Bacterial infections and antibiotic utilization varies by coronavirus disease 19 (COVID-19) severity in hospitalized cancer patients: Analysis from the first phase of the pandemic.

OBJECTIVE: To characterize bacterial infections and antibiotic utilization in hospitalized cancer patients with coronavirus disease 2019 (COVID-19). DESIGN: Retrospective cohort study. SETTING: Tertiary cancer center in New York City. PATIENTS: Hospitalized cancer patients ≥18 years with COVID-19 between March 1, 2020, and May 31, 2020. METHODS: Patients were classified with mild COVID-19 (ie, with room air), moderate COVID-19 (ie, using nasal cannula oxygen), or severe COVID-19 (ie, using high-flow oxygen or mechanical ventilation). The primary outcome was bacterial infection rate within 30 days of COVID-19 onset. Secondary outcomes included the proportion of patients receiving antibiotics and antibiotic length of therapy (LOT). RESULTS: Of 358 study patients, 133 had mild COVID-19, 97 had moderate COVID-19, and 128 had severe COVID-19. Of 358 patients, 234 (65%) had a solid tumor. Also, 200 patients (56%) had 245 bacterial infections, of which 67 (27%) were microbiologically confirmed. The proportion of patients with bacterial infection increased with COVID-19 severity: mild (n = 47, 35%) versus moderate (n = 49, 51%) versus severe (n = 104, 81%) (P < .0001). Also, 274 (77%) received antibiotics for a median of 4 days. The median antibiotic LOTs were 7 days with 1 infection and 20 days with multiple infections (P < .0001). Antibiotic durations were 1 day for patients with mild COVID-19, 4 days for patients with moderate COVID-19, and 8 days for patients with severe COVID-19 (P < .0001). CONCLUSIONS: Hospitalized cancer patients with COVID-19 had a high rate of bacterial infection. As COVID-19 severity increased, the proportion of patients diagnosed with bacterial infection and given antibiotics increased. In mild COVID-19 cases, antibiotic LOT was short, suggesting that empiric antibiotics can be safely avoided or discontinued in this group.

A unifying paradigm for transcriptional heterogeneity and squamous features in pancreatic ductal adenocarcinoma.

Pancreatic cancer expression profiles largely reflect a classical or basal-like phenotype. The extent to which these profiles vary within a patient is unknown. We integrated evolutionary analysis and expression profiling in multiregion-sampled metastatic pancreatic cancers, finding that squamous features are the histologic correlate of an RNA-seq-defined basal-like subtype. In patients with coexisting basal and squamous and classical and glandular morphology, phylogenetic studies revealed that squamous morphology represented a subclonal population in an otherwise classical and glandular tumor. Cancers with squamous features were significantly more likely to have clonal mutations in chromatin modifiers, intercellular heterogeneity for MYC amplification and entosis. These data provide a unifying paradigm for integrating basal-type expression profiles, squamous histology and somatic mutations in chromatin modifier genes in the context of clonal evolution of pancreatic cancer.