The efficacy of traditional Chinese medicine in the treatment of the COVID-19 pandemic in Henan Province: a retrospective study.

BACKGROUND: Since 2020, novel coronavirus disease (COVID-19) has posed serious threats to health systems and led to tremendous economic decline worldwide. Traditional Chinese medicine (TCM) is considered a promising treatment strategy for COVID-19 in China and is increasingly recognized as a key participant in the battle against COVID-19. Clinicians also need accurate evidence regarding the effectiveness of TCM treatments for COVID-19. METHODS: We retrospectively analyzed patients diagnosed with COVID-19 by collected from the electronic medical records of the hospitals in Henan Province from January 19, 2020, to March 2, 2020. Demographic characteristics, clinical data, frequency analysis of Chinese patent medicines (CPMs), Chinese medicine injections (CMIs), evaluation of baseline symptom scores, nucleic acid negative conversion, length of hospitalization, and mortality rates were studied. RESULTS: Between 15 January 2020 and 2 March 2020, 131 hospitals with 1245 patients were included. Survey response Chinese herbal decoction, CPMs, and CMIs combined with conventional Western medicine (CWM) used for the treatment of COVID-19. The top 8 CPMs were Lianhua Qingwen capsules, Shuanghuanglian oral liquid, Pudilan Xiaoyan oral liquid, Banlangen granules, Lanqin oral liquid, compound licorice tablets, Bailing capsules, montmorillonite powder. The most frequently used CMIs were Xuebijing, Tanreqing, Reduning, Xiyanping and Yanhuning. TCM combined with CWM improved the patients' symptom scores for fever, cough, chest tightness, shortness of breath, and fatigue. Nucleic acid negative conversion occurred at11.55 ± 5.91 d and the average length of hospitalization was 14.92 ± 6.15 d. The mortality rate was approximately 1.76%, which is a reduction in patient mortality. CONCLUSIONS: TCM combined with CWM improved clinical symptoms and reduced hospitalization and mortality rates.

Peritoneal dialysis first policy in Hong Kong for 35 years: Global impact.

Peritoneal dialysis (PD) first policy has been established in Hong Kong since 1985. After 35 years of practice, the PD first policy in Hong Kong has influenced many countries around the world including governments, health ministries, nephrologists and renal nurses on the overall health policy structure and clinical practice in treating kidney failure patients using PD as an important dialysis modality. In 2021, the International Association of Chinese Nephrologists and the Hong Kong Society of Nephrology jointly held a symposium celebrating the 35 years of PD first policy in Hong Kong. In that symposium, experts and opinion leaders from around the world have shared their perspectives on how the PD first policy has grown and how it has affected PD and home dialysis practice globally. The advantages of PD during COVID-19 pandemic were highlighted and the use of telemedicine as an important adjunct was discussed in treating kidney failure patients to improve the overall quality of care. Barriers to PD and the need for sustainability of PD first policy were also emphasized. Overall, the knowledge awareness of PD as a home dialysis for patients, families, care providers and learners is a prerequisite for the success of PD first. A critical mass of PD regional hubs is needed for training and mentorship. Importantly, the alignment of policy and clinical goals are enablers of PD first program.

Treatment with quercetin inhibits SARS-CoV-2 N protein-induced acute kidney injury by blocking Smad3-dependent G1 cell-cycle arrest.

Increasing evidence shows that SARS-CoV-2 can infect kidneys and cause acute kidney injury (AKI) in critically ill COVID-19 patients. However, mechanisms through which COVID-19 induces AKI are largely unknown, and treatment remains ineffective. Here, we report that kidney-specific overexpressing SARS-CoV-2 N gene can cause AKI, including tubular necrosis and elevated levels of serum creatinine and BUN in 8-week-old diabetic db/db mice, which become worse in those with older age (16 weeks) and underlying diabetic kidney disease (DKD). Treatment with quercetin, a purified product from traditional Chinese medicine (TCM) that shows effective treatment of COVID-19 patients, can significantly inhibit SARS-CoV-2 N protein-induced AKI in diabetic mice with or without underlying DKD. Mechanistically, quercetin can block the binding of SARS-CoV-2 N protein to Smad3, thereby inhibiting Smad3 signaling and Smad3-mediated cell death via the p16-dependent G1 cell-cycle arrest mechanism in vivo and in vitro. In conclusion, SARS-CoV-2 N protein is pathogenic and can cause severe AKI in diabetic mice, particularly in those with older age and pre-existing DKD, via the Smad3-dependent G1 cell-cycle arrest mechanism. Importantly, we identify that quercetin may be an effective TCM compound capable of inhibiting COVID-19 AKI by blocking SARS-CoV-2 N-Smad3-mediated cell death pathway.

