Inflammatory endobronchial polyps unleashing recurrent pneumothorax: A case report.

Inflammatory endobronchial polyps (IEPs) are rare benign lesions that originate from the bronchial mucosa. While pneumothorax is a well-known complication of various pulmonary conditions, its association with IEPs is exceedingly uncommon and poorly understood. This case report presents a unique and explosive encounter of a patient with an inflammatory endobronchial polyp who experienced a pneumothorax, shedding light on the clinical presentation, diagnostic challenges, and management strategies for this rare entity.

Metformin-associated lactic acidosis (MALA): Is it an underestimated entity? A retrospective, single-center case series.

INTRODUCTION: Metformin is widely considered a first-line antiglycemic agent due to its cost-effectiveness and favorable adverse effect profile. However, its use is prohibited in patients with an estimated glomerular filtration rate <30 mL/min/1.73 m2 , due to the risk of potentially lethal metformin-associated lactic acidosis (MALA). We sought to evaluate MALA cases and outcomes at our institution. METHODS: In this observational, retrospective case series, we reviewed our EMR for all patients who had a metformin level drawn between January 2013 and May 2022 to identify individuals who met the diagnostic criteria for MALA. We evaluated risk factors for MALA, the relationship between metformin level, blood pH, serum bicarbonate, and lactate level and clinical outcomes of ventilator dependency, renal replacement therapy requirement, renal recovery in acute kidney injury (AKI) patients, and survival. FINDINGS: A total of 107 patients had metformin levels drawn, of which 19 patients met the diagnostic criteria for MALA. In our case series, MALA was primarily seen in AKI (15 patients) secondary to dehydration and sepsis, followed by end-stage renal disease (ESRD) (4 patients). Intubation was required in 17 patients, of whom 8 were successfully extubated after a mean duration of 14 days. Sixteen patients received renal replacement therapy (RRT). Intermittent hemodialysis (IHD) was performed in nine, continuous renal replacement therapy (CRRT) in four, and sequential therapy of IHD and CRRT in three patients. Seven patients, all in the AKI group (46.7%), died while all ESRD patients survived, accounting for an overall mortality rate of 36.8%. Among the eight surviving AKI patients, four had complete renal recovery with renal function returning to baseline, three had partial renal recovery, and one continued to require IHD at the time of discharge to a rehabilitation facility. DISCUSSION: MALA may be an underrecognized entity. A high level of clinical suspicion leading to prompt and aggressive treatment with RRT may improve mortality rates. Provider and patient education is of paramount importance for safe use of metformin.

Incidence and risk factors associated with negative postoperative behavioral changes in children undergoing painless gastroscopy.

OBJECTIVE: To investigate the incidence of and risk factors associated with negative postoperative behavioral changes (NPOBCs) in children undergoing painless gastroscopy. METHODS: Inclusion criteria: ASA I-II and outpatients aged 6-12 years undergoing painless gastroscopy. EXCLUSION CRITERIA: history of surgery or anesthesia, children with developmental or intellectual abnormalities, refusal to participate, preoperative abdominal pain score > 3 points, history of chronic abdominal pain of > 3 months duration, and serious intraoperative complications. On the 1st, 14th, and 30th day after the gastroscopy, the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) was used to assess NPOBCs in children. RESULTS: A total of 1,670 children were included in this prospective observational cohort study. The incidence rates of NPOBCs were 14.13%, 4.55%, and 2.14% on the 1st, 14th, and 30th day after gastroscopy, respectively. The risk factors for the first day were female sex (OR 1.34, 95% CI 1.00-1.79), parental anxiety (OR 2.23, 95% CI 1.75-3.12), and severe anxiety in children (OR 2.83, 95% CI 1.96-4.07). The risk factors on the 14th day were parental anxiety (OR 3.71, 95% CI 2.19-6.29), a parental educational level above high school (OR 1.65, 95% CI 1.00-2.70), and severe anxiety in children (OR 11.87, 95% CI 5.85-24.07). The risk factors on the 30th day were female sex (OR 2.99, 95% CI 1.41-6.34), being an only child (OR 4.42, 95% CI 2.18-8.95), a parental educational level above high school (OR 2.66, 95% CI 1.27 NPOBCs 5.56), and severe anxiety in children (OR 6.84, 95% CI 2.84-16.49). CONCLUSION: In children undergoing painless gastroscopy, the incidence rates of NPOBCs on the 1st, 14th, and 30th day were 14.13%, 4.55%, and 2.14%, respectively. The risk factors for NPOBCs were severe anxiety in children, female sex, parental anxiety, and a parental educational level above high school. In particular, severe preoperative anxiety in children was a persistent risk factor for NPOBCs within 30 days.

