Inflammatory biomarkers and severity of COVID-19: Cross sectional study among Egyptian patients.

The newly emerging coronavirus disease 2019 (COVID-19) is characterized by multisystem inflammatory syndrome. The development of SARS-CoV-2 complications usually starts within few days following infection, and the severity of the disease determines its outcome. Vitamin D insufficiency is associated with risk of lung infections, also cell-based studies reported the ability of vitamin D to control enveloped virus growth. We aimed to investigate the relationship between the most eminent inflammatory biomarkers and the level of vitamin D aiming to provide a tool for early diagnosis and prediction of disease progression. The current study was approved by Research Ethics Committee (REC), Kasr Al-Ainy. After confirmation of being COVID-19 by PCR, the admitted patients were categorized as mild-moderate, and severe-critically ill based on clinical and radiologic data. The total levels of serum 25(OH)D, as well as other pro-inflammatory biomarkers were measured and were analyzed by receiver operating characteristic curve (ROC) analysis for detection of their association with COVID-19 disease severity and to determine their sensitivity and specificity at optimum cutoff points. The area under the curve (AUC) ROC for predicting COVID-19 disease severity was the highest (of 0.97) for vitamin D, inflammatory cytokines, liver enzymes, ferritin, and D-Dimer. In addition, high serum levels of creatinine, and elevated liver enzymes associated with severe-critical COVID-19. The low 25(OH)D was associated with the disease severity.

Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.