SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease
Authors: Barnes Eleanor , Goodyear Carl S. , Willicombe Michelle , Gaskell Charlotte , Siebert Stefan , I de Silva Thushan , Murray Sam M. , Rea Daniel , Snowden John A. , Carroll Miles , Pirrie Sarah , Bowden Sarah J. , Dunachie Susanna J. , Richter Alex , Lim Zixiang , Satsangi Jack , Cook Gordon , Pope Ann , Hughes Ana , Harrison Molly , Lim Sean H. , Miller Paul , Klenerman Paul ,   PITCH consortium, Richter Alex G. , Mentzer Alex , Deeks Alexandra , Jamsen Anni , Brown Anthony , Conlon Chris , Dold Chris , Duncan Christopher J. A. , Skelly Donal , Kronsteiner Barbara , Abraham Priyanka , Phillips Eloise , Jeffery Katie , Turtle Lance , Frending Lisa , Stafford Lizzie , Ali Mohammad , Rongkard Patpong , Payne Rebecca , Adele Sandra , Travis Simon , Gardiner Siobhan , Dobson Sue L. , Malone Tom , Bibi Sagida , Carroll Miles , Faustini Sian , Foulkes Sarah , Frater John , Hall Victoria , Hopkins Susan , Islam Jasmin , Lambe Teresa , Longet Stephanie , Moore Shona C. , Otter Ashley , Rowland-Jones Sarah L. , Thaventhir James E. D. , Wootton Daniel G. , Basu Neil , Gilmour Ashley , Irwin Sophie , Meacham Georgina , Marjot Thomas , Dimitriadis Stavros , Kelleher Peter , Prendecki Maria , Clarke Candice , Mortimer Paige , McIntyre Stacey , Selby Rachael , Meardon Naomi , Nguyen Dung , Tipton Tom , Longet Stephanie , Laidlaw Stephen , Orchard Kim , Ireland Georgina ,   CONSENSUS, Brown Kevin , Amirthalingam Gayatri , Thomas David , Kearns Pamela , Kirkham Amanda , McInnes Iain B. ,   OCTAVE Collaborative Group, Beesley Richard , Churchill Vicky , Loughton Holly , Insch Elspeth , MacDonald Eilean , Middleton Gary , Billingham Lucinda , Lowe Faye , Magwaro Sophia , Al-Taei Saly , Arnott Maxine , Bennett Louise , Brock James , Keillor Victora , Melville Andrew , Melville Lisa , Miller Samantha , Najm Aurelie , Paterson Caron , Rodgers Lewis , Rutherford Matthew , Rundell Suzann , Smith Emily , Stewart Lynn , Sunzini Flavia , Tong Andrew , Woolcock Kieran , Basheer Faisal , Crawley Charles , Malladi Ram , King Andrew , Lockey Sophie , Uttenthal Ben , Koh Mickey B. C. , Hansford Sam , Sandhar Gurjinder , Kesavan Murali , Moore Celia , Manousou Pinelopi , Hahn Gareth , Mullish Benjamin , Atta Maria , Gleeson Sarah , Lightstone Liz , Martin Paul , McAdoo Stephen , Thomson Tina , Avenoso Daniele , Sanderson Robin , Taylor Claire , Bhandal Khushpreet , Hull Diana , Trivedi Palak , Filer Andrew , Hurst Erin , Publicover Amy , Scouse Katy , Chalk Jem , Hanke Daniel , Hanke Josef , Healy Saoirse , Provine Nicholas , Thomas Sarah , Walker Victoria , Win Zay , Trown Doreen , Faria Patricia , Chackathayil Julie , Hutchison Clare , Richardson Deborah 
Published: July 2023

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.