Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19.

The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.

Identification of Asymptomatic COVID-19 Patients on Chest CT Images Using Transformer-Based or Convolutional Neural Network-Based Deep Learning Models.

Novel coronavirus disease 2019 (COVID-19) has rapidly spread throughout the world; however, it is difficult for clinicians to make early diagnoses. This study is to evaluate the feasibility of using deep learning (DL) models to identify asymptomatic COVID-19 patients based on chest CT images. In this retrospective study, six DL models (Xception, NASNet, ResNet, EfficientNet, ViT, and Swin), based on convolutional neural networks (CNNs) or transformer architectures, were trained to identify asymptomatic patients with COVID-19 on chest CT images. Data from Yangzhou were randomly split into a training set (n = 2140) and an internal-validation set (n = 360). Data from Suzhou was the external-test set (n = 200). Model performance was assessed by the metrics accuracy, recall, and specificity and was compared with the assessments of two radiologists. A total of 2700 chest CT images were collected in this study. In the validation dataset, the Swin model achieved the highest accuracy of 0.994, followed by the EfficientNet model (0.954). The recall and the precision of the Swin model were 0.989 and 1.000, respectively. In the test dataset, the Swin model was still the best and achieved the highest accuracy (0.980). All the DL models performed remarkably better than the two experts. Last, the time on the test set diagnosis spent by two experts-42 min, 17 s (junior); and 29 min, 43 s (senior)-was significantly higher than those of the DL models (all below 2 min). This study evaluated the feasibility of multiple DL models in distinguishing asymptomatic patients with COVID-19 from healthy subjects on chest CT images. It found that a transformer-based model, the Swin model, performed best.

Climate‐linked increasing vegetation fires in global high mountains

The spatiotemporal variability of vegetation fires is essential for understanding changes in the climate and ecosystem in mountainous regions. MODIS Collection 6 active fire products indicate that the area burned by vegetation fires declined globally from over 4.27 million km2 to less than 3.52 million km2 annually during 2001–2021. In contrast, global high mountains higher than 3000 m have experienced an overall increase in their burned area and suffered record‐breaking wildfires from August to December 2020. Although high mountains accounted for less than 0.03% of the global burned area during 2001–2021, this proportion had more than tripled by 2020. This unprecedented wildfire record in 2020 could be mainly caused by favorable fire weather conditions such as low relative humidity, low soil water and high temperature.

The impact of cryptocurrencies on China's carbon price variation during COVID-19: A quantile perspective

We aim to document the impact of cryptocurrencies on China's carbon price variation using some quantile techniques during COVID-19 with the daily data spanning from August 7, 2015 to April 30, 2021. In this paper, we show that cryptocurrencies have a very strong explanation power for carbon market with the non-parametric causality-in-quantiles method. In addition, cryptocurrencies can work as a good hedging candidate for carbon market at different investment horizons with the quantile coherency approach. Using hedging effectiveness measure, we further show that COVID-19 can reverse the optimal hedging ratios in our portfolio specification in cryptocurrencies‑carbon emission trading pairs while this pandemic does not have effects on the trading effectiveness. Finally, the heterogeneity and asymmetry features in the dynamic quantile-on-quantile effects are detected and the effects on carbon efficient index show relatively strong fluctuation while on carbon emission trading market are relatively strong in magnitude. Our empirical results conclude with many potential applications for policymakers and investors.

Time-frequency connectedness between energy and nonenergy commodity markets during COVID-19: Evidence from China.

We aim to investigate the static and dynamic time-frequency connectedness between energy and nonenergy commodity markets in China during COVID-19 based on Baruník and Krehlík (2018) method. First, in this paper, we find that the short-term connectedness dominates the long-term one, and the total connectedness increases after the COVID-19 outbreak. Second, the energy commodity is the receiver and is influenced much by the spillovers of non-energy commodity markets (e.g. chemical commodities and non-ferrous metals) in the short run. At the same time, the impact is less at the long-term investment horizons. In addition, chemical commodities and soft commodities are the primary transmitters in this system in the short run. In contrast, chemical commodities and coal steel iron commodities are the main long-run primary transmitters. Third, the spillover role varies with the time-frequency domain during COVID-19. To be more specific, the energy commodity shows a net receiver role in the short and long run before the COVID-19 pandemic, but after it, the role of the net transmitter can be seen in the long run with ease. Finally, we show that COVID can reduce the hedging effectiveness at different investment horizons. The mineral policymakers should note our dynamic empirical results between energy and nonenergy commodity.

m6A Demethylase ALKBH5 Restrains PEDV Infection by Regulating GAS6 Expression in Porcine Alveolar Macrophages.

