Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.

Prognostic Value of Leucocyte to High-Density Lipoprotein-Cholesterol Ratios in COVID-19 Patients and the Diabetes Subgroup.

Background: Blood parameters, such as neutrophil-to-lymphocyte ratio, have been identified as reliable inflammatory markers with diagnostic and predictive value for the coronavirus disease 2019 (COVID-19). However, novel hematological parameters derived from high-density lipoprotein-cholesterol (HDL-C) have rarely been studied as indicators for the risk of poor outcomes in patients with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection. Here, we aimed to assess the prognostic value of these novel biomarkers in COVID-19 patients and the diabetes subgroup. Methods: We conducted a multicenter retrospective cohort study involving all hospitalized patients with COVID-19 from January to March 2020 in five hospitals in Wuhan, China. Demographics, clinical and laboratory findings, and outcomes were recorded. Neutrophil to HDL-C ratio (NHR), monocyte to HDL-C ratio (MHR), lymphocyte to HDL-C ratio (LHR), and platelet to HDL-C ratio (PHR) were investigated and compared in both the overall population and the subgroup with diabetes. The associations between blood parameters at admission with primary composite end-point events (including mechanical ventilation, admission to the intensive care unit, or death) were analyzed using Cox proportional hazards regression models. Receiver operating characteristic curves were used to compare the utility of different blood parameters. Results: Of 440 patients with COVID-19, 67 (15.2%) were critically ill. On admission, HDL-C concentration was decreased while NHR was high in patients with critical compared with non-critical COVID-19, and were independently associated with poor outcome as continuous variables in the overall population (HR: 0.213, 95% CI 0.090-0.507; HR: 1.066, 95% CI 1.030-1.103, respectively) after adjusting for confounding factors. Additionally, when HDL-C and NHR were examined as categorical variables, the HRs and 95% CIs for tertile 3 vs. tertile 1 were 0.280 (0.128-0.612) and 4.458 (1.817-10.938), respectively. Similar results were observed in the diabetes subgroup. ROC curves showed that the NHR had good performance in predicting worse outcomes. The cutoff point of the NHR was 5.50. However, the data in our present study could not confirm the possible predictive effect of LHR, MHR, and PHR on COVID-19 severity. Conclusion: Lower HDL-C concentrations and higher NHR at admission were observed in patients with critical COVID-19 than in those with noncritical COVID-19, and were significantly associated with a poor prognosis in COVID-19 patients as well as in the diabetes subgroup.

Clinical characteristics of 1327 patients with coronavirus disease 2019 (COVID-19) in the largest Fangcang shelter hospital in Wuhan

This article aimed to study the clinical characteristics of these patients admitted to Jianghan Fangcang shelter hospital, the largest Fangcang shelter hospital in Wuhan, China. It is worth highlighting that six patients had anosmia without nasal congestion as the initial symptom. At the time of discharge from the Fangcang shelter hospital, the findings on chest CT were alleviated in 95.5% (1241/1300) of the patients. However, only one patient had chest CT findings suggestive of disease progression. Symptomatic patients have higher CRP level and lower lymphocytes counts than asymptomatic patients, which might suggest that higher CRP level and lower lymphocytes counts were related to the severity of symptoms. However, CT characteristics were not statistically different between symptomatic and asymptomatic patients, which might indicate that CT characteristics were not associated with the severity of symptoms in non-critical patients. In conclusion, patients with fever and anosmia but without nasal congestion are more likely to be suffering from COVID-19. Higher CRP level and lower lymphocytes counts might relate to the severity of symptoms, while CT abnormalities were not associated with the severity of symptoms in non-critical patients.

Comparisons in concentrations of chlorine compounds in urban section of nanfeihe river before and after COVID-19 epidemic

The spread of COVID-19 epidemic in early 2020 has led to the widespread use of medical disinfectants, which will inevitably impact the ecological balance of natural water environment. Based on the data collection, field investigation and sampling and analysis, the main disinfectant types, toxicity and their distribution characteristics in Nanfeihe River, an urban river in Hefei City, Anhui Province were analyzed and studied, with the emphasis on the impact on water environment and aquatic ecosystem. The results showed that the most widely used disinfectant is chlorine containing disinfectant in the COVID-19 epidemic, and the total amount of the disinfectants and its by-products as calculated by total chlorine in the urban section of the River is 5.52-48.7g/L, which is significantly higher than the measured value during non COVID-19 epidemic period. It shows that the use of chlorine containing disinfectants during the epidemic has caused residues in urban water. In addition, the sampling points near the effluent of sewage treatment plant and rainwater discharge had significantly higher chlorine compounds, as compared with other points, indicating the ways of the disinfectant and its by-products entering water environment mainly including effluent discharge from sewage treatment plants and non-point source pollution caused by urban surface rainwater runoff. In order to reduce or eliminate the adverse effects of use of disinfectants on the urban water environment and aquatic ecological health, source control, process reduction, and terminal treatment, as well as supervision of the whole process of plant-network-river integration should be considered in future work.

