Therapeutic potency of compound RMY-205 for pulmonary fibrosis induced by SARS-CoV-2 nucleocapsid protein.

Pulmonary fibrosis is a typical sequela of coronavirus disease 2019 (COVID-19), which is linked with a poor prognosis for COVID-19 patients. However, the underlying mechanism of pulmonary fibrosis induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. Here, we demonstrated that the nucleocapsid (N) protein of SARS-CoV-2 induced pulmonary fibrosis by activating pulmonary fibroblasts. N protein interacted with the transforming growth factor ß receptor I (TßRI), to disrupt the interaction of TßRI-FK506 Binding Protein12 (FKBP12), which led to activation of TßRI to phosphorylate Smad3 and boost expression of pro-fibrotic genes and secretion of cytokines to promote pulmonary fibrosis. Furthermore, we identified a compound, RMY-205, that bound to Smad3 to disrupt TßRI-induced Smad3 activation. The therapeutic potential of RMY-205 was strengthened in mouse models of N protein-induced pulmonary fibrosis. This study highlights a signaling pathway of pulmonary fibrosis induced by N protein and demonstrates a novel therapeutic strategy for treating pulmonary fibrosis by a compound targeting Smad3.

[Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial].

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION: Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Untangling the changing impact of non-pharmaceutical interventions and vaccination on European COVID-19 trajectories.

Non-pharmaceutical interventions (NPIs) and vaccination are two fundamental approaches for mitigating the coronavirus disease 2019 (COVID-19) pandemic. However, the real-world impact of NPIs versus vaccination, or a combination of both, on COVID-19 remains uncertain. To address this, we built a Bayesian inference model to assess the changing effect of NPIs and vaccination on reducing COVID-19 transmission, based on a large-scale dataset including epidemiological parameters, virus variants, vaccines, and climate factors in Europe from August 2020 to October 2021. We found that (1) the combined effect of NPIs and vaccination resulted in a 53% (95% confidence interval: 42-62%) reduction in reproduction number by October 2021, whereas NPIs and vaccination reduced the transmission by 35% and 38%, respectively; (2) compared with vaccination, the change of NPI effect was less sensitive to emerging variants; (3) the relative effect of NPIs declined 12% from May 2021 due to a lower stringency and the introduction of vaccination strategies. Our results demonstrate that NPIs were complementary to vaccination in an effort to reduce COVID-19 transmission, and the relaxation of NPIs might depend on vaccination rates, control targets, and vaccine effectiveness concerning extant and emerging variants.

Surveillance of SARS-CoV-2 in Sewage Treatment Plants between January 2020 and July 2021 in Taiwan.

An outbreak of a new type of coronavirus pneumonia (COVID-19) began in Wuhan, Hubei Province, China, at the end of 2019, and it later spread to other areas of China and around the world. Taiwan reported the first confirmed case from an individual who returned from Wuhan, China, in January 2020 for Chinese New Year. Monitoring microbes in environmental sewage is an important epidemiological indicator, especially for pathogens that can be shed in feces such as poliovirus. We have conducted additional SARS-CoV-2 sewage testing since January 2020 using a well-established poliovirus environmental sewage surveillance system in Taiwan. Wastewater samples were collected from 11 sewage treatment plants from different parts of Taiwan twice a month for laboratory testing. By the end of July 2021, 397 wastewater specimens had been tested, and two samples were positive for SARS-CoV-2. These two wastewater samples were collected in the northern region of Taiwan from Taipei (site A) and New Taipei City (site C) at the beginning of June 2021. This result is consistent with the significant increase in confirmed COVID-19 cases observed in the same period of time. As the pandemic ebbed after June, the wastewater samples in these areas also tested negative for SARS-CoV-2 in July 2021.

Impacts of worldwide individual non-pharmaceutical interventions on COVID-19 transmission across waves and space.