A meta-analytical review of transcranial direct current stimulation parameters on upper limb motor learning in healthy older adults and people with Parkinson's disease.

Current literature lacks consolidated evidence for the impact of stimulation parameters on the effects of transcranial direct current stimulation (tDCS) in enhancing upper limb motor learning. Hence, we aim to synthesise available methodologies and results to guide future research on the usage of tDCS on upper limb motor learning, specifically in older adults and Parkinson's disease (PD). Thirty-two studies (Healthy older adults, N = 526, M = 67.25, SD = 4.30 years; PD, N = 216, M = 66.62, SD = 6.25 years) were included in the meta-analysis. All included studies consisted of active and sham protocols. Random effect meta-analyses were conducted for (i) subjects (healthy older adults and PD); (ii) intensity (1.0, 1.5, 2 mA); (iii) electrode montage (unilateral anodal, bilateral anodal, unilateral cathodal); (iv) stimulation site (cerebellum, frontal, motor, premotor, SMA, somatosensory); (v) protocol (online, offline). Significant tDCS effect on motor learning was reported for both populations, intensity 1.0 and 2.0 mA, unilateral anodal and cathodal stimulation, stimulation site of the motor and premotor cortex, and both online and offline protocols. Regression showed no significant relationship between tDCS effects and density. The efficacy of tDCS is also not affected by the number of sessions. However, studies that reported only single session tDCS found significant negative association between duration with motor learning outcomes. Our findings suggest that different stimulation parameters enhanced upper limb motor learning in older adults and PD. Future research should combine tDCS with neuroimaging techniques to help with optimisation of the stimulation parameters, considering the type of task and population.

Clinical analysis of different types of neonatal sepsis: a multi-center retrospective study / 中国新生儿科杂志

Objective:To study the clinical characteristics of different types of neonatal sepsis.Methods:From January 2012 to December 2019, neonates with confirmed sepsis from 5 neonatal centers of central-south China were reviewed. The neonates were assigned into early-onset sepsis (EOS) and late-onset sepsis (LOS) group, and the latter was further subgrouped into hospital-acquired LOS (hLOS) group and community-acquired LOS (cLOS) group. The etiological and clinical characteristics were analyzed. SPSS 26.0 was used for statistical analysis.Results:A total of 580 neonates were enrolled, including 286 (49.3%) in the EOS group and 294 (50.7%) in the LOS group. In LOS group, 147 were in hLOS group and 147 were in cLOS group. The gestational age and birth weight of hLOS group were significantly lower than the other two groups [(32.7±3.6) weeks vs. (37.1±3.7) weeks and (37.7±3.0) weeks, (1 810±717) g vs. (2 837±865) g and (3 024±710) g] ( P<0.05). The common pathogens in EOS and cLOS groups were coagulase-negative staphylococci and Escherichia coli, while Klebsiella pneumoniae was common in hLOS group. Carbapenems usage in the hLOS group was significantly higher than the other two groups [62.6% vs. 28.7% and 16.2%] ( P<0.05). Antibiotics duration in the hLOS group was longer than the other two groups [19 (14, 27) d vs. 15 (12, 20) d and 14 (12, 19) d] ( P<0.05). Conclusions:The clinical characteristics of neonatal sepsis vary among different types of infections, and it is necessary to establish appropriate prevention, control, diagnosis and treatment protocols.

Supervision of Electronic Informed Consent in International Clinical Research and Its Implications for China / 中国医学伦理学

At present, China is still in the exploratory stage in the field of electronic informed consent (eIC), and relevant policies, regulations and application guidelines have not yet been established and improved. While the traditional informed consent supervision system is difficult to meet the needs of the innovative development of eIC, such as subject privacy and data security. Through sorting out and analyzing the legal norms and construction system of eIC supervision in Europe and the United States, combined with the current development status, problems, and challenges of eIC in China, this paper targeted proposed the path to construct the supervision of eIC in clinical research in China from the aspects of restricting the signing form and process of eIC, adjusting the ethical review paradigm of eIC, enhancing the strength of eIC ethical review, improving the construction of eIC legal system, and strengthening the training of relevant researchers.

