Secondary infections worsen the outcome of COVID-19 in patients with hematological malignancies: A report from the ITA-HEMA-COV.

The impact of secondary infections (SI) on COVID-19 outcome in patients with hematological malignancies (HM) is scarcely documented. To evaluate incidence, clinical characteristics, and outcome of SI, we analyzed the microbiologically documented SI in a large multicenter cohort of adult HM patients with COVID-19. Among 1741 HM patients with COVID-19, 134 (7.7%) had 185 SI, with a 1-month cumulative incidence of 5%. Median time between COVID-19 diagnosis and SI was 16 days (IQR: 5-36). Acute myeloid leukemia (AML) and lymphoma/plasma cell neoplasms (PCN) were more frequent diagnoses in SI patients compared to patients without SI (AML: 14.9% vs. 7.1%; lymphoma/PCN 71.7% vs. 65.3%). Patients with SI were older (median age 70 vs. 66 years, p = 0.002), with more comorbidities (median Charlson Comorbidity Index 5 vs. 4, p < 0.001), higher frequency of critical COVID-19 (19.5% vs. 11.5%, p = 0.046), and more frequently not in complete remission (75% vs. 64.7% p = 0.024). Blood and bronchoalveolar lavage were the main sites of isolation for SI. Etiology of infections was bacterial in 80% (n = 148) of cases, mycotic in 9.7% (n = 18) and viral in 10.3% (n = 19); polymicrobial infections were observed in 24 patients (18%). Escherichia coli represented most of Gram-negative isolates (18.9%), while coagulase-negative Staphylococci were the most frequent among Gram-positive (14.2%). The 30-day mortality of patients with SI was higher when compared to patients without SI (69% vs. 15%, p < 0.001). The occurrence of SI worsened COVID-19 outcome in HM patients. Timely diagnosis and adequate management should be considered to improve their prognosis.

Nano-GLADIATOR: real-time detection of copy number alterations from nanopore sequencing data.

MOTIVATION: The past few years have seen the emergence of nanopore-based sequencing technologies which interrogate single molecule of DNA and generate reads sequentially. RESULTS: In this paper, we demonstrate that, thanks to the sequentiality of the nanopore process, the data generated in the first tens of minutes of a typical MinION/GridION run can be exploited to resolve the alterations of a human genome at a karyotype level with a resolution in the order of tens of Mb, while the data produced in the first 6-12 h allow to obtain a resolution comparable to currently available array-based technologies, and thanks to a novel probabilistic approach are capable to predict the allelic fraction of genomic alteration with high accuracy. To exploit the unique characteristics of nanopore sequencing data we developed a novel software tool, Nano-GLADIATOR, that is capable to perform copy number variants/alterations detection and allelic fraction prediction during the sequencing run ('On-line' mode) and after experiment completion ('Off-line' mode). We tested Nano-GLADIATOR on publicly available ('Off-line' mode) and on novel whole genome sequencing dataset generated with MinION device ('On-line' mode) showing that our tool is capable to perform real-time copy number alterations detection obtaining good results with respect to other state-of-the-art tools. AVAILABILITY AND IMPLEMENTATION: Nano-GLADIATOR is freely available at https://sourceforge.net/projects/nanogladiator/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.