Increased Respiratory Viral Detection and Symptom Burden Among Patients with Primary Antibody Deficiency: Results from the BIPAD Study

Abstract

Background Patients with primary antibody deficiency (PAD) are at increased risk of respiratory tract infections but our understanding of their nature and consequences remains limited. Objective To define the symptomatic and microbial burden of upper airway infection in adults with PAD relative to age-matched controls. Methods Prospective 12-month observational study consisting of a daily upper and lower airway symptom score alongside fortnightly nasal swab with molecular detection of 19 pathogen targets. Results 44 patients and 42 controls (including 34 household pairs) were recruited, providing over 22,500 days of symptom scores and 1,496 nasal swabs. Swab and questionnaire compliance exceeded 70%. At enrolment, 64% of patients received prophylactic antibiotics with a 34% prevalence of bronchiectasis. On average, PAD patients experienced symptomatic respiratory exacerbations every 6 days compared to 6 weeks for controls, associated with significant impairment of respiratory-specific quality of life scores. Viral detections were associated with worsening of symptom scores from a participant’s baseline. PAD patients had increased odds ratio (OR) for pathogen detection, particularly viral (OR 2.73; 95% CI: 2.09 to 3.57), specifically human rhinovirus HRV (OR 3.60; 2.53-5.13), and parainfluenza (OR 3.06; 1.25-7.50). H. influenzae and S. pneumonia were also more frequent in PAD. Young child exposure, IgM deficiency, and presence of bronchiectasis were independent risk factors for viral detection. Prophylactic antibiotic use was associated with a lower risk of bacterial detection by PCR. Conclusion PAD patients have a significant respiratory symptom burden associated with increased viral infection frequency despite immunoglobulin replacement and prophylactic antibiotic use. This highlights a clear need for future therapeutic trials in the PAD-population, and informs future study design.

The Role of Respiratory Viruses in Children with Ataxia-Telangiectasia

“…Case control prospective studies performed in patients with primary antibody deficiencies have reported worsening of symptom scores from the participant’s baseline, with the impaired lung function associated with respiratory viral infections. Rhinovirus was the virus most frequently detected, as we have also observed [ 5 , 10 ]. These studies included a heterogeneity of diseases, such as combined immunodeficiency or immune dysregulation diseases, with immunological profiles similar to A-T [ 5 , 10 ].…”

“…Rhinovirus was the virus most frequently detected, as we have also observed [ 5 , 10 ]. These studies included a heterogeneity of diseases, such as combined immunodeficiency or immune dysregulation diseases, with immunological profiles similar to A-T [ 5 , 10 ].…”

“…In fact, S. pneumoniae is more frequently detected in the upper airway microbiome of patients with A-T than in healthy individuals [ 8 ]. Respiratory viruses could also have significant implications in the pathophysiology of respiratory complications in A-T [ 9 , 11 , 12 , 13 ] given that they are associated with substantial morbidity among other patients with primary immunodeficiency [ 5 , 6 , 7 , 8 , 9 , 10 ], although this has hardly been analyzed.…”

Update on Infections in Primary Antibody Deficiencies

“…The most common respiratory virus isolated in this study was human rhinovirus (HRV), followed by adenovirus, respiratory syncytial virus, and seasonal coronavirus (non-pandemic). Using a multiplex PCR approach, this study also showed that HRV and H. influenzae might frequently co-occur in patients with PADs ( 40 ). Furthermore, prolonged shedding of HRV after an acute infection has been shown by another group in patients with CVID and XLA compared to healthy controls (40 days versus 10 days) ( 41 ).…”

“…Bacterial infections and bronchiectasis are more commonly seen in patients with low IgG levels ( 64 , 103 , 158 , 159 ). IgRT may not significantly reduce viral respiratory infections ( 40 ).…”