Increased Severity of Pandemic H1N1 Influenza in Children and Young Adults with Sickle Cell Disease.
Authors: Strouse John J. , Amoako Martha , Reller Megan , Casella James F. 
Published: October 2019

Abstract
Abstract 264

Background:
Admission for influenza is more than 50 times more frequent in children with sickle cell disease (SCD) than in the general population. H1N1 influenza, a novel influenza A virus of swine origin, began circulating in the United States in the spring of 2009 and has now been detected in over 170 countries. H1N1 influenza has been reported to cause more severe illness in children and young adults than seasonal influenza. To compare the relative severity of H1N1 influenza vs. seasonal influenza A and B in young persons with SCD, we compared the clinical characteristics and complications associated with these infections in patients seen at our tertiary care hospital.

Methods:
We defined a case as laboratory-confirmed influenza infection with influenza A or B in a patient aged 0–21 years with SCD who was evaluated at Johns Hopkins Hospital from 1 September 1993 to 31 July 2009. Through July 2006, we searched the discharge and billing databases for Johns Hopkins Hospital to identify those with SCD and laboratory testing for respiratory infections. Thereafter, we prospectively identified cases through divisional records. We confirmed the diagnosis of influenza by review of microbiology results in each patient's paper and/or electronic medical record. All respiratory samples positive for influenza A after 1 May 2009 were tested for pandemic H1N1 at the Maryland Department of Health and Mental Hygiene using a real-time reverse transcription polymerase chain reaction assay. We used Fisher's exact test to compare proportions, Student's t-test or Wilcoxon rank-sum test to compare continuous variables, and logistic regression to evaluate associations.

Results:
We identified 99 patients with SCD and influenza (64 seasonal influenza A, 25 seasonal influenza B, and 10 pandemic influenza A) during the study period (Figure). Eighteen patients had pandemic (10) or seasonal (8) influenza during the 2008 – 2009 season and July of 2009. Clinical symptoms, such as reported fever (90%), cough (93%), and rhinorrhea (79%), were similar. However, those with pandemic influenza were more likely to have acute chest syndrome and to require intensive care and ventilator support (Table). In a multivariable logistic regression model, older age (OR 1.2 per year, 95% CI 1.04 –1.3, P=.004) and pandemic influenza vs. seasonal influenza (OR 11, 95% CI 1.3 –88, P=0.025) were associated with increased risk of intensive care.

Discussion:
We found pandemic influenza to be associated with a greater risk of life-threatening complications than seasonal influenza in young patients with SCD, including an estimated 3-fold increased risk of acute chest syndrome and a 9-fold increased risk of need for intensive care. Older age may also be a risk factor for more severe disease, but could also reflect referral bias (with only the sickest adolescents and young adults being referred for tertiary pediatric care). We conclude that vaccination against pandemic influenza, in addition to seasonal influenza, will be essential for children and young adults with SCD and others in their households.
The influenza season was defined as for 1995 (7/1/95–6/30/96) for each year.

Disclosures:
Casella: Boehringer Ingelheim: Consultancy, Honoraria; Cytrex: Research Funding; Ikaria: Research Funding.