Exploring an Integrative Therapy for Treating COVID-19: A Randomized Controlled Trial.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS: Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).

[Rapid establishment of traditional Chinese medicine prevention and treatment of 2019-nCoV based on clinical experience and molecular docking].

The coronavirus disease 2019(COVID-19) is raging in China and more than 20 other countries and regions since the middle of December 2019. Currently, there is no specific drug or vaccine besides symptomatic supportive therapy. Taking full advantage of the clinical experience of traditional Chinese medicine(TCM) in preventing and controlling major epidemics such as SARS, it is an important mission for TCM to propose effective formula with immediate response and solid evidence by using modern biomedical knowledge and techniques(molecular docking assisted TCM formulation for short). In view of the high homology between the gene sequences of the novel coronavirus and SARS virus, and the similarities between the two in terms of pathogenic mechanism and clinical manifestations, our team established a rapid screening and optimization model for the prevention and treatment of the novel coronavirus based on clinical experience and molecular docking technology. Firstly, the clinical team and the research team pre-developed and screened TCM formula by using "back-to-back" manner. Then, the formula was optimized and determined by comparing and analyzing the results of the two groups. The results showed that the research team screened out 46 active ingredients from candidate TCMs that could act on the novel coronavirus S-protein-binding site of human ACE2 protein, which were mainly attributed to 7 herbs such as Lonicerae Japonicae Flos and Mori Folium. The result was largely consistent with the formula raised by the clinical group, verifying and supporting its rationality. This provides evidence for the scientific and potential efficacy of the TCM prescription from the perspective of treatment target analysis, and also suggests that the TCM prescription has the potential to directly inhibit viral infection in addition to improving clinical symptoms or syndromes. Based on this, our team optimized and formed a new anti-coronavirus TCM prescription "Keguan Yihao", immediately providing the TCM prescription with certain clinical experience and objective evidence support for the prevention and treatment of new emergent infectious diseases in our hospital. The TCM prescription was combined with modern medicine symptomatic supportive treatment for clinical treatment, preliminary results showed better effect than symptomatic supportive therapy alone. This research has innovated the method mode in clinical practice and basic research integration of traditional Chinese medicine for the prevention and control of new emerging infectious diseases. It is of great significance to further improve the rapid response mechanism of TCM in face of major epidemics, and further improve the capability level of TCM to prevent and treat new emerging infectious diseases.

Association between the concurrence of pre-existing chronic liver disease and worse prognosis in patients with an herb- Polygonum multiflorum thunb. induced liver injury: a case-control study from a specialised liver disease center in China.

OBJECTIVES: The present study aimed to evaluate the association between the concurrence of pre-existing chronic liver diseases (CLD) and worse prognosis in patients with HILI. DESIGN: A case-control study. SETTING: Tertiary hospital specialising in liver diseases in China. PARTICIPANTS: 145 hospitalised HILI patients were assessed with respect to prognosis by comparing HILI with or without pre-existing CLD from February 2007 to January 2017. Twenty-five HILI cases with pre-existing alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD) and 200 ALD or NAFLD controls matched 1:8 for sex, age (±4 years old), body mass index (±2 kg/m2), the type of CLD, alcohol intake (±5 g/d) and the presence or absence of cirrhosis. PRIMARY OUTCOME MEASURES: Mortality and chronicity in HILI patients with or without pre-existing CLD, and matched CLD patients. RESULTS: Of the 193 714 hospitalised patients with liver diseases, 5703 patients met the diagnostic criteria for drug-induced liver injury (DILI), which was attributed to Polygonum multiflorum Thunb. (PMT) in 145 patients. Among these HILI patients, 22.8% (33 of 145) had pre-existing CLD, including 17 (51.5%) with ALD, 8 (24.2%) with NAFLD, 5 (15.2%) with chronic viral hepatitis and 3 (9.1%) with autoimmune liver disease. Compared with HILI patients without CLD, HILI patients with pre-existing CLD showed higher mortality (0.9% vs 9.1%, p=0.037) and higher chronicity (12.5% vs 30.3%, p=0.016). Compared with matched ALD (136 patients) or NAFLD (64 patients) patients, HILI patients with pre-existing ALD showed higher chronicity (35.3% vs 11.8%, p=0.019). Multivariate logistic regression analysis found that concurrence of pre-existing CLD was an independent risk factor for both of chronicity and mortality (OR 3.966, 95% CI 1.501 to 10.477, p=0.005), especially the chronicity (OR 3.035, 95% CI 1.115 to 8.259, p=0.030). CONCLUSIONS: Concurrence of pre-existing CLD could be an independent risk factor for worse prognosis, especially chronicity, in PMT-related HILI.

Prevalence of psychological symptoms among Ebola survivors and healthcare workers during the 2014-2015 Ebola outbreak in Sierra Leone: a cross-sectional study.

The 2014-2015 Ebola epidemic was considered to be the largest and most complex outbreak, which caused 11,310 reported deaths. The epidemic disease can cause a mental health crisis, however, there is only a small amount of scientific literature available related to this health issue so far. We evaluated the psychological symptoms of 161 participants including Ebola survivors and healthcare workers in Sierra Leone, analyzed the impact of job classification, education level on psychological status. We found that the order of total general severity index (GSI) scores from high to low was EVD survivors, SL medical staff, SL logistic staff, SL medical students, and Chinese medical staff. There were 5 dimensions (obsession-compulsion, anxiety, hostility, phobic anxiety, and paranoid ideation) extremely high in EVD survivors. GSI were associated with university education negatively. We believed our information is necessary to develop the comprehensive emergency response plan for emerging infectious disease outbreak.

Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone.

BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥106 copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients' survival was less than 15 % when blood viral load was greater than 106 copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1-4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients.