A Dual-Approach Strategy to Optimize the Safety and Efficacy of Anti-Zika Virus Monoclonal Antibody Therapeutics.

Antibody-dependent enhancement of infection (ADE) is clinically relevant to Dengue virus (DENV) infection and poses a major risk to the application of monoclonal antibody (mAb)-based therapeutics against related flaviviruses such as the Zika virus (ZIKV). Here, we tested a two-tier approach for selecting non-cross-reactive mAbs combined with modulating Fc glycosylation as a strategy to doubly secure the elimination of ADE while preserving Fc effector functions. To this end, we selected a ZIKV-specific mAb (ZV54) and generated three ZV54 variants using Chinese hamster ovary cells and wild-type (WT) and glycoengineered ΔXF Nicotiana benthamiana plants as production hosts (ZV54CHO, ZV54WT, and ZV54ΔXF). The three ZV54 variants shared an identical polypeptide backbone, but each exhibited a distinct Fc N-glycosylation profile. All three ZV54 variants showed similar neutralization potency against ZIKV but no ADE activity for DENV infection, validating the importance of selecting the virus/serotype-specific mAbs for avoiding ADE by related flaviviruses. For ZIKV infection, however, ZV54CHO and ZV54ΔXF showed significant ADE activity while ZV54WT completely forwent ADE, suggesting that Fc glycan modulation may yield mAb glycoforms that abrogate ADE even for homologous viruses. In contrast to the current strategies for Fc mutations that abrogate all effector functions along with ADE, our approach allowed the preservation of effector functions as all ZV54 glycovariants retained antibody-dependent cellular cytotoxicity (ADCC) against the ZIKV-infected cells. Furthermore, the ADE-free ZV54WT demonstrated in vivo efficacy in a ZIKV-infection mouse model. Collectively, our study provides further support for the hypothesis that antibody-viral surface antigen and Fc-mediated host cell interactions are both prerequisites for ADE, and that a dual-approach strategy, as shown herein, contributes to the development of highly safe and efficacious anti-ZIKV mAb therapeutics. Our findings may be impactful to other ADE-prone viruses, including SARS-CoV-2.

Evaluation of efficacy and safety of Qiangzhu-qinggan formula as an adjunctive therapy in adult patients with severe influenza: study protocol for a randomized parallel placebo-controlled double-blind multicenter trial.

BACKGROUND: Influenza can fall into three categories according to severity: mild influenza, severe influenza, and critical influenza. Severe influenza can result in critical illness and sometimes death particularly in patients with comorbidities, advanced age, or pregnancy. Neuraminidase inhibitors (NAIs) are the only antiviral drugs in widespread use for influenza. However, the effectiveness of NAIs against severe influenza is uncertain. New effective drugs or regimens are therefore urgently needed. Qiangzhu-qinggan (QZQG) formula has been found to be effective against influenza virus infection during long-term application in China, which lacks support of evidence-based clinical trial till now. This study is designed to assess the efficacy and safety of QZQG formula as an adjuvant therapy in adult patients with severe influenza. METHODS: This protocol is drawn up in accordance with the SPIRIT guidelines and CONSORT Extension for Chinese herbal medicine formulas. This is a randomized, placebo-controlled, double-blind, multicenter trial. Two hundred twenty-eight adults with severe influenza are randomly assigned in a 1:1 ratio to QZQG or placebo for 7 days. All participants need to receive 1 day of screening before randomization, 7 days of intervention, and 21 days of observation after randomization. The primary outcome is the proportion of clinical improvement, defined as the proportion of patients who met the criteria of 3 points or less in the seven-category ordinal scale or 2 points or less in National Early Warning Score 2 within 7 days after randomization. DISCUSSION: This is the first randomized, controlled, parallel, double-blind clinical trial to evaluate the efficacy and safety of traditional Chinese herbal formula granules as an adjuvant therapy in adult patients with severe influenza. This study aims to redefine the value of traditional Chinese herbal medicines in the treatment of virus-related respiratory infectious diseases and serves as an example of evidence-based clinical trials of other Chinese herbal medicines.

