Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases
Zitta Barrella Harboe, Sebastian Rask Hamm, Laura Pérez‐Alós, Pradeesh Sivapalan, Helene Priemé, Torgny Wilcke, Peter Kjeldgaard, Saher Burhan Shaker, Alexander Jordan, Dina Leth Møller, Line Dam Heftdal, Johannes Roth Madsen, Rafael Bayarri‐Olmos, Cecilie Bo Hansen, Mia Marie Pries‐Heje, Rasmus Bo Hasselbalch, Kamille Fogh, José Juan Almagro Armenteros, Linda Hilsted, Erik Sørensen, Birgitte Lindegaard, Andrea Browatzki, Tor Biering‐Sørensen, Ruth Frikke‐Schmidt, Sisse Rye Ostrowski, Kasper Iversen, Henning Bundgaard, Susanne Dam Nielsen, Peter Garred, Jens‐Ulrik Stæhr Jensen
Abstract
INTRODUCTION: Responses to COVID-19 vaccination in patients with chronic pulmonary diseases are poorly characterised. We aimed to describe humoral responses following two doses of BNT162b2 mRNA COVID-19 vaccine and identify risk factors for impaired responses. METHODS: Prospective cohort study including adults with chronic pulmonary diseases and healthcare personnel as controls (1:1). Blood was sampled at inclusion, 3 weeks, 2 and 6 months after first vaccination. We reported antibody concentrations as geometric means with 95% CI of receptor binding domain (RBD)-IgG and neutralising antibody index of inhibition of ACE-2/RBD interaction (%). A low responder was defined as neutralising index in the lowest quartile (primary outcome) or RBD-IgG <225 AU/mL plus neutralising index <25% (secondary outcome), measured at 2 months. We tested associations using Poisson regression. RESULTS: We included 593 patients and 593 controls, 75% of all had neutralising index ≥97% at 2 months. For the primary outcome, 34.7% of patients (n=157/453) and 12.9% of controls (n=46/359) were low responders (p<0.0001). For the secondary outcome, 8.6% of patients (n=39/453) and 1.4% of controls (n=5/359) were low responders (p<0.001). Risk factors associated with low responder included increasing age (per decade, adjusted risk ratio (aRR) 1.17, 95% CI 1.03 to 1.32), Charlson Comorbidity Index (per point) (aRR 1.15, 95% CI 1.05 to 1.26), use of prednisolone (aRR 2.08, 95% CI 1.55 to 2.77) and other immunosuppressives (aRR 2.21, 95% CI 1.65 to 2.97). DISCUSSION: Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Age, comorbidities and immunosuppression were associated with poor immunological responses.