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. 2016 May;161(5):1239-59.
doi: 10.1007/s00705-016-2781-3. Epub 2016 Feb 18.

Differences in the epidemiology and virology of mild, severe and fatal human infections with avian influenza A (H7N9) virus

Jianping Sha  1 , Xiaowen Chen  2 , Yajin Ren  3 , Haijun Chen  4 , Zuqun Wu  5 , Dong Ying  6 , Zhiruo Zhang  7 , Shelan Liu  8
Affiliations

Differences in the epidemiology and virology of mild, severe and fatal human infections with avian influenza A (H7N9) virus

Jianping Sha et al. Arch Virol. 2016 May.

Abstract

A novel avian influenza A (H7N9) virus caused 5-10 % mild and 30.5 % fatal human infections as of December 10, 2015. In order to investigate the reason for the higher rate of fatal outcome of this infection, this study compared the molecular epidemiology and virology of avian influenza A (H7N9) viruses from mild (N = 14), severe (N = 50) and fatal (N = 35) cases, as well as from non-human hosts (N = 73). The epidemiological results showed that the average age of the people in the mild, severe and fatal groups was 27.6, 52 and 62 years old, respectively (p < 0.001). Males accounted for 42.9 % (6/14), 58.0 % (29/50), and 74.3 % (26/35) of cases in the mild, severe and fatal group respectively (p = 0.094). Median days from onset to start of antiviral treatment were 2, 5 and 7 days in the mild, severe and fatal group, respectively (p = 0.002). The median time from onset to discharge/death was 12, 40 and 19 days in the mild, severe and fatal group, respectively (p < 0.001). Analysis of whole genome sequences showed that PB2 (E627K), NA (R294K) and PA (V100A) mutations were markedly associated with an increased fatality rate, while HA (N276D) and PB2 (N559T) mutations were clearly related to mild cases. There were no differences in the genotypes, adaptation to mammalian hosts, and genetic identity between the three types of infection. In conclusion, advanced age and delayed confirmation of diagnosis and antiviral intervention were risk factors for death. Furthermore, PB2 (E627K), NA (R294K) and PA (V100A) mutations might contribute to a fatal outcome in human H7N9 infection.

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Conflict of interest statement

None declared.

Figures

Fig. 1
Fig. 1
Geographical distribution of mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99)
Fig. 2
Fig. 2
Geographical distribution of six different subtypes of the novel avian influenza A(H7N9) viruses between March 2013 and December 2014 (N = 99). w1, wave 1 (from 31 March 2013 to 30 September 2013); w2, wave 2 (from 01 October 2013 to 30 September 2014); w3, wave 3 (from 01 October 2014 to 30 September 2015)
Fig. 3
Fig. 3
Age distribution (%) of mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses from March 2013 to December 2014 (N = 99)
Fig. 4
Fig. 4
The median time (days) from onset to outcome/discharge in mild, severe and fatal cases of infection with the novel (H7N9) avian influenza A viruses between March 2013 and December 2014 (N = 99)
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
Fig. 5
Fig. 5
Phylogenetic trees based on sequences of HA (a), NA (b), PB2 (c), MP (d), NP (e), NS (f), PA (g) and PB1 (h) generated from isolates from mild, severe and fatal cases of infection with the novel avian influenza A (H7N9) viruses between March 2013 and December 2014 (N = 99). Blue, mild isolates; green, severe isolates; red, fatal isolates
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