Spanish heart transplant registry. 35th official report of the Heart Failure Association of the Spanish Society of Cardiology.

INTRODUCTION AND OBJECTIVES: Our aim was to describe the characteristics and outcomes of heart transplants in Spain. METHODS: We analyzed trends in recipient and donor characteristics, recipient-donor interaction, surgical procedures, immunosuppression, and outcomes of patients included in the Spanish heart transplant registry from 2014 to 2023. Changes in survival were analyzed using the Kaplan-Meier method. RESULTS: In 2023, 325 cardiac transplants were performed (4.5% more than in the previous year), with a total of 2987 procedures from 2014 to 2023. There was a trend toward performing more transplants in women (29.2%), with etiologies other than cardiomyopathy (32.6%), and with better pretransplant status (less hepatic [12.5%], renal [glomerular filtration rate, 81.5 mL/min/1.73 m2], and respiratory [8.7%] involvement). In 2023, the number of urgent transplants increased (44% of the total), especially those performed after circulatory support with extracorporeal membrane oxygenation (36% of total assistance), and transplants performed with donation after circulatory death (17.9%). Survival improved in the triennium from 2020 to 2022 compared with 2014 to 2016 (83.0% at 1 year from 2020-2022 vs 79.0% from 2014-2016). CONCLUSIONS: The number of transplants performed in Spain showed an upward trend, with recipients with better clinical status and an increasing use of donation after circulatory death. Survival improved in the last triennium. Full English text available from: www.revespcardiol.org/en.

Structural heart transcatheter interventions in orthotopic cardiac transplant and left ventricular assist devices recipients: A nationwide study.

BACKGROUND: The current incidence and outcomes of structural transcatheter procedures in heart transplant (HTx) recipients and left-ventricular assist devices (LVAD) carriers is unknown. AIMS: To provide insights on structural transcatheter procedures performed across HTx and LVAD patients in Spain. METHODS: Multicenter, ambispective, observational nationwide registry. RESULTS: Until May/2023, 36 percutaneous structural interventions were performed (78% for HTx and 22% for LVAD) widely varying among centers (0%-1.4% and 0%-25%, respectively). Percutaneous mitral transcatheter edge-to-edge (TEER) was the most common (n = 12, 33.3%), followed by trancatheter aortic valve replacement (n = 11, 30.5%), and tricuspid procedures (n = 9, 25%). Mitral TEER resulted in mild residual mitral regurgitation in all but one case, mean gradient was <5 mmHg in 75% of them at 1-year, with no mortality and 8.3% re-admission rate. Tricuspid TEER resulted in 100% none/mild residual regurgitation with a 1-year mortality and readmission rates of 22% and 28.5%, respectively. Finally, trancatheter aortic valve replacement procedures (n = 8 in LVADs due to aortic regurgitation and n = 3 in HTx), were successful in all cases with one prosthesis degeneration leading to severe aortic regurgitation at 1-year, 18.2% mortality rate and no re-admissions. Globally, major bleeding rates were 7.9% and 12.5%, thromboembolic events 3.7% and 12.5%, readmissions 37% and 25%, and mortality 22% and 25%, in HTx and LVADs respectively. No death was related to the implanted transcatheter device. CONCLUSIONS: Most centers with HTx/LVAD programs perform structural percutaneous procedures but with very inconsistent incidence. They were associated with good safety and efficacy, but larger studies are required to provide formal recommendations.

Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV.

BACKGROUND: The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown. METHODS: 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform. RESULTS: 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7. CONCLUSION: Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

Pilot Study on the Prevalence of Diamine Oxidase Gene Variants in Patients with Symptoms of Histamine Intolerance.

A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants.

Dexamethasone treatment for COVID-19 is related to increased mortality in hematologic malignancy patients: results from the EPICOVIDEHA Registry.

Not available.

Application of Goat and Lamb Lipases on the Development of New Immobilized Biocatalysts Aiming at Fish Oil Hydrolysis.

