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Antibody and cellular immune responses following dual COVID-19 vaccination within infection-naive residents of long-term care facilities: an observational cohort study.
Tut, Gokhan; Lancaster, Tara; Sylla, Panagiota; Butler, Megan S; Kaur, Nayandeep; Spalkova, Eliska; Bentley, Christopher; Amin, Umayr; Jadir, Azar; Hulme, Samuel; Ayodele, Morenike; Bone, David; Tut, Elif; Bruton, Rachel; Krutikov, Maria; Giddings, Rebecca; Shrotri, Madhumita; Azmi, Borscha; Fuller, Christopher; Baynton, Verity; Irwin-Singer, Aidan; Hayward, Andrew; Copas, Andrew; Shallcross, Laura; Moss, Paul.
  • Tut G; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Lancaster T; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Sylla P; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Butler MS; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Kaur N; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Spalkova E; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Bentley C; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Amin U; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Jadir A; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Hulme S; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Ayodele M; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Bone D; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Tut E; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Bruton R; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
  • Krutikov M; Institute of Health Informatics, University College London, London, UK.
  • Giddings R; Institute of Health Informatics, University College London, London, UK.
  • Shrotri M; Institute of Health Informatics, University College London, London, UK.
  • Azmi B; Institute of Health Informatics, University College London, London, UK.
  • Fuller C; Institute of Health Informatics, University College London, London, UK.
  • Baynton V; Health Security Agency UK, London, UK.
  • Irwin-Singer A; Health Security Agency UK, London, UK.
  • Hayward A; Health Data Research UK, London, UK.
  • Copas A; Institute for Global Health, University College London, London, UK.
  • Shallcross L; Institute of Health Informatics, University College London, London, UK.
  • Moss P; Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK.
Lancet Healthy Longev ; 3(7): e461-e469, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1915222
ABSTRACT

Background:

Older age and frailty are risk factors for poor clinical outcomes following SARS-CoV-2 infection. As such, COVID-19 vaccination has been prioritised for individuals with these factors, but there is concern that immune responses might be impaired due to age-related immune dysregulation and comorbidity. We aimed to study humoral and cellular responses to COVID-19 vaccines in residents of long-term care facilities (LTCFs).

Methods:

In this observational cohort study, we assessed antibody and cellular immune responses following COVID-19 vaccination in members of staff and residents at 74 LTCFs across the UK. Staff and residents were eligible for inclusion if it was possible to link them to a pseudo-identifier in the COVID-19 datastore, if they had received two vaccine doses, and if they had given a blood sample 6 days after vaccination at the earliest. There were no comorbidity exclusion criteria. Participants were stratified by age (<65 years or ≥65 years) and infection status (previous SARS-CoV-2 infection [infection-primed group] or SARS-CoV-2 naive [infection-naive group]). Anticoagulated edetic acid (EDTA) blood samples were assessed and humoral and cellular responses were quantified.

Findings:

Between Dec 11, 2020, and June 27, 2021, blood samples were taken from 220 people younger than 65 years (median age 51 years [IQR 39-61]; 103 [47%] had previously had a SARS-CoV-2 infection) and 268 people aged 65 years or older of LTCFs (median age 87 years [80-92]; 144 [43%] had a previous SARS-CoV-2 infection). Samples were taken a median of 82 days (IQR 72-100) after the second vaccination. Antibody responses following dual vaccination were strong and equivalent between participants younger then 65 years and those aged 65 years and older in the infection-primed group (median 125 285 Au/mL [1128 BAU/mL] for <65 year olds vs 157 979 Au/mL [1423 BAU/mL] for ≥65 year olds; p=0·47). The antibody response was reduced by 2·4-times (467 BAU/mL; p≤0·0001) in infection-naive people younger than 65 years and 8·1-times (174 BAU/mL; p≤0·0001) in infection-naive residents compared with their infection-primed counterparts. Antibody response was 2·6-times lower in infection-naive residents than in infection-naive people younger than 65 years (p=0·0006). Impaired neutralisation of delta (1.617.2) variant spike binding was also apparent in infection-naive people younger than 65 years and in those aged 65 years and older. Spike-specific T-cell responses were also significantly enhanced in the infection-primed group. Infection-naive people aged 65 years and older (203 SFU per million [IQR 89-374]) had a 52% lower T-cell response compared with infection-naive people younger than 65 years (85 SFU per million [30-206]; p≤0·0001). Post-vaccine spike-specific CD4 T-cell responses displayed single or dual production of IFN-γ and IL-2 were similar across infection status groups, whereas the infection-primed group had an extended functional profile with TNFα and CXCL10 production.

Interpretation:

These data reveal suboptimal post-vaccine immune responses within infection-naive residents of LTCFs, and they suggest the need for optimisation of immune protection through the use of booster vaccination.

Funding:

UK Government Department of Health and Social Care.

Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Observational study / Prognostic study / Randomized controlled trials / Risk factors Topics: Long Covid / Vaccines / Variants Language: English Journal: Lancet Healthy Longev Year: 2022 Document Type: Article Affiliation country: S2666-7568(22)00118-0

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Etiology study / Observational study / Prognostic study / Randomized controlled trials / Risk factors Topics: Long Covid / Vaccines / Variants Language: English Journal: Lancet Healthy Longev Year: 2022 Document Type: Article Affiliation country: S2666-7568(22)00118-0