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)

Microbe-host interactions: structure and role of Gram-negative bacterial porins.

Gram negative bacteria have evolved many mechanisms of attaching to and invading host epithelial and immune cells. In particular, many outer membrane proteins (OMPs) are involved in this initial interaction between the pathogen and their host. The outer membrane (OM) of Gram-negative bacteria performs the crucial role of providing an extra layer of protection to the organism without compromising the exchange of material required for sustaining life. The OM, therefore, represents a sophisticated macromolecular assembly, whose complexity has yet to be fully elucidated. This review will summarize the structural information available for porins, a class of OMP, and highlight their role in bacterial pathogenesis and their potential as therapeutic targets. The functional role of porins in microbe-host interactions during various bacterial infections has emerged only during the last few decades, and their interaction with a variety of host tissues for adhesion to and invasion of the cell and for evasion of host-defense mechanisms have placed bacterial porins at the forefront of research in bacterial pathogenesis. This review will discuss the role that porins play in activating immunological responses, in inducing signaling pathways and their influence on antibiotic resistance mechanisms that involve modifications of the properties of the OM lipid barrier

Microbe-host interactions: structure and role of Gram-negative bacterial porins.

Gram negative bacteria have evolved many mechanisms of attaching to and invading host epithelial and immune cells. In particular, many outer membrane proteins (OMPs) are involved in this initial interaction between the pathogen and their host. The outer membrane (OM) of Gram-negative bacteria performs the crucial role of providing an extra layer of protection to the organism without compromising the exchange of material required for sustaining life. The OM, therefore, represents a sophisticated macromolecular assembly,whose complexity has yet to be fully elucidated.. This review will summarize the structural information available for porins, a class of OMP, and highlight their role in bacterial pathogenesis. The functional role of porins in microbe-host interactions during various bacterial infections has emerged only during the last few decades, and their interaction with a variety of host tissues for adhesion to and invasion of the cell and for evasion of host-defense mechanisms have placed bacterial porins at the forefront of research in bacterial pathogenesis. This review will discuss the role that porins play in activating immunological responses, in inducing signaling pathways and their influence on antibiotic resistance mechanisms that involve modifications of the properties of the OM lipid barrier

Post-mortem interval assessment by MALDI-TOF mass spectrometry analysis in murine cadavers

Aims: This study assessed the use of MALDI-TOF mass spectrometry as an alternative method to identify species associated with the thanatomicrobiota and epinecrotic communities. Methods and Results: The study was conducted on 10 murine cadavers, and microbiological swabs were collected from five external anatomical sites (eyes, ears, nose, mouth, and rectum) and four internal organs (brain, spleen, liver, heart), during 16 and 30 days, for the thanatomicrobiota and epinecrotic communities, respectively. Our results revealed that the post-mortem microbiota associated with the external cavities showed changes over time and reduced taxonomic diversity. The internal organs, initially sterile, showed signs of microbial invasion at 3 and 10 days post-mortem for the liver-spleen and heart-brain, respectively. The post-mortem microbiota was mainly dominated by Firmicutes and Proteobacteria. Conclusions: MALDI-TOF is a promising method for estimating post-mortem interval (PMI), associated with rapid sample handling, good reproducibility, and high productivity. Significance and Impact of Study: This study investigated microbial changes during the decomposition process and proposed a simple strategy for PMI estimation. Results introducing the application of the MALDI-TOF method in the field of forensi

Antimicrobial activity of bovine lactoferrin-derived peptides

Antimicrobial peptides, such as bovine lactoferrin (bLF), are produced by a wide variety of organisms. AMPs represent a first line defence against invading microbes and are found in large quantity in several secretory fluids [1] . They are relatively short, amphiphilic and positively charged. bLF is an 80- kDa iron-binding, multifunctional cationic glycoprotein of the transferrin family. This protein is active against a widespread range of microbiological organisms: bacteria, viruses, fungi and parasites [2,3,4]. In order to obtain novel active peptides from bLF, several approaches have been used. Two novel active peptides have been identified in our study. In agreement with the not disclosure agreement for the pending patent N°102015000044047*, we are not allowed to report the sequences in the abstract. These peptides, named respectively KFp and LKp, were synthesized using the standard solid-phase- 9-fluorenylmethoxycarbonyl (Fmoc) method. Antibacterial activity of KFp and LKp was analyzed by minimal inhibitory concentration (MIC) using the broth microdilution method outlined by the Clinical and Laboratory StandardsInstitute (CLSI) on two bacteria strains: Escherichia coli ATCC 11229 and Staphylococcus aureus ATCC 6538. Likewise, the antiviral activity was performed on HSV-1using a co-treatment assay. Moreover, their cytotoxicity activity was evaluated by the MTT assay.According to the study conducted, these novel peptides show a marked broad-spectrum antimicrobial and antiviral activity with a low toxicity. This can be a favorable prerequisite for the developing and for the use of these peptides in vivo, as additional therapeutic agents and/or as alternative to the conventional antibiotics