Search

Background Given the limited collaborative international studies that evaluated COVID-19 in patients with cancer in comparison to patients without cancer, we aimed to determine the independent risk factors associated with increased 30-day mortality and the impact of novel treatment modalities in a large group of cancer and non-cancer patients with COVID-19 from multiple countries. Methods We retrospectively collected de-identified data on cancer and non-cancer patients diagnosed with COVID-19 between January and November 2020, at 16 centers in Asia, Australia, Europe, North America, and South America. A logistic regression model was used to identify independent predictors of all-cause mortality within 30 days after COVID-19 diagnosis. Results Of the total 4015 COVID-19 confirmed patients entered, we analyzed 3966 patients, 1115 cancer and 2851 non-cancer patients. Cancer patients were older than non-cancer patients (median age, 61 vs 50 years; p< 0.0001); more likely to be pancytopenic , had pulmonary disorders, hypertension, diabetes mellitus. In addition, they were more likely to present with higher inflammatory biomarkers (D-dimer, ferritin and procalcitonin), but were less likely to present with clinical symptoms. By multivariable logistic regression analysis, cancer was an independent risk factor for 30-day mortality (OR 1.46; 95% CI 1.03 to 2.07; p=0.035). Older age (≥65 years) was the strongest predictor of 30-day mortality in all patients (OR 4.55; 95% CI 3.34 to 6.20; p< 0.0001). Remdesivir was the only therapeutic agent independently associated with decreased 30-day mortality (OR 0.58; CI 0.39-0.88; p=0.009). Among patients on low-flow oxygen at admission, patients who received remdesivir had a lower 30-day mortality rate than those who were on high flow oxygen (5.9% vs 17.6%; p=0.03). Patients transfused with convalescent plasma within 1 day of diagnosis had a lower 30-day mortality rate than those transfused later (1% vs 7%, p=0.04). Conclusion Cancer is an independent risk factor for increased 30-day all-cause mortality from COVID-19. Remdesivir, particularly in patients receiving low-flow oxygen, can reduce 30-day all-cause mortality, as well as convalescent plasma given early after COVID-19 diagnosis. Disclosures Roy F. Chemaly, MD, MPH, FACP, FIDSA, AiCuris (Grant/Research Support)Ansun Biopharma (Consultant, Grant/Research Support)Chimerix (Consultant, Grant/Research Support)Clinigen (Consultant)Genentech (Consultant, Grant/Research Support)Janssen (Consultant, Grant/Research Support)Karius (Grant/Research Support)Merck (Consultant, Grant/Research Support)Molecular Partners (Consultant, Advisor or Review Panel member)Novartis (Grant/Research Support)Oxford Immunotec (Consultant, Grant/Research Support)Partner Therapeutics (Consultant)Pulmotec (Consultant, Grant/Research Support)Shire/Takeda (Consultant, Grant/Research Support)Viracor (Grant/Research Support)Xenex (Grant/Research Support) Fareed Khawaja, MBBS, Eurofins Viracor (Research Grant or Support) Monica Slavin, MBBS,MD, F2G (Advisor or Review Panel member)Merck (Advisor or Review Panel member)Pfizer (Advisor or Review Panel member) Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Background There is a spectrum of pulmonary disease burden in pts with HEM and PM. There have not been any data comparing the sensitivity and findings of initial Chest X-Ray (CXR) and chest CT in these pts. Methods We compared the findings of the initial CXR and CT in all pts with proven or probable PM via EORTC/MSG criteria. We included only pts who had pulmonary symptoms and who had both CXR and CT within 5 days of each other and within seven days of symptom onset or date of culture at MD Anderson Cancer Center from April 2000 and April 2020. We collected data regarding demographics, status of HEM, clinical presentation, frequency and findings of BAL and imaging findings, mold-active prophylaxis and treatment regimens, and mortality. CXR findings were classified as normal or abnormal, and if abnormal sub-classified as mass-like/consolidative, nodular, cavitary or heterogenous/non-specific. CT findings were classified in a similar manner. Results We Identified such 39 pts with PM who had both CXR and CT within 5 d. All pts had positive CT. Five pts (13%) had a negative CXR. The majority of pts 28 (72%) were neutropenic (neutrophil count < 500). The most common CXR findings were consolidation or mass-like lesions (56%), followed by patchy, heterogenous or non-specific findings (33%) and nodules (13%). Only 3% had cavitary lesions. Similarly, consolidation or mass-like lesions were the most common finding on CT (69%), followed by nodular lesions with or without ground glass halos (56%). Cavitary lesions and/or reverse halo sign (RHS) were common (31%) on CT. Patients with normal CXR vs those with abnormal CXR were comparable in all clinical parameters we collected. The median survival from time of symptoms onset for all pts was 45 days. There was a trend for lower 42 day mortality in pts with normal CXR (20% vs 47%, P=.253). Conclusion A negative CXR does not preclude PM, especially in neutropenic pts. A CT is recommended for better sensitivity and although there was concordance in CXR with CT findings in some chest abnormalities (mass, consolidation), CT more commonly revealed nodules and signs highly suggestive of PM such as RHS. Although small numbers precluded a robust comparison, it is possible that HEM pts with PM and negative initial CXR have better prognosis, perhaps reflecting a lower burden of pulmonary involvement Disclosures Dimitrios P. Kontoyiannis, MD, Astellas (Consultant)Cidara Therapeutics (Advisor or Review Panel member)Gilead Sciences (Consultant, Grant/Research Support, Other Financial or Material Support, Honoraria)

