Clinical, virological, and histopathological manifestations of fatal human infections by avian influenza A(H7N9) virus.
BACKGROUND
Systematic analysis of histopathological and serial virological changes of fatal influenza A(H7N9) cases is lacking.


METHODS
Patients with A(H7N9) infection admitted to our intensive care unit during 10-23 April 2013 were included. Viral loads in the respiratory tract, as inferred from the cycle threshold (Ct) value of reverse transcription polymerase chain reaction (RT-PCR), and the serum hemagglutination inhibition (HAI) antibody titer, were analyzed. Postmortem biopsies of the lung, liver, kidney, spleen, bone marrow, and heart were examined.


RESULTS
Twelve patients (6 deaths, 6 survivors) were included. Median viral load was higher in sputa than the nasopharyngeal swabs for fatal cases (median Ct, 23 vs 30.5; P = .08). RT-PCR for A(H7N9) was positive in stool samples (4/6 [67%]) of fatal cases and (2/6 [33%]) of survivors, but was negative in the cerebrospinal fluid, urine, or blood of all patients. Nosocomial bacterial infections were more common in patients who died than in survivors (83% vs 50%). HAI titers increased by ≥4-fold in those with convalescent sera. Postmortem biopsy for 3 patients showed acute diffuse alveolar damage. Patient 1, who died 8 days after symptom onset, had intra-alveolar hemorrhage. Patients 2 and 3, who died 11 days after symptom onset, had pulmonary fibroproliferative changes. Reactive hemophagocytosis in the bone marrow and lymphoid atrophy in splenic tissues were compatible with laboratory findings of leukopenia, lymphopenia, and thrombocytopenia. Hypoxic and fatty changes of kidney and liver tissues are compatible with impaired renal or liver function.


CONCLUSIONS
Fatal A(H7N9) infection was characterized by viral and secondary bacterial pneumonia with 67% having positive RT-PCR in stool.
State Key Laboratory for Diagnosis and Treatment of Infectious Diseases.
Liang
L
Yu
Zhaoming
Z
Wang
Yu
Y
Chen
Wei
W
Ding
Hongyu
H
Jia
Jasper Fuk-Woo
JF
Chan
Kelvin Kai-Wang
KK
To
Honglin
H
Chen
Yida
Y
Yang
Weifeng
W
Liang
Shufa
S
Zheng
Hangping
H
Yao
Shigui
S
Yang
Hongcui
H
Cao
Xiahong
X
Dai
Hong
H
Zhao
Ju
J
Li
Qiongling
Q
Bao
Ping
P
Chen
Xiaoli
X
Hou
Lanjuan
L
Li
Kwok-Yung
KY
Yuen
D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006651:Histocytochemistry; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000276:immunology / Q000302:isolation & purification*; D007251:Influenza, Human / Q000097:blood / Q000473:pathology / Q000821:virology*; D008168:Lung / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009305:Nasopharynx / Q000821:virology; D013183:Sputum / Q000821:virology; D018709:Statistics, Nonparametric
D000914:Antibodies, Viral
H7N9; avian; clinical; histopathology; influenza