Seasonal flu, possible descendant of the Spanish flu

Preserved in formalin, deciphered by genetics, early 20th-century European lung tissue is bringing new insights into “Spanish” flu, of which one of the seasonal flu viruses may be a direct descendant, according to a study published Tuesday in the journal Nature.

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The most devastating respiratory pandemic of the 20th century, the 1918-1919 flu, known as “Spanish” – a misleading term as this pandemic was far from concentrated in Spain – was estimated to have killed a total of 50 to 100 million people .

The 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 expel them for twenty years, but their task is limited by the low number of victim specimens to be analysed.

After 15 failed steps, Sébastien Calvignac-Spencer, a specialist in viral evolution at the Robert Koch Institute (Germany), says he and his colleagues were “extremely lucky”. They had access to 13 lung samples preserved in formalin in museums in Berlin and Vienna, dating from 1901 to 1931, including six from 1918-1919.

And they discovered RNA fragments of 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 of 18 copies worldwide, two complete genomes, in the United States”, and “no genetic information about the early stages of the pandemic,” Sébastien Calvignac-Spencer underlined at a news conference.

The Spanish flu actually went through three major waves. The second and third were particularly deadly, more than the first developing in the spring of 1918.

In particular, their work has uncovered genomic variations over the course of the pandemic and its course across the globe via back and forth, favored by the transfers of soldiers at the end of World War I.

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

Above all, “these new analyzes are compatible with the scenario of a pure pandemic origin of seasonal flu viruses,” a direct relationship, the study said.

This undermines other hypotheses about the origin of seasonal flu, especially the idea — known as “reassembly” — that current viruses are composed of different fragments from heterogeneous ancestors.

On the other hand, it’s hard to describe how the 1918 flu pandemic gradually turned into a seasonal virus, “due to lack of data,” particularly over the 1920s, explains Thorsten Wolff, a virologist at the Robert Koch Institute.

Could this research provide some keys to the evolution of COVID?

If we can’t compare these two pandemics, given “different viruses, very different reproductive conditions, people organized and connected differently,” there may be certain similarities, according to Sébastien Calvignac-Spencer.

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

However, the study in Nature has a limit, the “very small sample size,” the authors acknowledge, stressing that their results remain “preliminary.”

“Additional samples taken around the pandemic period, as well as phenotypic characterization of various 1918 viruses in vitro and in vivo, will undoubtedly allow for a more robust analysis,” they say.

It remains to find new preserved pathological specimens.

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