Porcine epidemic diarrhea virus (PEDV) is a burdensome coronavirus for the global pig industry. Although its fecal-oral route has been well-recognized, increasing evidence suggests that PEDV can also spread through airborne routes, indicating that the infection may also occur in the respiratory tract. N6-methyladenosine (m6A) has been known to regulate viral replication and host immunity, yet its regulatory role and molecular mechanism regarding PEDV infection outside the gastrointestinal tract remain unexplored. In this study, we demonstrate that PEDV can infect porcine lung tissue and the 3D4/21 alveolar macrophage cell line, and the key m6A demethylase ALKBH5 is remarkably induced after PEDV infection. Interestingly, the disruption of ALKBH5 expression remarkably increases the infection's capacity for PEDV. Transcriptome profiling identified dozens of putative targets of ALKBH5, including GAS6, which is known to regulate virus infectivity. Further, MeRIP-qPCR and mRNA stability analyses suggest that ALKBH5 regulates the expression of GAS6 via an m6A-YTHDF2-dependent mechanism. Overall, our study demonstrates that PEDV can infect porcine lung tissue and 3D4/21 cells and reveals the crucial role of ALKBH5 in restraining PEDV infections, at least partly, by influencing GAS6 through an m6A-YTHDF2-dependent mechanism.

Incomplete occlusion and visual symptoms of peri-ophthalmic aneurysm after treatment with a pipeline embolization device: a multi-center cohort study.

OBJECTIVE: Peri-ophthalmic aneurysm is a special type of aneurysm. We assessed the relationship between ophthalmic artery (OA) origin and aneurysm and examined the effect of a pipeline embolization device (PED, Covidien/Medtronic) with or without coils on aneurysm occlusion rate and visual outcomes. METHODS: We retrospectively analyzed 194 peri-ophthalmic aneurysms in 189 patients among 1171 patients treated with a PED in a Chinese post-market multi-center registry study from November 2014 to October 2019. Peri-ophthalmic aneurysms were defined as carotid-ophthalmic segment aneurysms arising from the internal carotid artery dorsal wall at, or distal to, the OA origin, with a superior or superomedial projection. The relationship between OA origin and the aneurysm was classified as follows: type A, OA originating separate from the aneurysm; type B, OA originating from the aneurysm neck or dome. Patients with aneurysm were divided into the PED-only group and the PED + coils group according to treatment. RESULTS: The median follow-up time was 6.8 months (range, 5.3-20.2 months). There were 163 occluded aneurysms (84%) and 31 aneurysms with incomplete occlusion (16%). A multivariate analysis showed that type B aneurysm was a risk factor for incomplete occlusion in the PED-only group (odds ratio [OR] 4.854, 95% confidence interval [CI] 1.878-12.548, P = 0.001). Visual symptoms at final follow-up correlated with preoperative visual symptoms (OR 22.777, 95% CI 3.115-166.555, P = 0.002). CONCLUSIONS: Type B aneurysm is associated with a lower occlusion rate after PED-only treatment. Patients with preoperative visual symptoms should be treated promptly to avoid permanent visual symptoms.

China's NMPA perspective on the clinical performance of SARS-CoV-2 antigen test reagents.

The COVID-19 pandemic continues to spread all over the world. In the process of emergency use authorization, the Center for Medical Device Evaluation of the China National Medical Products Administration issued 'Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Detection Reagents' as the guidance of registration of antigen and antibody test reagents for the industry. In this document, clinical evaluation requirements of antigen detection reagents are elaborated. Based on the Key Points document and the authors' review practice, this article explains the evaluation methods and requirements of clinical performance of SARS-CoV-2 antigen-detecting rapid diagnostic tests, then analyzes the application scenarios and intended use of antigen detection reagents.

Impact of Gender Difference on Anxiety in COVID-19 Patients in Quarantine Wards.

