SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.
Barnes E., Goodyear CS., Willicombe M., Gaskell C., Siebert S., I de Silva T., Murray SM., Rea D., Snowden JA., Carroll M., Pirrie S., Bowden SJ., Dunachie SJ., Richter A., Lim Z., Satsangi J., Cook G., Pope A., Hughes A., Harrison M., Lim SH., Miller P., Klenerman P., PITCH consortium None., 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., CONSENSUS None., Thomas D., Kearns P., Kirkham A., McInnes IB., OCTAVE Collaborative Group None.
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.