COVID-19 infection in adult patients with hematological malignancies:a European Hematology Association Survey (EPICOVIDEHA)

Background: Patients with hematological malignancies (HM) are at high risk of mortality from SARS-CoV-2 disease 2019 (COVID-19). A better understanding of risk factors for adverse outcomes may improve clinical management in these patients. We therefore studied baseline characteristics of HM patients developing COVID-19 and analyzed predictors of mortality. Methods: The survey was supported by the Scientific Working Group Infection in Hematology of the European Hematology Association (EHA). Eligible for the analysis were adult patients with HM and laboratory-confirmed COVID-19 observed between March and December 2020. Results: The study sample includes 3801 cases, represented by lymphoproliferative (mainly non-Hodgkin lymphoma n = 1084, myeloma n = 684 and chronic lymphoid leukemia n = 474) and myeloproliferative malignancies (mainly acute myeloid leukemia n = 497 and myelodysplastic syndromes n = 279). Severe/critical COVID-19 was observed in 63.8% of patients (n = 2425). Overall, 2778 (73.1%) of the patients were hospitalized, 689 (18.1%) of whom were admitted to intensive care units (ICUs). Overall, 1185 patients (31.2%) died. The primary cause of death was COVID-19 in 688 patients (58.1%), HM in 173 patients (14.6%), and a combination of both COVID-19 and progressing HM in 155 patients (13.1%). Highest mortality was observed in acute myeloid leukemia (199/497, 40%) and myelodysplastic syndromes (118/279, 42.3%). The mortality rate significantly decreased between the first COVID-19 wave (March–May 2020) and the second wave (October–December 2020) (581/1427, 40.7% vs. 439/1773, 24.8%, p value < 0.0001). In the multivariable analysis, age, active malignancy, chronic cardiac disease, liver disease, renal impairment, smoking history, and ICU stay correlated with mortality. Acute myeloid leukemia was a higher mortality risk than lymphoproliferative diseases. Conclusions: This survey confirms that COVID-19 patients with HM are at high risk of lethal complications. However, improved COVID-19 prevention has reduced mortality despite an increase in the number of reported cases

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, which reduce both hospitalization and mortality rates. Nirmatrelvir/ritonavir was authorised in Europe in December 2021, while molnupiravir is not yet licensed in Europe as of February 2022. Molnupiravir may be an alternative to nirmatrelvir/ritonavir, because it displays less frequent drug-drug interactions and contraindications. A caveat connected to molnupiravir derives from the mode of action inducing viral mutations. In clinical trials on patients without haematological malignancy, mortality rate reduction of molnupiravir appeared less pronounced than that of nirmatrelvir/ritonavir. Little is known about the comparative efficacy of the two drugs in patients with haematological malignancy at high-risk of severe COVID-19. Thus, we here assess the effectiveness of molnupiravir compared to nirmatrelvir/ritonavir in our cohort of patients with haematological malignancies. Methods: Clinical data of patients treated either 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 baseline haematological malignancy severity 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 (IQR 53-74) for molnupiravir recipients and 64 years (IQR 54-73) for nirmatrelvir/ritonavir recipients; 57% (n=66) of the patients had controlled baseline haematological malignancy, 13% (n=15) stable, and 30% (n=35) had active disease at COVID-19 onset in each of the groups. During COVID-19 infection, one third of patients from each group were admitted to hospital. Although a similar proportion of vaccinated patients was observed in both groups (molnupiravir n=77, 66% vs nirmatrelvir/ritonavir n=87, 75%), those treated with nirmatrelvir/ritonavir had more often received four doses (n=27, 23%) as compared to patients treated with molnupiravir (n=5, 4%, p&lt;0.001). No differences were detected in COVID-19 severity (p=0.39) or hospitalization (p=1.0). No statistically significant differences were identified in overall mortality rate (p=0.78) or in survival probability (d30 p=0.19, d60 p=0.67, d90 p=0.68, last day of follow up p=0.68). In all patients, deaths were either attributed to COVID-19 or the infection contributed to death as per treating physician's judgement. Conclusions: In high-risk patients with haematological malignancies and COVID-19, molnupiravir showed rates of hospitalization and mortality comparable to those of nirmatrelvir/ritonavir in this matched-pair analysis. Molnupiravir appears to be a plausible alternative to nirmatrelvir/ritonavir for COVID-19 treatment in patients with haematological malignancy

Age, Successive Waves, Immunization, and Mortality in Elderly COVID-19 Haematological Patients: EPICOVIDEHA Findings

Introduction: elderly patients with haematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection impact in different age groups remains unstudied in detail. Methods: We analysed elderly patients (age groups: 65-70, 71-75, 76-80 and &gt;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 haematological malignancy. results: the study included data from 3,603 elderly patients (aged 65 or older) with haematological 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.tThe 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 leukaemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusions: These data underscore the heterogeneity of elderly haematological patients, highlight the different impact of COVID waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts

Breakthrough COVID-19 in vaccinated patients with hematologic malignancies: results from the EPICOVIDEHA survey

© 2022 The American Society of HematologyLimited data are available on breakthrough COVID-19 in patients with hematologic malignancy (HM) after antisevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Adult patients with HM, ≥1 dose of anti-SARS-CoV-2 vaccine, and breakthrough COVID-19 between January 2021 and March 2022 were analyzed. A total of 1548 cases were included, mainly lymphoid malignancies (1181 cases, 76%). After viral sequencing in 753 cases (49%), Omicron variant was prevalent (517, 68.7%). Most of the patients received ≤2 vaccine doses before COVID-19 (1419, 91%), mostly mRNA-based (1377, 89%). Overall, 906 patients (59%) received COVID-19-specific treatment. After 30-day follow-up from COVID-19 diagnosis, 143 patients (9%) died. The mortality rate in patients with Omicron variant was 7.9%, comparable to other variants, with a significantly lower 30-day mortality rate than in the prevaccine era (31%). In the univariable analysis, older age (P <.001), active HM (P <.001), and severe and critical COVID-19 (P =.007 and P <.001, respectively) were associated with mortality. Conversely, patients receiving monoclonal antibodies, even for severe or critical COVID-19, had a lower mortality rate (P <.001). In the multivariable model, older age, active disease, critical COVID-19, and 2-3 comorbidities were correlated with a higher mortality, whereas monoclonal antibody administration, alone (P <.001) or combined with antivirals (P =.009), was protective. Although mortality is significantly lower than in the prevaccination era, breakthrough COVID-19 in HM is still associated with considerable mortality. Death rate was lower in patients who received monoclonal antibodies, alone or in combination with antivirals

B-cell malignancies treated with targeted drugs and SARS-CoV-2 infection: A European Hematology Association Survey (EPICOVIDEHA)

Copyright © 2022 Infante, Salmanton-García, Fernández-Cruz, Marchesi, Jaksic, Weinbergerová, Besson, Duarte, Itri, Valković, Szotkovski, Busca, Guidetti, Glenthøj, Collins, Bonuomo, Sili, Seval, Machado, Cordoba, Blennow, Abu-Zeinah, Lamure, Kulasekararaj, Falces-Romero, Cattaneo, Van Doesum, Piukovics, Omrani, Magliano, Ledoux, de Ramon, Cabirta, Verga, López-García, Da Silva, Stojanoski, Meers, Lahmer, Martín-Pérez, Dávila-Vals, Van Praet, Samarkos, Bilgin, Karlsson, Batinić, Nordlander, Schönlein, Hoenigl, Ráčil, Mladenović, Hanakova, Zambrotta, De Jonge, Adžić-Vukičević, Nunes-Rodrigues, Prezioso, Navrátil, Marchetti, Cuccaro, Calbacho, Giordano, Cornely, Hernández-Rivas and Pagano.Patients with lymphoproliferative diseases (LPD) are vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we describe and analyze the outcome of 366 adult patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between February 2020 and January 2022. Median follow-up was 70.5 days (IQR 0-609). Most used targeted drugs were Bruton-kinase inhibitors (BKIs) (N= 201, 55%), anti-CD20 other than rituximab (N=61, 16%), BCL2 inhibitors (N=33, 9%) and lenalidomide (N=28, 8%).Only 16.2% of the patients were vaccinated with 2 or more doses of vaccine at the onset of COVID-19. Mortality was 24% (89/366) on day 30 and 36%(134/366) on the last day of follow-up. Age >75 years (p<0.001, HR 1.036), active malignancy (p<0.001, HR 2.215), severe COVID-19 (p=0.017, HR 2.270) and admission to ICU (p<0.001, HR 5.751) were risk factors for mortality at last day of follow up. There was no difference in OS rates in NHL vs CLL patients (p=0.306), nor in patients treated with or without BKIs (p=0.151). Mortality in ICU was 66% (CLL 61%, NHL 76%). Overall mortality rate decreased according to vaccination status, being 39% in unvaccinated patients, 32% and 26% in those having received one or two doses, respectively, and 20% in patients with a booster dose (p=0.245). Overall mortality rate dropped from 41% during the first semester of 2020 to 25% at the last semester of 2021. These results show increased severity and mortality from COVID-19 in LPDs patients treated with targeted drugs

HCV-specific lymphocyte responses in individuals with positive anti-HCV but negative HCV-RNA

Background: Hepatitis C virus (HCV) status cannot be reliably predicted in anti-HCV positive/HCV-RNA negative individuals who may either have recovered spontaneously or have a false-positive test due to antibody cross-reaction. Investigating T lymphocyte responses in individuals with different HCV status may help understand the cellular immune mechanisms underlying spontaneous recovery, treatment response, and chronicity. Objective: We aimed to determine whether anti-HCV positive, HCV-RNA negative individuals are truly spontaneous recoverers from acute HCV infection. Study design: We used enzyme-linked immunosorbent spot (ELISPOT) assay to compare HCV-specific lymphocyte response among anti-HCV positive/HCV-RNA negative individuals, patients with sustained virological response to interferon-gamma/ribavirin treatment, and patients with chronic HCV infection. Results: We found that 83% of anti-HCV positive/HCV-RNA negative individuals without a past medical history of acute icteric hepatitis had an HCV-specific T lymphocyte response in peripheral blood. Lymphocyte responses in these individuals were similar in magnitude to treatment responders unlike patients with chronic HCV whose virus-directed immunity was significantly suppressed. Conclusions: Detection of HCV-specific T lymphocyte responses using ELISPOT is a feasible method to ascertain past asymptomatic acute HCV infection. (C) 2015 Elsevier B.V. All rights reserved

