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Introduction: Hemophilia A is an inherited bleeding disorder caused by pathogenic variants in the factor VIII gene (F8), which leads to factor VIII (FVIII) deficiency. Immune tolerance induction (ITI) is a therapeutic approach to eradicate alloantibodies (inhibitors) against exogenous FVIII in people with inherited hemophilia A. Few studies have evaluated the role of F8 variants on ITI outcome., Material and Methods: We included people with severe hemophilia A (FVIII ˂ 1 international units/dL) and high-responding inhibitors (≥ 5 Bethesda units/mL lifelong) who underwent a first course of ITI. Socio-demographic, clinical and laboratory data were collected. ITI outcomes were defined as total, partial successes, and failure. Detection of intron 1 and 22 inversions was performed by polymerase-chain reaction, followed by F8 sequencing., Results: We included 168 people with inherited hemophilia A and high-responding inhibitors, median age 6 years at ITI start. Intron 22 inversion was the most prevalent variant (53.6 %), followed by nonsense (16.1 %), small insertion/deletion (11.3 %), and large deletion (10.7 %). In comparison with intron 22 inversion, the odds of ITI failure were 15.5 times higher (odds ratio [OR] 15.50; 95 % confidence interval [95 % CI] 4.59-71.30) and 4.25 times higher (95 % CI, 1.53-12.3) among carriers of F8 large deletions and small insertions and deletions, respectively., Conclusion: F8 large deletions and small insertions/deletions predicted ITI failure after a first course of ITI in patients with severe hemophilia A and high-responding inhibitors. This is the first study to show F8 large deletions and small insertions/deletions as predictors of ITI failure., Competing Interests: Declaration of competing interest RMC received speaker fees from Bayer, NovoNordisk, Hoffman-La Roche, and Takeda, consultancy fees from Hoffman-La Roche and Takeda, and sponsorship to attend scientific event grants from Bayer, NovoNordisk, Hoffman-La Roche, and Takeda. AGO received speaker fees and scientific event grants from NovoNordisk and Takeda. MRFR received speaker fees from NovoNordisk, scientific event grants from Hoffman-La Roche, Takeda and NovoNordisk, and consultancy fees from the Brazilian Ministry of Health. FMRAC received sponsorship to attend scientific event grants from Hoffman-La Roche and NovoNordisk. LYE received scientific event grants from Hoffman-La Roche. MAFC received sponsorship to attend scientific event grants from Hoffman-La Roche and NovoNordisk. ISSP received speaker fees from Hoffman-La Roche, NovoNordisk and Takeda, sponsorship to attend scientific event grants from Hoffman-La Roche, Takeda and NovoNordisk, consultancy fees from the Hoffman-La Roche, NovoNordisk, Bayer and Biomarin, and grants for scientific publication from Takeda. AAG received speaker fees from Takeda and NovoNordisk, sponsorship to attend scientific event grants from Takeda and NovoNordisk, and consultancy fees from NovoNordisk. THA received sponsorship to attend scientific event grants from Hoffman-La Roche and Takeda. DCFN received sponsorship to attend scientific event grants from Takeda. LWZ, RPS, MMD, MAPS, LLJ, RAR, MHC, CSL, DMT, VKBF, RPT, DGC, JVDB and SMR declare they have no competing interests which might be perceived as posing as a conflict., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: As the Coronavirus Disease 2019 (COVID-19) pandemic unfolds around the world; answers related to the antibody response against the virus are necessary to develop treatment and prophylactic strategies. We attempted to understand part of the immune response of convalescent plasma donation candidates., Method: We carried out a cross-sectional, observational, non-intervention study, testing 102 convalescent plasma donation candidates for antibodies against the virus, relating these data to the time interval between symptom onset and sample collection, age, disease severity, and gender., Results: In our sample, the individuals who developed a greater antibody response were the ones who had a longer time interval between symptom onset and sample collection, the ones who had been hospitalized and the subjects above 35 years old. Moreover, 17 individuals did not present any reactive antibodies., Conclusion: These results are important in that they raise questions about the role of the humoral response against the virus, as some individuals do not develop antibodies to fight it. In addition, they help develop recruitment strategies for convalescent plasma donors, who should be asymptomatic for at least 21 days and are possibly more likely to have reactive antibodies after 35 days without symptoms., Competing Interests: None., (© 2021 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier España, S.L.U.)