all case - patients were 58- to 73-year - old married men , farmers or retirees , and long - term residents of shanghai ( fengxian , baoshan , songjiang , and pudong districts , respectively ) .
case - patient 1 had a history of coronary heart disease and hepatic schistosomiasis ; case - patient 2 had no history of chronic disease ; case - patient 3 had a history of hypertension and gout ; and case - patient 4 had a history of hypertension and repetitive cough for > 10 years during spring and autumn . *
na , not applicable ; shphcc , shanghai public health clinical center ; ct , computed tomography scan ; ggo , ground - glass opacity ; bid , 2 times a day ; ecmo , extracorporeal membrane oxygenation .
case - patients 24 had no clear history of close contact with poultry ; however , each had visited various farmers markets that sold live poultry . none of the patients raised pigeons or live in or near a heavily pigeon - infested area . before being transferred to shphcc on april 6 , 2013 ( patients 1 and 2 ) and april 7 , 2013 ( patients 3 and 4 ) , the 4 patients had been treated in local hospitals ; infection with influenza a(h7n9 ) virus had been confirmed by real - time reverse transcription pcr of nasopharyngeal swab samples before transfer .
the case - patients had cough and fever and had been expectorating sputum for 67 days before admittance to shphcc . in addition , all had experienced cold - like symptoms and fatigue before influenza - like symptoms developed .
case - patient 4 had cough and fever for 18 and 10 days , respectively , before being transferred to shphcc ; his case was the most serious of the 4 , and the disease progressed rapidly after he was transferred to shphcc .
total leukocyte counts for case - patients 14 were within or slightly below reference values : 5.50 , 5.95 , 3.50 , and 4.60  10/l , respectively ( reference value 4.0010.00  10/l ) . the proportions of neutrophils were normal or slightly high : 79.6% , 62.6% , 72.4% , and 68.0% , respectively ( reference value 50.0%70.0% ) .
radiograph findings mainly included ground - glass opacity and consolidation ( figures 1 , 2 ; technical appendix figures 1 , 2 ) . computed tomography ( ct ) scans and radiograph findings
chest computed tomography ( ct ) scan and radiograph images of patient ( case - patient 1 ) in a study of 4 persons with early cases of influenza a(h7n9 ) virus infection , shanghai , china .
images were taken 1 , 5 , 7 , and 11 days after illness onset .
a , b ) ct scan images on day 1 , showing bilateral pleural effusion but no obvious lesions .
c ) ct scan image on day 5 , showing extensive ground - glass opacity and consolidation .
d , e ) x - ray images on days 7 and 11 , respectively , showing reduced light transmittance on both sides of the lung . chest computed tomography scan images of patient ( case - patient 2 ) in a study of 4 persons with early cases of influenza a(h7n9 ) virus infection , shanghai , china .
a ) image taken 6 days after illness onset shows ground - glass opacity in the left lower and right upper lobes .
b ) image taken 16 days after illness onset shows absorption of ground - glass opacity . to ensure proper treatment / management of the patients ,
an emergency team was established ; the team followed the procedures shown in technical appendix figure 3 .
case - patient 1 began treatment 6 days after the onset of hypoxia , when large areas of lung inflammation were seen on radiographs .
case - patient 2 was treated 4 days after the onset of fever , when ct scan results revealed inflammation in the left upper lung lobe .
case - patient 3 began treatment 4 days after the onset of cough , sputum , and shortness of breath and after ct scan results revealed inflammation in the left lower lung lobe .
case - patient 4 began treatment 16 days after onset of high fever , dyspnea on exertion , and hypoxemia .
additional details for each patient are included below , and results of viral testing done at admission and 5 days later are shown in technical appendix table 1 .
disease characteristics for infections caused by influenza virus subtypes h1n1 , h5n1 , and h7n9 are shown in technical appendix table 2 .
case - patient 1 was receiving noninvasive ventilator - assisted breathing when he arrived at shphcc .
