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.


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Barnes, E., Goodyear, C., Willicombe, M., Gaskell, C., Siebert, S., de Silva, T., Murray, S., Rea, D., Snowden, J., Carroll, M., Pirrie, S., Bowden, S., Dunachie, S., Richter, A., Lim, Z., Satsangi, J., Cook, G., Pope, A., Hughes, A., Harrison, M., Lim, S., Miller, P., Klenerman, P., Richter, A., Mentzer, A., Deeks, A., Jamsen, A., Brown, A., Conlon, C., Dold, C., Duncan, C., Skelly, D., Kronsteiner, B., Abraham, P., Phillips, E., Jeffery, K., Turtle, L., Frending, L., Stafford, L., Ali, M., Rongkard, P., Payne, R., Adele, S., Travis, S., Gardiner, S., Dobson, S., Malone, T., Bibi, S., Carroll, M., Faustini, S., Foulkes, S., Frater, J., Hall, V., Hopkins, S., Islam, J., Lambe, T., Longet, S., Moore, S., Otter, A., Rowland-Jones, S., Thaventhir, J., Wootton, D., Basu, N., Gilmour, A., Irwin, S., Meacham, G., Marjot, T., Dimitriadis, S., Kelleher, P., Prendecki, M., Clarke, C., Mortimer, P., McIntyre, S., Selby, R., Meardon, N., Nguyen, D., Tipton, T., Longet, S., Laidlaw, S., Orchard, K., Ireland, G., Brown, K., Amirthalingam, G., Thomas, D., Kearns, P., Kirkham, A., McInnes, I., Beesley, R., Churchill, V., Loughton, H., Insch, E., MacDonald, E., Middleton, G., Billingham, L., Lowe, F., Magwaro, S., Al-Taei, S., Arnott, M., Bennett, L., Brock, J., Keillor, V., Melville, A., Melville, L., Miller, S., Najm, A., Paterson, C., Rodgers, L., Rutherford, M., Rundell, S., Smith, E., Stewart, L., Sunzini, F., Tong, A., Woolcock, K., Basheer, F., Crawley, C., Malladi, R., King, A., Lockey, S., Uttenthal, B., Koh, M., Hansford, S., Sandhar, G., Kesavan, M., Moore, C., Manousou, P., Hahn, G., Mullish, B., Atta, M., Gleeson, S., Lightstone, L., Martin, P., McAdoo, S., Thomson, T., Avenoso, D., Sanderson, R., Taylor, C., Bhandal, K., Hull, D., Trivedi, P., Filer, A., Hurst, E., Publicover, A., Scouse, K., Chalk, J., Hanke, D., Hanke, J., Healy, S., Provine, N., Thomas, S., Walker, V., Win, Z., Trown, D., Faria, P., Chackathayil, J., Hutchison, C. & Richardson, D. 2023, 'SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease', Nature Medicine. https://doi.org/10.1038/s41591-023-02414-4

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Last updated: 23 November 2023
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