Interleukin 17-producing helper T cells (T(H)17 cells) have a major role in protection against infections and in mediating autoimmune diseases, yet the mechanisms involved are incompletely understood. We found that interleukin 26 (IL-26), a human T(H)17 cell-derived cytokine, is a cationic amphipathic protein that kills extracellular bacteria via membrane-pore formation. Furthermore, T(H)17 cell-derived IL-26 formed complexes with bacterial DNA and self-DNA released by dying bacteria and host cells. The resulting IL-26-DNA complexes triggered the production of type I interferon by plasmacytoid dendritic cells via activation of Toll-like receptor 9, but independently of the IL-26 receptor. These findings provide insights into the potent antimicrobial and proinflammatory function of T(H)17 cells by showing that IL-26 is a natural human antimicrobial that promotes immune sensing of bacterial and host cell death.

Objectives: A prospective international multicentre surveillance study was conducted to investigate the prevalence and amphotericin B susceptibility of Aspergillus terreus species complex infections. Methods: A total of 370 cases from 21 countries were evaluated. Results: The overall prevalence of A. terreus species complex among the investigated patients with mould-positive cultures was 5.2% (370/7116). Amphotericin B MICs ranged from 0.125 to 32 mg/L, (median 8 mg/L). Conclusions: Aspergillus terreus species complex infections cause a wide spectrum of aspergillosis and the majority of cryptic species display high amphotericin B MICs. Fil: Risslegger, Brigitte. Universidad de Innsbruck; Austria Fil: Zoran, Tamara. Universidad de Innsbruck; Austria Fil: Lackner, Michaela. Universidad de Innsbruck; Austria Fil: Aigner, María. Universidad de Innsbruck; Austria Fil: Sanchez Reus, Ferrán. Hospital de la Santa Creu I Sant Pau; España Fil: Rezusta, Antonio. Universidad de Zaragoza; España Fil: Chowdhary, Anuradha. University of Delhi; India Fil: Alcacer Sanchez, Juan Manuel. Hospital de la Santa Creu I Sant Pau; Fil: Taj Aldeen, Saad Jaber. Hamad Medical Corporation; Qatar Fil: Arendrup, Maiken C.. Universidad de Copenhagen; Dinamarca Fil: Oliveri, Salvatore. Università degli Studi di Catania; Italia Fil: Kontoyiannis, Dimitrios P.. The University of Texas MD Anderson Cancer Center; Estados Unidos Fil: Alastruey Izquierdo, Ana. Universidad Carlos III de Madrid. Instituto de Salud; España Fil: Lagrou, Katrien. Katholikie Universiteit Leuven; Bélgica Fil: Lo Cascio, Giuliana. Azienda Ospedaliera Universitaria Integrata; Italia Fil: Meis, Jacques F.. Canisius Wilhelmina Hospital; Países Bajos Fil: Buzina, Walter. Medical University of Graz; Austria Fil: Farina, Claudio. ASST Papa Giovanni XXIII. Microbiology Institute; Italia Fil: Drogari Apiranthitou, Miranda. Universidad Nacional y Kapodistriaca de Atenas; Grecia Fil: Grancini, Anna. Cà Granda Ospedale Maggiore Policlinico; Italia Fil: Tortorano, Anna Maria. Università degli Studi di Milano; Italia Fil: Willinger, Birgit. Universidad de Viena; Austria Fil: Hamprecht, Axel. Universitat Zu Köln; Alemania Fil: Johnson, Elizabeth. Public Health England. Mycology Reference Laboratory; Reino Unido Fil: Klingspor, Lena. Karolinska Huddinge Hospital; Suecia Fil: Arsic Arsenijevic, Valentina. University of Belgrade; Serbia Fil: Cornely, Oliver A.. Universitat Zu Köln; Alemania Fil: Meletiadis, Joseph. Universidad Nacional y Kapodistriaca de Atenas; Grecia Fil: Prammer, Wolfgang. Klinikum Wels-Grieskirchen; Austria Fil: Tullio, Vivian. Università di Torino; Italia Fil: Vehreschild, Jörg Janne. Universitat Bonn; Alemania. Universitat Zu Köln; Alemania Fil: Trovato, Laura. Università degli Studi di Catania; Italia Fil: Lewis, Russell E.. Universidad de Bologna; Italia Fil: Segal, Esther. Tel Aviv University; Israel Fil: Rath, Peter Michael. Universitat Essen; Alemania Fil: Hamal, Petr. Universtity Hospital Olomouc; República Checa. Palacky University Olomouc; República Checa Fil: Rodríguez Iglesias, Manuel. Universidad de Cádiz; España Fil: Roilides, Emmanuel. Aristotle University School of Health Sciences; Grecia Fil: Arikan Akdagli, Sevtap. Hacettepe University; Turquía Fil: Chakrabarti, Arunaloke. Postgraduate Institute of Medical Education and Research; India Fil: Colombo, Arnaldo L.. Universidade Federal de Sao Paulo; Brasil Fil: Fernández, Mariana Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Martin Gomez, M. Teresa. Vall d’Hebron University Hospital; España Fil: Badali, Hamid. Mazandaran University of Medical Sciences; Irán Fil: Petrikkos, Georgios. European University Cyprus; Chipre Fil: Klimko, Nikolai. North Western State Medical University; Rusia Fil: Heimann, Sebastian M.. Universitat Zu Köln; Alemania Fil: Houbraken, Jos. Fungal Biodiversity Centre; Países Bajos Fil: Uzun, Omrum. Hacettepe University Medical School; Turquía Fil: Edlinger, Michael. Universidad de Innsbruck; Austria Fil: de la Fuente, Sonia. Hospital Ernest Lluch Martin; España Fil: Lass Flörl, Cornelia. Universidad de Innsbruck; Austria

Breakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster infection model.

Objective Our objective was to develop a model that predicts a patient's risk of developing invasive mould disease (IMD) within 60 days of admission for treatment of a haematological malignancy. Methods We analysed 19 risk factors for IMD in a cohort of 1944 adult patients with haematological malignancies over 4127 admissions at a haematology referral centre in Northern Italy (2007-2016). We used a multivariable logistic regression to estimate the 60-day probability of developing probable or proven IMD. The model was internally validated using a bootstrap resampling procedure. Results The prevalence of IMD was 3.3% (90 probable cases, 43 proven cases). Seven risk factors were retained in the final risk model: (1) uncontrolled malignancy, (2) high-risk chemotherapy regimen, (3) high-dose corticosteroids, (4) severe lymphopenia, (5) CMV reactivation or disease, (6) prolonged neutropenia, and (7) a history of previous IMD within 90 days. The model displayed good calibration and discrimination in both the derivation (aROC 0.85, 95% CI 0.84-0.86) and validation (aROC 0.83 95% CI 0.79-0.89) populations. Conclusions Our model differentiated with 85% accuracy whether or not patients developed IMD within 60-days of admission. Individualized risk assessment, aided by validated prognostic models, could assist IMD management and improve antifungal stewardship.

Although the widespread use of mold-active agents (especially the new generation of triazoles) has resulted in reductions of documented invasive mold infections (IMIs) in patients with hematological malignancies and allogeneic hematopoietic stem cell transplantation (HSCT), a subset of such patients still develop breakthrough IMIs (bIMIs). There are no data from prospective randomized clinical trials to guide therapeutic decisions in the different scenarios of bIMIs. In this viewpoint, we present the current status of our understanding of the clinical, diagnostic, and treatment challenges of bIMIs in high-risk adult patients with hematological cancer and/or HSCT receiving mold-active antifungals and outline common clinical scenarios. As a rule, managing bIMIs demands an individualized treatment plan that takes into account the host, including comorbidities, certainty of diagnosis and site of bIMIs, local epidemiology, considerations for fungal resistance, and antifungal pharmacological properties. Finally, we highlight areas that require future investigation in this complex area of clinical mycology.