The characteristics and predictive role of lymphocyte subsets in COVID-19 patients.

OBJECTIVE: To investigate the characteristics and predictive roles of lymphocyte subsets in COVID-19 patients. METHOD: We evaluated lymphocyte subsets and other clinical features of COVID-19 patients, and analyzed their potential impacts on COVID-19 outcomes. RESULTS: 1. Lymphocyte subset counts in the peripheral blood of patients with COVID-19 were significantly reduced, especially in patients with severe disease. 2. In patients with non-severe disease, the time from symptom onset to hospital admission was positively correlated with total T cell counts. 3. Among COVID-19 patients who did not reach the composite endpoint, lymphocyte subset counts were higher than in patients who had reached the composite endpoint. 4. The Kaplan-Meier survival curves showed significant differences in COVID-19 patients, classified by the levels of total, CD8+, and CD4+ T cells at admission. CONCLUSION: Our study showed that total, CD8+, and CD4+ T cell counts in patients with COVID-19 were significantly reduced, especially in patients with severe disease. Lower T lymphocyte subsets were significantly associated with a higher occurrence of composite endpoint events. These subsets may help identify patients with a high risk of composite endpoint events.

Determinants of Attitude, Satisfaction and Behavioral Intention of Online Learning Usage Among Students During COVID-19

Purpose: The objective of this research is to examine determinants of behavioral intention to use online learning among students in a higher vocational collage in China;including perceived ease of use;perceived usefulness;attitude;trust and satisfaction. Technology Acceptance Model (TAM) and Theory of Planned Behavior (TPB) were the fundamental theories of this study. Research design;data and methodology: A quantitative approach was used to distribute questionnaire to 500 third-grade students in Tianfu Vocational College of Chengdu. Purposive sampling;stratified random sampling;and convenience sampling were employed. After the data collection;confirmatory factor analysis (CFA) and structural equation model (SEM) were accounted to analyze the data in measurement and structural models;measuring factor loading;reliability;validity and model fit. Results: Perceived ease of use had the strongest influence on perceived usefulness;followed by perceived ease of use on attitude;attitude on behavioral intention;and perceived usefulness on behavioral intention. In opposite;the non-supported relationships were perceived usefulness and attitude;trust and satisfaction;and satisfaction and behavioral intention. Conclusions: The findings implied that academic researchers and education's stakeholders should emphasize ease-of-use and benefits of using an online learning system that can help students' learning experience to be more conveniently and effectively.

Enhancement of Molecular Transport into Film Stacked Structures for Micro-Immunoassay by Unsteady Rotation.

A film-stacked structure consisting of polyethylene terephthalate (PET) films stacked in a gap of 20 µm that can be combined with 96-well microplates used in biochemical analysis has been developed by the authors. When this structure is inserted into a well and rotated, convection flow is generated in the narrow gaps between the films to enhance the chemical/bio reaction between the molecules. However, since the main component of the flow is a swirling flow, only a part of the solution circulates into the gaps, and reaction efficiency is not achieved as designed. In this study, an unsteady rotation is applied to promote the analyte transport into the gaps using the secondary flow generated on the surface of the rotating disk. Finite element analysis is used to evaluate the changes in flow and concentration distribution for each rotation operation and to optimize the rotation conditions. In addition, the molecular binding ratio for each rotation condition is evaluated. It is shown that the unsteady rotation accelerates the binding reaction of proteins in an ELISA (Enzyme Linked Immunosorbent Assay), a type of immunoassay.

Acute Lung Injury in aortic dissection : new insights in anesthetic management strategies.

Acute aortic dissection (AAD) is a severe cardiovascular disease characterized by rapid progress and a high mortality rate. The incidence of acute aortic dissection is approximately 5 to 30 per 1 million people worldwide. In clinical practice, about 35% of AAD patients are complicated with acute lung injury (ALI). AAD complicated with ALI can seriously affect patients' prognosis and even increase mortality. However, the pathogenesis of AAD combined with ALI remains largely unknown. Given the public health burden of AAD combined with ALI, we reviewed the anesthetic management advances and highlighted potential areas for clinical practice.

