Impact of pre-existing specific influenza antibodies as a determinant of disease severity on influenza virus infected patients: a multicenter observational cohort study

Abstract

Abstract It is unclear to what extent pre-existing antibody-mediated immunity shapes influenza virus infection in humans. Similarly, the influence of previous history of influenza vaccination on disease severity and clinical outcome is not well understood. In here, we aimed to determine the balance of pre-existing antibodies against the hemagglutinin (HA) and neuraminidase (NA) protein of influenza virus that correlates with protection in humans. We measured hemagglutination inhibition (HI) titers and anti-HA (stalk and full-length) and anti-NA antibodies at the onset of the influenza infection on a cohort of H1N1/Cal09 influenza virus-infected patients (solid organ transplant recipients, SOTRs). Results demonstrated that the antecedent of TIV vaccination was the only controllable factor associated with lower risk of severity of disease in influenza virus-infected SOTRs. The presence of lower respiratory symptoms (LRS) significantly determined disease outcome at hospital admission (severe vs. mild, 9, 75% vs. 19, 32·1%, OR 95% 6·3, p=0·01). Moreover, a predicted probability curve for both anti-HA full-length and stalk (OR 0·13, p=0·02 and OR 0·06, p=0·03, respectively) demonstrated that the probability of developing LRS decreased with increasing assay log-values. However, multivariate logit model adjusted for HI, anti-HA (full-length and stalk) and anti-NA titers demonstrated that only anti-HA stalk antibodies were independently associated with influenza severity. Our study demonstrated that when HI antibodies fail to confer protection from symptomatic influenza infection, pre-existing HA stalk antibodies protected against severe disease in SOTRs.