Governments worldwide have rapidly deployed non-pharmaceutical interventions (NPIs) to mitigate the COVID-19 pandemic. However, the effect of these individual NPI measures across space and time has yet to be sufficiently assessed, especially with the increase of policy fatigue and the urge for NPI relaxation in the vaccination era. Using the decay ratio in the suppression of COVID-19 infections and multi-source big data, we investigated the changing performance of different NPIs across waves from global and regional levels (in 133 countries) to national and subnational (in the United States of America [USA]) scales before the implementation of mass vaccination. The synergistic effectiveness of all NPIs for reducing COVID-19 infections declined along waves, from 95.4% in the first wave to 56.0% in the third wave recently at the global level and similarly from 83.3% to 58.7% at the USA national level, while it had fluctuating performance across waves on regional and subnational scales. Regardless of geographical scale, gathering restrictions and facial coverings played significant roles in epidemic mitigation before the vaccine rollout. Our findings have important implications for continued tailoring and implementation of NPI strategies, together with vaccination, to mitigate future COVID-19 waves, caused by new variants, and other emerging respiratory infectious diseases.

Constructing Sports Promotion Models for an Accessibility and Efficiency Analysis of City Governments

This study provides a systematic analysis of sports promotion efficiency in 22 administrative districts in Taiwan from 2011 to 2018. We first considered sports behavior and sports information promotion and connected the multiple intermediate products using network DEA, used the public performance and outputs to measure the total efficiency of sports promotion in the 22 administrative districts, and then established the final input–output indicators. The long-term tracking of sports promotion efficiency shows that, while Taipei and Taoyuan experienced upward trends, the other 20 administrative districts saw declining trends. We also used truncated regression to identify 14 environmental variables that affected the efficiency of sports promotion in the 22 administrative districts from 2016 to 2018, with the results showing that funding, satisfaction with life, and average BMI in each administrative district were significant factors, revealing the latest trends in and measurements of governance in terms of government accessibility.

Clinical value of laboratory indicators for predicting disease progression and death in patients with COVID-19: a retrospective cohort study.

OBJECTIVES: As early prediction of severe illness and death for patients with coronavirus disease 2019 (COVID-19) is important, we aim to explore the clinical value of laboratory indicators in evaluating the progression and prognosis of patients with COVID-19. DESIGN: Retrospective cohort study. SETTING: Hospital-based study in China. PARTICIPANTS: Adult patients with COVID-19 from December 15, 2019 to March 15, 2020. END POINT: Disease severity and mortality. METHODS: Clinical data of 638 patients with COVID-19 were collected and compared between severe and non-severe groups. The predictive ability of laboratory indicators in disease progression and prognosis of COVID-19 was analysed using the receiver operating characteristic curve. The survival differences of COVID-19 patients with different levels of laboratory indicators were analysed utilising Kaplan-Meier analysis. RESULTS: 29.8% (190/638) of patients with COVID-19 progressed to severe. Compared with patients with no adverse events, C reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and D-dimer were significantly higher in severe patients with adverse events, such as acute myocardial injury, respiratory failure, acute kidney injury, mechanical ventilation, intensive care unit admission, multiple organ dysfunction syndromes and death (all p<0.05). The multivariate logistic analysis suggested that CRP, NLR and D-dimer were independent risk factors for the disease progression of COVID-19 (all p<0.05). The model combining all of them owned the highest area under the receiver operating characteristic curve (AUC) predicting disease progression and death of COVID-19, with AUC of 0.894 (95% CI 0.857 to 0.931) and 0.918 (95% CI 0.873 to 0.962), respectively. Survival analysis suggested that the patients with a high level of CRP, NLR or D-dimer performed shorter overall survival time (all p<0.05). CONCLUSIONS: The combination of CRP, NLR and D-dimer could be an effective predictor for the aggravation and death in patients with COVID-19. The abnormal expression of these indicators might suggest a strong inflammatory response and multiple adverse events in patients with severe COVID-19.

Development of a Recombinant RBD Subunit Vaccine for SARS-CoV-2.

The novel coronavirus pneumonia (COVID-19) pandemic is a great threat to human society and now is still spreading. Although several vaccines have been authorized for emergency use, only one recombinant subunit vaccine has been permitted for widespread use. More subunit vaccines for COVID-19 should be developed in the future. The receptor binding domain (RBD), located at the S protein of SARS-CoV-2, contains most of the neutralizing epitopes. However, the immunogenicity of RBD monomers is not strong enough. In this study, we fused the RBD-monomer with a modified Fc fragment of human IgG1 to form an RBD-Fc fusion protein. The recombinant vaccine candidate based on the RBD-Fc protein could induce high levels of IgG and neutralizing antibody in mice, and these could last for at least three months. The secretion of IFN-γ, IL-2 and IL-10 in the RBD-stimulated splenocytes of immunized mice also increased significantly. Our results first showed that the RBD-Fc vaccine could induce both humoral and cellular immune responses and might be an optional strategy to control COVID-19.

Reminders of COVID-19 social distancing can intensify physical pain

Social distance regulations have been widely implemented to control the global COVID-19 pandemic. Individuals have thus been experiencing social pain through social distance regulations. Prior research has shown that social and physical pains share a common neural alarm system. Hence, COVID-19 social distancing should enhance sensitivity to physical pain. Two laboratory studies were conducted to test the spillover effect of COVID-19 social distancing on physical pain. The findings supported our hypothesis by showing that participants who were reminded of COVID-19 social distancing reported a higher level of pain perception in response to immersion in hot water (Experiment 1, N = 102) and expressed a lower pain threshold measured by a pressure algometer than did those of controls (Experiment 2, N = 140). This may be the first experimental evidence demonstrating that people primed with COVID-19 social distancing have increased sensitivity to physical pain. Our findings suggest that people might be more likely to experience physical pain under the impact of COVID-19 social distancing. The association between a heightened sense of social disconnection in a global pandemic and increased sensitivity to physical pain should receive more attention.

[Development Progress of Ventilator].

Ventilator is an indispensable emergency medical equipment in hospitals. The global outbreak of the coronavirus disease 2019 (COVID-19) has highlighted the importance of the ventilator, which has attracted the attention and research on ventilators of all countries in the world. This article reviews the development history of the ventilator, briefly introduces the main air circuit structure and working principle of the ventilator, and then deeply analyzes the key technologies of this device. In addition, it compares some major brands of ventilators from several aspects in the market. Finally, the development trend and perspective of ventilators are presented.

Thoughts of social distancing experiences affect food intake and hypothetical binge eating: Implications for people in home quarantine during COVID-19.

BACKGROND AND RATIONALE: Social distance regulations have been suggested as one of the best ways to control and prevent the spread of COVID-19. Social connection and food are intertwined because both have played critical evolutionary roles in human survival. We tested whether the substitutability hypothesis in human motivation applies here in that cues signaling scarcity in one domain (e.g., social connection) might enhance the desire to acquire resources in another domain (e.g., food). METHODS: We recruited 140 adults from Kaohsiung City (the largest city in southern Taiwan) to participate in a laboratory experiment. Participants were randomly assigned to receive either social distancing or neutral primes via an emotional-event recollection technique. The amount of ice cream eaten during a taste test and the self-reported likelihood of binge eating served as the dependent measures. RESULTS: We found that, compared with controls, participants primed with social distancing consumed more ice cream in a taste test and reported a greater likelihood that they would engage in binge eating if they were placed in home quarantine. CONCLUSIONS: We may be the first to provide experimental evidence that social distancing can enhance the desire for food. The link between social distancing and the desire for food is pertinent to understanding how strongly social distance regulations may influence weight gain. Our findings have far-reaching implications for weight control under social distance regulations for prevention and control of COVID-19.