Challenges and Suggestions for Improvement of the Electronic Informed Consent System in Clinical Application / 中国医学伦理学

The electronic informed consent (eIC) system is a product of modernization development of electronic and intelligent technology. In the context of COVID-19, the eIC system can adapt to the epidemic prevention and control requirements, showing its time-space advantages. By introducing the concept, form and the use of eIC system, this paper analyzed the challenges of acceptance, understanding, consent and information security faced by the eIC system. Based on this, some suggestions were put forward, including strengthening the training of the relevant personnel involved in the eIC system, enhancing and improving the functions of the eIC system, and perfecting the relevant laws and regulations of the eIC system, so as to provide reference for the future research and application of eIC.

Commonly Misdiagnosed Facial Lesion: Pilomatricoma.

Pilomatricoma, also known as Pilamatrixoma or Malherbe's calcifying epithelioma, is a benign skin tumour with a bimodal age distribution between the paediatric and elderly age groups. Although it was previously thought to be rare, recent studies have revealed that it is quite common. Typically, pilomatricoma is diagnosed following histopathological examination of the lesion as it is frequently misdiagnosed with other types of skin pathology. In our case, the child presented with painless swelling of the left infraauricular region. The initial cytology and imaging were unable to provide a definite diagnosis. An excision biopsy was done, and a histopathological examination was suggestive of Pilomatricoma. Therefore, Pilomatricoma ought to be considered in the differential diagnosis of head and neck lesions in hopes of providing a better understanding on this pathological lesion.

Correlation of DNA Damage Repair Gene FANCI with Prognosis and Immune Infiltration of Hepatocellular Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo evaluate the expression level of DNA damage repair gene FANCI in hepatocellular carcinoma （HCC） and its relationship with prognosis， clinical stage and immune infiltration. MethodsIn this study， TCGA， GTEx， TIMER2.0， HPA database and qRT-PCR， western blot and immunohistochemistry were used to analyze the expression of FANCI in HCC and its correlation with different clinical stages； Kaplan-Meier Plotter database was used to explore the relationship between FANCI and the prognosis of HCC； the TISIDB database was used to analyze the relationship between FANCI and immune cell infiltration and immune checkpoints in HCC； the STRING database was used to detect the protein binding with FANCI； the TCGA and GTEx databases were used for GO and KEGG enrichment analysis； Cell experiments were used to explore the role of FANCI in HCC. ResultsCompared with normal tissues， the mRNA and protein expression levels of FANCI in tumor tissues were up-regulated （P<0.001）； and HCC patients with high expression of FANCI had poor prognosis （P<0.001）； the expression of FANCI in tumor tissues was positively correlated with the number of activated CD4+ T cells， the number of Th2 cells and the expression of immune checkpoints， and B-cell and macrophage infiltration was significantly lower in the FANCI high expression group （P<0.01）； GO and KEGG enrichment analysis showed that FANCI-related genes were enriched in various biological processes such as amino acid transmembrane transporter activity； Cell experiments showed that knockdown of FANCI could inhibit the proliferation， invasion and migration of HCC （P<0.05）. ConclusionsFANCI is highly expressed in hepatocellular carcinoma tissues， which may play a role in suppressing anti-tumor immunity and acting on pathways such as amino acid transmembrane transport， and is associated with poor prognosis. The proliferation， invasion and migration ability of hepatocellular carcinoma are inhibited after knocking down FANCI.

Emergency Preparedness for the COVID-19 Pandemic: Social Determinants Predicting the Community Pharmacists' Preparedness and Perceived Response in Malaysia.

BACKGROUND: Pandemic preparedness of healthcare providers helps to mitigate future threats such as spread and fatality rates, as well as the management of the disease. Pharmacists are key partners with public health agencies, and the role of community pharmacists is becoming increasingly recognised in this COVID-19 pandemic. The study aimed to explore the emergency preparedness of community pharmacists (CPs) for COVID-19. METHODS: A cross-sectional study was performed among community pharmacists using cluster sampling followed by convenient sampling. A self-administered questionnaire was formulated using references from the previous literature and the WHO preparedness checklist. Descriptive analysis was undertaken for the participants' socio-demographic characteristics. All the data collected were entered into the Statistical Package for Social Sciences version 24 (SPSS V.24), (IBM SPSS Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.) for analysis. RESULTS: Most of the CPs had five or fewer years of practice experience, and they had all the mandatory information relating to the needs of their communities regarding the disease. The participants knew where to acquire these resources whenever needed. They were able to recognise the signs and symptoms of the disease. Most participants felt that they were confident to provide patient education and carry out their duties during these challenging times. There was a strong position correlation between preparedness and the perceived response of the participants. CONCLUSION: The community pharmacists in Malaysia are prepared enough for COVID-19 pandemic management and perceive that they can respond during any unprecedented situations, such as COVID-19. Community pharmacists were aware of the challenges that they need to face in their community regarding COVID-19.

Heartbeat-aware convolutional neural network for R-peak detection of wearable device ECG data / 南方医科大学学报

OBJECTIVE@#To develop a method for R-peak detection of ECG data from wearable devices to allow accurate estimation of the physiological parameters including heart rate and heart rate variability.@*METHODS@#A fully convolutional neural network was applied to predict the R-peak heatmap of ECG data and locate the R-peak positions. The heartbeat-aware (HA) module was introduced to enable the model to learn to predict the heartbeat number and R-peak heatmap simultaneously, thereby improving the capability of the model for extraction of the global context. The R-R interval estimated by the predicted heartbeat number was adopted to calculate the minimum horizontal distance for peak positioning. To achieve real-time R-peak detection on mobile devices, the deep separable convolution was adopted to reduce the number of parameters and the computational complexity of the model.@*RESULTS@#The proposed model was trained only with ECG data from wearable devices. At a tolerance window interval of 150 ms, the proposed method achieved R peak detection sensitivities of 100% for both wearable device ECG dataset and a public dataset (i.e. LUDB), and the true positivity rates exceeded 99.9%. As for the ECG signal of a 10 s duration, the CPU time of the proposed method for R-peak detection was about 23.2 ms.@*CONCLUSION@#The proposed method has good performance for R-peak detection of both wearable device ECG data and routine ECG data and also allows real-time R-peak detection of the ECG data.

Rational design of a 500 m3 fermenter for erythromycin production by Saccharopolyspora erythraea / 生物工程学报

Erythromycin is a macrolide antibiotic produced by Saccharopolyspora erythraea. Its yield is greatly affected by the fermentation conditions and the bioreactor configurations. In this study, a novel scale-up method for erythromycin fermentation was developed based on computational fluid dynamics (CFD) and time constant analysis. Firstly, the dissolved oxygen (DO) was determined as a key parameter according to the physiological properties of S. erythraea cultivated in a 50 L bioreactor. It was found that the time constant of oxygen supply (tmt) in a 500 m3 bioreactor should be less than 6.25 s in order to satisfy the organism's oxygen uptake rate (OUR). Subsequently, a 500 m3 bioreactor was designed using the time constant method combined with empirical correlations. The impeller combination with one BDT8 impeller at bottom and two MSX4 impellers at upper part was determined, and then validated by numerical simulation. The results indicated that the tmt of the bioreactor (< 6.25 s) and the fluid properties, including gas hold-up, shear stress and fluid vector, met the requirements of erythromycin fermentation. Finally, the industrial production of erythromycin in the 500 m3 showed the design method was applicable in large scale fermentation.

Propofol suppresses the growth and invasion of cervical carcinoma cells by inhibiting MIR155HG.

BACKGROUND: Cervical cancer is the most prevalent malignancy worldwide and propofol reportedly has anti-cancer efficiencies. Herein, we tried to address the potential anti-cancer effects of propofol in cervical carcinoma. MATERIALS AND METHODS: The suppression effects of propofol on the proliferation and invasion of cervical cancer cells were analyzed by Cell Counting Kit-8 (CCK-8), colony formation and Transwell invasion assay. The protein expressions of epithelial marker, E-cadherin and mesenchymal marker, N-cadherin were evaluated using western blot. The level of MIR155 host gene (MIR155HG) was determined by qRT-PCR assay. The anti-cancer impact of propofol on cervical cancer cells growth in vivo was determined by means of xenograft tumor model and lung metastasis model. RESULTS: In vitro, propofol inhibited the growth and colony-formation of cervical carcinoma cells. Meanwhile, propofol treatment reduced the invasive trait of cervical carcinoma cells. In addition, MIR155HG was identified to be distinctly upregulated in cervical carcinoma when compared within normal. Propofol treatment decreased the expression of MIR155HG in cervical cancer cells. Consistently, the results from in vivo xenograft model indicated that propofol repressed cervical cancer cells growth and decreased the expression of MIR155HG in vivo. Furthermore, reintroduction of MIR155HG into cervical cancer cells counteracted the inhibitory potency of propofol on the growth and aggressive phenotypes in cervical carcinoma cells. CONCLUSIONS: Altogether, these results indicated that propofol restrained the growth and invasion of cervical cancer cells partly via regulating MIR155HG expression.

