A game theory-based COVID-19 close contact detecting method with edge computing collaboration.

People all throughout the world have suffered from the COVID-19 pandemic. People can be infected after brief contact, so how to assess the risk of infection for everyone effectively is a tricky challenge. In view of this challenge, the combination of wireless networks with edge computing provides new possibilities for solving the COVID-19 prevention problem. With this observation, this paper proposed a game theory-based COVID-19 close contact detecting method with edge computing collaboration, named GCDM. The GCDM method is an efficient method for detecting COVID-19 close contact infection with users' location information. With the help of edge computing's feature, the GCDM can deal with the detecting requirements of computing and storage and relieve the user privacy problem. Technically, as the game reaches equilibrium, the GCDM method can maximize close contact detection completion rate while minimizing the latency and cost of the evaluation process in a decentralized manner. The GCDM is described in detail and the performance of GCDM is analyzed theoretically. Extensive experiments were conducted and experimental results demonstrate the superior performance of GCDM over other three representative methods through comprehensive analysis.

Alterations in the gut microbiome and metabolome profiles of septic mice treated with Shen FuHuang formula.

Sepsis has a high mortality rate, and treating sepsis remains a significant challenge worldwide. In former studies, our group found that traditional Chinese medicine, Shen FuHuang formula (SFH), is a promising medicine in treating coronavirus disease 2019 (COVID-19) patients with the septic syndrome. However, the underlying mechanisms remain elusive. In the present study, we first investigated the therapeutic effects of SFH on septic mice. To investigate the mechanisms of SFH-treated sepsis, we identified the gut microbiome profile and exploited untargeted metabolomics analyses. The results demonstrated that SFH significantly enhanced the mice's 7-day survival rate and hindered the release of inflammatory mediators, i.e., TNF-α, IL-6, and IL-1ß. 16S rDNA sequencing further deciphered that SFH decreased the proportion of Campylobacterota and Proteobacteria at the phylum level. LEfSe analysis revealed that the treatment of SFH enriched Blautia while decreased Escherichia_Shigella. Furthermore, serum untargeted metabolomics analysis indicated that SFH could regulate the glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. Finally, we found the relative abundance of Bacteroides, Lachnospiraceae_NK4A136_group, Escherichia_Shigella, Blautia, Ruminococcus, and Prevotella were closely related to the enrichment of the metabolic signaling pathways, including L-tryptophan, uracil, glucuronic acid, protocatechuic acid, and gamma-Glutamylcysteine. In conclusion, our study demonstrated that SFH alleviated sepsis by suppressing the inflammatory response and hence reduced mortality. The mechanism of SFH for treating sepsis may be ascribed to the enrichment of beneficial gut flora and modulation in glucagon signaling pathway, PPAR signaling pathway, galactose metabolism, and pyrimidine metabolism. To sum up, these findings provide a new scientific perspective for the clinical application of SFH in treating sepsis.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Real-time COVID-19 detection over chest x-ray images in edge computing.

Severe Coronavirus Disease 2019 (COVID-19) has been a global pandemic which provokes massive devastation to the society, economy, and culture since January 2020. The pandemic demonstrates the inefficiency of superannuated manual detection approaches and inspires novel approaches that detect COVID-19 by classifying chest x-ray (CXR) images with deep learning technology. Although a wide range of researches about bran-new COVID-19 detection methods that classify CXR images with centralized convolutional neural network (CNN) models have been proposed, the latency, privacy, and cost of information transmission between the data resources and the centralized data center will make the detection inefficient. Hence, in this article, a COVID-19 detection scheme via CXR images classification with a lightweight CNN model called MobileNet in edge computing is proposed to alleviate the computing pressure of centralized data center and ameliorate detection efficiency. Specifically, the general framework is introduced first to manifest the overall arrangement of the computing and information services ecosystem. Then, an unsupervised model DCGAN is employed to make up for the small scale of data set. Moreover, the implementation of the MobileNet for CXR images classification is presented at great length. The specific distribution strategy of MobileNet models is followed. The extensive evaluations of the experiments demonstrate the efficiency and accuracy of the proposed scheme for detecting COVID-19 over CXR images in edge computing.

