PCSK9 inhibitor recaticimab for hypercholesterolemia on stable statin dose: a randomized, double-blind, placebo-controlled phase 1b/2 study.

BACKGROUND: Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. METHODS: In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). RESULTS: A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from -48.37 to -59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. CONCLUSION: Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov , number NCT03944109.

Risk factors on admission associated with hospital length of stay in patients with COVID-19: a retrospective cohort study.

Treating patients with COVID-19 is expensive, thus it is essential to identify factors on admission associated with hospital length of stay (LOS) and provide a risk assessment for clinical treatment. To address this, we conduct a retrospective study, which involved patients with laboratory-confirmed COVID-19 infection in Hefei, China and being discharged between January 20 2020 and March 16 2020. Demographic information, clinical treatment, and laboratory data for the participants were extracted from medical records. A prolonged LOS was defined as equal to or greater than the median length of hospitable stay. The median LOS for the 75 patients was 17 days (IQR 13-22). We used univariable and multivariable logistic regressions to explore the risk factors associated with a prolonged hospital LOS. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were estimated. The median age of the 75 patients was 47 years. Approximately 75% of the patients had mild or general disease. The univariate logistic regression model showed that female sex and having a fever on admission were significantly associated with longer duration of hospitalization. The multivariate logistic regression model enhances these associations. Odds of a prolonged LOS were associated with male sex (aOR 0.19, 95% CI 0.05-0.63, p = 0.01), having fever on admission (aOR 8.27, 95% CI 1.47-72.16, p = 0.028) and pre-existing chronic kidney or liver disease (aOR 13.73 95% CI 1.95-145.4, p = 0.015) as well as each 1-unit increase in creatinine level (aOR 0.94, 95% CI 0.9-0.98, p = 0.007). We also found that a prolonged LOS was associated with increased creatinine levels in patients with chronic kidney or liver disease (p < 0.001). In conclusion, female sex, fever, chronic kidney or liver disease before admission and increasing creatinine levels were associated with prolonged LOS in patients with COVID-19.

Systematic analyses on the potential immune and anti-inflammatory mechanisms of Shufeng Jiedu Capsule against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia.

The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-caused pneumonia (Coronavirus disease -19, COVID-19), has resulted in a global health emergency. However, there is no vaccine or effective antiviral treatment against the newly emerged coronavirus and identifying the available therapeutics as soon as possible is critical for the response to the spread of SARS-CoV-2. Shufeng Jiedu Capsule (SFJDC), a well-known prescription of Traditional Chinese Medicine (TCM) in China, has been widely used in treating upper respiratory tract infections and acute lung injury, owing to its immunomodulatory and anti-inflammatory effects. Despite the definite evidence of effective use of SFJDC in the diagnosis and treatment of pneumonia caused by SARS-CoV-2, the underlying action mechanism remains unknown. Currently, a systematic study integrated with absorption, distribution, metabolism and excretion (ADME) evaluation, target prediction, network construction and functional bioinformatics analyses is proposed to illustrate the potential immune and anti-inflammatory mechanisms of SFJDC against SARS-CoV-2. Additionally, to further validate the reliability of the interactions and binding affinities between drugs and targets, docking, Molecular dynamics Simulations (MD) simulations and Molecular Mechanics/Poisson-Boltzmann Surface Area approach (MM-PBSA) calculations were carried out. The results demonstrate that SFJDC regulates the immunomodulatory and anti-inflammatory related targets on multiple pathways through its active ingredients, showing the potential anti-novel coronavirus effect. Overall, the work can provide a better understanding of the therapeutic mechanism of SFJDC for treating SARS-CoV-2 pneumonia from multi-scale perspectives, and may also offer a valuable clue for developing novel pharmaceutical strategies to control the current coronavirus.

The potential insights of Traditional Chinese Medicine on treatment of COVID-19.

Corona Virus Disease 2019 (COVID-19) broke out in 2019 and spread rapidly around the world. There is still no specific antiviral therapy to the current pandemic. In China, historical records show that Traditional Chinese Medicine (TCM) is effective in prevention and enhancing the resistance to pandemic with unique insights. To fight with COVID-19, National Health and Commission of PRC has recommended some TCM in the guideline, such as HuoxiangZhengqi, LianhuaQingwen ShufengJiedu and XueBijing, and actually displayed a remarkable effect in clinical treatment strategic for COVID-19. We review studies to provide an in-depth understanding into the effect of TCM, and also introduce the possible mechanism involved in COVID-19 treatment.

Potential therapeutic targets and promising drugs for combating SARS-CoV-2.

As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.

Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia.

Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ⁓ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and "Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)" in China, so as to provide reference for the treatment of COVID-19.

Novel coronavirus (SARS-CoV-2) infection in a renal transplant recipient: Case report.

An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in Wuhan, China, with cases now confirmed in multiple countries. The clinical course of patients remains to be fully characterized, clinical presentation ranges from asymptomatic infection to acute respiratory distress syndrome and acute renal failure, and no pharmacological therapies of proven efficacy yet exist. We report a case of SARS-CoV-2 infection in a renal transplant recipient with excellent outcome. This case states the importance of close monitoring of the concentration of cyclosporine in patients treated with lopinavir/ritonavir; the routine treatment of corticosteroid can be continued. This is a rare report of SARS-CoV-2 infection in a renal transplant recipient. Further data are needed to achieve better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of SARS-CoV-2 infections in solid organ transplant recipients.