OBJECTIVE: This study aimed to investigate the gender difference in anxiety in novel coronavirus pneumonia (COVID-19) patients in the quarantine ward during the outbreak. METHODS: The self-rating anxiety scale (SAS) was used on the seventh day of isolation to analyze the anxiety levels of a total of 242 suspected or confirmed COVID-19 patients in the quarantine wards of two hospitals; 232 of these patients (112 males and 120 females) completed the anxiety scoring. The anxiety scores were compared between male and female patients using the t-test, and a scatter diagram was used for analysis. RESULTS: The SAS scores of females in quarantine wards were higher than those of males at seven days of isolation. CONCLUSION: Women with COVID-19 are more prone to anxiety than men while in isolation. It is necessary to give more attention to female patients in quarantine wards in the future, and psychological counseling may be necessary.

Factors Influencing Residents' Psychological Status During Standardized Training in COVID-19.

Objectives: To explore the influencing factors of residents' psychological status during standardized training in COVID-19 for finding ways to promote their mental health. Methods: A total of 760 residents were surveyed with a structured questionnaire. Correlation analysis was used to analyze the influencing factors of psychological status of the residents, and a mediation model was constructed to verify the mediating role of satisfaction. Results: Age, willingness to study medicine, and satisfaction were positively correlated with negative psychological status (P < 0.05). And gender, only child or not, and annual household income (RMB) were negatively correlated with negative psychological status (P < 0.01). Residents' satisfaction with standardized training mode plays a complete mediating role between annual household income and negative psychological status. Conclusions: Our findings emphasize the importance of concentrating on resident's psychological status and family economic situation. And relative departments should take action to optimize the standardized training mode to improve the satisfaction.

Screening S protein - ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19.

The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination of SARS-CoV-2 S protein with Angiotensin converting enzyme II(ACE2) of host cell to promote membrane fusion is an initial critical step for SARS-CoV-2 infection. Therefore, screening natural products that inhibit the binding of SARS-CoV-2 S protein and ACE2 also provides a feasible strategy for the treatment of COVID-19. Establishment of high throughput screening model is an important basis and key technology for screening S protein-ACE2 blockers. Based on this, the molecular structures of SARS-CoV-2 and ACE2 and their processes in the life cycle of SARS-CoV-2 and host cell infection were firstly reviewed in this paper, with emphasis on the methods and techniques of screening S protein-ACE2 blockers, including Virtual Screening (VS), Surface Plasmon Resonance (SPR), Biochromatography, Biotin-avidin with Enzyme-linked Immunosorbent assay and Gene Chip Technology. Furthermore, the technical principle, advantages and disadvantages and application scope were further elaborated. Combined with the application of the above screening technologies in S protein-ACE2 blockers, a variety of natural products, such as flavonoids, terpenoids, phenols, alkaloids, were summarized, which could be used as S protein-ACE2 blockers, in order to provide ideas for the efficient discovery of S protein-ACE2 blockers from natural sources and contribute to the development of broad-spectrum anti coronavirus drugs.

[Response of Air Quality to COVID-19 Lockdown in Xiamen Bay].

Air pollutant concentrations in the Xiamen Bay cities during the period before and after COVID-19 lockdown(from January 11 to February 21, 2020) were studied to determine the influence of human activities on air quality in this region. During the Chinese Spring Festival holiday and the lockdown period, the concentrations of SO2, NO2, CO, PM10, and PM2.5 decreased by 6%-22%, 53%-70%, 34%-48%, 47%-64%, and 53%-60%, respectively. However, the changes in O3 concentrations were not consistent with the variations of human activities. The reduction rates for PM2.5, PM10, CO, and NO2 during the Spring Festival were greater than in previous years(2018 and 2019), but the reduction rates for SO2 were comparable. The concentrations of NO2 increased sharply(38%-138%), and much higher those of SO2(2%-42%), after the resumption of socioeconomic activities, indicating the importance of traffic reductions due to the lockdown measures on NO2. Higher wind speeds and rainfall after the Spring Festival were also favorable for the decline of SO2, NO2, and PM. The spatio-temporal distributions of the six criterial pollutants in the Xiamen Bay city cluster were obtained based on the Inverse Distance Weight method. The variability in regions with high NO2 concentrations was strongly linked to traffic emissions, while spatial patterns for CO and SO2 changed little over the six-week study period. The concentrations of PM2.5 and PM10 increased notably in the region, linked to more construction activity, but changed comparatively little in regions with dense populations and traffic networks. O3 remained relatively stable but low-value regions corresponded to those regions with high NO2 concentrations, indicating the significant titration effect of NO2 on O3. These results provide valuable information that can inform O3 pollution reduction measures.