Clinical characteristics and prognostic factors of COVID-19 patients progression to severe: a retrospective, observational study.

The outbreak of coronavirus disease 2019 (COVID-19) has become a world-wide emergency. The severity of COVID-19 is highly correlated with its mortality rate. We aimed to disclose the clinical characteristics and prognostic factors of COVID-19 patients who developed severe COVID-19. The study enrolled cases (no=1848) with mild or moderate type of COVID-19 in Fangcang shelter hospital of Jianghan. A total of 56 patients progressed from mild or moderate to severe. We used least absolute shrinkage and selection operator regression model to select prognostic factors for this model. The case-severity rate was 3.6% in the shelter hospital. They were all symptomatic at admission. Fever, cough, and fatigue were the most common symptoms. Hypertension, diabetes and coronary heart diseases were common co-morbidities. Predictors contained in the prediction nomogram included fever, distribution of peak temperature (>38°C), myalgia or arthralgia and distribution of C-reactive protein (≥10 mg per L). The distribution of peak temperature (>38°C) on set, myalgia or arthralgia and C-reactive protein (≥10 mg per L) were the prognostic factors to identify the progression of COVID-19 patients with mild or moderate type. Early attention to these risk factors will help alleviate the progress of the COVID-19.

Impaired Fasting Glucose and Diabetes Are Related to Higher Risks of Complications and Mortality Among Patients With Coronavirus Disease 2019.

Background: Diabetes correlates with poor prognosis in patients with COVID-19, but very few studies have evaluated whether impaired fasting glucose (IFG) is also a risk factor for the poor outcomes of patients with COVID-19. Here we aimed to examine the associations between IFG and diabetes at admission with risks of complications and mortality among patients with COVID-19. Methods: In this multicenter retrospective cohort study, we enrolled 312 hospitalized patients with COVID-19 from 5 hospitals in Wuhan from Jan 1 to Mar 17, 2020. Clinical information, laboratory findings, complications, treatment regimens, and mortality status were collected. The associations between hyperglycemia and diabetes status at admission with primary composite end-point events (including mechanical ventilation, admission to intensive care unit, or death) were analyzed by Cox proportional hazards regression models. Results: The median age of the patients was 57 years (interquartile range 38-66), and 172 (55%) were women. At the time of hospital admission, 84 (27%) had diabetes (and 36 were new-diagnosed), 62 (20%) had IFG, and 166 (53%) had normal fasting glucose (NFG) levels. Compared to patients with NFG, patients with IFG and diabetes developed more primary composite end-point events (9 [5%], 11 [18%], 26 [31%]), including receiving mechanical ventilation (5 [3%], 6 [10%], 21 [25%]), and death (4 [2%], 9 [15%], 20 [24%]). Multivariable Cox regression analyses showed diabetes was associated increased risks of primary composite end-point events (hazard ratio 3.53; 95% confidence interval 1.48-8.40) and mortality (6.25; 1.91-20.45), and IFG was associated with an increased risk of mortality (4.11; 1.15-14.74), after adjusting for age, sex, hospitals and comorbidities. Conclusion: IFG and diabetes at admission were associated with higher risks of adverse outcomes among patients with COVID-19.

Clinical characteristics and outcomes of COVID-19 patients with gastrointestinal symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan, China.

Coronavirus disease 2019 (COVID-19) is a health emergency worldwide, and gastrointestinal (GI) symptoms are increasingly reported in COVID-19 patients. However, sample size was small and the incidence of GI symptoms in patients was variable across studies, and the correlation between these symptoms and clinical outcomes remains incompletely understood. The objective of this study is to compare clinical characteristics and outcomes between patients with and without GI symptoms admitted to Jianghan Fangcang Shelter Hospital in Wuhan. This retrospective study recruited 1320 COVID-19 patients admitted to hospital from 5 February 2020 to 9 March 2020. On the basis of the presence of GI symptoms, the sample was divided into a GI group (n = 192) and a non-GI group (n = 1128). The three most common GI symptoms were diarrhea (8.1%), anorexia (4.7%), and nausea and vomiting (4.3%). The rate of clinical deterioration was significantly higher in the GI group than in the non-GI group (15.6% vs. 10.1%, P = .032). GI symptoms (P = .045), male gender P < .001), and increased C-reactive protein (P = .008) were independent risk factors for clinical worsening. This study demonstrated that the rate of clinical deterioration was significantly higher in the GI group. Furthermore, potential risk factors for developing GI symptoms, male gender, and increased C-reactive protein can help clinicians predict clinical outcomes in COVID-19 patients.