MicroRNA-215-5p Inhibits the Proliferation and Migration of Wilm's Tumor Cells by Targeting CRK.

OBJECTIVE: Wilm's tumor is a common renal malignancy in childhood with unsatisfactory prognosis. microRNA-215-5p (miR-215-5p) has been reported as a tumor-suppressive miRNA in different types of human cancers, but rarely in the Wilm's tumor. In light of this, we tried to investigate the regulatory role and underlying mechanism of miR-215-5p in the Wilm's tumor. METHODS: After sample collection and cell culture, the expression of miR-215-5p and CT10 Regulator of Kinase (CRK) was detected. Then rhabdoid tumor cell lines (formerly classified as Wilms' tumor cell lines), G401 and WT-CLS1 cells were transfected with pcDNA3.1, pcDNA3.1-CRK, sh-NC, sh-CRK, agomir NC, miR-215-5p agomir, antagomir NC or miR-215-5p antagomir to explore the function of miR-215-5p and CRK in the Wilm's tumor cell proliferation and migration. Moreover, the relationship between miR-215-5p and CRK was analyzed by dual luciferase reporter gene assay. RESULTS: Lowly-expressed miR-215-5p and highly-expressed CRK were observed in the Wilm's tumor tissues and cells. Transfection of pcDNA3.1-CRK or miR-215-5p antagomir could promote G401 and WT-CLS1 cell proliferation and enhance migration ability, while transfection of sh-CRK or miR-215-5p agomir led to opposite results. Additionally, miR-215-5p may bind to CRK. Moreover, transfection of pcDNA3.1-CRK in G401 and WT-CLS1 cells could partially reverse the inhibitory effect of miR-215-5p agomir on the proliferation and migration of Wilm's tumor cells. CONCLUSION: Our study highlighted that miR-215-5p could suppress the proliferation and migration of Wilm's tumor cells by regulating the expression of CRK, providing new ideas for molecular targeted therapy for Wilm's tumor.

Recurrent vulvar rashes in a girl aged 22 months for more than half a year / 中国当代儿科杂志

A girl, aged 22 months, attended the hospital due to recurrent vulvar rashes for more than half a year. Skin biopsy showed Langerhans cell histiocytosis, and evaluation of systemic conditions showed no systemic involvement. Therefore, the girl was diagnosed with Langerhans cell histiocytosis (skin type). In conclusion, for rashes on the vulva alone, if there are no specific clinical manifestations, the possibility of Langerhans cell histiocytosis should be considered after molluscum contagiosum, sexually transmitted diseases, and Fordyce disease are excluded.

Are contralateral submental artery perforator flaps feasible for the reconstruction of postoperative defects of oral cancer?

BACKGROUND: We evaluated the clinical applications of the reconstruction of postoperative defects of the oral cavity using contralateral submental artery flaps. METHODS: A retrospective study of 18 patients with postoperative intraoral cancer defects reconstructed with contralateral submental artery perforator flaps between October 2018 and October 2019 in our department was conducted. The defect area, flap size, and complications were evaluated. RESULTS: All patients were diagnosed based on pathological examinations: 2 with adenoid cystic carcinoma and 16 with squamous cell carcinoma. The submental artery perforator flap used for simultaneous repair was 8 to 15 cm in length and 4 to 6.5 cm in width. The survival rate of flap reconstruction was 100% with no donor site complications. CONCLUSIONS: Contralateral submental artery flap reconstruction is a suitable alternative for moderate to large intraoral defects, postoperative mouth floor defects, and oral cavity composite defects of oral malignant tumors without contralateral lymph node metastases.

Going Beyond Antibiotics: Natural Plant Extracts as an Emergent Strategy to Combat Biofilm-Associated Infections.

