Risk factors for clinical outcomes of COVID-19 pneumonia have not yet been well established in patients with underlying liver diseases. Our study aimed to describe the clinical characteristics and outcomes of COVID-19 infection among patients with underlying liver diseases and determine the risk factors for severe COVID-19 among them. In a retrospective analytical study, 1002 patients with confirmed COVID-19 pneumonia were divided into two groups: patients with and without underlying liver diseases. The admission period was from 5 March to 14 May 2020. The prevalence of underlying conditions, Demographic data, clinical parameters, laboratory data, and participants' outcomes were evaluated. Logistic regression was used to estimate the predictive factors. Eighty-one (8%) of patients had underlying liver diseases. The frequencies of gastrointestinal symptoms such as diarrhea and vomiting were significantly higher among patients with liver diseases (48% vs. 25% and 46.1% vs. 30% respectively, both P < 0.05). Moreover, ALT and AST were significantly higher among patients with liver diseases (54.5 ± 45.6 vs. 37.1 ± 28.4, P = 0.013 and 41.4 ± 27.2 vs. 29.2 ± 24.3, P = 0.028, respectively). Additionally, the mortality rate was significantly high in patients with liver disease (12.4% vs. 7%, P = 0.018). We also observed that the parameters such as neutrophil to leukocyte ratio [Odds Ratio Adjusted (ORAdj) 1.81, 95% CI 1.21–3.11, P = 0.011] and blood group A (ORAdj 1.59, 95% CI 1.15–2.11, P = 0.001) were associated with progression of symptoms of COVID-19. The presence of underlying liver diseases should be considered one of the poor prognostic factors for worse outcomes in patients with COVID-19.
Background and purpose: The lack of a new effective treatment for small cell lung cancer (SCLC) is an unresolved problem. Due to the new identification of delta-like ligand 3 (DLL3) and its high expression in SCLC patients, the use of DLL3 in target therapy can be effective. The use of bacterial toxins belonging to the ADP-ribosyl transferase toxins family and human enzymes to remove cancerous cells has been effective in the structure of immunotoxins. In this study, single-chain fragment variable of rovalpituzumab antibody fused to granzyme B (Rova-GrB) and PltA of typhoid toxin (Rova-Typh) as immunotoxins were designed, and bioinformatics analysis was done. Experimental approach: In silico analysis including the physicochemical properties, evaluation of the secondary and tertiary structure, refinement and validation of 3D models, and docking were performed. Immunotoxin genes were cloned and expressed in the Escherichia coli BL21 (DE3) host, purified, subsequently confirmed by western blotting and their secondary structure was evaluated by the circular dichroism method. Findings/Results: The bioinformatics analysis showed that Rova-GrB and Rova-Typh had hydrophilic properties, their codon optimization parameters were standard, validation parameters were improved after immunotoxin refinement, and docking analysis showed that the binding domain of immunotoxins could bind the N-terminal region of DLL3. immunotoxins had high expression and after purification under denaturing condition by Ni-NTA column, the immunotoxins were dialyzed against PBS buffer. Conclusion and implications: The immunotoxins had the right structure and can be produced in a prokaryotic host. The recombinant immunotoxins against DLL3 can be promising therapeutic agents for SCLC cancer.
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