Accurate and efficient pulmonary CT imaging workflow for COVID-19 patients by the combination of intelligent guided robot and automatic positioning technology.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has put radiologists at a higher risk of infection during the computer tomography (CT) examination for the patients. To help settling these problems, we adopted a remote-enabled and automated contactless imaging workflow for CT examination by the combination of intelligent guided robot and automatic positioning technology to reduce the potential exposure of radiologists to 2019 novel coronavirus (2019-nCoV) infection and to increase the examination efficiency, patient scanning accuracy and better image quality in chest CT imaging . METHODS: From February 10 to April 12, 2020, adult COVID-19 patients underwent chest CT examinations on a CT scanner using the same scan protocol except with the conventional imaging workflow (CW group) or an automatic contactless imaging workflow (AW group) in Wuhan Leishenshan Hospital (China) were retrospectively and prospectively enrolled in this study. The total examination time in two groups was recorded and compared. The patient compliance of breath holding, positioning accuracy, image noise and signal-to-noise ratio (SNR) were assessed by three experienced radiologists and compared between the two groups. RESULTS: Compared with the CW group, the total positioning time of the AW group was reduced ((118.0 ± 20.0) s vs. (129.0 ± 29.0) s, P = 0.001), the proportion of scanning accuracy was higher (98% vs. 93%), and the lung length had a significant difference ((0.90±1.24) cm vs. (1.16±1.49) cm, P = 0.009). For the lesions located in the pulmonary centrilobular and subpleural regions, the image noise in the AW group was significantly lower than that in the CW group (centrilobular region: (140.4 ± 78.6) HU vs. (153.8 ± 72.7) HU, P = 0.028; subpleural region: (140.6 ± 80.8) HU vs. (159.4 ± 82.7) HU, P = 0.010). For the lesions located in the peripheral, centrilobular and subpleural regions, SNR was significantly higher in the AW group than in the CW group (centrilobular region: 6.6 ± 4.3 vs. 4.9 ± 3.7, P = 0.006; subpleural region: 6.4 ± 4.4 vs. 4.8 ± 4.0, P < 0.001). CONCLUSIONS: The automatic contactless imaging workflow using intelligent guided robot and automatic positioning technology allows for reducing the examination time and improving the patient's compliance of breath holding, positioning accuracy and image quality in chest CT imaging.

Homo-harringtonine (HHT) - A highly effective drug against coronaviruses and the potential for large-scale clinical applications (preprint)

In the search for treatment schemes of COVID-19, we start by examining the general weakness of coronaviruses and then identify approved drugs attacking that weakness. The approach, if successful, should identify drugs with a specific mechanism that is at least as effective as the best drugs proposed and are ready for clinical trials. All coronaviruses translate their non-structural proteins (~16) in concatenation, resulting in a very large super-protein. Homo-harringtonine (HHT), which has been approved for the treatment of leukemia, blocks protein elongation very effectively. Hence, HHT can repress the replication of many coronaviruses at the nano-molar concentration. In two mouse models, HHT clears SARS-CoV-2 in 3 days, especially by nasal dripping of 40 ug per day. We also use dogs to confirm the safety of HHT delivered by nebulization. The nebulization scheme could be ready for large-scale applications at the onset of the next epidemics. For the current COVID-19, a clinical trial has been approved by the Ditan hospital of Beijing but could not be implemented for want of patients. The protocol is available to qualified medical facilities.

Impacts of worldwide individual non-pharmaceutical interventions on COVID-19 transmission across waves and space (preprint)

Governments worldwide have rapidly deployed non-pharmaceutical interventions (NPIs) to mitigate the COVID-19 pandemic. However, the effect of these individual NPI measures across space and time has yet to be sufficiently assessed, especially with the increase of policy fatigue and the urge for NPI relaxation in the vaccination era. Using the decay ratio in the suppression of COVID-19 infections, we investigated the changing performance of different NPIs across waves from global and regional levels (in 133 countries) to national and subnational (in the United States of America [USA]) scales before the implementation of mass vaccination. The synergistic effectiveness of all NPIs for reducing COVID-19 infections declined along waves, from 95.4% in the first wave to 56.0% in the third wave recently at the global level and similarly from 83.3% to 58.7% at the USA national level, while it had fluctuating performance across waves on regional and subnational scales. Regardless of geographical scale, gathering restrictions and facial coverings played significant roles in epidemic mitigation before the vaccine rollout. Our findings have important implications for continued tailoring and implementation of NPI strategies, together with vaccination, to mitigate future COVID-19 waves, caused by new variants, and other emerging respiratory infectious diseases.

Effect of different resumption strategies to flatten the potential COVID-19 outbreaks amid society reopens: a modeling study in China.