Biofilms are a collective of multiple types of bacteria that develop on a variety of surfaces. Biofilm development results in heightened resistance to antibiotics. Quorum sensing plays an important role in biofilm development as it is one of the common communication mechanisms within cells, which balances and stabilizes the environment, when the amount of bacteria increases. Because of the important implications of the roles biofilms play in infectious diseases, it is crucial to investigate natural antibacterial agents that are able to regulate biofilm formation and development. Various studies have suggested that natural plant products have the potential to suppress bacterial growth and exhibit chemopreventive traits in the modulation of biofilm development. In this review, we discuss and collate potential antibiofilm drugs and biological molecules from natural sources, along with their underlying mechanisms of action. In addition, we also discuss the antibiofilm drugs that are currently under clinical trials and highlight their potential future uses.

Clinical characteristics and outcomes of critically ill patients with COVID-19 in a tertiary community hospital in upstate New York

BackgroundThere are limited reports describing critically ill COVID-19 patients in New York. MethodsWe conducted a retrospective analysis of 32 adult critically ill patients admitted to a tertiary community hospital in upstate NY, between March 14th and April 12th, 2020. We collected demographic, laboratory, ventilator, and treatment data, which were analyzed and clinical outcomes tabulated. Results32 patients admitted to the ICU were included, with mean ({+/-}SD) follow-up duration 21 {+/-} 7 days. Mean ({+/-}SD) age was 62.2 {+/-} 11.2 years, and 62.5% were men. 27 (84.4%) of patients had one or more medical co-morbidities and 50% of the patients were current or former smokers. The mean ({+/-}SD) duration of symptoms was 6.6 ({+/-}4.4) days before presentation, with cough (81.3%), dyspnea (68.7%), and fever (65.6%) being most common. 23 (71.9%) patients received invasive mechanical ventilation. 5 (15.6%) had died, 11 (34.4%) had been discharged home, and 16 (50%) remained hospitalized, 8 (25%) of which were still in ICU. Mean ({+/-}SD) length of ICU stay was 10.2 ({+/-}7.7) days, and mean ({+/-}SD) length of hospital stay was 14.8 ({+/-}7.7) days. ConclusionMajority of patients were of older age and with medical co-morbidities. With adequate resource utilization, mortality of critically ill COVID-19 patients may not be as high as previously suggested.

Data on monthly physicochemical variation of Tropical Island groundwater of Pulau Bidong, South China Sea.

The groundwater samples of Pulau Bidong, Terengganu, Malaysia were collected from five sampling stations from June to October 2016. Physical parameters such as temperature, specific conductivity, dissolved oxygen (DO), pH, salinity, and DO saturation were measured in-situ by using handheld device. Meanwhile, total suspended solid (TSS), total dissolved solid (TDS), nitrate (NO3 -), nitrite (NO2 -), ammonium (NH4 +) and phosphate (PO4 3-) were analysed and detected using UV-Vis Spectrophotometer. The inorganic nutrients (NO3 -, NO2 -, NH4 + and PO4 3-) were ranged from 0.000 to 4.310 mg/L, 0.000 to 0.190 mg/L, 0.000 to 0.807 mg/L and 0.003 to 0.028 mg/L, respectively. The monthly trends of specific conductivity, DO, salinity, DO saturation, NO3 -, NO2 - and NH4 + demonstrated significant variation in June (the lowest rainfall) compared to other months. Correlation matrix revealed that temperature was associated with the specific conductivity, and NH4 + strongly correlated with DO, NO3 - and NO2 -. Nevertheless, there is a strong negative correlation between physicochemical parameters and monthly rainfall distribution. Notably, future studies are required for long-term monitoring to ensure the good quality of groundwater from Pulau Bidong. The spatial and temporal variability of the present data has been reported by Tan et al. [1].

A Novel Protein Drug, Novaferon, as the Potential Antiviral Drug for COVID-19

BackgroundNovaferon, a novel protein drug approved for the treatment of chronic hepatitis B in China, exhibits potent antiviral activities. We aimed to determine the anti-SARS-CoV-2 effects of Novaferon in vitro, and conducted a randomized, open-label, parallel group study to explore the antiviral effects of Novaferon for COVID-19. MethodsIn laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon were evaluated in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to the SARS-CoV-2 clearance in COVID-19 patients ResultsNovaferon inhibited the viral replication in infected cells (EC50=1.02 ng/ml), and protected healthy cells from SARS-CoV-2 infection (EC50=0.1 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher SARS-CoV-2 clearance rates on day 6 than the Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to SARS-CoV-2 clearance were 6 days, 6 days, and 9 days for three groups respectively, suggesting a 3-dayreduction of time to SARS-CoV-2 clearance in both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. ConclusionsNovaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon.