Association between Antibody Responses Post-Vaccination and Severe COVID-19 Outcomes: National Population-Based Cohort Study in Scotland

Abstract

Background: Immune responses to COVID-19 vaccines differ between individuals. Identifying characteristics associated with insufficient post-vaccination IgG antibody responses and describing the association between post-vaccination IgG and subsequent SARS-CoV-2 infection and severe COVID-19 outcomes could inform future vaccination strategies.    

Methods: We linked population-based SARS-CoV-2 seroprevalence surveillance data to national cohort data from Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II), comprising primary care, RT-PCR testing, vaccination, hospitalisation, and mortality data. We used logistic regression to examine risk factors for an insufficient response (defined as only negative SARS-CoV-2 IgG tests ≥14 days post-vaccination) and Cox regression to investigate the association between IgG titres and subsequent severe COVID-19 outcomes. 

Findings: Among 23,607 vaccinated individuals with seroprevalence data, 2,633 (11·2%) had an insufficient response. Individuals with multimorbidity had increased adjusted odds (1·94 [95% CI 1·45-2·60]) of generating an insufficient response compared to those without COVID-19 risk factors, as did those with certain single conditions: haematological cancer (1·85 [1·21-2·83]); rare neurological conditions (1·94 [1·18-3·19]); respiratory cancer (2·32 [1·13-4.78]); and sickle cell disease (2·55 [1·16-5·59]). Antibody titres showed a dose-dependent association with severe COVID-19: those with undetectable IgG were at greatest risk of COVID-19 hospitalisation or death (HR 8·25 [4·39-15·49]) compared to those with average levels.  

Interpretation: We have identified predictors of insufficient antibody response post-vaccination and found a direct dose-dependent association between insufficient antibody levels and severe COVID-19 outcomes. Identification of people at risk of insufficient vaccine responses and prioritising them for COVID-19 therapeutics may be warranted.

Funding: This study is part of the EAVE II project. EAVE II is funded by the MRC (MC_PC_19075) with the support of BREATHE—The Health Data Research Hub for Respiratory Health (MC_PC_19004), which is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Additional funding for this work was received by National Core Studies Immunity. This research is part of the Data and Connectivity National Core Study, led by Health Data Research UK in partnership with the Office for National Statistics and funded by UK Research and Innovation (grant ref MC_PC_20058). Additional support has been provided through Public Health Scotland, the Scottish Government Director General Health and Social Care and the University of Edinburgh. The original EAVE project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme (11/46/23). The views expressed are those of the authors and not necessarily those of the NIHR, the Department of Health and Social Care, or the UK government.

Declaration of Interests: AS and CR are members of the Scottish Government Chief Medical Officer’s COVID-19 Advisory Group and AS its Standing Committee on Pandemics. AS is also a member of the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) Risk Stratification Subgroup. AS was a member of AstraZeneca’s Thrombotic Thrombocytopenic Taskforce. All AS’ roles are unremunerated. CR is a member of SPI-M. JM was a member of the National Incident Management Team COVID-19, and lead of Enhanced Surveillance of COVID-19 in Scotland during this project. IR is a member of the Scientific Council on COVID-19 pandemic of the Government of the Republic of Croatia and the co-Editor-in-Chief of the Journal of Global Health.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: COVID-19, SARS-CoV-2, igg, antibody, antibodies, vaccine, vaccination, vaccinated, serology, serum, diabetes, ckd, cancer, immune, immunology, impaired, insufficient, insufficient-response, impaired-response, non-responders, risks, QCOVID, clinical-risks, multimorbidity, comorbidity