Effect of Lianhua Qingwen capsules on the positive rate of COVID-19 close contacts: A retrospective analysis of a large-scale population-based cohort study.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is still spreading worldwide. COVID-19 close contact is a key point of this epidemic. However, no medication is now available for close contact. This study aims to evaluate the beneficial effect and safety of the Lianhua Qingwen capsule (LHQW) on COVID-19 close contacts via a large, retrospective cohort study. METHODS: A total of 25,002 close contacts from 199 quarantine sites in Changchun, Jilin, who underwent medical observation, were included. The information about these close contacts were collected for further epidemiological research. Moreover, subjects were divided into an exposure group (LHQW group, oral, 4 capsules/time, t.i.d.; 18,579 subjects) and a non-exposure group (control group; 6,423 subjects). Inverse probability of treatment weighting (IPTW) with propensity score was employed to evaluate the positive rate of the SARS-CoV-2 nucleic acid test in nasal and throat swabs confirmed by polymerase chain reaction (PCR). RESULTS: A total of 22,975 subjects were included in the analysis, 17,286 cases in the LHQW group and 5,689 cases in the control group. The positive rate of nucleic acid testing in the LHQW group was 5.12%, and that in the control group was 9.70% before the adjustment of IPTW of the propensity score; the difference between the two groups was -4.58% (95% CI -5.44- -3.77%, p <  0.001). After adjusting IPTW, the positive rate of nucleic acid testing in the LHQW group and the control group was 5.10% and 9.80%, respectively; the difference between the two groups was -4.70% (95% CI -5.18- -4.23, p < 0.001). The conclusions before and after the IPTW adjustment were consistent. No test drug-related adverse reactions were observed during the study period. CONCLUSION: LHQW has a beneficial effect and safety on the close contacts of SARS-CoV-2 who are under medical observation at the quarantine sites and can be used as an optional drug for those close contacts.

Effect of Lianhua Qingwen Capsules on the Positive Rate of COVID-19 Close Contacts: A Retrospective Analysis of a Large-Scale Population-Based Cohort Study

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Effectiveness of Lianhua Qingwen Capsule in Treatment of Asymptomatic COVID-19 Patients: A Randomized, Controlled Multicenter Trial.

Background: Asymptomatic patients are unneglected sources in propagating transmission chain due to their high viral loads. However, treatments available based on symptoms seem not applicable to asymptomatic patients. In this study, the authors want to estimate the effectiveness of Lianhua Qingwen (LH) capsule on asymptomatic coronavirus disease 2019 (COVID-19) patients. Methods: A randomized controlled trial (RCT) was performed to explore the effectiveness and safety of LH capsule in treating asymptomatic COVID-19 patients. Patients were randomized to control group (isolated observation) and treatment group (LH, 4 capsules, thrice daily) for 14 days. The primary endpoints were the rate and time of nucleic acid turning negative during the isolation observation. Results: A total of 120 participants were included in the full analysis set (60 each in the control and treatment groups). Data showed that the rate of nucleic acid turning negative during the isolation observation in the treatment group was higher than that in the control group (rate difference: 21.66%, 95% confidence interval [CI]: 4.34 to 37.27, p = 0.0142). Patients in the treatment group have a shorter time of nucleic acid turning negative (7.5 vs. 14.5 days, p = 0.018). Moreover, the rate of clinical symptoms appearance in the treatment group was lower compared with that in the control group (rate difference: -31.67, 95% CI: -46.83 to -13.82, p = 0.0005). The proportion of confirmed mild and common cases in the treatment group was also lower (35.00% vs. 66.67%, p = 0.0005). No serious adverse events were documented. Conclusions: In this study, the authors illustrated that LH capsule is beneficial to asymptomatic COVID-19 patients. Considering the lack of interventions for treating asymptomatic COVID-19 patients at this stage, LH capsule could be considered as a choice. Chinese Clinical Trial Registry: ChiCTR2100042066.

Hundreds-Dollar-Level Multiplex Integrated RT-qPCR Quantitative System for Field Detection.

The COVID-19 pandemic poses a threat to global health. Due to its high sensitivity, specificity, and stability, real-time fluorescence quantitative (real-time PCR) detection has become the most extensively used approach for diagnosing SARS-CoV-2 pneumonia. According to a report from the World Health Organization, emerging and underdeveloped nations lack nucleic acid detection kits and polymerase chain reaction (PCR) instruments for molecular biological detection. In addition, sending samples to a laboratory for testing may result in considerable delays between sampling and diagnosis, which is not favorable to the timely prevention and control of new crown outbreaks. Concurrently, there is an urgent demand for accurate PCR devices that do not require a laboratory setting, are more portable, and are capable of completing testing on-site. Hence, we report on HDLRT-qPCR, a new, low-cost, multiplexed real-time fluorescence detection apparatus that we have developed for on-site testing investigations of diverse diseases in developing nations. This apparatus can complete on-site testing rapidly and sensitively. The entire cost of this instrument does not exceed USD 760. In order to demonstrate the applicability of our PCR instrument, we conducted testing that revealed that we achieved gradient amplification and melting curves comparable to those of commercially available equipment. Good consistency characterized the testing outcomes. The successful detection of target genes demonstrates the reliability of our inexpensive PCR diagnostic technique. With this apparatus, there is no need to transport samples to a central laboratory; instead, we conduct testing at the sampling site. This saves time on transportation, substantially accelerates overall testing speed, and provides results within 40 min.