The use of lipases from animal sources for the synthesis of new biocatalysts is barely studied in the literature. The present work focused on the immobilization of lipases from kid goat's and lamb's epiglottis in different ionic supports. For this, anionic supports (monoaminoethyl-N-aminoethyl-agarose (MANAE) and diethylaminoethyl-agarose (DEAE)) and cationic supports (carboxymethyl-agarose and sulfopropyl-agarose) were used. The immobilization parameters were evaluated, as well as the thermal stability of the immobilized enzymes and their stability at different values of pH. Then, the performance of the biocatalysts was evaluated in hydrolysis reactions for obtaining omega-3 fatty acids from fish oil (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)). Values of 100% of recovered activity were obtained for lipase from goats, indicating that it was possible to maintain all the enzymatic activities of the immobilized enzymes on the supports. The immobilized enzymes were more stable in different pH conditions and at a temperature of 50 °C, reaching values of stabilization factor of 12.17 and t1/2 of 9.86 h-1, for lamb lipase immobilized in sulfopropyl agarose. In general, the anionic supports led to lower Km values and the cationic ones to a higher Vmax. Lamb lipase showed the highest selectivity values for EPA/DHA, reaching values of 6.43 using MANAE. Thus, the high potential for using such biocatalysts from animal sources in the food or pharmaceutical industries is observed.

Performance of amplicon and capture based next-generation sequencing approaches for the epidemiological surveillance of Omicron SARS-CoV-2 and other variants of concern.

To control the SARS-CoV-2 pandemic, healthcare systems have focused on ramping up their capacity for epidemiological surveillance through viral whole genome sequencing. In this paper, we tested the performance of two protocols of SARS-CoV-2 nucleic acid enrichment, an amplicon enrichment using different versions of the ARTIC primer panel and a hybrid-capture method using KAPA RNA Hypercap. We focused on the challenge of the Omicron variant sequencing, the advantages of automated library preparation and the influence of the bioinformatic analysis in the final consensus sequence. All 94 samples were sequenced using Illumina iSeq 100 and analysed with two bioinformatic pipelines: a custom-made pipeline and an Illumina-owned pipeline. We were unsuccessful in sequencing six samples using the capture enrichment due to low reads. On the other hand, amplicon dropout and mispriming caused the loss of mutation G21987A and the erroneous addition of mutation T15521A respectively using amplicon enrichment. Overall, we found high sequence agreement regardless of method of enrichment, bioinformatic pipeline or the use of automation for library preparation in eight different SARS-CoV-2 variants. Automation and the use of a simple app for bioinformatic analysis can simplify the genotyping process, making it available for more diagnostic facilities and increasing global vigilance.

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022.

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

A Neurological Surgery Care Protocol for the LGBTQIA+ Community.

This research aims to propose a neurological surgery care protocol for the lesbian, gay, bisexual, transgender, queer, questioning, intersex, or asexual (LGBTQIA+) community. In recent years, people belonging to the LGBTQIA+ community have started to come out and express their identity due to growing awareness and various factors like the implementation of legal protections and rights in several countries; it is well documented in the literature that this community faces unique health needs as well as barriers and inequalities in healthcare. The lack of tailored training for medical specialists affects the level of quality and access to medical care for these individuals, and neurosurgical care is no exception. This literature review included studies in scientific journals and articles discussing problems, best practices, and gaps in the existing neurological surgical care protocols for LGBTQIA+ people. Accordingly, it highlights shared challenges such as healthcare-related difficulties, communication barriers, discrimination, and stigmatization. The primary aim is to create a safe and respectful care environment that ensures fair medical treatment to all patients regardless of their sexual orientation or gender identity. The review sheds light on the need for inclusive and sensitive neurosurgical care to improve clinical outcomes and the experience of patients belonging to the LGBTQIA+ community, thereby ensuring an environment of dignified treatment and satisfactory recovery from neurosurgical events.

Use of a surgically implanted, nondischargeable, extracorporeal continuous flow circulatory support system as a bridge to heart transplant.

INTRODUCTION AND OBJECTIVES: We aimed to describe the clinical outcomes of the use of the CentriMag acute circulatory support system as a bridge to emergency heart transplantation (HTx). METHODS: We conducted a descriptive analysis of the clinical outcomes of consecutive HTx candidates included in a multicenter retrospective registry who were treated with the CentriMag device, configured either for left ventricular support (LVS) or biventricular support (BVS). All patients were listed for high-priority HTx. The study assessed the period 2010 to 2020 and involved 16 transplant centers around Spain. We excluded patients treated with isolated right ventricular support or venoarterial extracorporeal membrane oxygenation without LVS. The primary endpoint was 1-year post-HTx survival. RESULTS: The study population comprised 213 emergency HTx candidates bridged on CentriMag LVS and 145 on CentriMag BVS. Overall, 303 (84.6%) patients received a transplant and 53 (14.8%) died without having an organ donor during the index hospitalization. Median time on the device was 15 days, with 66 (18.6%) patients being supported for> 30 days. One-year posttransplant survival was 77.6%. Univariable and multivariable analyses showed no statistically significant differences in pre- or post-HTx survival in patients managed with BVS vs LVS. Patients managed with BVS had higher rates of bleeding, need for transfusion, hemolysis and renal failure than patients managed with LVS, while the latter group showed a higher incidence of ischemic stroke. CONCLUSIONS: In a setting of candidate prioritization with short waiting list times, bridging to HTx with the CentriMag system was feasible and resulted in acceptable on-support and posttransplant outcomes.

