SARS-CoV-2-reactive antibody waning, booster effect and breakthrough SARS-CoV-2 infection in hematopoietic stem cell transplant and cell therapy recipients at one year after vaccination.

The kinetics of SARS-CoV-2 reactive IgG antibodies after full vaccination and booster in allogeneic and autologous stem cell transplantation (allo-HSCT, ASCT) and chimeric antigen receptor T-cell therapy (CAR-T) are of utmost importance for estimating risk of infection. A prospective multicenter registry-based cohort study, conducted from December 2020 to July 2022 was used to analyze antibody waning over time, booster effect and the relationship of antibody response and breakthrough infection in 572 recipients (429 allo-HSCT, 121 ASCT and 22 CAR-T cell therapy). A significant decline in antibody titers was observed at 3 and 6 months after full vaccination in recipients without pre-vaccine SARS-CoV-2 infection, whereas recipients infected prior to vaccination showed higher and stable antibody titers over time. In poor responders, a booster dose was able to increase antibody titers in 83% of allo-HSCT and 58% of ASCT recipients but not in CART-T cell recipients [0%] (p < 0.01). One-year cumulative incidence of breakthrough infection was 15%, similar among cell therapy procedures. Immunosuppressive drugs at the time of vaccination [hazard ratio (HR) 1.81, p = 0.0028] and reduced intensity conditioning (HR 0.49, p = 0.011) were identified as the only conditions associated with different risk of breakthrough infection in allo-HSCT recipients. Antibody titers were associated with breakthrough infection and disease severity. No death was observed among the 72 breakthrough infections. Antibody level decay after the first two vaccine doses was common except in recipients with pre-vaccination SARS-CoV-2 infection. Poorly responding allo-HSCT recipients showed a response advantage with the booster as compared to ASCT and, especially, the null response found in CAR-T cell recipients. Antibody titers were positively correlated with the risk of breakthrough SARS-CoV-2 infection which was mainly driven by the immunosuppression status.

One-year breakthrough SARS-CoV-2 infection and correlates of protection in fully vaccinated hematological patients.

The long-term clinical efficacy of SARS-CoV-2 vaccines according to antibody response in immunosuppressed patients such as hematological patients has been little explored. A prospective multicenter registry-based cohort study conducted from December 2020 to July 2022 by the Spanish Transplant and Cell Therapy group, was used to analyze the relationship of antibody response over time after full vaccination (at 3-6 weeks, 3, 6 and 12 months) (2 doses) and of booster doses with breakthrough SARS-CoV-2 infection in 1551 patients with hematological disorders. At a median follow-up of 388 days after complete immunization, 266 out of 1551 (17%) developed breakthrough SARS-CoV-2 infection at median of 86 days (range 7-391) after full vaccination. The cumulative incidence was 18% [95% confidence interval (C.I.), 16-20%]. Multivariate analysis identified higher incidence in chronic lymphocytic leukemia patients (29%) and with the use of corticosteroids (24.5%), whereas female sex (15.5%) and more than 1 year after last therapy (14%) were associated with a lower incidence (p < 0.05 for all comparisons). Median antibody titers at different time points were significantly lower in breakthrough cases than in non-cases. A serological titer cut-off of 250 BAU/mL was predictive of breakthrough infection and its severity. SARS-CoV-2 infection-related mortality was encouragingly low (1.9%) in our series. Our study describes the incidence of and risk factors for COVID-19 breakthrough infections during the initial vaccination and booster doses in the 2021 to mid-2022 period. The level of antibody titers at any time after 2-dose vaccination is strongly linked with protection against both breakthrough infection and severe disease, even with the Omicron SARS-CoV-2 variant.

Applicability of probabilistic graphical models for early detection of SARS-CoV-2 reactive antibodies after SARS-CoV-2 vaccination in hematological patients.

