Like SARS-CoV-2, Spanish Flu-Causing Virus Also Mutated Several Times Before Fizzling Out

Since the coronavirus pandemic hit the world, another once-in-a-lifetime global health crisis has been in the news—1918 Spanish flu.

In the early months of the Covid-19 pandemic, many people compared it with the 1918 pandemic, which killed almost 50 to 100 million people worldwide.

Now, an analysis of the century-old influenza virus samples has revealed that the virus, which caused the 1918 pandemic, mutated into several variants and caused further pandemic waves, which were worse than the first one.

An expert told Live Science that the recent findings of the influenza virus showed that variants are expected, and humanity ultimately can overcome them.

According to the lead author of the new study, published in bioRxiv, Sébastien Calvignac-Spencer, an evolutionary biologist at the Berlin's Robert Koch Institute, which is the federal disease control and prevention agency in Germany, "Those [viral infections] in the second wave look like they were better adapted to humans."

"Just like today, we wonder whether the new variations behaved differently or not than the original," he added.

The team of researchers analysed six human lungs that dated to the pandemic years of 1918 and 1919 to conduct the study.

These human organs had been preserved in formalin in pathology archives in Germany and Austria.

The team determined that three of those lungs contained the influenza virus from 1918.

Two of those lungs belonged to young soldiers who died in Berlin, and one was from a young woman who died during the 1918 pandemic in Munich.

As per Calvignac-Spencer, estimates suggest the Spanish flu-causing virus strain infected up to 1 billion people worldwide when the population was only 2 billion and millions of people died in three successive waves.

He explained that decades ago, this virus was much deadlier, and now the threat has reduced because humans today are descended from those people who survived the Spanish flu, and they have inherited some form of genetic immunity.

The first wave of Spanish flu, which appeared in early 1918, was less deadly than the next two waves, said the expert.

The Research

The team of researchers extracted viral RNA from the lung samples of the two soldiers who died on the same day during the first wave.

The viral RNA was extracted to reconstruct about 60 per cent and 90 per cent of the genomes of the flu virus, respectively, that killed the soldiers.

The researchers found no genetic differences between the genomes of the virus that caused their deaths.

But as per the study, the form of the virus found in the lungs of the soldiers had multiple genetic differences compared to the virus that infected and killed the young woman in Munich who is believed to have died in a later wave of the pandemic.

The study also added that the virus, which killed the soldiers, diverged even more from two genomes of the virus from New York and Alaska that dated from the second wave in late 1918.

When the researchers compared the genomes from the United States, as well as Germany and conducted lab studies, they found that the influenza virus mutated to become more effective between the first and later waves of the pandemic.

Calvignac-Spencer said that the virus mutated and evolved to better overcome cellular defences against infection.

It is believed that the mutations between first and second waves may have made the virus better adapted to spreading among people, while another mutation may have changed how the influenza virus interacts with a human protein called MxA, which helps to orchestrate the immune response to new pathogens.

The lead author said that scientists have no clear idea about how genetic variations changed the behaviour of the virus. Still, it is predicted that such changes helped the virus to evade the mechanism that human cells use to block influenza viruses.

Calvignac-Spencer said that the same process can be seen now during the SARS-CoV-2 pandemic.

"It's interesting to make parallels — for example, the fact that there were multiple successive waves is a pattern which is intriguing," he added.

He believes that due to the progress in science over the years, now scientists have the opportunity to learn more from the Covid-19 that was not available during the 1918 pandemic.