Epidemiology of influenza in pregnant women hospitalized with respiratory illness in Moscow, 2012/2013-2015/2016: a hospital-based active surveillance study.

BACKGROUND: To better understand the impact of seasonal influenza in pregnant women we analyzed data collected during four seasons at a hospital for acute respiratory infection that specializes in treating pregnant women. METHODS: This was a single-center active surveillance study of women 15-44 years of age hospitalized for acute respiratory diseases between 2012/2013 and 2015/2016 in Moscow, Russian Federation. Women had to have been hospitalized within 7 days of the onset of symptoms. Swabs were taken within 48 h of admission, and influenza was detected by reverse transcription-polymerase chain reaction. RESULTS: During the four seasons, of the 1992 hospitalized women 1748 were pregnant. Laboratory-confirmed influenza was detected more frequently in pregnant women (825/1748; 47.2%) than non-pregnant women (58/244; 23.8%) (OR for influenza = 2.87 [95% CI, 2.10-3.92]; p <  0.001). This pattern was homogenous across seasons (p = 0.112 by test of homogeneity of equal odds). Influenza A(H1N1)pdm09 was the dominant strain in 2012/2013, A(H3N2) in 2013/2014, B/Yamagata lineage and A(H3N2) in 2014/2015, and A(H1N1)pdm09 in 2015/2016. Influenza-positive pregnant admissions went to the hospital sooner than influenza-negative pregnant admissions (p <  0.001). The risk of influenza increased by 2% with each year of age and was higher in women with underlying conditions (OR = 1.52 [95% CI, 1.16 to 1.99]). Pregnant women positive for influenza were homogeneously distributed by trimester (p = 0.37 for homogeneity; p = 0.49 for trend). Frequencies of stillbirth, delivery, preterm delivery, and caesarean delivery did not significantly differ between influenza-positive and influenza-negative hospitalized pregnant women or between subtypes/lineages. CONCLUSIONS: Pregnant women are at increased risk for hospitalization due to influenza irrespective of season, circulating viruses, or trimester.

Pleiotropic effects of hemagglutinin amino acid substitutions of influenza A(H1N1)pdm09 virus escape mutants.

In the present study we assessed pleiotropic characteristics of the antibody-selected mutations. We investigated pH optimum of fusion, temperatures of HA heat inactivation, in vivo and in vitro replication kinetics, and connectivity with panel of sera of survivors patients in different epidemic seasons of the previously obtained influenza H1 escape mutants. Our results showed that N133D (H3 numbering) mutation significantly lowered the pH of fusion optimum. Several amino acid substitutions, including K163 N, Q192 L, D190E, G228E, and K285 M, reduced the stability of HA as determined by heat inactivation, whereas A198E substitution is associated with significant increase in HA thermostability compared to the wild-type virus. We found that amino acid change D190 N was associated with a significant decrease in viral growth in eggs and mice. Our potential antigenic variants, except readapted variant, which contained A198E mutation, did not reach fixation in infected people. Overall, a co-variation between antigenic specificity and different HA phenotypic properties was demonstrated.