Serial laboratory biomarkers are associated with ICU outcomes in patients hospitalized with COVID-19.

BackgroundClinical utility of routinely measured serial biomarkers in predicting escalation of inpatient care intensity and mortality among hospitalized patients with COVID-19 remains unknown.MethodsThis retrospective cohort study included patients with COVID-19 who admitted to the Massachusetts General Hospital between March and June 2020 and January to March 2021. White blood cell (WBC) count, platelet count, C-reactive protein (CRP), and D-dimer values were measured on days 1, 3, and 7 of admission. Clinical outcomes include 30- and 60-day morality, ICU transfer, and overall survival (OS) over a follow-up period of 90 days. The association between serial biomarkers and outcomes were assessed using multivariable logistic regression and Cox proportional hazards models.Measurements and main resultsOf the 456 patients hospitalized with COVID-19, 199 (43.6%) were ICU, 179 (39.3%) were medical floor, and 78 (17.1%) were initially admitted to the medical floor and then transferred to the ICU. In adjusted analyses, each unit increase in the slope of CRP was associated with a 42% higher odds of ICU transfer after controlling for the initial admission level (OR = 1.42, 95% CI: 1.25-1.65, P ConclusionsSerial change in CRP levels from admission is associated with escalations of inpatient care intensity and mortality among hospitalized patients with COVID-19

A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening

COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system