To what extent the traffic restriction policies can improve its air quality? An inspiration from COVID-19.

In hazy days, several local authorities always implemented the strict traffic-restriction measures to improve the air quality. However, owing to lack of data, the quantitative relationships between them are still not clear. Coincidentally, traffic restriction measures during the COVID-19 pandemic provided an experimental setup for revealing such relationships. Hence, the changes in air quality in response to traffic restrictions during COVID-19 in Spain and United States was explored in this study. In contrast to pre-lockdown, the private traffic volume as well as public traffic during the lockdown period decreased within a range of 60-90%. The NO2 concentration decreased by approximately 50%, while O3 concentration increased by approximately 40%. Additionally, changes in air quality in response to traffic reduction were explored to reveal the contribution of transportation to air pollution. As the traffic volume decreased linearly, NO2 concentration decreased exponentially, whereas O3 concentration increased exponentially. Air pollutants did not change evidently until the traffic volume was reduced by less than 40%. The recovery process of the traffic volume and air pollutants during the post-lockdown period was also explored. The traffic volume was confirmed to return to background levels within four months, but air pollutants were found to recover randomly. This study highlights the exponential impact of traffic volume on air quality changes, which is of great significance to air pollution control in terms of traffic restriction policy. Supplementary Information: The online version contains supplementary material available at 10.1007/s00477-022-02351-7.

Triacetyl Resveratrol Inhibits PEDV by Inducing the Early Apoptosis In Vitro.

PEDV represents an ancient Coronavirus still causing huge economic losses to the porcine breeding industry. Resveratrol has excellent antiviral effects. Triacetyl resveratrol (TCRV), a novel natural derivative of resveratrol, has been recently discovered, and its pharmacological effects need to be explored further. This paper aims to explore the relationship between PEDV and TCRV, which offers a novel strategy in the research of antivirals. In our study, Vero cells and IPEC-J2 cells were used as an in vitro model. First, we proved that TCRV had an obvious anti-PEDV effect and a strong inhibitory effect at different time points. Then, we explored the mechanism of inhibition of PEDV infection by TCRV. Our results showed that TCRV could induce the early apoptosis of PEDV-infected cells, in contrast to PEDV-induced apoptosis. Moreover, we observed that TCRV could promote the expression and activation of apoptosis-related proteins and release mitochondrial cytochrome C into cytoplasm. Based on these results, we hypothesized that TCRV induced the early apoptosis of PEDV-infected cells and inhibited PEDV infection by activating the mitochondria-related caspase pathway. Furthermore, we used the inhibitors Z-DEVD-FMK and Pifithrin-α (PFT-α) to support our hypothesis. In conclusion, the TCRV-activated caspase pathway triggered early apoptosis of PEDV-infected cells, thereby inhibiting PEDV infections.

Clinical significance of serum interleukin 6 in elderly patients infected with severe acute respiratory syndrome Coronavirus 2 Omicron variant and its correlation with underlying diseases

Objective: To investigate the clinical significance of serum interleukin 6 (IL-6) in elderly patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant and its correlation with underlying diseases. Methods: A total of 22 elderly patients (> 80 years old) infected with omicron variant, who were admitted to Department of Infectious Diseases, The First Affiliated Hospital of Naval Medical University (Second Military Medical University) from Apr. to Jun. 2022 and tested positive for SARS-CoV-2 RNA, were included. The level of serum IL-6 was measured by flow cytometry, and the level of serum C reactive protein (CRP) was measured by immunonephelometry. Patients were divided into pneumonia group (16 cases) and non-pneumonia group (6 cases) according to the imaging examination results, and were divided into severe group (severe and critical type, 5 cases) and non-severe group (mild and normal type, 17 cases) according to the condition. Binary logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the correlation between serum IL-6 and CRP levels and the severity of the disease and whether it would progress to pneumonia. Meanwhile, the relationships between underlying diseases and serum IL-6 level were explored. Results: Among the 22 patients, 6 were mild, 11 were normal, 3 were severe, and 2 were critical. The baseline serum IL-6 level in the pneumonia group was significantly higher than that in the non-pneumonia group ([20.16+or-12.36] pg/mL vs [5.42+or-1.57] pg/mL, P=0.009), and there was no significant difference in baseline serum CRP level between the 2 groups (P > 0.05). There were no significant differences in baseline serum IL-6 or CRP levels between the severe group and the non-severe group (both P > 0.05). Logistic regression analysis showed that the baseline serum IL-6 and CRP might be related to pneumonia after infection with omicron variant (odds ratio [OR]=2.407, 95% confidence interval [CI] 0.915-6.328;OR=1.030, 95% CI 0.952-1.114). ROC curve analysis showed that the area under curve values of serum IL-6 and CRP in predicting the progression to pneumonia were 0.969 (95% CI 0.900-1.000) and 0.656 (95% CI 0.380-0.932), respectively, with statistical significance (Z=2.154, P=0.030). There were no significant differences in the baseline serum IL-6 level or proportions of severe patients or pneumonia patients among patients with or without hypertension, diabetes mellitus, coronary heart disease, chronic kidney disease or chronic obstructive pulmonary disease (all P > 0.05). The baseline serum IL-6 levels of the omicron variant infected elderly patients with 1, 2, and 3 or more underlying diseases were 12.50 (9.15, 21.75), 23.55 (9.63, 50.10), and 10.90 (5.20, 18.88) pg/mL, respectively, with no statistical significance (P > 0.05). Conclusion: For omicron variant infected patients, serum IL-6 level is significantly increased in patients with pneumonia manifestations and is correlated with disease progression. Serum IL-6 level is of great guiding significance to judge disease progression and evaluate efficacy and prognosis of elderly coronavirus disease 2019 patients.

Pulmonary Findings of [18F]FDG PET/CT Images on Asymptomatic COVID-19 Patients.

During the coronavirus disease 2019 (COVID-19) pandemic, several case studies demonstrated that many asymptomatic patients with COVID-19 underwent fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography/computed tomography (PET/CT) examination for various indications. However, there is a lack of literature to characterize the pattern of [18F]FDG PET/CT imaging on asymptomatic COVID-19 patients. Therefore, a systematic review to analyze the pulmonary findings of [18F]FDG PET/CT on asymptomatic COVID-19 patients was conducted. This systematic review was performed under the guidelines of PRISMA. PubMed, Medline, and Web of Science were used to search for articles for this review. Articles with the key words: "asymptomatic", "COVID-19", "[18F]FDG PET/CT", and "nuclear medicine" were searched for from 1 January 2020 to 20 May 2021. Thirty asymptomatic patients with COVID-19 were included in the eighteen articles. These patients had a mean age of 62.25 ± 14.85 years (male: 67.71 ± 12.00; female: 56.79 ± 15.81). [18F]FDG-avid lung lesions were found in 93.33% (28/30) of total patients. The major lesion was [18F]FDG-avid multiple ground-glass opacities (GGOs) in the peripheral or subpleural region in bilateral lungs, followed by the consolidation. The intensity of [18F]FDG uptake in multiple GGOs was 5.605 ± 2.914 (range from 2 to 12) for maximal standardized uptake value (SUVmax). [18F]FDG-avid thoracic lymph nodes (LN) were observed in 40% (12/40) of the patients. They mostly appeared in both mediastinal and hilar regions with an SUVmax of 5.8 ± 2.93 (range from 2.5 to 9.6). The [18F]FDG uptake was observed in multiple GGOs, as well as in the mediastinal and hilar LNs. These are common patterns in PET/CT of asymptomatic patients with COVID-19.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

Evaluation of an automated CRISPR-based diagnostic tool for rapid detection of COVID-19.

The performance of an automated commercial CRISPR/Cas based technology was evaluated and compared with routine RT-PCR testing to diagnose COVID-19. Suspected and discharged COVID-19 cases were included and tested with CRISPR-based SARS-CoV-2 test and RT-PCR assay using throat swab and sputum specimens. The diagnostic yield was calculated and compared using the McNemar test. A total of 437 patients were included for analysis, including COVID-19 (n = 171), discharged cases (n = 155), and others (n = 111). For the diagnosis of COVID-19, the CRISPR-SARS-CoV-2 test had a sensitivity and specificity of 98.2% (168/171) and 100.0% (266/266), respectively; the RT-PCR test had a sensitivity and specificity of 100.0% (171/171) and 100.0% (266/266), respectively. No significant difference was found in the sensitivity of CRISPR-SARS-CoV-2 and RT-PCR. In conclusion, the CRISPR-SARS-CoV-2 test had a comparable performance with RT-PCR and showed several advantages, such as short assay time, low cost, and no requirement for expensive equipment.

Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination.

Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.

Hierarchical Superstructure of Plant Polyphenol and Arginine Surfactant for Long-Lasting and Target-Selective Antimicrobial Application.

Antimicrobial agents are massively used to disinfect the pathogen contaminated surfaces since the Corona Virus Disease 2019 (COVID-19) outbreak. However, their defects of poor durability, strong irritation, and high environmental accumulation are exposed. Herein, a convenient strategy is developed to fabricate long-lasting and target-selective antimicrobial agent with the special hierarchical structure through bottom-up assembly of natural gallic acid with arginine surfactant. The assembly starts from rodlike micelles, further stacking into hexagonal columns and finally interpenetrating into spherical assemblies, which avoid explosive release of antimicrobial units. The assemblies show anti-water washing and high adhesion on various surfaces; and thus, possess highly efficient and broad-spectrum antimicrobial activities even after using up to eleven cycles. Both in vitro and in vivo experiments prove that the assemblies are highly selective in killing pathogens without generating toxicity. The excellent antimicrobial virtues well satisfy the increasing anti-infection demands and the hierarchical assembly exhibits great potential as a clinical candidate.

Post-COVID-19 Syndrome Comprehensive Assessment: From Clinical Diagnosis to Imaging and Biochemical-Guided Diagnosis and Management.

The COVID-19 outbreak was first reported in 2019, causing massive morbidity and mortality. The majority of the COVID-19 patients survived and developed Post-COVID-19 Syndrome (PC19S) of varying severity. Currently, the diagnosis of PC19S is achieved through history and symptomatology that cannot be explained by an alternative diagnosis. However, the heavy reliance on subjective reporting is prone to reporting errors. Besides, there is no unified diagnostic assessment tool to classify the clinical severity of patients. This leads to significant difficulties when managing patients in terms of public resource utilization, clinical progression monitorization and rehabilitation plan formulation. This narrative review aims to review current evidence of diagnosis based on triple assessment: clinical symptomatology, biochemical analysis and imaging evidence. Further assessment tools can be developed based on triple assessment to monitor patient's clinical progression, prognosis and intervals of monitoring. It also highlights the high-risk features of patients for closer and earlier monitoring. Rehabilitation programs and related clinical trials are evaluated; however, most of them focus on cardiorespiratory fitness and psychiatric presentations such as anxiety and depression. Further research is required to establish an objective and comprehensive assessment tool to facilitate clinical management and rehabilitation plans.

Cross-protective humoral immunity to coronaviruses from SARS coronavirus 2-naïve sera of children with Kawasaki disease.

OBJECTIVES: SARS coronavirus 2 (SARS-CoV-2)-associated multi-system inflammatory syndrome in children indicates that viruses can trigger a Kawasaki disease (KD)-like hyperinflammation. A plausible hypothesis was that coronavirus-specific 'holes' in humoral immunity could cause both diseases. METHODS: To determine whether SARS-CoV-2-naïve patients with KD have inferior humoral immunity for the novel coronavirus, sera of children with KD and control children from year 2015 to 2021 were subjected to ELISA, microwestern, and neutralization assays to evaluate the capabilities in recognizing the receptor-binding domain of SARS-CoV-2, spotting spike proteins of three respiratory syndromic coronaviruses, and blocking SARS-CoV-2 from binding to angiotensin-converting enzyme 2 receptors in vitro, respectively. RESULTS: 29 patients with KD before 2019, 74 patients with KD in 2019 or 2020, 54 non-febrile controls, and 24 febrile controls were included in the study. SARS-CoV-2 was recognized on ELISA for both patients with KD in 2016 and those with KD in 2020. Microwestern demonstrated cross-reactive IgG in an all-or-none manner towards three spike proteins of syndromic coronaviruses regardless of sample year or KD status. The ratio between the sera that recognized all spike proteins and those that recognized none (51 vs. 47) was significantly higher from patients with KD than from non-febrile controls (17 vs. 32; p 0.047) but not from febrile controls (13 vs. 11; p 0.85). Most positive sera (12 of 17 controls, 5 of 8 patients with KD before 2019, and 28 of 33 patients with KD in 2019 or 2020) offered protection comparable to low-titre sera from the WHO reference panel. DISCUSSION: Humoral immunity of SARS-CoV-2-naïve children with KD was not inferior to that of controls in offering cross-protection against the novel coronavirus.

Immune Repertoire Sequencing Reveals an Abnormal Adaptive Immune System in COVID-19 Survivors.

Accumulating evidence suggests that SARS-CoV-2 impairs the adaptive immune system during acute infection. Still, it remains largely unclear whether the frequency and functions of T and B cells return to normal after the recovery of COVID-19. Here, we analyzed immune repertoires and SARS-CoV-2-specific neutralization antibodies in a prospective cohort of 40 COVID-19 survivors with a six-month follow-up after hospital discharge. Immune repertoire sequencing revealed abnormal T- and B-cell expression and function with large TCR/BCR clones, decreased diversity, abnormal class switch recombination and somatic hypermutation. A decreased number of B cells but an increased proportion of CD19+ CD138+ B cells were found in COVID-19 survivors. The proportion of CD4+ T cells, especially circulating follicular helper T (cTfh) cells, was increased, whereas the frequency of CD3+ CD4- T cells was decreased. SARS-CoV-2-specific neutralization IgG and IgM antibodies were identified in all survivors, especially those recorded with severe COVID-19 who showed a higher inhibition rate of neutralization antibodies. All severe cases complained of more than one COVID-19 sequelae after 6 months of recovery. Overall, our findings indicate that SARS-CoV-2-specific antibodies remain detectable even after 6 months of recovery. Because of their abnormal adaptive immune system with a low number of CD3+ CD4- T cells and high susceptibility to infections, COVID-19 patients might need more time and medical care to fully recover from immune abnormalities and tissue damage. This article is protected by copyright. All rights reserved.

Dynamic lead–lag relationship between Chinese carbon emission trading and stock markets under exogenous shocks

Using the non-parametric thermal optimal path method, we investigate the dynamic lead–lag relationship between carbon emission trading and stock markets in China, and further consider the impact of different types of exogenous shocks on the lead–lag relationship. The empirical results show that the stock market leads the carbon market on most trading days, and the relationship reverses when the mean values of carbon market return are significantly smaller than zero. In addition, the lead–lag relationships when the carbon market leads the high energy-consuming stock market sectors are more obvious. We also find that there exist significant heterogeneous effects of different types of exogenous shocks on the lead–lag relationship between the two markets, including government policy, the Sino-US trade war and the Covid-19 outbreak. These findings have the potential to help regulators understand the interrelationship between components of the financial market, and be of great value for investors to optimize portfolio allocation by incorporating carbon assets into the portfolio.

3- to 24-month Follow-up on COVID-19 with Pulmonary Tuberculosis Survivors after Discharge: Results from a Prospective, Multicenter Study.

Objective: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods: From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13 hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results: Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9%) were men. Among them, nearly two-thirds (62.5%) of the survivors were moderate, three (9.4%) were severe, and more than half (59.4%) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6% at 3 months to 15.8% at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1%) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion: The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.