Cytokine Profiles in the Detection of Severe Lung Involvement in Hospitalized Patients With COVID-19: the IL-8 – IL-32 axis (preprint)

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a “cytokine storm”, characterized by anomalous release of various pro-inflammatory cytokines which contribute to alveolar exudation and lung damage. Overproduction of the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-α and low of expression IFN-γ have been found in severe COVID-19 patients. The mechanism by which IL-32 exerts its signalling properties is unclear. IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. A total of 64 COVID-19 patients, stratifying as mild moderate and severe patients and 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1β, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32.The best model performance for severe group was obtained by the combination of IL-32, IL-6 and IFN-γ, and serum concentrations of CRP increased model performance, showing AUC=0.83. New insights into the cytokine storm in COVID-19 patients, highlighting specific cytokine signatures among patients with different severity of infection. 

Clinical and molecular characterization of COVID-19 hospitalized patients (preprint)

Clinical and molecular characterization by Whole Exome Sequencing (WES) is reported in 35 COVID-19 patients attending the University Hospital in Siena, Italy, from April 7 to May 7, 2020. Eighty percent of patients required respiratory assistance, half of them being on mechanical ventilation. Fiftyone percent had hepatic involvement and hyposmia was ascertained in 3 patients. Searching for common genes by collapsing methods against 150 WES of controls of the Italian population failed to give straightforward statistically significant results with the exception of two genes. This result is not unexpected since we are facing the most challenging common disorder triggered by environmental factors with a strong underlying heritability (50%). The lesson learned from Autism-Spectrum-Disorders prompted us to re-analyse the cohort treating each patient as an independent case, following a Mendelian-like model. We identified for each patient an average of 2.5 pathogenic mutations involved in virus infection susceptibility and pinpointing to one or more rare disorder(s). To our knowledge, this is the first report on WES and COVID-19. Our results suggest a combined model for COVID-19 susceptibility with a number of common susceptibility genes which represent the favorite background in which additional host private mutations may determine disease progression.