Impaired kidney function biomarkers and risk of severe COVID-19: Analysis of population-based cohort data.

BACKGROUND: Patients with impaired kidney function were found at a high risk of COVID-19 hospitalization and mortality in many observational, cross-sectional, and hospital-based studies, but evidence from large-scale prospective cohorts has been lacking. We aimed to examine the association of kidney function-related biomarkers and their genetic predisposition with the risk of developing severe COVID-19 in population-based data. METHODS: We analyzed data from UK Biobank to examine the prospective association of abnormal kidney function biomarkers with severe COVID-19, defined by laboratory-confirmed COVID-19 hospitalizations. Using genotype data, we constructed polygenic risk scores (PRS) to represent an individual's overall genetic risk for these biomarkers. We also identified tipping points where the risk of severe COVID-19 began to increase significantly for each biomarker. RESULTS: Of the 502,506 adults, 1650 (0.32%) were identified as severe COVID-19, before August 12, 2020. High levels of cystatin C (OR: 1.3; 95% CI: 1.2-1.5; FDR = 1.5 × 10-5 ), serum creatinine (OR: 1.7; 95% CI: 1.3-2.1; p = 3.5 × 10-4 ; FDR = 3.5 × 10-4 ), microalbuminuria (OR: 1.4; 95% CI: 1.2-1.6; FDR = 4 × 10-4 ), and UACR (urinary albumin creatinine ratio; OR: 1.4; 95% CI: 1.2-1.6; p = 3.5 × 10-4 ; FDR = 3.5 × 10-4 ) were found significantly associated with severe COVID-19. Individuals with top 10% of PRS for elevated cystatin C, urate, and microalbuminuria had 28% to 43% higher risks of severe COVID-19 than individuals with bottom 30% PRS (p < 0.05). Tipping-point analyses further supported that severe COVID-19 could occur even when the values of cystatin C, urate (male), and microalbuminuria were within their normal value ranges (OR >1.1, p < 0.05). CONCLUSIONS: Findings from this study might point to new directions for clinicians and policymakers in optimizing risk-stratification among patients based on polygenic risk estimation and tipping points of kidney function markers. Our results call for further investigation to develop a better strategy to prevent severe COVID-19 outcomes among patients with genetic predisposition to impaired kidney function. These findings could provide a new tool for clinicians and policymakers in the future especially if we need to live with COVID-19 for a long time.

Signaling mechanisms of SARS-CoV-2 Nucleocapsid protein in viral infection, cell death and inflammation.

COVID-19 which is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has posed a worldwide pandemic and a major global public health threat. SARS-CoV-2 Nucleocapsid (N) protein plays a critical role in multiple steps of the viral life cycle and participates in viral replication, transcription, and assembly. The primary roles of N protein are to assemble with genomic RNA into the viral RNA-protein (vRNP) complex and to localize to the replication transcription complexes (RTCs) to enhance viral replication and transcription. N protein can also undergo liquid-liquid phase separation (LLPS) with viral genome RNA and inhibit stress granules to facilitate viral replication and assembly. Besides the function in viral life cycle, N protein can bind GSDMD to antagonize pyroptosis but promotes cell death via the Smad3-dependent G1 cell cycle arrest mechanism. In innate immune system, N protein inhibits IFN-ß production and RNAi pathway for virus survival. However, it can induce expression of proinflammatory cytokines by activating NF-κB signaling and NLRP3 inflammasome, resulting in cytokine storms. In this review article, we are focusing on the signaling mechanisms of SARS-CoV-2 N protein in viral replication, cell death and inflammation.

