Potential herb‒drug interactions between anti-COVID-19 drugs and traditional Chinese medicine.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread worldwide. Effective treatments against COVID-19 remain urgently in need although vaccination significantly reduces the incidence, hospitalization, and mortality. At present, antiviral drugs including Nirmatrelvir/Ritonavir (PaxlovidTM), Remdesivir, and Molnupiravir have been authorized to treat COVID-19 and become more globally available. On the other hand, traditional Chinese medicine (TCM) has been used for the treatment of epidemic diseases for a long history. Currently, various TCM formulae against COVID-19 such as Qingfei Paidu decoction, Xuanfei Baidu granule, Huashi Baidu granule, Jinhua Qinggan granule, Lianhua Qingwen capsule, and Xuebijing injection have been widely used in clinical practice in China, which may cause potential herb-drug interactions (HDIs) in patients under treatment with antiviral drugs and affect the efficacy and safety of medicines. However, information on potential HDIs between the above anti-COVID-19 drugs and TCM formulae is lacking, and thus this work seeks to summarize and highlight potential HDIs between antiviral drugs and TCM formulae against COVID-19, and especially pharmacokinetic HDIs mediated by metabolizing enzymes and/or transporters. These well-characterized HDIs could provide useful information on clinical concomitant medicine use to maximize clinical outcomes and minimize adverse and toxic effects.

Complement and complement regulatory proteins are upregulated in lungs of COVID-19 patients.

We explored the pathological changes and the activation of local complement system in COVID-19 pneumonia. Lung paraffin sections of COVID-19 infected patients were analyzed by HE (hematoxylin-eosin) staining. The deposition of complement C3, the deposition of C3b/iC3b/C3d and C5b-9, and the expression of complement regulatory proteins, CD59, CD46 and CD55 were detected by immunohistochemistry. In COVID-19 patients' lung tissues, fibrin exudation, mixed with erythrocyte, alveolar macrophage and shed pneumocyte are usually observed in the alveoli. The formation of an "alveolar emboli" structure may contribute to thrombosis and consolidation in lung tissue. In addition, we also found that compared to normal tissue, the lung tissues of COVID-19 patients displayed the hyper-activation of complement that is represented by extensive deposition of C3, C3b/iC3b/C3d and C5b-9, and the increased expression level of complement regulatory proteins CD55, and especially CD59 but not CD46. The thrombosis and consolidation in lung tissues may contribute to the pathogenesis of COVID-19. The increased expression of CD55 and CD59 may reflect a feedback of self-protection on the complement hyper-activation. Further, the increased C3 deposition and the strongly activated complement system in lung tissues may suggest the rationale of complement-targeted therapeutics in conquering COVID-19.

Identification of the Hub Genes and the Signaling Pathways in Human iPSC-Cardiomyocytes Infected by SARS-CoV-2.

Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) is an enveloped single-stranded RNA virus that can lead to respiratory symptoms and damage many organs such as heart, kidney, intestine, brain and liver. It has not been clearly documented whether myocardial injury is caused by direct infection of cardiomyocytes, lung injury, or other unknown mechanisms. The gene expression profile of GSE150392 was obtained from the Gene Expression Omnibus (GEO) database. The processing of high-throughput sequencing data and the screening of differentially expressed genes (DEGs) were implemented by R software. The R software was employed to analyze the Gene Ontology (GO) analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The protein-protein interaction (PPI) network of the DEGs was constructed by the STRING website. The Cytoscape software was applied for the visualization of PPI network and the identification of hub genes. The statistical analysis was performed by the GraphPad Prism software to verify the hub genes. A total of 516 up-regulated genes and 191 down-regulated genes were screened out. The top 1 enrichment items of GO in biological process (BP), Cellular Component (CC), and Molecular Function (MF) were type I interferon signaling pathway, sarcomere, and receptor ligand activity, respectively. The top 10 enrichment pathways, including TNF signaling pathway, were identified by KEGG enrichment analysis. A PPI network was established, consisting of 613 nodes and 3,993 edges. The 12 hub genes were confirmed as statistically significant, which was verified by GSE151879 dataset. In conclusion, the hub genes of human iPSC-cardiomyocytes infected with SARS-CoV-2 were identified through bioinformatics analysis, which may be used as biomarkers for further research.

Simulation Studies Provide Evidence of Aerosol Transmission of SARS-CoV-2 in a Multi-Story Building via Air Supply, Exhaust and Sanitary Pipelines.

