Factors associated with prompt recovery among hospitalised patients with coronavirus disease 2019.

BACKGROUND: Patients who survived hospitalisation for COVID-19 experienced varying durations of illness but the factors associated with prompt recovery are unknown. This study identifies factors differentiating hospitalised patients who recovered promptly versus survived a prolonged course of illness because of COVID-19. METHODS: This was a retrospective study from March-August 2020 of hospitalised adults with COVID-19 which were grouped based on time to recovery: short (≤3 days), intermediate (4-10 days) and prolonged (>10 days). Recovery was defined as resolution of fever, tachypnea, hypotension, extubation and return of mental status at baseline. Multivariate analysis was used to evaluate factors associated with prompt recovery. RESULTS: Among 508 patients hospitalised for COVID-19, 401 (79%) survived. Of those, prompt recovery (within 3 days) was achieved in 43% (174/401), whereas 23% (92/401) recovered after a prolonged period of >10 days. Overall, median age was 64 years with 73% admitted from home and 25% from a skilled nursing facility. Predictors for prompt recovery upon admission included female sex (OR, 1.8; 95% CI, 1.1-2.7; P = .01), no fever (OR, 1.6; 95% CI, 1.1-2.6; P = .03), longer time from symptom onset to hospitalisation (OR, 1.1; 95% CI, 1.0-1.1; P = .001), no supplemental oxygen (OR, 1.9; 95% CI, 1.2-3.0; P = .004), no direct ICU admission (OR, 41.7; 95% CI, 2.4-740.4; P = .01) and absence of bacterial co-infections (OR, 2.5; 95% CI, 1.5-4.0, P = .0003). CONCLUSIONS: Our study provides relevant data that could help clinicians triage competing resources in health systems that are challenged by the ebb and flow of COVID-19 cases by identifying clinical features of COVID-19 patients who may require less intensive management including avoidance of unnecessary antibacterial therapy.

Light-Triggered Genome Editing: Cre Recombinase Mediated Gene Editing with Near-Infrared Light.

A light-activated genome editing platform based on the release of enzymes from a plasmonic nanoparticle carrier when exposed to biocompatible near-infrared light pulses is described. The platform relies on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of copper which is attached to double-stranded nucleic acids self-assembled on the gold nanoparticle surface. A protein fusion of the Cre recombinase containing a TAT internalization peptide sequence to achieve endosomal localization is also employed. High-resolution gene knock-in of a red fluorescent reporter is observed using a commercial two-photon microscope. High-throughput irradiation is described to generate useful quantities of edited cells.

Affinity-Based Assembly of Peptides on Plasmonic Nanoparticles Delivered Intracellularly with Light Activated Control.

We report a universal strategy for functionalizing near-infrared light-responsive nanocarriers with both a peptide "cargo" and an orthogonal cell-penetrating peptide. Modularity of both the cargo and the internalization peptide attachment is an important feature of these materials relying on the robust affinity of polyhistidine tags to nitrilotriacetic acid in the presence of nickel as well as the affinity of biotin labeled peptides to streptavidin. Attachment to the gold surface uses thiol-labeled scaffolds terminated with the affinity partner. These materials allow for unprecedented spatiotemporal control over the release of the toxic α-helical amphipathic peptide (KLAKLAK)2 which disrupts mitochondrial membranes and initiates apoptotic cell death. Laser treatment at benign near-infrared wavelengths releases peptide from the gold surface as well as breaches the endosome barrier for cytosolic activity (with 105-fold improved response to peptide activity over the free peptide) and can be monitored in real time.

Risk factors and outcome associated with infection or colonization due to carbapenem-heteroresistant Escherichia coli.

BACKGROUND: Up to 32% of ESBL-producing Enterobacterales strains display a carbapenem-heteroresistant (cHR) phenotype but its clinical relevance is unknown. OBJECTIVES: To determine risk factors and clinical outcome associated with infection due to cHR ESBL-producing Escherichia coli (ESBL-EC). METHODS: A retrospective, case-control study was conducted on patients from whom a pair of clonally related E. coli strains were isolated during separate healthcare encounters with (case) or without (control) development of cHR phenotype in the latter strain. Study groups were compared for host and microbial characteristics and carbapenem exposure. Outcome measures included ICU admission, length of hospitalization, and mortality. RESULTS: Study patients (15 cases, 10 controls) were elderly (median age: 74 years) with half admitted from home (52%), most (80%) having ≥3 comorbid conditions and severe functional impairment. Case patients were more likely to have 'index' ESBL-EC isolating from blood (27% versus 0%; P = 0.125) and have greater cumulative amount and duration of carbapenem exposure than controls. All control 'subsequent' isolates were from urine whereas five cHR case isolates were from blood or respiratory sources. More hospitalized case patients required ICU admission (23% versus 0%; P = 0.257) and prolonged hospital stay (>7 days) than controls (62% versus 38%%; P = 0.387). CONCLUSIONS: Our findings deserve confirmation with a larger study population and call attention to the potential for increased morbidity with cHR ESBL-EC infections, which underscores the need to screen for cHR phenotype in patients with repeated growth of ESBL-EC, particularly from systemic sites and patients that have had extensive carbapenem exposure.