Survival in multiple myeloma and SARS-COV-2 infection through the COVID-19 pandemic: Results from the EPICOVIDEHA registry.

Patients affected by multiple myeloma (MM) have an increased risk of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection and subsequent coronavirus (20)19 disease (COVID-19)-related death. The changing epidemiological and therapeutic scenarios suggest that there has been an improvement in severity and survival of COVID-19 during the different waves of the pandemic in the general population, but this has not been investigated yet in MM patients. Here we analyzed a large cohort of 1221 patients with MM and confirmed SARS-CoV-2 infection observed between February 2020, and August 2022, in the EPICOVIDEHA registry from 132 centers around the world. Median follow-up was 52 days for the entire cohort and 83 days for survivors. Three-hundred and three patients died (24%) and COVID-19 was the primary reason for death of around 89% of them. Overall survival (OS) was significantly higher in vaccinated patients with both stable and active MM versus unvaccinated, while only a trend favoring vaccinated patients was observed in subjects with responsive MM. Vaccinated patients with at least 2 doses showed a better OS than those with one or no vaccine dose. Overall, according to pandemic waves, mortality rate decreased over time from 34% to 10%. In multivariable analysis, age, renal failure, active disease, hospital, and intensive care unit admission, were independently associated with a higher number of deaths, while a neutrophil count above 0.5 × 109 /L was found to be protective. This data suggests that MM patients remain at risk of SARS-CoV-2 infection even in the vaccination era, but their clinical outcome, in terms of OS, has progressively improved throughout the different viral phases of the pandemic.

The mortality of COVID-19 in CML patients from 2020 until 2022: results from the EPICOVIDEHA survey.

Since the beginning of the COVID-19 pandemic, there has been an overall improvement in patient mortality. However, haematological malignancy patients continue to experience significant impacts from COVID-19, including high rates of hospitalization, intensive care unit (ICU) admissions, and mortality. In comparison to other haematological malignancy patients, individuals with chronic myeloid leukemia (CML) generally have better prognosis. This study, conducted using a large haematological malignancy patient database (EPICOVIDEHA), demonstrated that the majority of CML patients experienced mild infections. The decline in severe and critical infections over the years can largely be attributed to the widespread administration of vaccinations and the positive response they elicited. Notably, the mortality rate among CML patients was low and exhibited a downward trend in subsequent years. Importantly, our analysis provided confirmation of the effectiveness of vaccinations in CML patients.

Immunoglobulin G4-Related Disease, A Diagnosis to Take into Account: About a Case

Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated and multisystemic condition associated with developing fibroinflammatory lesions in any organ. The diagnosis is made based on the sum of clinical, serological, radiological, and histopathological criteria; however, this is often difficult due to its similarity to neoplasms, infections, or other immune-mediated diseases. Treatment is based on corticosteroids, in a possible combination with immunomodulators. The present case concerns a 59-year-old man with a history of jaundice syndrome and weight loss, admitted for suspected malignant neoplasia of the bile duct. Imaging revealed stricture with dilation of the intrahepatic bile ducts, prominent pancreas, pancreatic duct stricture, and nodular renal lesions. Due to the history of left submandibulectomy two years before the current disease and histology compatible with Küttner's tumor, plus the high IgG4 serum values, the diagnosis of IgG4-RD was established. He started treatment with corticosteroids and was asymptomatic during follow-up.

