Demographic characteristics and comorbidities
From 11 May to 31 July 2009 a total of 2126 confirmed cases of 2009 H1N1 were reported. We included 1291 (61%) with available data for chart review reported from 94 prefectures in 25 provinces (see appendix 1 on bmj.com), which represented 90% (1291/1438) of patients discharged before 31 July. See bmj.com for details of patients’ enrolment (appendix 2) and a comparison of the characteristics of patients with and without medical records for review (appendix 3). Of the 1291 patients, 406 (31%) were aged <15 years and were classed as children.
The median age of the patients was 20 years (interquartile range 12-26) and 54% were male (table 1); most (71%) were aged ≤24. Of the 1291 patients, 64 (5%) had a comorbidity associated with severe influenza; the most common were asthma (2%), other chronic pulmonary disease (0.8%), and chronic liver disease (0.8%). Two patients were pregnant, both in the second trimester.
Table 1 Demographic characteristic and comorbidities of 1291 patients with 2009 H1N1 virus infection in China, May-July 2009. Figures are numbers (percentages) unless stated otherwise
Clinical symptoms and laboratory findings
The most common symptoms on admission were fever (820, 64%), cough (864, 67%), sore throat (425, 33%), sputum (239, 19%), and rhinorrhoea (228, 18%) (table 2). Only 4% of the patients reported gastrointestinal tract symptoms including diarrhoea, nausea, or vomiting. The most common signs were pharyngeal congestion (1026, 79%) and swollen tonsils (442, 34%). None of 1291 patients developed symptoms of lower respiratory tract disease such as dyspnoea or shortness of breath. More children than adults experienced cough, vomiting, and swollen tonsils (table 2).
Table 2 Clinical symptoms and signs in 1291 patients with 2009 H1N1 virus infection at hospital admission in China, May-July 2009. Figures are numbers (percentages) unless stated otherwise
Table 3 gives details of abnormal haematological findings at admission, which included leucopenia (451, 36%), neutropenia (483, 39%), lymphopenia (252, 21%), thrombocytopenia (34, 3%), and anaemia (109, 9%) in children and adults. Some patients had mildly raised biochemical markers including alanine aminotransferase (110, 10%), aspartate aminotransferase (127, 12%), creatine kinase (100, 19%), creatine phosphokinase isoenzymes (51, 11%), lactic dehydrogenase (119, 17%), and C reactive protein (271, 38%). Compared with adults, children more often had leucopenia, anaemia, or raised aspartate aminotransferase, creatine phosphokinase isoenzymes, and lactic dehydrogenase levels (table 3).
Table 3 Laboratory findings of 1291 patients with 2009 H1N1 virus infection at hospital admission in China, May-July 2009. Figures are numbers (percentages) unless stated otherwise
Of the 920 patients who underwent chest radiography during their stay in hospital, 110 (12%) had abnormal findings consistent with pneumonia. Radiography was carried out at a median of two days (interquartile range, 1-3) after onset of symptoms in 28 (10%) children and 82 (13%) adults (table 3). Findings included infiltration in 105 patients and consolidation in five. The most common features of these abnormalities were local patchy shadowing and lobular infiltration. None of 36 patients who were tested had bacterial growth from blood cultures.
Treatment and clinical course
The 1291 patients were admitted to hospital a median of two days (interquartile range 1-3) after onset of symptoms (table 4). During admission, 983 (76%) patients were treated with oseltamivir from a median of day three of symptom onset (2-4) and 363 (37%) patients within two days of symptom onset. Some 735 (75%) patients received a standard course of oseltamivir (five days), and 110 (11%) received prolonged treatment for persistently positive viral RNA. During hospital admission, 479 (37%) patients received empirical antibiotics, most commonly cephalosporins (51%) and macrolides or azithromycin (46%). Few patients received corticosteroids (three) or supplementary oxygen via either mask (five) or nasal catheter (13). None of 1291 patients required admission to an intensive care unit or invasive mechanical ventilation.
