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

Abstract

Oncohematologic patients have been a population especially susceptible to COVID-19 since the beginning of the pandemic. This has motivated a special interest in ensuring early vaccination against COVID-19 in them, although the efficacy that could be obtained in severely immunosuppressed individuals who had been excluded from clinical trials of vaccines was unknown. The purpose of this thesis, presented as a compendium of 4 articles, is to describe the humoral and cellular immune response of 211 individuals with oncohematological malignancies, divided into well-defined cohorts by type of disease and treatments. For this purpose, we conducted a 16-months follow-up, studying antibody titers, neutralization activity, B-lymphocyte and cytotoxic subpopulations, direct cellular immunity studies on epithelial cells infected with SARS-CoV-2 and antibody-dependent cellular immunity, at different times of vaccination. The aim is to provide a view as close as possible to a real immune response in these individuals through the vaccination process. Our results revealed that oncohematological patients who have received their conventional COVID-19 vaccination regimen or who have been naturally infected and subsequently undergo a bone marrow transplant will have a lower baseline humoral and cellular response than immunocompetent individuals. Although this response may maintain some protection during the post-transplant phase until revaccination can be restarted, the tendency is for it to progressively decrease through time. On the other hand, patients with Chronic Myeloid Leukemia starting their vaccination regimen will present an excellent humoral and cellular response after the first dose, contrary to what happens in patients with Chronic Lymphocytic Leukemia, who will present a very low seroconversion rate, due to the severe B lymphocyte dysfunction that these patients present. Surprisingly, in them a discrepancy is observed between the humoral response, clearly insufficient, with an efficient cellular response based on effective cytotoxic populations that may counteract this humoral deficit. Patients with Multiple Myeloma and those who initiate the first dose of the vaccine after receiving an allogeneic transplant present intermediate seroconversion and cellular cytotoxicity data, with a dysfunction in the reactivity of cytotoxic populations that is compensated by an increase in their number, allowing an appropriate control of viral replication in cells infected with SARS-CoV-2. Finally, we analyzed the effect of the booster dose in patients treated with rituximab, who present a low seroconversion due to the anti-CD20 effect of rituximab on the B lymphocyte line. Our results confirm that the booster improves humoral response outcomes in patients in the recovery period of B-cells aplasia, after almost 12 months without receiving rituximab. Breakthrough infection results during follow-up reflect a clear improvement in patient prognosis compared to data obtained prior to vaccines approval, with mainly mild infections and less than a 1.5% mortality rate. In conclusion, the results of vaccination against COVID-19 in oncohematological patients vary greatly depending on the type of neoplasm or treatment, but it is effective. Vaccination against COVID-19 is recommended for these patients, with a clear clinical benefit even in the absence of seroconversion, probably due to an underlying cellular response.