Prior studies of antibody response after full SARS-CoV-2 vaccination in hematological patients have confirmed lower antibody levels compared to the general population. Serological response in hematological patients varies widely according to the disease type and its status, and the treatment given and its timing with respect to vaccination. Through probabilistic machine learning graphical models, we estimated the conditional probabilities of having detectable anti-SARS-CoV-2 antibodies at 3-6 weeks after SARS-CoV-2 vaccination in a large cohort of patients with several hematological diseases (n= 1166). Most patients received mRNA-based vaccines (97%), mainly Moderna® mRNA-1273 (74%) followed by Pfizer-BioNTech® BNT162b2 (23%). The overall antibody detection rate at 3 to 6 weeks after full vaccination for the entire cohort was 79%. Variables such as type of disease, timing of anti-CD20 monoclonal antibody therapy, age, corticosteroids therapy, vaccine type, disease status, or prior infection with SARS-CoV-2 are among the most relevant conditions influencing SARS-CoV-2-IgG-reactive antibody detection. A lower probability of having detectable antibodies was observed in patients with B-cell non-Hodgkin's lymphoma treated with anti-CD20 monoclonal antibodies within 6 months before vaccination (29.32%), whereas the highest probability was observed in younger patients with chronic myeloproliferative neoplasms (99.53%). The Moderna® mRNA-1273 compound provided higher probabilities of antibody detection in all scenarios. This study depicts conditional probabilities of having detectable antibodies in the whole cohort and in specific scenarios such as B cell NHL, CLL, MM, and cMPN that may impact humoral responses. These results could be useful to focus on additional preventive and/or monitoring interventions in these highly immunosuppressed hematological patients.

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.

SARS-CoV-2-reactive antibody detection after SARS-CoV-2 vaccination in hematopoietic stem cell transplant recipients: Prospective survey from the Spanish Hematopoietic Stem Cell Transplantation and Cell Therapy Group.

This is a multicenter prospective observational study that included a large cohort (n = 397) of allogeneic (allo-HSCT; (n = 311) and autologous (ASCT) hematopoietic stem cell transplant (n = 86) recipients who were monitored for antibody detection within 3-6 weeks after complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from February 1, 2021, to July 20, 2021. Most patients (n = 387, 97.4%) received mRNA-based vaccines. Most of the recipients (93%) were vaccinated more than 1 year after transplant. Detectable SARS-CoV-2-reactive antibodies were observed in 242 (78%) of allo-HSCT and in 73 (85%) of ASCT recipients. Multivariate analysis in allo-HSCT recipients identified lymphopenia < 1 × 109 /ml (odds ratio [OR] 0.33, 95% confidence interval [95% CI] 0.16-0.69, p = .003), active graft versus host disease (GvHD; OR 0.51, 95% CI 0.27-0.98, p = .04) and vaccination within the first year of transplant (OR 0.3, 95% CI 0.15-0.9, p = .04) associated with lower antibody detection whereas. In ASCT, non-Hodgkin's lymphoma (NHL; OR 0.09, 95% CI 0.02-0.44, p = .003) and active corticosteroid therapy (OR 0.2, 95% CI 0.02-0.87, p = .03) were associated with lower detection rate. We report an encouraging rate of SARS-CoV-2-reactive antibodies detection in these severe immunocompromised patients. Lymphopenia, GvHD, the timing of vaccine, and NHL and corticosteroids therapy should be considered in allo-HSCT and ASCT, respectively, to identify candidates for SARS-CoV-2 antibodies monitoring.

The direct and indirect effects of COVID-19 pandemic in a real-life hematological setting.

BACKGROUND: Clinical outcomes of novel coronavirus 2019 disease (COVID-19) in onco-hematological patients are unknown. When compared to non-immunocompromised patients, onco-hematological patients seem to have higher mortality rates. AIMS: We describe the characteristics and outcomes of a consecutive cohort of 24 onco-hematological patients with COVID-19 during the first month of the pandemic. We also describe variations in healthcare resource utilization within our hematology department. METHODS AND RESULTS: Data from patients between the first month of the pandemic were retrospectively collected. Clinical and logistic data were also collected and compared with the average values from the prior 3 months of activity. Prevalence of COVID-19 in our hematological population was 0.4%. Baseline characteristics were as follows: male sex: 83%, lymphoid diseases: 46%, median age: 69 (22-82) years. Median follow-up in survivors was 14 (9-28) days and inpatient mortality rate was 46%. Average time to moderate/severe respiratory insufficiency and death were 3 (1-10) and 10 (3-18) days, respectively. Only 1 out of every 12 patients who developed moderate to severe respiratory insufficiency recovered. Upon univariate analysis, the following factors were associated with higher mortality: age ≥ 70 years (P = .01) and D-dimer ≥900 mcg/L (P = .04). With respect to indirect effects during the COVID-19 pandemic, and when compared with the prior 3 months of activity, inpatient mortality (excluding patients with COVID-19 included in the study) increased by 56%. This was associated with a more frequent use of vasoactive drugs (+300%) and advanced respiratory support (+133%) in the hematology ward. In the outpatient setting, there was a reduction in initial visits (-55%) and chemotherapy sessions (-19%). A significant increase in phone visits was reported (+581%). CONCLUSION: COVID-19 pandemic is associated with elevated mortality in hematological patients. Negative indirect effects are also evident within this setting.

