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.EPICOVIDEHA has received funds from Optics COMMITTM (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223)

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

Anti-MRSA activity of abietane diterpenes from Coleus blumei Benth

Two heretofore uncharacterised abietane diterpenes, sincoetsin C (1) and 3-hydroxyspirocoleon 7-O-β-D-glucoside (4), were isolated from a methanolic extract of Coleus blumei Benth. (Lamiaceae), along with the known compounds, scutellarioidone A (2) and spirocoleon 7-O-β-D-glucoside (3) using chromatographic techniques. Their structures were determined by 1D and 2D nuclear magnetic resonance including HSQC, HMBC, COSY and NOESY experiments, mass spectrometry (HR-MS) and other spectroscopic methods (UV, IR). Their antibacterial activity against the reference strain of methicillin-resistant Staphylococcus aureus subsp. aureus CCM 4750 (MRSA) was evaluated using optical absorption to obtain quantitative information on their growth. All isolated compounds displayed anti-MRSA 4750 activity at the concentration of 512 μg/mL. Sincoetsin C (1) was the abietane diterpene most active against MRSA 4750, with a minimum inhibitory concentration of 128 μg/mL

New diterpenoid glucoside and flavonoids from Plectranthus scutellarioides (L.) R. Br

Three new compounds, diterpenoid glucoside (13S,15S)-6\u3b2,7\u3b1,12\u3b1-trihydroxy-13\u3b2,16-cyclo-8-abietene-11,14-dione 7-O-\u3b2-D-glucoside 1, flavonoids apigenin 7-O-(3\u2032\u2032-O-acetyl)-\u3b2-D-glucuronide 2 and apigenin 5-O-(3\u2032\u2032-O-acetyl)-\u3b2-D-glucuronide 3, together with known compounds caffeic acid 4, luteolin 5-O-\u3b2-D-glucoside 5 and rosmarinic acid 6 were isolated from the aerial parts of Plectranthus scutellarioides (L.) R. Br. The structures of the new compounds were elucidated by spectroscopic and mass-spectrometric analyses, including 1D- and 2D-NMR. Compound 1 inhibited hyaluronidase by 25% at the concentration of 200 \u3bcM, compounds 2 and 3 showed inhibitory activity on butyrylcholinesterase better than standard galanthamine at the concentration of 100 \u3bcM, and compound 6 is a potent antioxidant with an ORAC value of 2.15 \ub1 0.12

ARResT/Interrogate: an interactive immunoprofiler for IG/TR NGS data

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RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer

Wnt/β-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligase RNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class of RNF43 truncating cancer mutations that induce β-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with a ubiquitin-independent suppressor role of the RNF43 cytosolic tail that involves Casein kinase 1 (CK1) binding and phosphorylation. Mechanistically, truncated RNF43 variants trap CK1 at the plasma membrane, thereby preventing β-catenin turnover and propelling ligand-independent target gene transcription. Gene editing of human colon stem cells shows that RNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, these RNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine

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.</p