La enfermedad relacionada con inmunoglobulina G4 (ER-IgG4) es una condición inmunomediada y multisistémica asociada al desarrollo de lesiones fibroinflamatorias en cualquier órgano. El diagnóstico se realiza bajo la suma de criterios clínicos, serológicos, radiológicos e histopatológicos; sin embargo, este suele ser difícil debido a su similitud con neoplasias, infecciones u otras enfermedades inmunomediadas. El tratamiento se basa en corticosteroides, en una posible combinación con inmunomoduladores. El presente caso trata de un varón de 59 años con historia de síndrome ictérico y baja de peso, admitido por sospecha de neoplasia maligna de la vía biliar. Las imágenes revelaron estenosis con dilatación de las vías biliares intrahepáticas, páncreas prominente, estenosis del conducto pancreático y lesiones nodulares renales. Debido al antecedente de submandibulectomía izquierda 2 años antes de la enfermedad actual e histología compatible con tumor de Küttner, más los valores elevados de IgG4 sérico, se estableció el diagnóstico de ER-IgG4. Inició tratamiento con corticosteroides y cursó asintomático durante el seguimiento.

Patrones de presión arterial de 24 horas en pacientes con insuficiencia cardiaca estable. Prevalencia y factores asociados / Twenty-four hour ambulatory blood pressure monitoring in patients with stable heart failure. Prevalence and associated factors

Introducción y objetivos: La hipertensión arterial (HTA) está muy presente en la insuficiencia cardiaca (IC). Sin embargo, su prevalencia, su variación circadiana y la relación con los fenotipos de IC es poco conocida. Nuestro objetivo es describir esta prevalencia y sus patrones en la IC.Métodos: Estudio observacional y transversal sobre la IC crónica estable optimizada. Se obtuvo la presión arterial (PA) en consulta y monitorización ambulatoria durante 24 h. Se estimó la prevalencia de HTA, sus patrones diurnos (controlada, no controlada, de bata blanca y enmascarada) y nocturnos (dipper, nondipper y reverse dipper). Se analizaron factores asociados con patrones y fenotipos de IC.Resultados: Entre 2017 y 2021, se incluyó a 266 pacientes con una media de edad de 72±12 años; el 67% eran varones y el 46% tenían IC con FEVI reducida. El 83% tenía HTA: el 68% controlada, el 10% no controlada, el 10% de bata blanca y el 11% enmascarada. El 51% de los pacientes con PA elevada en consulta resultaron en HTA de bata blanca. El 14% de los pacientes con PA normal en consulta tenían HTA enmascarada. Las prevalencias de dipper, nondipper y reverse dipper fueron del 31, el 43 y el 26% respectivamente. La PA sistólica fue menor en la IC con FEVI reducida que en la IC con FEVI conservada (p <0,001).Conclusiones: La monitorización ambulatoria de la PA en IC identificó HTA de bata blanca en más de la mitad de los pacientes con PA elevada en consulta y un porcentaje relevante de HTA enmascarada. La distribución de patrones diurnos fue similar a la de la población sin IC descrita. Sin embargo, la mayoría tuvo un patrón nocturno patológico.(AU)

Introduction and objectives: Hypertension is highly common in heart failure (HF). However, there is limited information on its prevalence, circadian variation, and relationship with the various HF phenotypes. The objective of this study was to describe the prevalence of hypertension and its patterns in HF.Methods: This was a cross-sectional observational study of patients with optimized stable chronic HF. The patients underwent blood pressure (BP) measurement in the office and 24-hour ambulatory monitoring. We estimated the prevalence of hypertension, and its diurnal (controlled, uncontrolled, white coat, and masked) and nocturnal (dipper, nondipper, and reverse dipper) patterns. We also analyzed the factors associated with the different patterns and HF phenotypes.Results: From 2017 to 2021, 266 patients were included in the study (mean age, 72±12 years, 67% male, 46% with reduced ejection fraction). Hypertension was present in 83%: controlled in 68%, uncontrolled in 10%, white coat in 10%, and masked in 11%. Among patients with high office BP, 51% had white coat hypertension. Among those with normal office BP, 14% had masked hypertension. The prevalence of dipper, nondipper, and reverse dipper patterns was 31%, 43%, and 26%, respectively. Systolic BP was lower in HF with reduced ejection fraction than in HF with preserved ejection fraction (P <.001).Conclusions: Ambulatory BP monitoring in HF identified white coat hypertension in more than half of patients with high office BP and masked hypertension in a relevant percentage of patients. The distribution of daytime patterns was similar to that of the population without HF in the literature, but most of the study patients had a pathological nocturnal pattern.(AU)

Age, successive waves, immunization, and mortality in elderly COVID-19 hematological patients: EPICOVIDEHA findings.

