misleading term since this pandemic was far from being concentrated in Spain – killed 50 to 100 million people.

Its viral origin was not confirmed until the 1930s. Subsequent research identified the culprit: an influenza A virus of the H1N1 subtype.

But there are still mysteries about the Spanish flu. Geneticists have been trying to dispel them for twenty years, but their task is limited by the low number of victim specimens to be analyzed.

After about fifteen fruitless steps, Sébastien Calvignac-Spencer, specialist in viral evolution at the Robert Koch Institute (Germany), says that he and his colleagues were extremely lucky. They had access to 13 lung samples kept in formalin in museums in Berlin and Vienna, dating from 1901 to 1931, including 6 from 1918-1919.

And they detected RNA fragments from the Spanish flu virus in three samples from 1918.

These researchers managed to sequence large parts of the virus that infected two people, but also an entire genome in the third case. Previously, there were only sequences from 18 specimens worldwide, two complete genomes, in the United Statesand no genetic information on the early stages of the pandemicunderlined Sébastien Calvignac-Spencer during a press briefing.

The Spanish flu has, in fact, experienced three major waves. The second and third were particularly deadly, more than the first having developed in the spring of 1918.

In particular, their work detected genomic variations over the course of the pandemic and its course around the world via round trips favored by the transfers of soldiers at the end of the First World War.

From the earliest days of the Spanish flu, a gene in the virus appears to have evolved to counter the human immune response.

Above all, these new analyzes are compatible with the scenario of a pure pandemic origin of seasonal influenza virusesa direct parentage, according to the study.

This defeats other hypotheses on the emergence of seasonal influenza, in particular the idea – known as the reassortment – that current viruses would be made up of several fragments from heterogeneous ancestors.

On the other hand, it is difficult to describe how the influenza pandemic of 1918 gradually transformed into a seasonal virus, due to lack of data especially in the 1920s, explained Thorsten Wolff, virologist at the Robert Koch Institute.

Can this research give some keys to the evolution of COVID?

If we cannot compare these two pandemics, given different viruses, very different propagation conditions, differently organized and connected humanssome similarities may exist, according to Sébastien Calvignac-Spencer.

For example, the 1918 flu had several waves like COVID, but unlike the current pandemic, where the waves are associated with new variants, this was probably not the case for the 1918 pandemic according to our study.he noted.

The study published in Nature however, has a limit, its very small sample sizerecognize its authors, emphasizing that their results remain foreplay.

Additional genomes from samples surrounding the pandemic period, as well as phenotypic characterization of several 1918 viruses in vitro and livewill undoubtedly allow a more robust analysisthey say.

It remains to find new preserved pathological specimens.

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