Peripheral innate and adaptive immune cells during COVID-19: Functional neutrophils, pro-inflammatory monocytes, and half-dead lymphocytes

Background A better understanding of innate and adaptive cells in COVID-19 is necessary for the development of effective treatment methods and vaccines. Methods We studied phenotypic features of innate and adaptive immune cells, oxidative burst, phagocytosis, and apoptosis. One hundred and three patients with COVID-19 were grouped according to their clinical features into the categories of mild (35%), moderate (40.8%), and severe (24.3%). Results Monocytes were CD16(+) pro-inflammatory monocytes and tended to shed their HLA-DR, especially in severe cases (p < 0.01). Neutrophils were mature and functional, although a decline of their CD10 and CD16 was observed (p < 0.01). No defect was found in the reactive oxygen species production and their apoptosis. The percentage of natural killer cells was in the normal range, whereas the percentages of CD8(+)NK and CD56(+)T lymphocytes were found to be high (p < 0.01). Although the absolute numbers of all lymphocyte subsets were low and showed a tendency for a gradual decrease in accordance with the disease progression, the most decreased absolute number was that of B lymphocytes, followed by CD4(+) T cells in the severe cases. The percentages of double-negative T cells; HLA-DR(+)CD3(+) and CD28(-)CD8(+) subsets were found to be significantly increased. Importantly, we demonstrated the increased baseline activation of caspase-3 and increased lymphocyte apoptosis. Conclusion We suggest that SARS-CoV-2 primarily affects the lymphocytes and not the innate cells. The increased baseline activation of Caspase-3 could make the COVID-19 lymphocytes more vulnerable to cell death. Therefore, this may interrupt the crosstalk between the adaptive and innate immune systems

Simultaneous Onset of Haematological Malignancy and COVID: An Epicovideha Survey

© 2022 by the authors.Background: The outcome of patients with simultaneous diagnosis of haematological malignancies (HM) and COVID-19 is unknown and there are no specific treatment guidelines. Methods: We describe the clinical features and outcome of a cohort of 450 patients with simultaneous diagnosis of HM and COVID-19 registered in the EPICOVIDEHA registry between March 2020 to February 2022. Results: Acute leukaemia and lymphoma were the most frequent HM (35.8% and 35.1%, respectively). Overall, 343 (76.2%) patients received treatment for HM, which was delayed for longer than one month since diagnosis in 57 (16.6%). An overall response rate was observed in 140 (40.8%) patients after the first line of treatment. After a median follow-up of 35 days, overall mortality was 177/450 (39.3%); 30-day mortality was significantly higher in patients not receiving HM treatment (42.1%) than in those receiving treatment (27.4%, p = 0.004), either before and/or after COVID-19, or compared to patients receiving HM treatment at least after COVID-19 (15.2%, p 500/mcl at COVID-19 onset was protective. Conclusions: HM treatment should be delivered as soon as possible for patients with simultaneous diagnosis of COVID-19 and HM requiring immediate therapy

Admission code status and end-of-life care for hospitalized patients with COVID-19

© 2022 American Academy of Hospice and Palliative MedicineContext: The COVID-19 pandemic has highlighted variability in intensity of care. We aimed to characterize intensity of care among hospitalized patients with COVID-19. Objectives: Examine the prevalence and predictors of admission code status, palliative care consultation, comfort-measures-only orders, and cardiopulmonary resuscitation (CPR) among patients hospitalized with COVID-19. Methods: This cross-sectional study examined data from an international registry of hospitalized patients with COVID-19. A proportional odds model evaluated predictors of more aggressive code status (i.e., Full Code) vs. less (i.e., Do Not Resuscitate, DNR). Among decedents, logistic regression was used to identify predictors of palliative care consultation, comfort measures only, and CPR at time of death. Results: We included 29,923 patients across 179 sites. Among those with admission code status documented, Full Code was selected by 90% (n = 15,273). Adjusting for site, Full Code was more likely for patients who were of Black or Asian race (ORs 1.82, 95% CIs 1.5–2.19; 1.78, 1.15–3.09 respectively, relative to White race), Hispanic ethnicity (OR 1.89, CI 1.35–2.32), and male sex (OR 1.16, CI 1.0–1.33). Of the 4951 decedents, 29% received palliative care consultation, 59% transitioned to comfort measures only, and 29% received CPR, with non-White racial and ethnic groups less likely to receive comfort measures only and more likely to receive CPR. Conclusion: In this international cohort of patients with COVID-19, Full Code was the initial code status in the majority, and more likely among patients who were Black or Asian race, Hispanic ethnicity or male. These results provide direction for future studies to improve these disparities in care