Use of Telehealth for Domiciliary Follow-up After Hematopoietic Cell Transplantation During the COVID-19 Pandemic: Prospective Pilot Study.

BACKGROUND: Patients who have recently received a hematopoietic cell transplant (HCT) are at higher risk of acute complications in the first weeks after discharge, especially during the COVID-19 pandemic. OBJECTIVE: The aim of this study was to test the use of a telehealth platform for the follow-up of HCT patients during the first two weeks after discharge. METHODS: In total, 21 patients who received autologous or allogeneic HCT for hematological malignancies were screened from April 30, 2020, to July 15, 2020. The telehealth platform assisted in the daily collection of vital signs as well as physical and psychological symptoms for two weeks after hospital discharge. The required medical devices (oximeter and blood pressure monitor) were given to patients and a dedicated smartphone app was developed to collect this data. The data were reviewed daily through web-based software by a hematologist specializing in HCT. RESULTS: Only 12 of 21 patients were able to join and complete the study. Technological barriers were the most frequent limiting factor in this study. Among the 12 patients who completed the study, adherence to data reporting was high. The patients' experience of using such a system was considered good. In two cases, the system enabled the early recognition of acute complications. CONCLUSIONS: This pilot study showed that telehealth systems can be applied in the early posttransplant setting, with evident advantages for physicians and patients for both medical and psychological aspects. Technological issues still represent a challenge for the applicability of such a system, especially for older adult patients. Easier-to-use technologies could help to expand the use of telehealth systems in this setting in the future.

Factores de riesgo de morbimortalidad en pacientes hospitalizados por insuficiencia cardíaca aguda / Risk factors of morbimortality in patients hospitalised with acute heart failure

La insuficiencia cardíaca (IC) es el conjunto de signos y síntomas generados tras una falla de bomba cardíaca que origina incapacidad del corazón para proveer requerimientos metabólicos suficientes. Objetivo: Identificar los factores de riesgo de morbimortalidad en pacientes hospitalizados por IC aguda. Método: se obtuvieron datos de 60 historias que cumplían con criterios de inclusión, del periodo 2002-2012. Resultados: 60% de la población correspondía al género masculino con edad promedio de 64 años (DE +14 años). La presencia de enfermedades subyacentes se registró en 96,7% siendo la hipertensión arterial la más frecuente. La principal causa de descompensación fueron procesos infecciosos (33,3%). Las alteraciones electrocardiográficas más frecuentes fueron arritmias (33,4%), anormalidad auricular izquierda (50%) e hipertrofia ventricular izquierda (32,1%), mientras que en el ecocardiograma se evidenció fracción de eyección <45% en 73,7% de los casos y disfunción sistólica del ventrículo izquierdo en 47,4%. El tratamiento farmacológico más utilizado al ingreso se correspondió con diuréticos de asa (88%), seguido de fármacos moduladores del Sistema Renina Angiotensina Aldosterona (SRAA) con 76,7%, invirtiéndose esta proporción al egreso (moduladores del SRAA 90% y diuréticos de asa 85%). Conclusiones: predominó el género masculino con edades menores a la reportada en la literatura. La hipertensión arterial fue la patología subyacente más frecuente. Los hallazgos electrocardiográficos y ecocardiográficos concuerdan con los de estudios previos. El tratamiento de elección en nuestro centro es el recomendado en las guías de actuación(AU)

Heart failure (HF) is defined as the set of symptoms and signs secundary to cardiac pump failure, which causes inability to provide the tissues's metabolics requirements. Objective: To identify the risk factors of morbimortality in patients hospitalized with acute HF. Methods: Data from 60 medical charts were obtained, between 2002-2012. Results: 60% of the patients were males with an average age of 64 years (SD + 14 years). Underlaying diseases were recorded in 96.7% of population being the most common, hypertension. The main cause of decompensation was secondary to infectious processes (33.3%). The most frequent electrocardiographic abnormalities were arrhythmias (33.4%), left atrial abnormality (50%) and left ventricular hypertrophy (32.1%), while in the echocardiogram, ejection fraction <45% was evident in 73.7% of cases and left ventricular systolic dysfunction in 47.4%. Loop diuretics were the most widely used drug treatment at admission (88%), followed by Renin Angiotensin Aldosterone System (RAAS) modulating drugs (76.7%), reversing this ratio at discharge (RAAS modulating drugs 90% and loop diurectics 85%). Conclusions: Patients with HF are predominantly male, with younger ages than those reported in the literature. Cardiovascular diseases are the most frequent underlying pathologies. The electrocardiographic and echocardiographic findings are consistent with previous studies. The treatment of choice in our center is the recommended by the practice guidelines(AU)