A Systematic Review and Meta-Analysis of Immunogenicity and Safety of the Influenza Vaccine in COPD Patients, and Its Relevance with Real-World Effectiveness

Objective: A systematic review and meta-analysis was conducted to evaluate the immunogenicity and adverse events of influenza vaccines in patients with chronic obstructive pulmonary disease (COPD) and explored their relevance to real-world vaccine effectiveness (VE). Methods: A systematic search of PubMed, Cochrane Library (Wiley), Google Scholar, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform using keywords of “influenza vaccine”, “immunogenicity”, “COPD”, and “Chronic Obstructive Pulmonary Disease” to identify relevant studies published up to April 24, 2024. These are randomized controlled trials and cross-sectional, prospective, and observational studies that included COPD patients, particularly those aged ≥ 50 years, which assessed the immunogenicity of inactivated trivalent and quadrivalent, split-virion influenza vaccines. The outcomes were geometric mean titer (GMT), seroprotection rate (SPR), seroconversion rate (SCR), and safety. Results: Six studies involving 672 participants were retrieved. The pooled SCR in the intradermal subgroup was highest for A/H1N1 (68.6% [95% CI = 48.6– 83.5%]) and A/H3N2 (65.8% [95% CI = 57.9– 73.0%]). SPR was highest via subcutaneous route, reaching 96.0% for A/H3N2 however only one study was available, hence the findings should be interpreted with caution. The pooled mean difference in GMT was higher for intradermal than intramuscular vaccination, particularly for the A/H1N1 strain (8.38 vs 7.98) and A/H3N2 (7.97 vs 7.44). Local adverse events were more frequent with intradermal vaccination, particularly erythema (31.5%) and swelling (28.7%), while systemic events such as fever were rare (< 5%). Conclusion: The GMT, SPR, and SCR of influenza vaccination in COPD patients were more robust in laboratory settings than in real-world VE, indicating a gap between antibody responses in real-world clinical practice and laboratory settings. Keywords: immunogenicity, influenza vaccine, COPD, GMT, seroprotection, seroconversion