Infectious Diseases

All Major Flu Outbreaks Since 1918 Can Be Traced Back to Spanish Flu

Posted on 28 July 2020

The influenza pandemic of 1918 was one of the most devastating in human history, with some estimating that the influenza A (H1N1) virus responsible claimed over 50 million lives around the world. While Spanish flu may have ended there, it’s easy to forget that the virus lived on, contributing its genes to new viruses and giving rise to new pandemics.

The Persistent Legacy of the 1918 Influenza Virus | NEJM. (2020). Retrieved 28 July 2020, from

H1N1 originated in birds, which form a vast reservoir in which influenza viruses can mutate and exchange the 8 genes that make up their genetic code. This means that a near endless variety of new viruses are constantly being produced.

The influenza A virus has a gene coding for 1 of 16 possible haemagglutinin (HA) surface proteins and another coding for 1 of 9 possible neuraminidase (NA) surface proteins. These are critical for the infection of host cells. Of the 144 possible combinations, only 3 have ever been found to infect humans: H1N1, H2N2, and H3N2. While it is rare for an influenza A virus to cross over to humans or other mammals, once it does so, it is highly capable of countering the immunity developed by its host, evolving through mutation (drift) and gene exchange with other circulating viruses (shift).

Genetic Relationships among Human and Relevant Swine Influenza Viruses, 1918–2009.
Yellow arrows: exportation of avian influenza A virus genes
Red arrows: evolutionary path of human influenza virus
Blue arrows: evolutionary path of swine influenza virus
The Persistent Legacy of the 1918 Influenza Virus | NEJM. (2020). Retrieved 28 July 2020, from

In this way, the 1918 influenza virus and its descendants have undergone a century of evolution as they have competed against the human immune system. Almost all influenza A cases are now caused by descendants of 1918 H1N1, from the 2009 swine flu outbreak to seasonal influenza that most of us experience.

It remains to be seen whether the coronavirus responsible for the current pandemic will have a similar legacy. While Sars-Cov-2 appears to mutate more slowly than influenza, the likelihood of Covid entering regular circulation alongside other human coronaviruses depends largely on how long immunity lasts, a question that has still not been fully answered. One study suggests that if duration of immunity to SARS-CoV-2 is similar to other related coronaviruses, then recurrent outbreaks are likely.


The Persistent Legacy of the 1918 Influenza Virus: DOI: 10.1056/NEJMp0904819

1918 Influenza: the Mother of All Pandemics: doi: 10.3201/eid1201.050979

Projecting the transmission dynamics of SARS-CoV-2 through the postpandemic period: DOI: 10.1126/science.abb5793

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