From September 2009 through February 2010, a total of 31,562 confirmed case patients were hospitalized throughout China and were reported to the China CDC, including 793 (2.5%) who died and 24,268 (77%) who were discharged from the hospital. Of these patients, 9966 (32%), including 783 (8%) who died and 8491 (85%) who were discharged from the hospital, had complete chart abstractions and were included in analyses of risk factors. These represented 35% of all discharged patients (8491 of 24,268 patients) and 99% of deaths (783 of 793 deaths) reported from 30 of 31 provinces (Supplementary Figure 1
). Illness onsets of included case patients peaked in late November and decreased after early December 2009 (). The characteristics of included case patients and reported case patients without chart abstractions are shown in Supplementary Table 1
; details of case patients’ enrollments are provided in Supplementary Figure 2
Case patients hospitalized with 2009 pandemic influenza A (H1N1) virus infection (n = 9966) with chart review data, by date of illness onset, China, September 2009–February 2010. ICU, intensive care unit.
A total of 31,562 reported hospitalized case patients, including 793 patients who died, were used to calculate hospitalization and mortality rates, as well as death-hospitalization ratios. The overall hospitalization and mortality rates during the 6-month study period were 2.4 hospitalizations per 100,000 population and 0.6 deaths per 1,000,000 population. Hospitalization rates ranged from 6.1 hospitalizations per 100,000 population among children 5–14 years of age to 0.6 hospitalizations per 100,000 population among persons ≥65 years of age. Mortality rates ranged from 1.2 deaths per 1,000,000 population in children <5 years of age to 0.3 deaths per 1,000,000 population in children 5–14 years of age (). Death-hospitalization ratios were highest among those ≥65 years of age (0.115) and lowest among children 5–14 years of age (0.007) ().
Figure 2. Hospitalization and mortality rates and death-hospitalization ratios by age group. A, Hospitalization rates (n = 31,562) and mortality rates (n = 793) per 100,000 population. B, Death-hospitalization ratios. Error bars indicates 95% confidence intervals. (more ...)
Demographic Characteristics and Underlying Risk Conditions
The median age of the 9966 case patients was 22 years (range, 1 day–93 years), 58% were <25 years of age, and 56% were male (). The median age of case patients increased with increasing disease severity, from 18 years for those without ICU admission, to 27 years for those with ICU admission, to 30 years for those with fatal outcomes. Of 9503 case patients with known information, 21% had at least 1 high-risk chronic medical condition; high-risk conditions were uncommon among those <25 years of age (found in <10% of such patients). The prevalence of chronic medical conditions among hospitalized case patients increased with increasing disease severity, from 14% among those without ICU admission, to 31% among those with ICU admission, to 38% among those with fatal outcome.
Demographic Characteristics and Underlying Conditions of Case Patients Hospitalized with 2009 Pandemic Influenza A (H1N1)
A total of 1014 case patients (10%) were considered to be pregnant, including 19 postpartum women who had delivered within 2 weeks after illness onset. Of these, most (95%) were <35 years of age, and only 63 (7%) had chronic high-risk medical conditions. Of 563 pregnant women (56%) who required ICU admission, 156 (15%) died. Of 968 pregnant case patients with known gestational age, 63% were in the 3rd and 29% were in the 2nd trimester.
Of the 8456 nonpregnant case patients ≥2 years of age with known BMI, 1002 (12%) or 1336 (16%) were obese, based on US criteria and Chinese criteria, respectively; only 33 (0.7%) of the adults were morbidly obese (BMI ≥40). Of the 1336 case patients who were obese according to Chinese criteria, 559 (42%) required ICU admission, and 91 (7%) died. Twenty-four percent of obese case patients (311 of 1287) also had chronic high-risk medical conditions. Among obese case patients, 62% of patients with nonsevere illness were <15 years of age, whereas 68% of deaths were in those ≥25 years of age.
Treatment and Outcomes
Case patients were admitted to the hospital a median of 3 days (interquartile range [IQR], 1–5 days) after illness onset (). During hospitalization, 7266 case patients (76%), including 2683 (90%) of the case patients with ICU admission and 622 (83%) of those with fatal outcomes, were treated with neuraminidase inhibitors; all received oseltamivir, except 2 patients who only received inhaled zanamivir. Oseltamivir treatment was started within 2 days after symptom onset for 1155 case patients (17%), on days 3–4 after symptom onset in 1703 (26%), and ≥5 days after symptom onset in 3807 (57%).