A cross-layer non-vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in a quarantine hotel in Guangzhou, Guangdong Province, China in June 2021. To explore the cross-layer transmission path and influencing factors of viral aerosol, we set up different scenarios to carry out simulation experiments. The results showed that the air in the polluted room can enter the corridor by opening the door to take food and move out the garbage, then mix with the fresh air taken from the outside as part of the air supply of the central air conditioning system and re-enter into different rooms on the same floor leading to the same-layer transmission. In addition, flushing the toilet after defecation and urination will produce viral aerosol that pollutes rooms on different floors through the exhaust system and the vertical drainage pipe in the bathroom, resulting in cross-layer vertical transmission, also aggravating the transmission in different rooms on the same floor after mixing with the air of the room and entering the corridor to become part of the air supply, and meanwhile, continuing to increase the cross-layer transmission through the vertical drainage pipe. Therefore, the air conditioning and ventilation system of the quarantine hotel should be operated in full fresh air mode and close the return air; the exhaust volume of the bathroom should be greater than the fresh air volume. The exhaust pipe of the bathroom should be independently set and cannot be interconnected or connected in series. The riser of the sewage and drainage pipeline of the bathroom should maintain vertical to exhaust independently and cannot be arbitrarily changed to horizontal pipe assembly.

An ultra-low-cost electroporator with microneedle electrodes (ePatch) for SARS-CoV-2 vaccination.

Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other pathogens with pandemic potential requires safe, protective, inexpensive, and easily accessible vaccines that can be developed and manufactured rapidly at a large scale. DNA vaccines can achieve these criteria, but induction of strong immune responses has often required bulky, expensive electroporation devices. Here, we report an ultra-low-cost (<1 USD), handheld (<50 g) electroporation system utilizing a microneedle electrode array ("ePatch") for DNA vaccination against SARS-CoV-2. The low cost and small size are achieved by combining a thumb-operated piezoelectric pulser derived from a common household stove lighter that emits microsecond, bipolar, oscillatory electric pulses and a microneedle electrode array that targets delivery of high electric field strength pulses to the skin's epidermis. Antibody responses against SARS-CoV-2 induced by this electroporation system in mice were strong and enabled at least 10-fold dose sparing compared to conventional intramuscular or intradermal injection of the DNA vaccine. Vaccination was well tolerated with mild, transient effects on the skin. This ePatch system is easily portable, without any battery or other power source supply, offering an attractive, inexpensive approach for rapid and accessible DNA vaccination to combat COVID-19, as well as other epidemics.

Field Simulation of Aerosol Transmission of SARS-CoV-2 in a Special Building Layout - Guangdong Province, China, 2021.

WHAT IS ALREADY KNOWN ON THIS TOPIC?: Aerosol transmission was one route for the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and usually occurred in confined spaces. WHAT IS ADDED BY THIS REPORT?: Aerosol transmission was found to exist between handshake buildings, i.e., buildings with extremely close proximity that formed relatively enclosed spaces. Transmission was mainly affected by the airflow layout caused by switching air conditioners on and off as well as opening and closing doors and windows. WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?: Centralized isolation and home isolation in handshake buildings creates a risk of SARS-CoV-2 aerosol transmission under certain conditions. Attention should be paid to the influence of air distribution layout on aerosol diffusion in isolation wards, and disinfection of isolation venues should be strengthened.

Predictors of mortality for hospitalized young adults aged less than 60 years old with severe COVID-19: a retrospective study.

BACKGROUND: To analyze the clinical characteristics and predictors for mortality of adult younger than 60 years old with severe coronavirus disease 2019 (COVID-19). METHODS: We retrospectively retrieved data for 152 severe inpatients with COVID-19 including 60 young patients in the Eastern Campus of Wuhan University affiliated Renmin Hospital in Wuhan, China, from January 31, 2020 to February 20, 2020. We recorded and analyzed patients' demographic, clinical, laboratory, and chest CT findings, treatment and outcomes data. RESULTS: Of those 60 severe young patients, 15 (25%) were died. Male was more predominant in deceased young patients (12, 80%) than that in recovered young patients (22, 49%). Hypertension was more common among deceased young patients (8, 53%) than that in recovered young patients (7, 16%). Compared with the recovered young patients, more deceased young patients presented with sputum (11, 73%), dyspnea (12, 80%) and fatigue (13, 87%). Only sputum, PSI and neutrophil counts were remained as independent predictors of death in a multivariate logistic regression model. Among ARDS patients, the recovered were administrated with corticosteroid earlier and anticoagulation. The addition of neutrophil counts >6.3×109/L to the SMART-COP score resulted in improved area under the curves. CONCLUSIONS: Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection in young deceased patients appears to cause exuberant inflammatory responses, leading to compromised oxygen exchange, coagulation and multi-organ dysfunction. In addition, young patients with ARDS could benefit from adjuvant early corticosteroid and anticoagulation therapy. The expanded SMART-COP could predict the fatal outcomes with optimal efficiency.

