A rapid review of the avian influenza PB2 E627K mutation in human infection studies.

Background: The current avian influenza A(H5N1) epizootic poses a significant threat to public health, with sporadic infections in humans raising concerns about potential adaptation for efficient human transmission. Laboratory studies have provided evidence that the polymerase basic protein 2 (PB2) E627K mutation facilitates more efficient replication in mammals and humans. This mutation has been detected in Canadian poultry, wild birds and mammals. Objective: Our objective was to summarize the current state of evidence on the impact of the avian influenza PB2 E627K mutation on human adaptation, transmission, epidemiology and clinical outcomes in natural human infections. Methods: We employed a search strategy across MEDLINE, Embase, Scopus, Global Health and CAB Abstracts for articles published from each database's inception until mid-May 2023. Results: We identified nine eligible articles for review that addressed human transmission or adaptation (n=5), epidemiological or clinical implication (n=1) or both topics (n=3). Some studies suggested that the PB2 E627K mutation may play a role in zoonotic transmission from birds to humans, with studies indicating its association with parallel evolution and positive selection in A(H5) and A(H7) viruses. Other studies presented analyses that supported the notion of an increased fatality rate among cases with the PB2 E627K mutation, highlighting its potential role as a virulence factor. Conclusion: The association of the PB2 E627K mutation with human adaptation, transmission and increased fatality rates highlights the importance of genomic surveillance under One Health umbrella. Further research is warranted to explore the role of this mutation and determine how it interacts with other mutations.