Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.

BACKGROUND: The SARS-CoV-2 pandemic is currently leading to increasing numbers of COVID-19 patients all over the world. Clinical presentations range from asymptomatic, mild respiratory tract infection, to severe cases with acute respiratory distress syndrome, respiratory failure, and death. Reports on a dysregulated immune system in the severe cases call for a better characterization and understanding of the changes in the immune system. METHODS: In order to dissect COVID-19-driven immune host responses, we performed RNA-seq of whole blood cell transcriptomes and granulocyte preparations from mild and severe COVID-19 patients and analyzed the data using a combination of conventional and data-driven co-expression analysis. Additionally, publicly available data was used to show the distinction from COVID-19 to other diseases. Reverse drug target prediction was used to identify known or novel drug candidates based on finding from data-driven findings. RESULTS: Here, we profiled whole blood transcriptomes of 39 COVID-19 patients and 10 control donors enabling a data-driven stratification based on molecular phenotype. Neutrophil activation-associated signatures were prominently enriched in severe patient groups, which was corroborated in whole blood transcriptomes from an independent second cohort of 30 as well as in granulocyte samples from a third cohort of 16 COVID-19 patients (44 samples). Comparison of COVID-19 blood transcriptomes with those of a collection of over 3100 samples derived from 12 different viral infections, inflammatory diseases, and independent control samples revealed highly specific transcriptome signatures for COVID-19. Further, stratified transcriptomes predicted patient subgroup-specific drug candidates targeting the dysregulated systemic immune response of the host. CONCLUSIONS: Our study provides novel insights in the distinct molecular subgroups or phenotypes that are not simply explained by clinical parameters. We show that whole blood transcriptomes are extremely informative for COVID-19 since they capture granulocytes which are major drivers of disease severity.

Effect of edge pruning on structural controllability and observability of complex networks.

Controllability and observability of complex systems are vital concepts in many fields of science. The network structure of the system plays a crucial role in determining its controllability and observability. Because most naturally occurring complex systems show dynamic changes in their network connectivity, it is important to understand how perturbations in the connectivity affect the controllability of the system. To this end, we studied the control structure of different types of artificial, social and biological neuronal networks (BNN) as their connections were progressively pruned using four different pruning strategies. We show that the BNNs are more similar to scale-free networks than to small-world networks, when comparing the robustness of their control structure to structural perturbations. We introduce a new graph descriptor, 'the cardinality curve', to quantify the robustness of the control structure of a network to progressive edge pruning. Knowing the susceptibility of control structures to different pruning methods could help design strategies to destroy the control structures of dangerous networks such as epidemic networks. On the other hand, it could help make useful networks more resistant to edge attacks.