International Comparisons of Harmonized Laboratory Value Trajectories to Predict Severe COVID-19: Leveraging the 4CE Collaborative Across 342 Hospitals and 6 Countries: A Retrospective Cohort Study (preprint)

Objectives: To perform an international comparison of the trajectory of laboratory values among hospitalized patients with COVID-19 who develop severe disease and identify optimal timing of laboratory value collection to predict severity across hospitals and regions. Design: Retrospective cohort study. Setting: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), an international multi-site data-sharing collaborative of 342 hospitals in the US and in Europe. Participants: Patients hospitalized with COVID-19, admitted before or after PCR-confirmed result for SARS-CoV-2. Primary and secondary outcome measures: Patients were categorized as ''ever-severe'' or ''never-severe'' using the validated 4CE severity criteria. Eighteen laboratory tests associated with poor COVID-19-related outcomes were evaluated for predictive accuracy by area under the curve (AUC), compared between the severity categories. Subgroup analysis was performed to validate a subset of laboratory values as predictive of severity against a published algorithm. A subset of laboratory values (CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin) was compared between North American and European sites for severity prediction. Results: Of 36,447 patients with COVID-19, 19,953 (43.7%) were categorized as ever-severe. Most patients (78.7%) were 50 years of age or older and male (60.5%). Longitudinal trajectories of CRP, albumin, LDH, neutrophil count, D-dimer, and procalcitonin showed association with disease severity. Significant differences of laboratory values at admission were found between the two groups. With the exception of D-dimer, predictive discrimination of laboratory values did not improve after admission. Sub-group analysis using age, D-dimer, CRP, and lymphocyte count as predictive of severity at admission showed similar discrimination to a published algorithm (AUC=0.88 and 0.91, respectively). Both models deteriorated in predictive accuracy as the disease progressed. On average, no difference in severity prediction was found between North American and European sites. Conclusions: Laboratory test values at admission can be used to predict severity in patients with COVID-19. There is a need for prediction models that will perform well over the course of the disease in hospitalized patients.

Statistical and network-based analysis of Italian COVID-19 data: communities detection and temporal evolution (preprint)

Coronavirus disease (COVID-19) outbreak started at Wuhan, China, and it has rapidly spread across China and many other countries. Italy is one of the European countries most affected by the COVID-19 disease, and it has registered high COVID-19 death rates and the death toll. In this article, we analyzed different Italian COVID-19 data at the regional level for the period February 24 to March 29, 2020. The analysis pipeline includes the following steps. After individuating groups of similar or dissimilar regions with respect to the ten types of available COVID-19 data using statistical test, we built several similarity matrices (reported in Supplementary file). Then, we mapped those similarity matrices into networks where nodes represent Italian regions and edges represent similarity relationships (edge length is inversely proportional to similarity). Then, network-based analysis was performed mainly discovering communities of regions that show similar behaviour. Then, network-based analysis was performed by running several community detection algorithms on those networks and by underlying communities of regions that show similar behaviour. The network-based analysis of Italian COVID-19 data is able to elegantly show how regions form communities, i.e. how they join and leave them, along time and how community consistency changes along time and with respect to the different available data.