Airway and Systemic Immune Responses Following the Third COVID-19 Vaccination in COPD Patients

Abstract

Introduction

Booster vaccinations are required to maintain protection against COVID-19. COPD patients are at higher risk of developing severe illness following SARS-CoV-2 infection. Previous cross-sectional analysis after the second COVID-19 booster showed similar immune responses in COPD patients and controls, but pre-vaccination samples were not available. This longitudinal study evaluated systemic and airway immune responses in COPD patients using samples obtained pre- and post-third COVID-19 vaccination.

Methods

Twelve COPD patients were recruited, with plasma, nasal and sputum (n = 10) samples collected pre-vaccination and 4- and 14-weeks post vaccination. Samples were analyzed for anti-spike IgA and IgG and cellular immunity. The ability of plasma and nasal samples to block ACE2-spike protein interaction was assessed for Wild type, Delta, and Omicron spike variants.

Results

Vaccinations increased anti-spike IgG in plasma (p < 0.001), nasal (IgG p < 0.001) and sputum (p = 0.002) samples, IgA in plasma (p < 0.001) and blood cellular immunity (p = 0.001). Plasma and nasal anti-spike IgA levels correlated (rho: 0.6, p = 0.02), with similar results for IgG (rho: 0.79, p = 0.003). Post-vaccination nasal (p = 0.002) and plasma (p < 0.001) samples were less effective at blocking Omicron spike binding to ACE2 compared to the Wild type spike variant.

Discussion

Airway and systemic immune responses against SARS-CoV-2 increased in COPD patients following a third COVID-19 vaccination. Nasal and systemic responses in COPD patients were less effective against Omicron variant compared to previous variants.

Keywords:

• COVID-19
• vaccination
• chronic obstructive pulmonary disease
• omicron
• airway
• immunoglobulin

Abbreviations

ACE2, angiotensin-converting enzyme 2; BMI, Body mass index; CAT, Chronic obstructive pulmonary disease assessment test; COPD, Chronic obstructive pulmonary disease; ELISA, Enzyme-linked immunosorbent assay; FEV₁, First second of forced expiration; FVC, Forced vital capacity; GOLD, Global Initiative for Chronic Obstructive Pulmonary Disease; ID50, Half maximal inhibitory dilution; IFNγ, Interferon gamma; Ig A/G, Immunoglobulin A/G; mRNA, Messenger ribonucleic acid; ng/mL, Nanogram per millilitre; SARS-CoV-2, Severe acute respiratory coronavirus 2; U/mL, Units per millilitre; UK, United Kingdom.

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Informed Consent

Subjects all provided written informed consent using a protocol that complied with the Declaration of Helsinki and was approved by the local ethics committee (North West Research Ethic Committee; reference: 10/H1003/108).

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

DS reports personal consulting fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Orion, Pulmatrix, Sanofi, Synairgen, Teva, Theravance Biopharm and Verona Pharma. TS and NJ declare no competing interests for this work.

Additional information

Funding

This research was supported by the Medicines Evaluation Unit and the North West Lung Centre Charity, Manchester, UK. DS receives support from the NIHR Manchester Biomedical Research Centre. This report is independent research, and the views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.