Treatment, Complications, and Clinical Course of Case Patients Hospitalized with 2009 Pandemic Influenza A (H1N1)
The median time from illness onset to initiation of oseltamivir treatment was significantly shorter for case patients with nonsevere illness, compared with those who had severe illness, among nonpregnant case patients ≥2 years of age (P
<.001; Supplementary Table 2
); this was also observed for female case patients of reproductive age and for those who were pregnant (Supplementary Tables 3
). In multivariable analyses of the effectiveness of early oseltamivir treatment (initiated within 2 days after illness onset) among nonpregnant case patients ≥2 years of age (), later initiation (3–4 days after onset) was associated with a trend toward an increased risk of severe illness, and initiating oseltamivir treatment ≥5 days after illness onset was associated with a statistically significant risk of severe illness (OR, 1.42; 95% CI, 1.20–1.67); this observation was consistent for female case patients of reproductive age and for those who were pregnant (data not shown).
Multivariable Analyses of Risk Factors associated with Severe Illness due to 2009 Pandemic Influenza A (H1N1) Virus Infection
Of the 9966 case patients, 3797 (38%), including 783 patients with fatal outcome, were admitted to an ICU for a median of 5 days (IQR, 2–10 days), and 1961 (52%) of case patients admitted to the ICU required mechanical ventilation. Of the 9966 hospitalized patients, 8491 (85%) were discharged from the hospital; 783 (8%) died after a median of 11 days (IQR, 6–19 days) after illness onset.
Risk Factors Associated with Severe Illness
The proportion of case patients with at least 1 high-risk chronic medical condition (33% vs 14%; P < .001), pregnancy (15% vs 7%; P < .001), or obesity by Chinese criteria (19% vs 14%; P < .001) were all significantly higher among case patients with severe illness than they were among case patients with nonsevere illness (). The proportion of case patients with severe illness who had any of these 3 risk factors was significantly higher than the proportion of case patients with nonsevere illness who had any of these 3 risk factors (54% vs 31%; P < .001).
In multivariable analyses (), male sex (OR, 1.19; 95% CI, 1.07–1.31) and delayed time to hospital admission (OR, 1.27; 95% CI, 1.13–1.42) were significantly associated with severe illness among nonpregnant patients ≥2 years of age. In a multivariable “main effects” model that did not account for any interactions, obesity (OR, 1.54; 95% CI, 1.35–1.76) and having a chronic disease (OR, 2.72; 95% CI, 2.41–3.08) were independent risk factors for severe illness among all ages of nonpregnant case patients (data not shown). Although age was a modifier of the effect of both chronic medical conditions and obesity on severe illness, results of the multivariable model that accounted for interactions between age, chronic medical conditions, and obesity indicated that having a chronic medical condition significantly increased the risk of severe outcomes with increasing age >18 years; the highest risk was observed among patients ≥60 years of age and those with chronic medical conditions (OR, 6.88; 95% CI, 5.54–8.55), compared with patients without chronic medical conditions. When obese patients were compared with nonobese patients, multivariable analyses indicated that obesity significantly increased the risk of severe outcomes among those 2–17 years of age (OR, 1.34; 95% CI, 1.10–1.63) and 18–59 years of age (OR, 1.91; 95% CI, 1.57–2.31) but not in persons ≥60 years of age.
Age ≥35 years (OR, 1.40; 95% CI, 1.10–1.77) and delayed time to hospital admission (OR, 1.80; 95% CI, 1.47–2.19) were independent risk factors for severe illness among female case patients of reproductive age (15–49 years of age) in multivariable analyses. Chronic medical conditions modified the effect of pregnancy on severe illness. Compared with previously healthy nonpregnant female case patients, pregnant women with chronic medical conditions had the highest risk for severe illness (OR, 3.69; 95% CI, 2.15–6.31) in multivariable analyses (). The risk of severe illness was markedly higher in the second (OR, 6.10; 95% CI, 3.12–11.94) or third trimester (OR, 7.62; 95% CI, 3.99–14.55) among pregnant case patients; the risk of severe illness appeared higher in the third trimester than in the second trimester (OR, 1.25; 95% CI, 0.92–1.70) but was not significantly different (P = .152). Pregnant multigravida case patients had a higher risk of severe illness than did primgravida case patients (OR, 1.56; 95% CI, 1.16–2.08).
The proportion of pregnant women among case patients with nonsevere illness was higher than that among the general Chinese population of reproductive-age women (31% vs 3%; OR, 13.20; 95% CI, 11.82–14.75); a higher proportion of pregnant women experienced severe illness than experienced nonsevere illness (51% vs 31%; OR, 2.39; 95% CI, 2.03–2.81) ().
Comparison of Prevalence of Pregnancy and Obesity between Case Patients with Nonsevere and Severe 2009 Pandemic Influenza A (H1N1) Illness and the General Chinese Population
Except for those case patients ≥60 years of age, the proportion of individuals with obesity was higher among patients with nonsevere illness than it was among the general population, including those 2–17 years of age (18% vs 2%; OR, 10.45; 95% CI, 9.49–11.52) and those 18–59 years of age (11% vs 8%; OR, 1.35; 95% CI, 1.18–1.54); the proportion of individuals with obesity was also significantly higher among case patients with severe illness than among case patients with nonsevere illness ().