Caracterización de la respuesta inmune humoral y celular desarrollada tras la vacunación para covid-19 en pacientes con neoplasias hematológicas

Los pacientes oncohematológicos han sido una población especialmente susceptible a la COVID-19 desde el inicio de la pandemia. Esto ha motivado un interés especial en asegurar en ellos una pronta vacunación frente a la COVID-19, si bien se desconocía la eficacia que se podría obtener en individuos severamente inmunodeprimidos y que habían sido excluidos de los ensayos clínicos de las vacunas. El propósito de esta tesis, presentada por compendio de 4 artículos, es describir la respuesta inmune humoral y celular de 211 individuos con neoplasias oncohematológicas, divididos en cohortes bien definidas por tipo de enfermedad y tratamiento. Para ello realizamos un seguimiento durante 16 meses estudiando, en distintos momentos de la vacunación, títulos de anticuerpos, capacidad de neutralización, subpoblaciones citotóxicas y de linfocitos B, estudios de inmunidad celular directa sobre células epiteliales infectadas con SARS-CoV-2 e inmunidad celular dependiente de anticuerpos. El objetivo es proporcionar una visión lo más cercana posible a la respuesta inmune real de estos individuos a lo largo del proceso de vacunación. Nuestros resultados muestran que pacientes oncohematológicos que se someten a un trasplante de médula ósea tras recibir su pauta de vacunación convencional frente a la COVID-19, o haberse infectado de forma natural, van a presentar de forma basal (previa al trasplante) una respuesta tanto humoral como celular inferior a individuos inmunocompetentes. Si bien esta respuesta puede proporcionar cierta protección en el período post-trasplante hasta poder reiniciar la revacunación, la tendencia es que disminuya progresivamente en el tiempo. Por otro lado, los pacientes con Leucemia Mieloide Crónica que inician su pauta vacunal van a presentar una excelente respuesta humoral y celular tras la primera dosis, al contrario que lo que sucede pacientes con Leucemia Linfocítica Crónica, que presentarán muy baja tasa de seroconversió

Strong Cellular Immune Response, but Not Humoral, against SARS-CoV-2 in Oncohematological Patients with Autologous Stem Cell Transplantation after Natural Infection

Oncohematological patients show a low immune response against SARS-CoV-2, both to natural infection and after vaccination. Most studies are focused on the analysis of the humoral response; therefore, the information available about the cellular immune response is limited. In this study, we analyzed the humoral and cellular immune responses in nine individuals who received chemotherapy for their oncohematological diseases, as well as consolidation with autologous stem cell transplantation (ASCT), after being naturally infected with SARS-CoV-2. All individuals had asymptomatic or mild COVID-19 and were not vaccinated against SARS-CoV-2. These results were compared with matched healthy individuals who also had mild COVID-19. The humoral response against SARS-CoV-2 was not detected in 6 of 9 oncohematological individuals prior to ASCT. The levels of antibodies and their neutralization capacity decreased after ASCT. Conversely, an enhanced cytotoxic activity against SARS-CoV-2-infected cells was observed after chemotherapy plus ASCT, mostly based on high levels of NK, NKT, and CD8+TCRγδ+ cell populations that were able to produce IFNγ and TNFα. These results highlight the importance of performing analyses not only to evaluate the levels of IgGs against SARS-CoV-2, but also to determine the quality of the cellular immune response developed during the immune reconstitution after ASCT.This work was supported by the Coordinated Research Activities at the Centro Nacional de Microbiología (CNM, Instituto de Salud Carlos III) (COV20_00679) to promote an integrated response against SARS-CoV-2 in Spain (Spanish Ministry of Science and Innovation) that is coordinated by Dr Inmaculada Casas (WHO National Influenza Center of the CNM), the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00), and AES 2021 grant from Instituto de Salud Carlos III (PI21/00877). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Montserrat Torres is supported by Instituto de Salud Carlos III (COV20_00679). The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER).S

SARS-CoV-2 vaccine response and rate of breakthrough infection in patients with hematological disorders

Background: The clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has not yet been established. Patients and methods: A prospective multicenter registry-based cohort study conducted from December 2020 to December 2021 by the Spanish transplant and cell therapy group was used to analyze the relationship of antibody response at 3-6 weeks after full vaccination (2 doses) with breakthrough SARS-CoV-2 infection in 1394 patients with hematological disorders. Results: At a median follow-up of 165 days after complete immunization, 37 out of 1394 (2.6%) developed breakthrough SARS-CoV-2 infection at median of 77 days (range 7-195) after full vaccination. The incidence rate was 6.39 per 100 persons-year. Most patients were asymptomatic (19/37, 51.4%), whereas only 19% developed pneumonia. The mortality rate was 8%. Lack of detectable antibodies at 3-6 weeks after full vaccination was the only variable associated with breakthrough infection in multivariate logistic regression analysis (Odds Ratio 2.35, 95% confidence interval 1.2-4.6, p = 0.012). Median antibody titers were lower in cases than in non-cases [1.83 binding antibody units (BAU)/mL (range 0-4854.93) vs 730.81 BAU/mL (range 0-56,800), respectively (p = 0.007)]. We identified 250 BAU/mL as a cutoff above which incidence and severity of the infection were significantly lower. Conclusions: Our study highlights the benefit of developing an antibody response in these highly immunosuppressed patients. Level of antibody titers at 3 to 6 weeks after 2-dose vaccination links with protection against both breakthrough infection and severe disease for non-Omicron SARS-CoV-2 variants