OBJECTIVES: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. METHODS: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. RESULTS: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. CONCLUSION: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Prevalence, Characteristics, and Prognostic Relevance of Donor-Transmitted Coronary Artery Disease in Heart Transplant Recipients.

BACKGROUND: The reported prevalence of donor-transmitted coronary artery disease (TCAD) in heart transplantation (HT) is variable, and its prognostic impact remains unclear. OBJECTIVES: The goal of this study was to characterize TCAD in a contemporary multicentric cohort and to study its prognostic relevance. METHODS: This was a retrospective study of consecutive patients >18 years old who underwent HT in 11 Spanish centers from 2008 to 2018. Only patients with a coronary angiography (c-angio) within the first 3 months after HT were studied. Significant TCAD (s-TCAD) was defined as any stenosis ≥50% in epicardial coronary arteries, and nonsignificant TCAD (ns-TCAD) as stenosis <50%. Clinical outcomes were assessed by means of Cox regression and competing risks regression. Patients were followed-up for a median period of 6.3 years after c-angio. RESULTS: From a cohort of 1,918 patients, 937 underwent c-angio. TCAD was found in 172 patients (18.3%): s-TCAD in 65 (6.9%) and ns-TCAD in 107 (11.4%). Multivariable Cox regression analysis did not show a statistically significant association between s-TCAD and all-cause mortality (adjusted HR: 1.44; 95% CI: 0.89-2.35; P = 0.141); however, it was an independent predictor of cardiovascular mortality (adjusted HR: 2.25; 95% CI: 1.20-4.19; P = 0.011) and the combined event cardiovascular death or nonfatal MACE (adjusted HR: 2.42; 95% CI: 1.52-3.85; P < 0.001). No statistically significant impact of ns-TCAD on clinical outcomes was detected. The results were similar when reassessed by means of competing risks regression. CONCLUSIONS: TCAD was not associated with reduced survival in patients alive and well enough to undergo post-HT angiography within the first 3 months; however, s-TCAD patients showed increased risk of cardiovascular death and MACE.

Molnupiravir compared to nirmatrelvir/ritonavir for COVID-19 in high-risk patients with haematological malignancy in Europe. A matched-paired analysis from the EPICOVIDEHA registry.

INTRODUCTION: Molnupiravir and nirmatrelvir/ritonavir are antivirals used to prevent progression to severe SARS-CoV-2 infections and decrease hospitalisation and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, whereas molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir because it is associated with fewer drug-drug interactions and contraindications. A caveat for molnupiravir is the mode of action induces viral mutations. Mortality rate reduction with molnupiravir was less pronounced than that with nirmatrelvir/ritonavir in patients without haematological malignancy. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, molnupiravir and nirmatrelvir/ritonavir were compared in a cohort of patients with haematological malignancies. METHODS: Clinical data from patients treated with molnupiravir or nirmatrelvir/ritonavir monotherapy for COVID-19 were retrieved from the EPICOVIDEHA registry. Patients treated with molnupiravir were matched by sex, age (±10 years), and severity of baseline haematological malignancy to controls treated with nirmatrelvir/ritonavir. RESULTS: A total of 116 patients receiving molnupiravir for the clinical management of COVID-19 were matched to an equal number of controls receiving nirmatrelvir/ritonavir. In each of the groups, 68 (59%) patients were male; with a median age of 64 years (interquartile range [IQR] 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 56.9% (n=66) of the patients had controlled baseline haematological malignancy, 12.9% (n=15) had stable disease, and 30.2% (n=35) had active disease at COVID-19 onset in each group. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of patients in the two groups were vaccinated (molnupiravir n=77, 66% vs. nirmatrelvir/ritonavir n=87, 75%), more of those treated with nirmatrelvir/ritonavir had received four vaccine doses (n=27, 23%) compared with those treated with molnupiravir (n=5, 4%) (P<0.001). No differences were detected in COVID-19 severity (P=0.39) or hospitalisation (P=1.0). No statistically significant differences were identified in overall mortality rate (P=0.78) or survival probability (d30 P=0.19, d60 P=0.67, d90 P=0.68, last day of follow up P=0.68). Deaths were either attributed to COVID-19, or the infection was judged by the treating physician to have contributed to death. CONCLUSIONS: Hospitalisation and mortality rates with molnupiravir were comparable to those with nirmatrelvir/ritonavir in high-risk patients with haematological malignancies and COVID-19. Molnupiravir is a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy.