Published Online: August 22, 2020
We are all used to fighting off the occasional cold virus during the winter months, but what happens in patients unable to produce antibodies normally? For patients with Primary Antibody Deficiency (PAD), Immunoglobulin (antibody) Replacement Therapy (IgRT) is the mainstay of treatment and has made a huge difference in reducing bacterial infections, especially pneumonia. But IgRT only replaces one class of antibody, IgG, often leaving the other two major classes IgA and IgM low or absent. In addition, access of IgG to the conducting airways of the upper respiratory tract may be limited. Improved understanding of the extent of and impact from upper airway viral and bacterial infection in this patient group is key to improving patient care, preventing progression to involve the lower respiratory tract and defining the limits of current therapy.
In the recently published Burden of Infection in Primary Antibody Deficiency (BIPAD) study in The Journal of Allergy and Clinical Immunology (JACI): In Practice, Ponsford et al followed 44 patients with PAD and 42 healthy controls (including 34 household pairs) over 12 months. Participants were trained to perform and return a nasal swab to detect 15 viruses and 4 bacteria every two weeks for a year. They also provided a range of quality-of-life measures, including a study-specific daily symptom diary, enabling changes in upper and lower airway symptom burden to be tracked alongside the viral and bacterial detections.
Together, the participants returned over 22,500 days of symptom scores and 1,496 nasal swabs between August 2015 and January 2018. Swab and questionnaire compliance exceeded 70%. On average, PAD patients experienced symptomatic respiratory exacerbations every 6 days; compared to 6 weeks for controls. PAD patients were almost 3 times more likely to test positive for a virus than controls (Odds Ratio (OR): 2.73; 95% Confidence Interval (CI): 2.09-3.57). Differences between patients and controls for a subset of pathogens tested were particularly marked. These were human rhinovirus (OR 3.60; 95% CI: 2.53-5.13), parainfluenza (OR 3.06; 95% CI: 1.25-7.50) dual positive viral and bacterial detections (OR 2.85; 95% CI: 1.87-4.32) and Haemophilus Influenzae (OR 5.65; 95% CI: 3.74-8.54). Remarkably, the viral detections, more so than bacterial detections, drove worsening of symptom scores from a participant’s baseline and were observed all year round, in contrast to the seasonal winter peak found in the controls – suggesting that, for PAD patients, winter is truly here. This highlights the often-overlooked impact of viral infections and the gulf in quality of life between healthy individuals and those with primary immunodeficiency. Key clinical risk factors associated with viral detections – such as young child exposure, bronchiectasis, and low levels of IgM were also identified. Strikingly, all of these patients were already receiving IgRT and often prophylactic antibiotics.
This identifies a clear need for the development of new ways to address the ongoing burden of viral infections in the PAD-population and informs study design. Although conducted prior to the COVID-19 pandemic, the study highlights the prolonged symptom and viral detection reported in immunocompromised individuals which may prove relevant when considering infection control to halt ongoing transmission chains.
The Journal of Allergy and Clinical Immunology: In Practice is an official journal of the AAAAI, focusing on practical information for the practicing clinician.