Therapy With Allogeneic Severe Acute Respiratory Syndrome Coronavirus-2-Specific T Cells for Persistent Coronavirus Disease 2019 in Immunocompromised Patients.

We administered severe acute respiratory syndrome coronavirus-2 viral-specific T cells (VSTs) under emergency investigational new drug applications to 6 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) and characterized clinical and virologic responses. Three patients had partial responses after failing other therapies but then died. Two patients completely recovered, but the role of VSTs in recovery was unclear due to concomitant use of other antivirals. One patient had not responded to 2 courses of remdesivir and experienced sustained recovery after VST administration. The use of VSTs in immunocompromised patients with persistent COVID-19 requires further study.

Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting.

PURPOSE: Viral infections are a major cause of morbidity and mortality following allogeneic hematopoietic cell transplantation (allo-HCT). In the absence of safe and effective antiviral treatments, virus-specific T cells have emerged as a promising therapeutic option. Posoleucel is a multivirus-specific T-cell therapy for off-the-shelf use against six viral infections that commonly occur in allo-HCT recipients: adenovirus, BK virus (BKV), cytomegalovirus, Epstein-Barr virus, human herpes virus-6, and JC virus. PATIENTS AND METHODS: We conducted an open-label, phase II trial to determine the feasibility and safety of posoleucel in allo-HCT recipients infected with one or more of these viruses. Infections were either unresponsive to or patients were unable to tolerate standard antiviral therapies. Fifty-eight adult and pediatric patients were enrolled and treated. RESULTS: Posoleucel was well tolerated, with no cytokine release syndrome or other infusion-related toxicities; two patients (3.4%) developed Grade 2 and one patient (1.7%) Grade 3 GvHD during the trial. The overall response rate 6 weeks after the first posoleucel infusion was 95%, with a median plasma viral load reduction of 97%. Of the 12 patients who had two or more target viral infections identified at study entry, 10 (83%) had a clinical response for all evaluable viruses. Of the 23 patients treated for refractory BKV-associated hemorrhagic cystitis, 74% had resolution of symptoms and macroscopic hematuria by 6 weeks post-infusion. CONCLUSIONS: In this open-label trial, treatment of refractory viral infections/disease in allo-HCT recipients with posoleucel was feasible, safe, and effective.

Using the Comprehensive Unit-based Safety Program model for sustained reduction in hospital infections.

BACKGROUND: Prompted by the high number of central line-associated bloodstream infections (CLABSIs), our institution joined the national On the CUSP: Stop BSI initiative. We not only report the significant impact that the Comprehensive Unit-based Safety Program (CUSP) had in reducing CLABSI, but also report catheter-associated urinary tract infections (CAUTIs) and ventilator-associated pneumonia (VAP) in 2 intensive care units (ICUs). METHODS: At our community-based academic health care system, 2 ICUs implemented CUSP tools and developed local interventions to reduce CLABSI and other safety problems. We measured CLABSI, CAUTI, and VAP during baseline, the CUSP period, and a post-CUSP period. RESULTS: CLABSIs decreased from 3.9 per 1,000 catheter days at baseline to 1.2 during the CUSP period to 0.6 during the post-CUSP period (rate ratio, 0.16; 95% confidence interval [CI], 0.07-0.35). CAUTIs decreased from 2.4 per 1,000 patient days to 1.2 during the post-CUSP period (rate ratio, 0.4; 95% CI, 0.24-0.65). VAP rate decreased from 2.7 per 1,000 ventilator days to 1.6 during the CUSP and post-CUSP periods (rate ratio, 0.58; 95% CI, 0.30-1.10). Device utilization decreased significantly in both ICUs. CONCLUSIONS: Implementation of CUSP was associated with significant decreases in CLABSI, CAUTI, and VAP. The CUSP model, allowing for implementation of evidence-based practices and engagement of frontline staff, creates sustainable improvements that reach far beyond the initial targeted problem.

An Interdepartmental Care Model to Expedite Admission from the Emergency Department to the Medical ICU.

BACKGROUND: Early evidence suggests that multidisciplinary programs designed to expedite transfer from the emergency department (ED) may decrease boarding times. However, few models exist that provide effective ways to improve the ED- to-ICU transition process. In 2012 Christiana Care Health System (Newark, Delaware) created and implemented an interdepartmental program designed to expedite the transition of care from the ED to the medical ICU (MICU). METHODS: This quasi-experimental study compared ED length of stay (LOS), MICU LOS, and overall hospital LOS before and after the MICU Alert Team (MAT) intervention program. The MAT consisted of a MICU nurse and physician assistant, with oversight by a MICU attending physician. The ED triggered the MAT after patients were stabilized and determined to require MICU admission. Following bedside face-to-face hand off, the MAT providers then assumed responsibly of a patient's care. If no MICU bed was available, the MAT cared for patients in the ED until they were transferred to the MICU. RESULTS: ED LOS was reduced by 30% (2.6 hours) from baseline (p < .001). There were no significant differences in MICU LOS (p = .26), overall hospital LOS (p = .43), or mortality (p = .59). ED LOS was shortened (p < .001) at each increasing level of MICU bed availability (31% when 0 MICU beds available; 26% when 1 or more MICU beds available). Time series analysis identified a 1.5-hour drop in ED LOS (p = .02) for patients transferred from the MICU immediately following intervention implementation and was sustained over time. CONCLUSION: Early outcomes demonstrate that the MAT intervention can reduce ED LOS for critically ill patients. Additional studies should determine optimal approaches to improve clinical outcomes.