Archival influenza virus genomes from Europe reveal genomic and phenotypic variability during the 1918 pandemic

Abstract

The 1918 influenza pandemic was the deadliest respiratory pandemic of the 20th century and determined the genomic make-up of subsequent human influenza A viruses (IAV). Here, we analyze the first 1918 IAV genomes from Europe and from the first, milder wave of the pandemic. 1918 IAV genomic diversity is consistent with local transmission and frequent long-distance dispersal events and in vitro polymerase characterization suggests potential phenotypic variability. Comparison of first and second wave genomes shows variation at two sites in the nucleoprotein gene associated with resistance to host antiviral response, pointing at a possible adaptation of 1918 IAV to humans. Finally, phylogenetic estimates based on extended molecular clock modelling suggests a pure pandemic descent of seasonal H1N1 IAV as an alternative to the hypothesis of an intrasubtype reassortment origin.

Racial Disparities in Mortality During the 1918 Influenza Pandemic in United States Cities

“…Although the overwhelming majority of 1918 influenza deaths occurred in the United States between September and December, a less lethal flu strain began circulating during an earlier "herald wave." Beginning between January and March, this wave led to a mortality increase in excess of normal seasonal mortality fluctuations (26)(27)(28); recent evidence suggests that this influenza strain subsequently evolved to evade immune responses, accounting for its radically increased lethality by September (29). Crosby (12: p.229) has speculated that exposure to this herald wave may have primed the immune system for a more efficient response during the fall.…”

“…! , measured as the proportion of city residents aged [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. A second set of models adds additional controls for the delay (/ ! )…”