Increased procoagulant platelet levels are predictive of death in COVID-19.

Prior research has identified abnormal platelet procoagulant responses in COVID-19. Coated-platelets, a form of procoagulant platelets, support thrombin formation and are elevated in ischemic stroke patients with increased risk for recurrent infarction. Our goal was to examine changes in coated-platelet levels over the course of COVID-19 infection and determine their association with disease severity, thrombosis, and death. Coated-platelet levels were assayed after admission and repeated weekly in COVID-19 patients, and in COVID-19 negative controls. Receiver operator characteristic (ROC) analysis was used to calculate area under the curve (AUC) values for a model including baseline coated-platelets to predict death. Kaplan-Meier and Cox proportional hazards analysis was used to predict risk for death at 90 days. We enrolled 33 patients (22 with moderate and 11 with severe infection) and 20 controls. Baseline coated-platelet levels were lower among moderate (mean ± SD; 21.3 ± 9.8%) and severe COVID-19 patients (28.5 ± 11.9%) compared to controls (38.1 ± 10.4%, p < 0.0001). Coated-platelet levels increased during follow-up in COVID-19 patients by 7% (relative) per day from symptom onset (95% CI 2-12%, p = 0.007). A cut-off of 33.9% for coated-platelet levels yielded 80% sensitivity and 96% specificity for death at 90 days, with resulting AUC of 0.880 (95% CI 0.680-1.0, p = 0.0002). The adjusted hazard ratio for death in patients with coated-platelet levels > 33.9% was 40.99 when compared to those with levels ≤ 33.9% (p < 0.0001). Platelet procoagulant potential is transiently decreased in most patients during COVID-19; however, increased baseline platelet procoagulant levels predict death. Defining the mechanisms involved and potential links with aging may yield novel treatment targets.

Analysis on the spatio-temporal characteristics of COVID-19 in mainland China.

COVID-19 has brought many unfavorable effects on humankind and taken away many lives. Only by understanding it more profoundly and comprehensively can it be soundly defeated. This paper is dedicated to studying the spatial-temporal characteristics of the epidemic development at the provincial-level in mainland China and the civic-level in Hubei Province. Moreover, a correlation analysis on the possible factors that cause the spatial differences in the epidemic's degree is conducted. After completing these works, three different methods are adopted to fit the daily-change tendencies of the number of confirmed cases in mainland China and Hubei Province. The three methods are the Logical Growth Model (LGM), Polynomial fitting, and Fully Connected Neural Network (FCNN). The analysis results on the spatial-temporal differences and their influencing factors show that: (1) The Chinese government has contained the domestic epidemic in early March 2020, indicating that the number of newly diagnosed cases has almost zero increase since then. (2) Throughout the entire mainland of China, effective manual intervention measures such as community isolation and urban isolation have significantly weakened the influence of the subconscious factors that may impact the spatial differences of the epidemic. (3) The classification results based on the number of confirmed cases also prove the effectiveness of the isolation measures adopted by the governments at all levels in China from another aspect. It is reflected in the small monthly grade changes (even no change) in the provinces of mainland China and the cities in Hubei Province during the study period. Based on the experimental results of curve-fitting and considering the time cost and goodness of fit comprehensively, the Polynomial(Degree = 18) model is recommended in this paper for fitting the daily-change tendency of the number of confirmed cases.

Key points of technical review for the registration of SARS-CoV-2 antigen/antibody tests.

Coronavirus disease-2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally since its first report and become a worldwide pandemic. In response to the outbreak of COVID-19, Center for Medical Device Evaluation, NMPA (CMDE) initiated emergency review and approval procedures to accelerate the process of reviewing emergent medical products and issued the Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Tests (Key Points) to provide the requirements on the technical review of the tests. With uncontrolled spread and evolution of COVID-19 in the world, continuous prevention and measurements are necessary for fighting this pandemic and SARS-CoV-2 antigen/antibody tests are still urgently needed. This article is an attempt to expand clarification of the Key Points to wider audiences based on current understanding of SARS-CoV-2 to facilitate the development and application of SARS-CoV-2 antigen/antibody tests.

