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SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml^-1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.

SUBMITTER: Barnes E

PROVIDER: S-EPMC10353927 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

Barnes Eleanor E Goodyear Carl S CS Willicombe Michelle M Gaskell Charlotte C Siebert Stefan S I de Silva Thushan T Murray Sam M SM Rea Daniel D Snowden John A JA Carroll Miles M Pirrie Sarah S Bowden Sarah J SJ Dunachie Susanna J SJ Richter Alex A Lim Zixiang Z Satsangi Jack J Cook Gordon G Pope Ann A Hughes Ana A Harrison Molly M Lim Sean H SH Miller Paul P Klenerman Paul P Basu Neil N Gilmour Ashley A Irwin Sophie S Meacham Georgina G Marjot Thomas T Dimitriadis Stavros S Kelleher Peter P Prendecki Maria M Clarke Candice C Mortimer Paige P McIntyre Stacey S Selby Rachael R Meardon Naomi N Nguyen Dung D Tipton Tom T Longet Stephanie S Laidlaw Stephen S Orchard Kim K Ireland Georgina G Thomas David D Kearns Pamela P Kirkham Amanda A McInnes Iain B IB

Nature medicine 20230706 7

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml<sup>-1</sup>). Vaccine failure rates were highest in ANCA-associated vasculitis on rit ...[more]

PMID: 37414897

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Project description:BackgroundIndividual doses of dual-dose vaccine-regimens are sequentially administered into the deltoid muscle, but little attention has so far been paid to the immunological effects of choosing the ipsilateral or the contralateral side for the second dose.MethodsIn an observational study, 303 previously naive individuals were recruited, who received the second dose of the COVID-19 vaccine BNT162b2 on either the ipsilateral (n = 147) or the contralateral side (n = 156). Spike-specific IgG, IgG-avidity, and neutralizing antibodies were quantified using ELISA and a surrogate assay 2 weeks after dose 2. A subgroup of 143 individuals (64 ipsilateral, 79 contralateral) was analysed for spike-specific CD4 and CD8 T-cells using flow-cytometry.FindingsMedian spike-specific IgG-levels did not differ after ipsilateral (4590 (IQR 3438) BAU/ml) or contralateral vaccination (4002 (IQR 3524) BAU/ml, p = 0.106). IgG-avidity was also similar (p = 0.056). However, neutralizing activity was significantly lower after contralateral vaccination (p = 0.024). Likewise, median spike-specific CD8 T-cell levels were significantly lower (p = 0.004). Consequently, the percentage of individuals with detectable CD8 T-cells was significantly lower after contralateral than after ipsilateral vaccination (43.0% versus 67.2%, p = 0.004). Spike specific CD4 T-cell levels were similar in both groups, but showed significantly higher CTLA-4 expression after contralateral vaccination (p = 0.011). These effects were vaccine-specific, as polyclonally stimulated T-cell levels did not differ.InterpretationBoth ipsilateral and contralateral vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming. Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells may have implications for protection from infection and severe disease and support general preference for ipsilateral vaccination.FundingFinancial support was provided in part by the State chancellery of the Saarland to M.S.

Dataset Information

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

Publications

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

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