Should More Patients with Kidney Failure Bring Treatment Home? What We Have Learned from COVID-19.

Background: The COVID-19 pandemic is challenging healthcare systems worldwide and has placed hospitals and healthcare providers (HCPs) at the center of a global crisis. Disruptions to hospital priorities, and limitations placed on the mobility of societies, have contributed to changes in the way HCPs and patients view and access dialysis for kidney failure, including which dialysis modality is preferred. Summary: This article explores the dialysis experience within the COVID-19 pandemic environment in the Asia Pacific region and presents evidence that peritoneal dialysis (PD) provides benefits to patients, HCPs, and health systems. As the number of people infected with COVID-19 has increased, the advantages of PD as a dialysis modality for limiting the spread of COVID-19 infection has been recognized. Key Message: The utility of PD has been demonstrated during the COVID-19 pandemic; thus, ensuring that the usage of PD is maintained and increased in a post-pandemic future is key. Such a scenario could enhance our ability to care for patients without interruption in circumstances of unforeseen obstacles and supports the ability of healthcare systems and patients to overcome barriers to dialysis access.

A Deep Learning Model for Accurate Diagnosis of Infection Using Antibody Repertoires.

The adaptive immune receptor repertoire consists of the entire set of an individual's BCRs and TCRs and is believed to contain a record of prior immune responses and the potential for future immunity. Analyses of TCR repertoires via deep learning (DL) methods have successfully diagnosed cancers and infectious diseases, including coronavirus disease 2019. However, few studies have used DL to analyze BCR repertoires. In this study, we collected IgG H chain Ab repertoires from 276 healthy control subjects and 326 patients with various infections. We then extracted a comprehensive feature set consisting of 10 subsets of repertoire-level features and 160 sequence-level features and tested whether these features can distinguish between infected individuals and healthy control subjects. Finally, we developed an ensemble DL model, namely, DL method for infection diagnosis (https://github.com/chenyuan0510/DeepID), and used this model to differentiate between the infected and healthy individuals. Four subsets of repertoire-level features and four sequence-level features were selected because of their excellent predictive performance. The DL method for infection diagnosis outperformed traditional machine learning methods in distinguishing between healthy and infected samples (area under the curve = 0.9883) and achieved a multiclassification accuracy of 0.9104. We also observed differences between the healthy and infected groups in V genes usage, clonal expansion, the complexity of reads within clone, the physical properties in the α region, and the local flexibility of the CDR3 amino acid sequence. Our results suggest that the Ab repertoire is a promising biomarker for the diagnosis of various infections.

SARS-CoV-2 N Protein Induces Acute Kidney Injury via Smad3-Dependent G1 Cell Cycle Arrest Mechanism.

COVID-19 is infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can cause severe multiple organ injury and death. Kidney is one of major target organs of COVID-19 and acute kidney injury (AKI) is common in critically ill COVID-19 patients. However, mechanisms through which COVID-19 causes AKI remain largely unknown and treatment remains unspecific and ineffective. Here, the authors report that normal kidney-specifically overexpressing SARS-CoV-2 N develops AKI, which worsens in mice under ischemic condition. Mechanistically, it is uncovered that SARS-CoV-2 N-induced AKI is Smad3-dependent as SARS-CoV-2 N protein can interact with Smad3 and enhance TGF-ß/Smad3 signaling to cause tubular epithelial cell death and AKI via the G1 cell cycle arrest mechanism. This is further confirmed in Smad3 knockout mice and cells in which deletion of Smad3 protects against SARS-CoV-2 N protein-induced cell death and AKI in vivo and in vitro. Most significantly, it is also found that targeting Smad3 with a Smad3 pharmacological inhibitor is able to inhibit SARS-CoV-2 N-induced AKI. In conclusion, the authors identify that SARS-CoV-2 N protein is a key mediator for AKI and induces AKI via the Smad3-dependent G1 cell cycle arrest mechanism. Targeting Smad3 may represent as a novel therapy for COVID-19-asscoaited AKI.

RAPID: A Rep-Seq Dataset Analysis Platform With an Integrated Antibody Database.

The antibody repertoire is a critical component of the adaptive immune system and is believed to reflect an individual's immune history and current immune status. Delineating the antibody repertoire has advanced our understanding of humoral immunity, facilitated antibody discovery, and showed great potential for improving the diagnosis and treatment of disease. However, no tool to date has effectively integrated big Rep-seq data and prior knowledge of functional antibodies to elucidate the remarkably diverse antibody repertoire. We developed a Rep-seq dataset Analysis Platform with an Integrated antibody Database (RAPID; https://rapid.zzhlab.org/), a free and web-based tool that allows researchers to process and analyse Rep-seq datasets. RAPID consolidates 521 WHO-recognized therapeutic antibodies, 88,059 antigen- or disease-specific antibodies, and 306 million clones extracted from 2,449 human IGH Rep-seq datasets generated from individuals with 29 different health conditions. RAPID also integrates a standardized Rep-seq dataset analysis pipeline to enable users to upload and analyse their datasets. In the process, users can also select set of existing repertoires for comparison. RAPID automatically annotates clones based on integrated therapeutic and known antibodies, and users can easily query antibodies or repertoires based on sequence or optional keywords. With its powerful analysis functions and rich set of antibody and antibody repertoire information, RAPID will benefit researchers in adaptive immune studies.

Psychological impact and implementation of preventative measures in hemodialysis centers during the COVID-19 pandemic: a provincial questionnaire survey in China.

OBJECTIVES: This study investigated the psychological status of patients and staff, and the implementation of preventative measures in hemodialysis centers in Guangdong province, China, during the 2019 novel coronavirus disease (COVID-19) pandemic. METHODS: An electronic questionnaire survey was carried out anonymously between March 28 and April 3, 2020. All of the 516 hemodialysis centers registered in Guangdong province were invited to participate in the survey. The questionnaires were designed to investigate the psychological status of hemodialysis patients and general staff members (doctors, nurses, technicians, and other staff), and to address the implementation of preventative measures for administrators (directors or head nurses) of the hemodialysis centers. RESULTS: A total of 1782 patients, 3400 staff, and 420 administrators voluntarily participated in this survey. Patients living in rural areas reported a higher incidence of severe anxiety compared to those living in other areas (in rural areas, towns, and cities, the incidence rate was 17.0%, 9.0%, and 8.9%, respectively, P < 0.001). Medical staff were less likely to worry about being infected than non-medical staff (13.1% vs 30.3%, respectively, P < 0.001). With respect to the implementation of preventative measures, hemodialysis centers in general hospitals outperformed stand-alone blood purification centers, while tertiary hospitals outperformed hospitals of other levels. However, restrictions regarding the admission of non-resident patients were lower in tertiary hospitals than in other hospitals. In this situation, only one patient imported from Hubei province was diagnosed with COVID-19. CONCLUSIONS: COVID-19 did not significantly affect the psychological status of most patients and medical staff members. Due to the implementation of comprehensive preventative measures, there were no cluster outbreaks of COVID-19 in hemodialysis centers. This provincial-level survey may provide referential guidance for other countries and regions that are experiencing a similar pandemic.

Inflammatory stress in SARS-COV-2 associated Acute Kidney Injury.

Increasing clinical evidence shows that acute kidney injury (AKI) is a common and severe complication in critically ill COVID-19 patients. The older age, the severity of COVID-19 infection, the ethnicity, and the history of smoking, diabetes, hypertension, and cardiovascular disease are the risk factor for AKI in COVID-19 patients. Of them, inflammation may be a key player in the pathogenesis of AKI in patients with COVID-19. It is highly possible that SARS-COV-2 infection may trigger the activation of multiple inflammatory pathways including angiotensin II, cytokine storm such as interleukin-6 (IL-6), C-reactive protein (CRP), TGF-ß signaling, complement activation, and lung-kidney crosstalk to cause AKI. Thus, treatments by targeting these inflammatory molecules and pathways with a monoclonal antibody against IL-6 (Tocilizumab), C3 inhibitor AMY-101, anti-C5 antibody, anti-TGF-ß OT-101, and the use of CRRT in critically ill patients may represent as novel and specific therapies for AKI in COVID-19 patients.