China NMPA perspective on clinical evaluation of SARS-CoV-2 antibody test reagents in the process of emergency approval.

Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 antibody testing an important supplement to nucleic acid testing. In the process of emergency approval, the Center for Medical Device Evaluation of the China National Medical Products Administration released The Key Points of Technical Review for the Registration of SARS-CoV-2 Antigen/Antibody Detection Reagents. The Clinical Study Requirement section of the Key Point has put forward requirements in terms of reference methods and subject enrolment among others, which can ensure that the test results can meet the clinical needs. This article draws on the experience of the China NMPA in evaluating diagnostic reagents used to supplement the gold standard test method in the early stage of an epidemic of an infectious disease, as well as to serve as reference for clinicians and regulators.

CD-sACE2 inclusion compounds: An effective treatment for coronavirus disease 2019 (COVID-19).

Coronaviruses are common human viruses and include the severe acute respiratory syndrome coronavirus (SARS-CoV), the middle east respiratory syndrome coronavirus and the SARS-CoV-2. Coronaviruses mainly bind to transmembrane receptor proteins on the human cell membrane through spike proteins (S-proteins), thus releasing the RNA of the virus into the interior of the host cell to cause an infection. In this article, we discuss the mechanism and production of cyclodextrin-soluble angiotensin-converting enzyme 2 (CD-sACE2) inclusion compounds in the treatment of SARS-CoV-2 infections by blocking S-proteins. On the basis of the current research evidence, we believe that CD-sACE2 inclusion compounds have the potential to treat COVID-19. We hope that our article can provide a theoretical basis for later experiments.

Associations of procalcitonin, C-reaction protein and neutrophil-to-lymphocyte ratio with mortality in hospitalized COVID-19 patients in China.

Coronavirus disease 2019 (COVID-19) is an important and urgent threat to global health. Inflammation factors are important for COVID-19 mortality, and we aim to explore whether the baseline levels of procalcitonin (PCT), C-reaction protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) are associated with an increased risk of mortality in patients with COVID-19. A retrospective study was conducted and a total of 76 patients with confirmed COVID-19 were included between January 17, 2020 to March 2, 2020, of these cases, 17 patients were dead. After adjusting covariates, PCT (≥ 0.10 ng/mL) and CRP (≥ 52.14 mg/L) exhibited independent increasing risks of mortality were used hazard ratio (HR) of 52.68 (95% confidence interval [CI]: 1.77-1571.66) and 5.47 (95% CI: 1.04-28.72), respectively. However, NRL (≥ 3.59) was not found to be an independent risk factor for death in our study. Furthermore, the elevated PCT levels were still associated with increasing risk of mortality in the old age group (age ≥ 60 y), and in the critically severe and severe patients after adjustment for complications. Thu Baseline levels of PCT and CRP have been addressed as independent predictors of mortality in patients with COVID-19.

Comparison and application of different immunoassay methods for the detection of SARS-CoV-2.

The detection data of IgM and IgG antibodies in 169 patients with coronavirus disease-2019 (COVID-19) were analyzed to evaluate differences in clinical performance between the colloidal gold method and chemiluminescence method. In this study, chemiluminescence detection of IgM antibody showed a positive conversion earlier (about 1-2 days earlier), positive conversion rates higher in different stages of disease, and a trend of declining positive rate later than colloidal gold method. For IgG antibody, the chemiluminescence method showed a positive conversion earlier and the positive rate climbing more quickly than the colloidal gold method. No obvious negative-converting tendency of IgG detection was observed within 35 days after the onset of disease. Although colloidal gold method is generally less sensitive than chemiluminescence method, it shows advantages of shorter turn-around time, more simple procedure, and no special equipment required. The two methodologies can be chosen according to different laboratory conditions. A reasonable understanding of the performance of reagents with different methodologies can help in clinical disease diagnosis effectively and assist in the diagnosis of the progression of COVID-19, for which the dynamic changes of antibody will provide reliable evidence.

Initial chest CT findings in COVID-19: correlation with clinical features.

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).