Severe H1N1 infection appears to be associated with immunoglobulin G₂ subclass deficiency in both nonpregnant and pregnant patients. Healthy pregnant women were mildly deficient in immunoglobulin G₂, but pregnant women with severe H1N1 infection had lower levels. Immunoglobulin G₂ deficiency persisted after recovery in the majority (73%) of cases.

Background . Severe pandemic 2009 influenza A virus (H1N1) infection is associated with risk factors that include pregnancy, obesity, and immunosuppression. After identification of immunoglobulin G₂ (IgG₂) deficiency in 1 severe case, we assessed IgG subclass levels in a cohort of patients with H1N1 infection.

Methods . Patient features, including levels of serum IgG and IgG subclasses, were assessed in patients with acute severe H1N1 infection (defined as infection requiring respiratory support in an intensive care unit), patients with moderate H1N1 infection (defined as inpatients not hospitalized in an intensive care unit), and a random sample of healthy pregnant women.

Results . Among the 39 patients with H1N1 infection (19 with severe infection, 7 of whom were pregnant; 20 with moderate infection, 2 of whom were pregnant), hypoabuminemia (P<.001), anemia (P<.001), and low levels of total IgG (P=.01), IgG₁ (P=.022), and IgG₂ (15 of 19 vs 5 of 20; P=.001; mean value ± standard deviation [SD], 1.8±1.7 g/L vs 3.4±1.4 g/L; P=.003) were all statistically significantly associated with severe H1N1 infection, but only hypoalbuminemia (P=.02) and low mean IgG₂ levels (P=.043) remained significant after multivariate analysis. Follow-up of 15 (79%) surviving IgG₂-deficient patients at a mean (±SD) of 90±23 days (R, 38–126) after the initial acute specimen was obtained found that hypoalbuminemia had resolved in most cases, but 11 (73%) of 15 patients remained IgG₂ deficient. Among 17 healthy pregnant control subjects, mildly low IgG₁ and/or IgG₂ levels were noted in 10, but pregnant patients with H1N1 infection had significantly lower levels of IgG₂ (P=.001).

Conclusions . Severe H1N1 infection is associated with IgG₂ deficiency, which appears to persist in a majority of patients. Pregnancy-related reductions in IgG₂ level may explain the increased severity of H1N1 infection in some but not all pregnant patients. The role of IgG₂ deficiency in the pathogenesis of H1N1 infection requires further investigation, because it may have therapeutic implications.