Search

The high morbimortality due to SARS-CoV-2 infection in oncohematological diseases (OHD) and hematopoietic stem cell transplant (HSCT) recipients in the pre-vaccine era has made vaccination a priority in this group. After HSCT, the immune responses against common vaccines such as tetanus, varicella, rubella, and polio may be lost. However, the loss of immunity developed by COVID-19 vaccination after HSCT has not been completely defined. In this study, both humoral and cellular immunity against SARS-CoV-2 were analyzed in 29 individuals with OHD who were vaccinated before receiving allogeneic (n = 11) or autologous (n = 18) HSCT. All participants had low but protective levels of neutralizing IgGs against SARS-CoV-2 after HSCT despite B-cell lymphopenia and immaturity. Although antibody-dependent cellular cytotoxicity was impaired, direct cellular cytotoxicity was similar to healthy donors in participants with autologous-HSCT, in contrast to individuals with allogeneic–HSCT, which severely deteriorated. No significant changes were observed in the immune response before and after HSCT. During follow-up, all reported post-HSCT SARS-CoV-2 infections were mild. This data emphasizes that COVID-19 vaccination is effective, necessary, and safe for individuals with OHD and also supports the persistence of some degree of immune protection after HSCT, at least in the short term, when patients cannot yet be revaccinated. This work was supported by projects PI21/00877 and PI22CIII/00059, funded by the Strategic Action in Health of the Instituto de Salud Carlos III (SICIII) and co-funded by European Regional Development Fund (ERDF), “A way to make Europe”; the Coordinated Research Activities at the National Center of Microbiology (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); a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain); and the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Montserrat Torres and Guiomar Casado are financed by CIBERINFEC, co-financed by ERDF, “A way to make Europe”. The work of Clara Sánchez-Menéndez is financed by Programa Investigo, FIBio HRC-IRYCIS, co-financed by ERDF, “A way to make Europe”. Sí

The main objective of this study was to determine the influence of the cytotoxic activity of peripheral blood mononuclear cells (PBMCs) on the outcome of unvaccinated individuals with critical COVID-19 admitted to the ICU. Blood samples from 23 individuals were collected upon admission and then every 2 weeks for 13 weeks until death (Exitus group) (n = 13) or discharge (Survival group) (n = 10). We did not find significant differences between groups in sociodemographic, clinical, or biochemical data that may influence the fatal outcome. However, direct cellular cytotoxicity of PBMCs from individuals of the Exitus group against pseudotyped SARS-CoV-2-infected Vero E6 cells was significantly reduced upon admission (−2.69-fold; p = 0.0234) and after 4 weeks at the ICU (−5.58-fold; p = 0.0290), in comparison with individuals who survived, and it did not improve during hospitalization. In vitro treatment with IL-15 of these cells did not restore an effective cytotoxicity at any time point until the fatal outcome, and an increased expression of immune exhaustion markers was observed in NKT, CD4+, and CD8+ T cells. However, IL-15 treatment of PBMCs from individuals of the Survival group significantly increased cytotoxicity at Week 4 (6.18-fold; p = 0.0303). Consequently, immunomodulatory treatments that may overcome immune exhaustion and induce sustained, efficient cytotoxic activity could be essential for survival during hospitalization due to critical COVID-19. This work was supported by the Coordinated Research Activities at the National Center of Microbiology (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); a generous donation provided by Chiesi España, S.A.U. (Barcelona, Spain); the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Guiomar Casado is financed by CIBERINFEC, co-financed by the European Regional Development Fund (FEDER) “A way to make Europe”. The work of Montserrat Torres is supported by Instituto de Salud Carlos III (COV20_00679). The work of Fernando Ramos Martín is financed by the Spanish Ministry of Science and Innovation (PID2019-110275RB-I00). The work of Mario Manzanares is supported by a pre-doctoral grant from Instituto de Salud Carlos III (ISCIII-PFIS FI20CIII/00021). The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). The work of Sara Rodríguez-Mora is financed by NIH grant R01AI143567. No

