We present an integrated analysis of the clinical measurements, immune cells and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

Implementation of an updated ICU analgesia, sedation, and delirium protocol was associated with an increase in RASS and CAM-ICU assessment and documentation; reduced hourly benzodiazepine dose; and decreased delirium and median durations of mechanical ventilation, ICU stay, and hospitalization.

PURPOSE:Common labs such as a daily complete blood count or a daily basic metabolic panel represent possible waste and have been targeted by professional societies and the Choosing Wisely campaign for critical evaluation. We undertook a multifaceted quality-improvement (QI) intervention in a large community hospitalist group to decrease unnecessary common labs. METHODS:The QI intervention was composed of academic detailing, audit and feedback, and transparent reporting of the frequency with which common labs were ordered as daily within the hospitalist group. We performed a pre-post analysis, comparing a cohort of patients during the 10-month baseline period before the QI intervention and the 7-month intervention period. Demographic and clinical data were collected from the electronic medical record. The primary endpoint was number of common labs ordered per patient-day as estimated by a clustered multivariable linear regression model clustering by ordering hospitalist. Secondary endpoints included length of stay, hospital mortality, 30-day readmission, blood transfusion, amount of blood transfused, and laboratory cost per patient. RESULTS:The baseline (n 5 7824) and intervention (n 5 5759) cohorts were similar in their demographics, though the distribution of primary discharge diagnosisrelated groups differed. At baseline, a mean of 2.06 (standard deviation 1.40) common labs were ordered per patientday. Adjusting for age, sex, and principle discharge diagnosis, the number of common labs ordered per patient-day decreased by 0.22 (10.7%) during the intervention period compared to baseline (95% confidence interval [CI], 0.34 to 0.11; P < 0.01). There were nonsignificant reductions in hospital mortality in the intervention period compared to baseline (2.2% vs 1.8%, P 5 0.1) as well as volume of blood transfused in patients who received a transfusion (127.2 mL decrease; 95% CI, 2257.9 to 3.6; P 5 0.06). No effect was seen on length of stay or readmission rate. The intervention decreased hospital direct costs by an estimated $16.19 per admission or $151,682 annualized (95% CI, $119,746 to $187,618).CONCLUSION: Implementation of a multifaceted QI intervention within a community-based hospitalist group was associated with a significant, but modest, decrease in the number of ordered lab tests and hospital costs. No effect was seen on hospital length of stay, mortality, or readmission rate. This intervention suggests that a communitybased hospitalist QI intervention focused on daily labs can be effective in safely reducing healthcare waste without compromising quality of care. Journal