Association of procalcitonin levels with the progression and prognosis of hospitalized patients with COVID-19.

Rationale: Coronavirus disease 2019 (COVID-19) was first announced in Wuhan, and has rapidly evolved into a pandemic. However, the risk factors associated with the severity and mortality of COVID-19 are yet to be described in detail. Methods: We retrospectively reviewed the information of 1525 cases from the Leishenshan Hospital in Wuhan. Univariate and multivariate Cox regression analyses were generated to explore the relationship between procalcitonin (PCT) level and the progression and prognosis of COVID-19. Univariate and multivariate logistic regression analyses were performed to explore the relationship between disease severity in hospitalized patients and their PCT levels. Survival curves and the cumulative hazard function for COVID-19 progression were conducted in the two groups. To further detect the relationship between the computed tomography score and survival days, curve-fitting analyses were performed. Results: Patients in the elevated PCT group had a higher incidence of severe and critical severity conditions (P < 0.001), death, and higher computed tomography (CT) scores. There was an association between elevated PCT levels and mortality in the univariate ((hazard ratio [1], 3.377; 95% confidence interval [2], 1.012-10.344; P = 0.033) and multivariate Cox regression analysis (HR, 4.933; 95% CI, 1.170-20.788; P = 0.030). Similarly, patients with elevated PCT were more likely to have critically severe disease conditions in the univariate (odds ratio [2], 7.247; 95% CI, 3.559-14.757; P < 0.001) and multivariate logistic regression analysis (OR, 10.679; 95% CI, 4.562-25.000; P < 0.001). Kaplan-Meier curves showed poorer prognosis for patients with elevated PCT (P = 0.024). The CT score 1 for patients with elevated PCT peaked at day 40 following the onset of symptoms then decreased gradually, while their total CT score was relatively stable. Conclusion: PCT level was shown as an independent risk factor of in-hospital mortality among COVID-19 patients. Compared with inpatients with normal PCT levels, inpatients with elevated PCT levels had a higher risk for overall mortality and critically severe disease. These findings may provide guidance for improving the prognosis of patients with critically severe COVID-19.

Investigation on mechanism and active components of Shufeng Jiedu Capsule in treatment of COVID-19 based on network pharmacology and molecular docking

Objective: To explore the novel coronavirus disease 2019 (COVID-19) treatment mechanism and active ingredients of Shufeng Jiedu Capsule by network pharmacology and molecular docking. Methods: TCMSP databases were used to search the chemical composition and target of Shufeng Jiedu Capsule, which was composed of Isatidis Radix, Polygonum cuspidatum, Forsythia suspensa, Phragmitis Rhizoma, Patrinia, Verbena officinalis, Bupleurum chinense, and Glycyrrhiza uralensis. The Swiss target prediction database was used to remove the target with possibility of 0. The corresponding targets of the disease were searched in the GeneCards and OMIM databases with the key words of "coronavirus", "pneumonia", "cough", and "fever". Through the UniProt databases to correct the name of the target point, take the intersection of Shufeng Jiedu Capsule and the disease target point, then use the software of Cytoscape 3.7.2 to build the network of traditional Chinese medicine-compound-target for visualization, through DAVID databases to carry out the GO function enrichment analysis and KEGG pathway enrichment analysis, predict the interaction mechanism of the target, and draw the column and bubble chart for visualization. The novel coronavirus (SARS-CoV-2) 3CL hydrolase was then docking with all compounds and the first five compounds with the least binding energy were selected for docking with angiotensin-converting enzyme II (ACE2). Results: The traditional Chinese medicine-compound-target compound target network contains eight kinds of traditional Chinese medicine-compound-target, 157 compounds and 260 corresponding targets. The key targets were PTGS2, ESR1, AR, etc. There were 393 items in GO functional enrichment analysis (P < 0.05), and 139 signaling pathways in KEGG pathway enrichment analysis. Molecular docking results showed that SARS-CoV-2 3CL hydrolase and ACE2 binding energy of the five core compounds, including 6-(3-oxoindolin-2-ylidene) indolo [2,1-b] quinazolin-12-one, bicuculline, physciondiglucoside, dihydroverticillatine, and licoisoflavanone, was smaller than that of recommended chemical drugs, and the binding energy to ACE2 was similar to that of the recommended chemical drug. Conclusion: The compounds in Shufeng Jiedu Capsule can regulate the signaling pathway of human cytomegalovirus infection, Kaposi's sarcoma associated herpesvirus infection, IL-17 signaling pathway, small cell lung cancer, etc. to treat COVID-19 by binding with SARS-CoV-2 3CL hydrolase and ACE2.