Factor de impacto: 5,858 Q1 The latent viral reservoir formed by HIV-1, mainly in CD4+ T cells, is responsible for the failure of antiretroviral therapy (ART) to achieve a complete elimination of the virus in infected individuals. We previously determined that CD4+ T cells from individuals with chronic myeloid leukemia (CML) on treatment with dasatinib are resistant to HIV-1 infection ex vivo. The main mechanism for this antiviral effect is the preservation of SAMHD1 activity. In this study, we aimed to evaluate the impact of dasatinib on the viral reservoir of HIV-infected individuals with CML who were on simultaneous treatment with ART and dasatinib. Due to the low estimated incidence of HIV-1 infection and CML (1:65,000), three male individuals were recruited in Spain and Germany. These individuals had been on treatment with standard ART and dasatinib for median 1.3 years (IQR 1.3-5.3 years). Reservoir size and composition in PBMCs from these individuals was analyzed in comparison with HIV-infected individuals on triple ART regimen and undetectable viremia. The frequency of latently infected cells was reduced more than 5-fold in these individuals. The reactivation of proviruses from these cells was reduced more than 4-fold and, upon activation, SAMHD1 phosphorylation was reduced 40-fold. Plasma levels of the homeostatic cytokine IL-7 and CD4 effector subpopulations TEM and TEMRA in peripheral blood were also reduced. Therefore, treatment of HIV-infected individuals with dasatinib as adjuvant of ART could disturb the reservoir reactivation and reseeding, which might have a beneficial impact to reduce its size. This work was supported by NIH grant R01AI143567; the Spanish Ministry of Science and Innovation (PID2019-110275RB- 23I00); the Spanish AIDS Research Network RD16CIII/0002/0001 that is included in Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2016-2020, Instituto de Salud Carlos III, European Region Development Fund (ERDF). The work of María Rosa López-Huertas and Sara Rodríguez-Mora is financed by NIH grant R01AI143567. The work of Lorena Vigón is supported by a pre-doctoral grant from Instituto de Salud Carlos III (FIS PI16CIII/00034-ISCIII-FEDER). Jose M. Miró received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) (Barcelona, Spain) during 2017–2021. Sí

Introduction Chemohyperthermia (CHT) with mitomycin C (MMC) is together with Bacillus Calmette-Guerin (BCG), and passive MMC, a treatment option for patients with non muscle-invasive bladder cancer. There are no data published about the impact of CHT in quality of life (QoL). We evaluated QoL and adverse events (AE) in this 3-arm observational study. Patients and Methods Prospective observational study from September 2016 to March 2017, we recruited consecutive patients that received adjuvant treatment after transurethral resection of bladder tumor. Patients received induction courses of either BCG, CHT, or passive MMC. Patients filled the questionnaires Functional assessment of cancer therapy for bladder cancer patients (FACT-Bl) and International prostate symptom score (IPSS) before, during, and after the induction course. A urologist documented AE using Common Terminology Criteria for AE (CTCAE criteria). Results A total of 56 patients, receiving a total of 296 bladder instillations (BCG n = 27, CHT n = 14 and MMC n = 15). FACT-Bl showed statistically significant differences in the fourth week in favor of CHT versus BCG, IPSS did not show statistically significant differences before, during, and after induction course in all 3 arms. All patients recovered their baseline QoL at the end of the induction treatment. Overall 55.5%, 50% and 20% of patients presented any grade of AE in the BCG, CHT and MMC groups respectively. About 7% of patients in BCG and CHT arms had to discontinue treatment due to AE. BCG and CHT showed a similar rate of AE but in CHT were mostly grade I and BCG had grade I, II, and IV. Passive MMC had the safest profile. Conclusion There are no clinically significant differences between BCG, CHT, and passive MMC regarding QoL and lower urinary tract symptoms during the induction course. CHT has a more favorable AE profile when compared with BCG.