Integrated CNN and Federated Learning for COVID-19 Detection on Chest X-Ray Images.

Currently, Coronavirus Disease 2019 (COVID-19) is still endangering world health and safety and deep learning (DL) is expected to be the most powerful method for efficient detection of COVID-19. However, patients' privacy concerns prohibit data sharing between medical institutions, leading to unexpected performance of deep neural network (DNN) models. Fortunately, federated learning (FL), as a novel paradigm, allows participating clients to collaboratively train models without exposing source data outside original location. Nevertheless, the current FL-based COVID-19 detection methods prefer optimizing secondary objectives including delay, energy consumption and privacy, while few works focus on improving the model accuracy and stability. In this paper, we propose a federated learning framework with dynamic focus for COVID-19 detection on CXR images, named FedFocus. Specifically, to improve the training efficiency and accuracy, the training loss of each model is taken as the basis for parameter aggregation weights. As training layer deepens, a constantly updated dynamic factor is designed to stabilize the aggregation process. In addition, to highly restore the real dataset, the training sets in our experiments are divided based on the population and the infection of three real cities. Extensive experiments conducted on the real-world CXR images dataset demonstrate that FedFocus outperforms the baselines in model training efficiency, accuracy and stability.

Efficacy and Safety of Lianhua Qingke Tablets in the Treatment of Mild and Common-Type COVID-19: A Randomized, Controlled, Multicenter Clinical Study.

BACKGROUND: Lianhua Qingke (LH) tablets is an effective traditional Chinese medicine against various viral infections, especially in relieving coughing. However, its effects on COVID-19 are unknown. METHODS: To examine the therapeutic effectiveness of LH tablets in COVID-19 patients with mild and common types, a randomized, multicenter, controlled study was carried out. COVID-19 cases were randomized to undergo routine treatment with or without LH tablets (4 tablets, three times a day) for 14 days. The primary endpoints were the rate of achieving clinical symptom resolution and the corresponding time. RESULTS: There were 144 participants in the full analysis set (72 each in the LH and control groups). The LH group participants had elevated symptom alleviation rate at 14 days compared with control cases (FAS: 98.61% vs. 84.72%, p = 0.0026). In comparison with control group participants, the LH group participants had reduced median time to clinical symptom alleviation (median: 4 vs. 7 days, p < 0.0001). Higher resolution rates of coughing (98.44% vs. 84.51%, p = 0.0045) and expectoration (100% vs. 82.35%, p = 0.0268) were observed in the LH group. Times to recovery of fever (median: 2 vs. 3 days, p = 0.0007), coughing (median: 4 vs. 7 days, p < 0.0001), and expectoration (median: 3 vs. 6 days, p < 0.0001) were also notably shorter in the LH group. Moreover, the LH group had elevated improvement rates in chest computed tomography signs (FAS: 86.11% vs. 72.22%, p = 0.0402) and clinical cure at day 28 (FAS: 83.33% vs. 68.06%, p = 0.0326). However, no differences were found in the laboratory test and viral assay. Serious adverse events were not detected. CONCLUSION: These preliminary findings indicate LH tablets may be effective in symptomatic COVID-19, especially in relieving coughing. This trial was registered in Chinese Clinical Trial Registry (ChiCTR2100042069).

Development of potent and selective inhibitors targeting the papain-like protease of SARS-CoV-2.

The COVID-19 pandemic has been disastrous to society and effective drugs are urgently needed. The papain-like protease domain (PLpro) of SARS-CoV-2 (SCoV2) is indispensable for viral replication and represents a putative target for pharmacological intervention. In this work, we describe the development of a potent and selective SCoV2 PLpro inhibitor, 19. The inhibitor not only effectively blocks substrate cleavage and immunosuppressive function imparted by PLpro, but also markedly mitigates SCoV2 replication in human cells, with a submicromolar IC50. We further present a convenient and sensitive activity probe, 7, and complementary assays to readily evaluate SCoV2 PLpro inhibitors in vitro or in cells. In addition, we disclose the co-crystal structure of SCoV2 PLpro in complex with a prototype inhibitor, which illuminates their detailed binding mode. Overall, these findings provide promising leads and important tools for drug discovery aiming to target SCoV2 PLpro.

Efficacy and safety of Reduning injection in the treatment of COVID-19: a randomized, multicenter clinical study.

