ABSTRACT
Seasonal influenza viruses frequently acquire mutations that have the potential to alter both virus replication and antigenic profile. Recent seasonal H1N1 viruses have acquired mutations to their hemagglutinin (HA) protein receptor binding site (RBS) and antigenic sites, and have branched into the clades 5a.2a and 5a.2a.1. Both clades demonstrated improved in vitro fitness compared with the parental 5a.2 clade as measured through plaque formation, infectious virus production in human nasal epithelial cells, and receptor binding diversity. Both clades also showed reduced neutralization by serum from healthcare workers vaccinated in the 2022-23 Northern Hemisphere influenza season compared to the vaccine strain. To investigate the phenotypic impact of individual clade-defining mutations, recombinant viruses containing single HA mutations were generated on a 5a.2 genetic background. The 5a.2a mutation Q189E improved plaque formation and virus replication, but was more efficiently neutralized by serum from individuals vaccinated in 2022-23. In contrast, the 5a.2a mutation E224A and both 5a.2a.1 mutations P137S and K142R impaired aspects of in vitro fitness but contributed significantly to antigenic drift. Surprisingly, the E224A mutation and not Q189E caused broader receptor binding diversity seen in clinical isolates of 5a.2a and 5a.2a.1, suggesting that receptor binding diversity alone may not be responsible for the phenotypic effects of the Q189E mutation. These data document an evolutionary trade-off between mutations that improve viral fitness and those that allow for the evasion of existing host immunity.
ABSTRACT
Background: The circulation and the genomic evolution of influenza A(H3N2) viruses during the 2021/2022 and 2022/2023 seasons were studied and associated with infection outcomes. Methods: Remnant influenza A-positive samples following standard-of-care testing from patients across the Johns Hopkins Health System (JHHS) were used for the study. Samples were randomly selected for whole viral genome sequencing. The sequence-based pEpitope model was used to estimate the predicted vaccine efficacy (pVE) for circulating H3N2 viruses. Clinical data were collected and associated with viral genomic data. Results: A total of 121 683 respiratory specimens were tested for influenza at JHHS between 1 September 2021 and 31 December 2022. Among them, 6071 (4.99%) tested positive for influenza A. Of these, 805 samples were randomly selected for sequencing, with hemagglutinin (HA) segments characterized for 610 samples. Among the characterized samples, 581 were H3N2 (95.2%). Phylogenetic analysis of HA segments revealed the exclusive circulation of H3N2 viruses with HA segments of the 3C.2a1b.2a.2 clade. Analysis of a total of 445 complete H3N2 genomes revealed reassortments; 200 of 227 of the 2022/2023 season genomes (88.1%) were found to have reassorted with clade 3C.2a1b.1a. The pVE was estimated to be -42.53% for the 2021/2022 season and 30.27% for the 2022/2023 season. No differences in clinical presentations or admissions were observed between the 2 seasons. Conclusions: The increased numbers of cases and genomic diversity of influenza A(H3N2) during the 2022/2023 season were not associated with a change in disease severity compared to the previous influenza season.
ABSTRACT
The rapidity with which SARS-CoV-2 XBB variants rose to predominance has been alarming. We used a large cohort of patients diagnosed with Omicron infections between September 2022 and mid-February 2023 to evaluate the likelihood of admission or need for supplemental oxygen in patients infected with XBB variants. Our data showed no significant association between XBB or XBB.1.5 infections and admissions. Older age groups, lack of vaccination, immunosuppression and underlying heart, kidney, and lung disease showed significant associations with hospitalization.