Table 4 Treatments and clinical course of 1291 patients with 2009 H1N1 virus infection in China, May-July 2009. Figures are numbers (percentages) unless stated otherwise
Seventy two (6%) patients had no fever throughout the clinical course. Of the remaining 1219 (94%) patients who developed fever, most (76%) had fever on the same day as onset of symptoms, and fever most commonly disappeared two (24%) or three days (25%) after onset (fig 1and fig 2). Fever persisted for a median of two days (interquartile range 1-3). Overall, the median body temperature of febrile patients had returned to normal (<37.3°C) three days after onset (fig 1), and 90% of fevers had disappeared within five days (fig 3). All 1291 patients’ symptoms resolved fully at a median of five days (4-7) after onset, and patients were discharged at a median of eight days (6-10) after onset. In the final multivariable model (table 5), no oseltamivir treatment (β 0.05, 95% confidence interval 0.001 to 0.10) or oseltamivir treatment starting more than two days after symptom onset (0.15, 0.11 to 0.19) and presence of radiographic pneumonia (0.07, 0.01 to 0.12) were independent factors associated with a prolonged duration of fever.
Fig 1 Onset and disappearance of fever over clinical course by days after onset of symptoms in 1219 febrile patients with 2009 influenza H1N1 virus infection
Fig 2 Body temperature over clinical course in 1219 febrile patients with 2009 influenza H1N1 virus infection
Fig 3 Cumulative disappearance of fever and proportion of patients with undetectable viral RNA by days after onset of symptoms
Table 5 Multivariable analyses* of risk factors associated with prolonged duration of fever and duration of viral RNA shedding
Risk factors associated with radiographic pneumonia
In the final multivariable model, which included 920 patients who underwent chest radiography during their admission to hospital, treatment with oseltamivir starting within two days (odds ratio 0.17, 95% confidence interval 0.10 to 0.29) or more than two days (0.09, 0.05 to 0.15) after onset of symptoms were identified as significant protective factors for radiographic pneumonia (table 6). When we combined oseltamivir treatment starting within two days or after two days for multivariable analyses, there was no significant change in the estimate of overall impact on presence of radiographic pneumonia (0.12, 0.08 to 0.18, P<0.001). To prevent one 2009 H1N1 patient developing radiographic pneumonia, four patients (number needed to treat 4, 3 to 5) would need to be treated with oseltamivir. With regard to development of radiographic pneumonia, there seemed to be no more benefit with early initiation of oseltamivir (within two days of symptom onset) than with initiation after two days.
Table 6 Multivariable analyses* of risk factors associated with presence of radiographic diagnosis of pneumonia
Viral RNA shedding
We had data on the first positive and undetectable viral RNA results in respiratory specimens for almost all patients (1289). Those specimens were collected at a median of one day (0-2) and six days (4-7) after the onset of symptoms. Specimens with first positive results were usually collected on the day (29%) of symptom onset or one day (32%) after, while the sample with undetectable viral RNA was most commonly collected at five (16%) or six days (17%) after onset (fig 4). Specimens positive for viral RNA were collected from 11 patients one day before onset of symptoms, while they were under medical observation as close contacts of cases. Overall, viral RNA was undetectable among most patients (91%) within nine days after symptom onset (fig 3). Of the 119 (9%) remaining patients whose first test with undetectable viral RNA was later than nine days after symptom onset, 45 (38%) were children and five (4%) had one comorbidity associated with severe influenza, but none of them were immunosuppressed. The median interval between the first sample positive for viral RNA and the undetectable RNA was four days (3-6), and the median interval between disappearance of fever and an undetectable viral RNA level was three days (1-4).
Fig 4 Proportion of samples with first positive for viral RNA and samples with undetectable viral RNA by days after onset of symptoms
Two previously healthy men had the longest duration of viral RNA shedding (21 days). One was a 20 year old student with acute respiratory illness; he also had the longest duration of fever of 16 days. He received oseltamivir treatment for five days, beginning two weeks after onset of symptoms. The other was a 28 year old patient with radiographic pneumonia after five days of fever. He received oseltamivir treatment for 15 days, starting two days after onset.
In the final multivariable model (table 5), no oseltamivir treatment (β 0.04, 95% confidence interval, 0.01 to 0.07) or oseltamivir treatment starting more than two days after symptom onset (0.13, 0.10 to 0.16), presence of cough (0.07, 0.03 to 0.10), sputum (0.04, 0.004 to 0.05), and prolonged duration of fever (0.026, 0.020 to 0.032) were independent factors associated with prolonged viral RNA shedding.