his oxygen saturation remained at 95% , and he was given continuous intravenous dopamine infusion .
he had acute respiratory failure , coronary heart disease ( stage 2 heart failure ) , and renal function insufficiency at admission .
on april 11 , 11 days after the onset of the symptoms and 2 hours after endotracheal intubation and mechanical ventilation began , he died from respiratory failure .
case - patient 2 arrived at shphcc with a nasal cannula inserted to maintain oxygen saturation at 95% .
his general condition improved steadily after commencing antiviral drug treatment , and he was discharged 18 days after illness onset .
case - patient 3 arrived at shphcc with a nasal cannula inserted to maintain oxygen saturation at 95% .
he was treated with oseltamivir , antimicrobial drugs , and steroids to suppress lung inflammation .
case - patient 4 arrived at shphcc in critical condition : oxygen saturation was 88% , and he had shortness of breath ( 3035 breaths / min ) .
one day after admission , his condition deteriorated ; multiple organ dysfunctions in lung and kidney developed .
two days after admission , invasive mechanical ventilation and then extracorporeal membrane oxygenation were implemented .
clinical manifestations of disease in the 4 case - patients were consistent with those reported for other persons infected with influenza a(h7n9 ) virus ( 3 ) . case - patients 1 and 4 had a more severe disease course than case - patients 2 and 3 .
all patients sought medical care for unresolved fever , cough , expectoration of sputum , and shortness of breath .
the severe cases progressed rapidly : body temperature was mostly sustained > 39c , and breathing was difficult and sometimes accompanied by hemoptysis . a rapid progression of acute respiratory distress syndrome occurred in case - patients 1 and 4 , along with mediastinal emphysema , shock , disturbed consciousness , and acute kidney injury .
the currently available drug treatment for influenza a(h7n9 ) virus infection is neuraminidase inhibitors ( e.g. , oseltamivir ) .
case - patient 4 only began neuraminidase inhibitors 16 days after the onset of symptoms , by which time he was in a severe condition .
case - patient 1 was treated with oseltamivir 6 days after the onset of symptoms and , despite treatment , died 6 days after admission to shphcc .
earlier , higher doses combined with continuous treatment might improve patient outcomes ( 5 ) .
on the basis of clinical judgment , we now use 150 mg of oseltamivir twice daily for severe cases , monitoring for toxicity
. the benefits of oseltamivir treatment of influenza a(h7n9 ) virus infections are debatable ; for example , case - patients 2 and 3 remained positive for the virus after 911 days of oseltamivir treatment ( technical appendix table 1 ) .
thus , it is essential to determine whether the virus has developed resistance to oseltamivir .
ineffectiveness of the oral oseltamivir formulations may also have contributed to treatment failure , especially for case - patients 1 and 4 : the drug may not have been well absorbed , especially by patients in severe condition . if available in the future , systemic delivery of oseltamivir may be superior . of the 4 patients reported here ,
however , it is not clear that this contact contributed to the rapid progression of disease in case - patient 1 , especially given the fact that case - patient 4 , who is still in critical condition , also had rapid progression of disease
. the other patients did not raise birds at home , but they visited live poultry markets .
prompt and early communication of the clinical features of persons infected with avian influenza a(h7n9 ) virus is crucial to the development of effective treatment strategies ( 6 ) .
research to understand the transmission pattern and effective control of this virus is urgently needed ( 79 ) .
virus detection in 4 influenza a(h7n9 ) virus  infected persons in shanghai , china ; variables for infection with influenza a subtypes h1n1 , h5n1 , and h7n9 ; computer tomography scan and radiograph findings for case - patients 3 and 4 ; and outline of procedures followed by emergency team managing / treating case - patients 14 .
 a novel strain of influenza a(h7n9 ) virus has emerged in china and is causing mild to severe clinical symptoms in infected humans . 
 some case - patients have died . to further knowledge of this virus , 
 we report the characteristics and clinical histories of 4 early case - patients . 