BACKGROUND: The effect of the COVID-19 outbreak has led policymakers around the world to attempt transmission control. However, lockdown and shutdown interventions have caused new social problems and designating policy resumption for infection control when reopening society remains a crucial issue. We investigated the effects of different resumption strategies on COVID-19 transmission using a modeling study setting. METHODS: We employed a susceptible-exposed-infectious-removed model to simulate COVID-19 outbreaks under five reopening strategies based on China's business resumption progress. The effect of each strategy was evaluated using the peak values of the epidemic curves vis-à-vis confirmed active cases and cumulative cases. Two-sample t-test was performed in order to affirm that the pick values in different scenarios are different. RESULTS: We found that a hierarchy-based reopen strategy performed best when current epidemic prevention measures were maintained save for lockdown, reducing the peak number of active cases and cumulative cases by 50 and 44%, respectively. However, the modeled effect of each strategy decreased when the current intervention was lifted somewhat. Additional attention should be given to regions with significant numbers of migrants, as the potential risk of COVID-19 outbreaks amid society reopening is intrinsically high. CONCLUSIONS: Business resumption strategies have the potential to eliminate COVID-19 outbreaks amid society reopening without special control measures. The proposed resumption strategies focused mainly on decreasing the number of imported exposure cases, guaranteeing medical support for epidemic control, or decreasing active cases.

Assessment of Use and Fit of Face Masks Among Individuals in Public During the COVID-19 Pandemic in China.

Importance: Face masks are recommended to prevent transmission of coronavirus disease 2019 (COVID-19); however, there is scarce evidence on their protection efficacy and ways to improve it. Objective: To determine the proportion of improper face mask use, the factors associated with face mask protection efficacy, and ways to improve efficacy. Design, Setting, and Participants: This population-based cross-sectional study was conducted in China from July to August 2020 in 5 kinds of public places. Participants included convenience samples of individuals wearing face masks and able to taste the check solution. Exposures: Demographic and socioeconomic characteristics, including sex, age, and education level; information on face mask model and the worn duration was recorded. Main Outcomes and Measures: The main outcome as airtightness, assessed by detecting face-to-face mask gaps, movement of cotton fiber placed at the face mask edges, and using a qualitative fit test with a bitter solution spray. Masks were further assessed for whether sealing the upper face mask edge with an adhesive tape strip was associated with improved face mask airtightness. Results: Among 6003 face mask wearers enrolled, the mean (SD) age of participants was 31.1 (13.7) years, and 3047 participants (50.8%) were female. The first qualitative fit test found air leakage in 2754 participants (45.9%; 95% CI, 44.6%-47.1%), which was mostly attributable to gaps at the upper face mask edge. After sealing the upper face mask edge with an adhesive tape strip, 69.7% (95% CI, 68.0%-71.5%) of masks that had exhibited leakage became airtight in the second qualitative fit test, and the rate of airtightness reached 96.2% (95% CI, 95.4%-96.8%) in a third qualitative fit test after new surgical face masks with tape on the upper edge were provided to those who had not converted initially. The tape was well tolerated; overall, 6 participants (1.2%) reported a rash and 24 participants (5.8%) reported significant discomfort. Conclusions and Relevance: In this study of face mask fit among participants in China, although most people used face masks in public places, compromised protection due to suboptimal airtightness was common. The simple approach of sealing the upper edge of the face mask with an adhesive tape strip was associated with substantially improved its airtightness.

An unintended consequence of social distance regulations: COVID-19 social distancing promotes the desire for money.

Social distance regulations have been widely adopted during the global COVID-19 pandemic. From an evolutionary perspective, social connection and money are interchangeable subsistence resources for human survival. The substitutability principle of human motivation posits that scarcity in one domain (e.g., social connection) could motivate people to acquire or maintain resources in another domain (e.g., money). Two experiments were conducted to test the possibility that COVID-19 social distancing enhances the desire for money. Results showed that compared with controls, participants receiving social distancing primes (via recollection of experiences of social distancing or a Chinese glossary-search task) offered less money in the dictator game, showed lower willingness towards charitable donation (Experiment 1; N = 102), donated less money to a student fund, and rated money as having more importance (Experiment 2; N = 140). Our findings have far-reaching implications for financial decisions, charitable donations, and prosociality during and after the COVID-19 pandemic.