The Spanish flu

The Spanish flu occurred at the end of the First world war, in disastrous epidemiological conditions on popu-lations exhausted by four years of war. At that time, there were no vaccines, no antibiotics, no oxygen and no resuscitation. It was even thought that the infectious agent was a bacterium. Humanity was poorly equipped to fight against a pandemic that caused 50-100 million deaths. The first palpable signs of the outbreak were the rapidly spreading multiple epidemics among young recruits in the American military training camps in March 1918. The flu then spread to the civilian populations and circled the globe twice, sparing no country, even the most remote islands, in tropical as well as polar climates, evolving in successive waves up until April 1919. The first was mild (lethality 0.21%), the second was lethal (lethality 2-4%), and during the third wave, lethality declined (1%), after which the flu became seasonal, with low lethality (0.1%). Between 20 and 40 years of age, patients often died within a few days of pneumonia, with respiratory distress leading to cya-nosis, frequently associated with bacterial superinfection. The influenza virus, Myxovirus influenzae, was first discovered in 1931 by Richard Shope in pigs, and then in 1933 by Wilson Smith, Patrick Laidlaw and Christo-pher Andrews in humans during a seasonal influenza epidemic in London. In 1943, it was first observed under the electron microscope. Hemagglutinin and neuraminidase, the two main virulence factors, were dis-covered in the 1940s by George Hirst and Alfred Gottschalk. An RNA virus composed of 13,500 nucleotides in eight segments, it was initially sequenced in the 1980s, when Jeffrey Taubenberger determined the complete nucleotide sequence of the 1918 virus from lung tissue samples from patients who died of influenza. The 1918 H1N1 virus was found to have originated in birds. In 2005, it was successfully resuscitated in cell cul-ture. It is 40,000 times more virulent in primates than the seasonal H1N1 virus. The lethality of the second wave could have been due to mutations in the hemagglutinin H1 gene, which would have resulted in a stron-ger affinity for a,2-6 galactose sialic acids, the virus' receptors on human epithelial cells. That said, the origin of the Spanish flu virus remains controversial. It probably emerged and circulated in the population before March 1918 in America, although European origin has also been evoked. The high mortality in the 20-40 age group remains an enigma. Some experts point to reduced immune response in patients previously exposed to related viral hemagglutinins during the 1889 pandemic. In any event, even though it concerns a markedly different virus, the history of the Spanish flu sheds light on the difficulties of management during today's pandemic. (C) 2022 Elsevier Masson SAS. All rights reserved.

Automated summary

The Spanish flu, occurring at the end of World War I, resulted in 50-100 million deaths in a population that lacked sufficient medical resources. The flu virus was initially discovered in pigs and then studied in humans. The mortality rate varied in different waves, and the high death rate among the 20-40 age group remains unexplained. Despite the differences in the virus involved, the history of the Spanish flu provides insights into the challenges of managing current pandemics.