Background : Oncohematological patients may have a lower immune response against SARS-CoV-2, both to natural infection and to vaccines. Most studies have focused on the analysis of the humoral response, which means that the information available on the cellular response against SARS-CoV-2 in these patients is limited. Current recommendations include vaccination against SARS-CoV-2 in patients undergoing autologous hematopoietic stem cell transplantation (AHSTC), regardless of whether they have been previously exposed to the virus. These recommendations are based on previous studies with other vaccines. Therefore, it is necessary to analyze the immune response that is developed in these patients in order to make specific recommendations for COVID-19 vaccination. Objective : To study the humoral and cellular immune response before and after AHSTC in patients with oncohematological neoplasms who were exposed to SARS-CoV-2 before the transplantation. Materials & methods : Nine patients with previous exposure to SARS-CoV-2 who underwent AHSTC (Table 1) and 8 healthy donors who recovered from mild COVID-19 were recruited from Hospital Ramón y Cajal and Primary Healthcare Center Pedro Laín Entralgo (Madrid, Spain), respectively. Specific direct cellular cytotoxicity (DCC) of PBMCs from these patients against Vero E6 cells infected with pseudotyped SARS-CoV-2 was determined. The activation of caspase-3 in Vero cells was measured after 1 hour of co-culture with PBMCs, in which cytotoxic cell populations were analyzed by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was analyzed by quantifying the binding of Annexin V to rituximab-coated Raji cells as targets of PBMCs. Results : 1) 66% of AHSTC patients did not develop detectable levels of IgGs against SARS-CoV-2 (Fig. 1). In 33% of these patients with detectable IgG, the titers decreased after AHSTC, as well as their neutralizing capacity (Fig. 1B and C). 2) AHSTC patients showed increased levels of immature B cells (9.5-fold; p=0.0586) and plasmablasts (28.8-fold), in comparison with healthy donors who had mild COVID-19, while naive and resting memory B cells decreased 1.7- and 6.9-fold, respectively. 3) Specific DCC against SARS-CoV-2-infected cells increased 1.5-fold in comparison with healthy donors (Fig. 2A). Cytotoxic populations with NK phenotypes (CD3-CD56+CD16+), NKT (CD3+CD56+CD16+), and CD8+ T cells (CD3+CD8+TCRγδ+) increased 1.9- (p=0.0311), 1.9- (p=0.0592), and 1.6-fold, respectively (Fig. 2B). ADCC increased 2.1-fold in PBMCs from AHSTC patients in comparison with healthy donors (p = 0.0592). Conclusions : Our data show for the first time how the humoral and cellular immune response against the natural infection by SARS-Cov-2 may be modified in patients who were subsequently subjected to AHSTC. Although the humoral response may be reduced after AHSTC, the specific cellular response showed an increased cytotoxic activity. These results could be extrapolated to patients who were vaccinated against COVID-19 prior to AHSTC. Therefore, this information could be useful to define the recommendations for COVID-19 vaccination after AHSTC. Figure 1 Figure 1. Disclosures Garcia-Gutiérrez: Pfizer: Research Funding; Incyte: Consultancy; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy.

Background: Oncohematological patients present a variable immune response against many vaccines, due to the immunodeficiency caused by the disease and its treatment. The experience of vaccination against COVID-19 in oncohematological patients is low and mostly limited to studies of humoral immunity. However, the humoral and cellular immune responses between different oncohematological diseases (OHD) have not been compared. Objective: To compare the humoral and cellular immune responses in four groups of patients with OHD after receiving the first dose of one COVID-19 vaccine. Materials & methods: We recruited 53 patients in four groups according to diagnosis: Chronic Lymphatic Leukemia (CLL) (n=14), Chronic Myeloid Leukemia (CML) (n=11), Multiple Myeloma (MM) (n=15), and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) (n=13) (Table 1). Samples were collected prior to vaccination and 3 weeks after receiving one dose of COMIRNATY (BioNTech-Pzifer), mRNA-1273 (Moderna), or AZD1222 (AstraZeneca). Twenty-six healthy donors with similar vaccination pattern were recruited. IgG titers against SARS-CoV-2 were quantified by Euroimmun-Anti-SARS-CoV-2 ELISA. Direct cellular cytotoxicity (DCC) was determined against Vero E6 cells infected with pseudotyped SARS-CoV-2, measuring caspase-3 activation after co-culture with PBMCs, in which cytotoxic populations were phenotyped by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) analyses were performed using Annexin V on Raji cells as a target. Results: 1) Early humoral response against COVID-19 vaccination in patients with CML was 5.1- (p Conclusions: We found significant differences in the early humoral immune response after one single dose of COVID-19 vaccine depending on the OHD analyzed. It was observed for the first time that the early cytotoxic immune response is efficient in all groups of patients, although superior in those who were not exposed to ASCT. Most cytotoxic activity relied on CD8+ T cells. These data can be useful to determine the efficacy of COVID-19 vaccines in patients with OHD. Figure 1 Figure 1. Disclosures Garcia Gutierrez: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.