BACKGROUND: Reduning injection is a traditional Chinese medicine (TCM) with known efficacy against a variety of viral infections, but there is no data about its efficacy against coronavirus disease 2019 (COVID-19). METHODS: To explore the efficacy and safety of Reduning injection in the treatment of COVID-19, a randomized, open-labeled, multicenter, controlled trial was conducted from 12 general hospitals between 2020.02.06 and 2020.03.23. Patients with COVID-19 who met the diagnostic criteria of the "Diagnosis and Treatment Program for Novel Coronavirus Infection Pneumonia (Trial Fifth Edition)". Patients were randomized to routine treatment with or without Reduning injection (20 mL/day for 14 days) (ChiCTR2000029589). The primary endpoint was the rate of achieving clinical symptom recovery on day 14 of treatment. RESULTS: There were 77 and 80 participants in the Reduning and control groups. The symptom resolution rate at 14 days was higher in the Reduning injection than in controls [full-analysis set (FAS): 84.4% vs. 60.0%, P=0.0004]. Compared with controls, the Reduning group showed shorter median time to resolution of the clinical symptoms (143 vs. 313.5 h, P<0.001), shorter to nucleic acid test turning negative (146.5 vs. 255.5 h, P<0.001), shorter hospital stay (14.1 vs. 18.1 days, P<0.001), and shorter time to defervescence (29 vs. 71 h, P<0.001). There was no difference in AEs (3.9% vs. 8.8%, P=0.383). CONCLUSIONS: This preliminary trial suggests that Reduning injection might be effective and safe in patients with symptomatic COVID-19.

Systems Pharmacology and Verification of ShenFuHuang Formula in Zebrafish Model Reveal Multi-Scale Treatment Strategy for Septic Syndrome in COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) has affected millions of people worldwide. Critically ill COVID-19 patients develop viral septic syndrome, including inflammatory damage, immune dysfunction, and coagulation disorder. In this study, we investigated ShenFuHuang formula (SFH), a traditional Chinese medicine, which has been widely used as complementary therapy for clinical treatment of COVID-19 in Wuhan, to understand its pharmacological properties. Results of systems pharmacology identified 49 active compounds of SFH and their 69 potential targets, including GSK3ß, ESR1, PPARG, PTGS2, AKR1B10, and MAPK14. Network analysis illustrated that the targets of SFH may be involved in viral disease, bacterial infection/mycosis, and metabolic disease. Moreover, signaling pathway analysis showed that Toll-like receptors, MAPK, PPAR, VEGF, NOD-like receptor, and NF-kappa B signaling pathways are highly connected with the potential targets of SFH. We further employed multiple zebrafish models to confirm the pharmacological effects of SFH. Results showed that SFH treatment significantly inhibited the inflammatory damage by reducing the generation of neutrophils in Poly (I:C)-induced viral infection model. Moreover, SFH treatment could improve the phagocytosis of macrophages and enhance the expression of immune genes in an immune deficiency model. Furthermore, SFH treatment exhibited promising anti-thrombosis effect in a thrombus model. This study provided additional evidence of SFH formula for treating COVID-19 patients with septic syndrome using multiple-scale estimation.

Air pollution and temperature are associated with increased COVID-19 incidence: A time series study.

OBJECTIVES: Although COVID-19 is known to be caused by human-to-human transmission, it remains largely unclear whether ambient air pollutants and meteorological parameters could promote its transmission. METHODS: A retrospective study was conducted to study whether air quality index (AQI), four ambient air pollutants (PM2.5, PM10, NO2 and CO) and five meteorological variables (daily temperature, highest temperature, lowest temperature, temperature difference and sunshine duration) could increase COVID-19 incidence in Wuhan and XiaoGan between Jan 26th to Feb 29th in 2020. RESULTS: First, a significant correlation was found between COVID-19 incidence and AQI in both Wuhan (R2=0.13, p<0.05) and XiaoGan (R2=0.223, p<0.01). Specifically, among four pollutants, COVID-19 incidence was prominently correlated with PM2.5 and NO2 in both cities. In Wuhan, the tightest correlation was observed between NO2 and COVID-19 incidence (R2=0.329, p<0.01). In XiaoGan, in addition to the PM2.5 (R2=0.117, p<0.01) and NO2 (R2=0.015, p<0.05), a notable correlation was also observed between the PM10 and COVID-19 incidence (R2=0.105, p<0.05). Moreover, temperature is the only meteorological parameter that constantly correlated well with COVID-19 incidence in both Wuhan and XiaoGan, but in an inverse correlation (p<0.05). CONCLUSIONS: AQI, PM2.5, NO2, and temperature are four variables that could promote the sustained transmission of COVID-19.