Multi-chain Fudan-CCDC model for COVID-19-a revisit to Singapore's case.

BACKGROUND: COVID-19 has been impacting on the whole world critically and constantly since late December 2019. Rapidly increasing infections has raised intense worldwide attention. How to model the evolution of COVID-19 effectively and efficiently is of great significance for prevention and control. METHODS: We propose the multi-chain Fudan-CCDC model based on the original single-chain model in [Shao et al. 2020] to describe the evolution of COVID-19 in Singapore. Multi-chains can be considered as the superposition of several single chains with different characteristics. We identify the parameters of models by minimizing the penalty function. RESULTS: The numerical simulation results exhibit the multi-chain model performs well on data fitting. Though unsteady the increments are, they could still fall within the range of _30% fluctuation from simulation results. CONCLUSION: The multi-chain Fudan-CCDC model provides an effective way to early detect the appearance of imported infectors and super spreaders and forecast a second outbreak. It can also explain the data from those countries where the single-chain model shows deviation from the data.

Clinical predictors of COVID-19 disease progression and death: Analysis of 214 hospitalised patients from Wuhan, China.

INTRODUCTION: COVID-19 has spread rapidly worldwide and has been declared a pandemic. OBJECTIVES: To delineate clinical features of COVID-19 patients with different severities and prognoses and clarify the risk factors for disease progression and death at an early stage. METHODS: Medical history, laboratory findings, treatment and outcome data from 214 hospitalised patients with COVID-19 pneumonia admitted to Eastern Campus of Renmin Hospital, Wuhan University in China were collected from 30 January 2020 to 20 February 2020, and risk factors associated with clinical deterioration and death were analysed. The final date of follow-up was 21 March 2020. RESULTS: Age, comorbidities, higher neutrophil cell counts, lower lymphocyte counts and subsets, impairment of liver, renal, heart, coagulation systems, systematic inflammation and clinical scores at admission were significantly associated with disease severity. Ten (16.1%) moderate and 45 (47.9%) severe patients experienced deterioration after admission, and median time from illness onset to clinical deterioration was 14.7 (IQR 11.3-18.5) and 14.5 days (IQR 11.8-20.0), respectively. Multivariate analysis showed increased Hazards Ratio of disease progression associated with older age, lymphocyte count <1.1 × 109/L, blood urea nitrogen (BUN)> 9.5 mmol/L, lactate dehydrogenase >250 U/L and procalcitonin >0.1 ng/mL at admission. These factors were also associated with the risk of death except for BUN. Prediction models in terms of nomogram for clinical deterioration and death were established to illustrate the probability. CONCLUSIONS: These findings provide insights for early detection and management of patients at risk of disease progression or even death, especially older patients and those with comorbidities.

Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City, Zhejiang, China.

Rationale: Many clinical studies have focused on the epidemiological and clinical characteristics of inpatients with coronavirus disease (COVID-19). However, there are few reports about the clinical follow-up of discharged patients.Objectives: To describe the follow-up of patients with COVID-19 in Wenzhou City, Zhejiang, China.Methods: We retrospectively reviewed 4-week follow-ups in patients with COVID-19, including computed tomographic (CT) chest scanning, blood testing, and oropharyngeal-swab testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid. The chest CT scans and blood tests were performed on the last day before discharge and 2 weeks and 4 weeks after discharge. The oropharyngeal-swab tests were performed at both 1 week and 2 weeks after discharge. Fifty-one patients with common COVID-19 were enrolled in the study. All the CT and clinical data were collected between January 23 and March 28, 2020.Results: Compared with the abnormalities found on the the last CT scans before discharge, the abnormalities in the lungs at the first and second follow-ups after discharge had been gradually absorbed. The cases with focal ground-glass opacity were reduced from 17.7% to 9.8% of cases. The cases with multiple ground-glass opacities decreased from 80.4% to 23.5%. The cases with consolidation were reduced from 49.0% to 2.0%. The cases with interlobular septal thickening were reduced from 80.4% to 35.3%. The cases with subpleural lines were reduced from 29.4% to 7.8%. The cases with irregular lines were reduced from 41.2% to 15.7%. The lung lesions of 25.5% patients were shown to be fully absorbed on the first CT scans after discharge, and the rate of lung recovery increased to 64.7% after the second follow-up. Nucleic-acid test results became recurrently positive in 17.6% of discharged patients, of whom only 33.3% complained of clinical symptoms. There were no differences in the characteristics of the last CT scans before discharge between the patients with recurrently positive test results and the patients with negative test results. The lung damage was fully absorbed in 55.6% of discharged patients with recurrence of positive test results for SARS-CoV-2 ribonucleic acid.Conclusions: The lung damage due to COVID-19 could be reversible for patients with common COVID-19. A few cases showed recurring positive results of nucleic-acid tests after discharge.

A nationwide survey of online teaching strategies in dental education in China.

OBJECTIVES: Due to the time and cost effectiveness, online teaching has played a significant role in the provision of education and has been a well-accepted strategy for higher education in the world. The aim of this study was to survey the current online undergraduate education status in dental medicine in mainland China during the critical stage of the COVID-19 outbreak, as well to provide a better understanding of practicing this learning strategy for the improvement and development of dental education. METHODS: For the cross-sectional survey, recruitment emails regarding to the implementation of online education were sent to 42 dental colleges and universities in mainland China between March and April 2020. RESULTS: Ninety-seven percent of the respondents have opened online courses during COVID-19 pandemic in China, 74% of which chose live broadcast as the major teaching way. As compared with theoretical courses, fewer specialized practical curriculums were set up online with a lower satisfaction from students in most dental schools. For the general evaluation of online learning from students of different dental schools, the "online learning content" received the highest support, while the "interaction between teachers and students" showed the lowest satisfaction. Most schools reported that the difficulty in assurance of students' learning motivation was the main problem in online education. CONCLUSIONS: Our findings indicate the necessity and efficacy of the overall online teaching for dental education during the epidemic that can be further improved with the education model and pedagogical means to boost the informationization of dental education for future reference.

Efficacy and safety of the extracorporeal shockwave therapy in patients with postherpetic neuralgia: study protocol of a randomized controlled trial

BACKGROUND: Postherpetic neuralgia (PHN) is one of the most common types of chronic neuropathic pain, which seriously affects quality of the life because of pain severity and poor response to the currently available treatments. The main strategies for PHN management are medication and invasive interventional therapies;however, these approaches have many adverse effects, so it is important to find another effective and safe treatment for PHN. METHODS: A single-center, single-blind randomized clinical trial will evaluate 98 study participants randomized in a 1:1 ratio into control and experimental groups. The control group will receive conventional treatment including medication therapy and invasive interventional therapy. The experimental group will receive extracorporeal shockwave therapy (ESWT) in addition to conventional therapy. The primary outcome is pain intensity assessed on a visual analogue scale (VAS);the secondary outcomes are the following: quality of life assessed by the 36-Item Short-Form Health Survey (SF-36), psychological state for anxiety and depression measured by the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), and sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI). Assessors blinded to the randomization will collect data during the intervention period at baseline and weeks 1, 4, and 12. The plasma levels of tumor necrosis factor-αand interleukin-6 will be assessed before and after ESWT to explore the biochemical mechanisms of ESWT in the treatment of PHN. DISCUSSION: This randomized controlled trial will evaluate the effectiveness and safety of ESWT in patients with PHN and thus will provide clinical evidence for its use in the management of PHN and explore the potential biochemical mechanisms of this treatment. TRIAL REGISTRATION: www.ChiCTR.org.cn , identifier: ChiCTR1900025828. Registered on 10 September 2019.

Tocilizumab exerts anti-inflammatory activity in six critically ill COVID-19 patients: a retrospective analysis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic, affecting countries across the globe. With no current vaccine, treatment is still a critical intervention for minimizing morbidity and preventing disease-specific mortality. This study aimed to assess the clinical outcomes of critically ill COVID-19 patients using Tocilizumab treatment to provide recommendations for the treatment of COVID-19 patients with severe disease. METHODS: This was a retrospective analysis of medical records of six critically ill patients admitted to the Third People's Hospital of Shenzhen, China, from January 11 to February 26, 2020. Patient-related outcomes, including demographic, clinical, and laboratory characteristics before and after the initiation of Tocilizumab, were descriptively analyzed. Four to eight milligrams (mg)/kilogram (kg) of Tocilizumab was prescribed, with Chinese treatment guidelines. RESULTS: By the end of the last follow-up, Patient 1 and Patient 2 developed complications and died after using Tocilizumab for three to four days. Patient 4 died of multiple organ failure caused by cerebral infarction after using Tocilizumab for 39 days. Patient 3 and Patient 6 were discharged after 29 days and 33 days on Tocilizumab, respectively. Clinical symptoms, including fever, heart rate, and oxygen levels, improved after Tocilizumab use. Two patients appeared transient abnormal of liver or renal function indicator, and they can gradually recover. All elevated serum levels of inflammatory factors gradually decreased, except in Patient 2. Patient 3 and Patient 6's inflammatory lesions also significantly improved after initiating Tocilizumab. CONCLUSIONS: Anti-inflammatory treatment with Tocilizumab was found to improve inflammatory responses in critically ill COVID-19 patients. Although some side reactions will occur, patients can gradually recover without affecting the efficacy of the therapy. However, the proper timing to start patients on Tocilizumab patients should be explored. Further prospective, randomized controlled clinical trials are called for.

Emergency Response Measures for Anesthesia Nursing During the COVID-19 Pandemic: West China Hospital Experiences.

During the COVID-19 pandemic, ensuring the gradual recovery of anesthesia nursing unit and avoiding cross-infection between surgical patients and staff are difficult problems for hospital managers. We outlined the emergency response measures and the transition to normal operation of the anesthesia nursing unit in West China Hospital, which is a large teaching hospital. This mainly included hospital and operating room channel management, three-level screening management of patients and medical staff, classification management of patients undergoing anesthesia and recovery, training management of medical personnel, strict environmental management, and online teaching management.

Assessing risk factors for SARS-CoV-2 infection in patients presenting with symptoms in Shanghai, China: a multicentre, observational cohort study.

Background: The outbreak of COVID-19 has led to international concern. We aimed to establish an effective screening strategy in Shanghai, China, to aid early identification of patients with COVID-19. Methods: We did a multicentre, observational cohort study in fever clinics of 25 hospitals in 16 districts of Shanghai. All patients visiting the clinics within the study period were included. A strategy for COVID-19 screening was presented and then suspected cases were monitored and analysed until they were confirmed as cases or excluded. Logistic regression was used to determine the risk factors of COVID-19. Findings: We enrolled patients visiting fever clinics from Jan 17 to Feb 16, 2020. Among 53 617 patients visiting fever clinics, 1004 (1·9%) were considered as suspected cases, with 188 (0·4% of all patients, 18·7% of suspected cases) eventually diagnosed as confirmed cases. 154 patients with missing data were excluded from the analysis. Exposure history (odds ratio [OR] 4·16, 95% CI 2·74-6·33; p<0·0001), fatigue (OR 1·56, 1·01-2·41; p=0·043), white blood cell count less than 4 × 109 per L (OR 2·44, 1·28-4·64; p=0·0066), lymphocyte count less than 0·8 × 109 per L (OR 1·82, 1·00-3·31; p=0·049), ground glass opacity (OR 1·95, 1·32-2·89; p=0·0009), and having both lungs affected (OR 1·54, 1·04-2·28; p=0·032) were independent risk factors for confirmed COVID-19. Interpretation: The screening strategy was effective for confirming or excluding COVID-19 during the spread of this contagious disease. Relevant independent risk factors identified in this study might be helpful for early recognition of the disease. Funding: National Natural Science Foundation of China.

2019 novel coronavirus of pneumonia in Wuhan, China: emerging attack and management strategies.

An ongoing outbreak of 2019-nCoV pneumonia was first identified in Wuhan, Hubei province, China at the end of 2019. With the spread of the new coronavirus accelerating, person-to-person transmission in family homes or hospitals, and intercity spread of 2019-nCoV occurred. At least 40,261 cases confirmed, 23,589 cases suspected, 909 cases death and 3444 cases cured in China and worldwide 24 countries confirmed 383 cases being diagnosed, 1 case death in February 10th, 2020. At present, the mortality of 2019-nCoV in China is 2.3%, compared with 9.6% of SARS and 34.4% of MERS reported by WHO. It seems the new virus is not as fatal as many people thought. Chinese authorities improved surveillance network, made the laboratory be able to recognize the outbreak within a few weeks and announced the virus genome that provide efficient epidemiological control. More comprehensive information is required to understand 2019-nCoV feature, the epidemiology of origin and spreading, and the clinical phenomina. According to the current status, blocking transmission, isolation, protection, and alternative medication are the urgent management strategies against 2019-nCoV.