Qi-Dong-Huo-Xue-Yin balances the immune microenvironment to protect against LPS induced acute lung injury.

COVID-19 induces acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and leads to severe immunological changes that threatens the lives of COVID-19 victims. Studies have shown that both the regulatory T cells and macrophages were deranged in COVID-19-induced ALI. Herbal drugs have long been utilized to adjust the immune microenvironment in ALI. However, the underlying mechanisms of herbal drug mediated ALI protection are largely unknown. This study aims to understand the cellular mechanism of a traditional Chinese medicine, Qi-Dong-Huo-Xue-Yin (QD), in protecting against LPS induced acute lung injury in mouse models. Our data showed that QD intrinsically promotes Foxp3 transcription via promoting acetylation of the Foxp3 promoter in CD4+ T cells and consequently facilitates CD4+CD25+Foxp3+ Tregs development. Extrinsically, QD stabilized ß-catenin in macrophages to expedite CD4+CD25+Foxp3+ Tregs development and modulated peripheral blood cytokines. Taken together, our results illustrate that QD promotes CD4+CD25+Foxp3+ Tregs development via intrinsic and extrinsic pathways and balanced cytokines within the lungs to protect against LPS induced ALI. This study suggests a potential application of QD in ALI related diseases.

Parents' willingness to vaccinate themselves and their children with the booster vaccine against SARS-CoV-2: A cross-sectional study in Puyang city, China.

We aimed to investigate the hesitancy and willingness of parents to vaccinate themselves and their children with a booster dose against severe acute respiratory syndrome coronavirus 2 and related factors. We conducted a cross-sectional study in Puyang city, China. The information was collected, including demographic characteristics, willingness to receive a booster dose of coronavirus disease 2019 (COVID-19) vaccine, and attitudes and concerns toward COVID-19 and vaccines. Vaccine hesitancy was assessed in individuals completing the first two doses and booster eligible, while vaccine willingness was assessed in those completing the first two doses and not yet booster eligible. Among the participants completing two primary doses while not meeting the booster criteria, 95.4% (1465/1536) and 95.0% (1385/1458) had a willingness to a booster dose of COVID-19 vaccine for themselves and their children, respectively. Among the participants who met the booster criteria, 40.3% had vaccine hesitancy. Vaccine hesitancy and unwillingness tended to occur in people who were younger, less educated, less healthy, and with unsureness of vaccines' efficacy and adverse events (AE). The younger age of children, children in poorer health, and concern about the efficacy and AE of vaccines contributed to the participants' unwillingness to vaccinate their children. We observed a high willingness to the booster dose of COVID-19 vaccine both for the parents and their children, regardless of the eligibility to a booster dose. However, 40% of people had delayed vaccination behaviors. The promotion of scientific knowledge of vaccines' effectiveness and safety is needed, especially for people in poor health and parents with young children. Timely disclosure of AE caused by COVID-19 vaccines and proper aiding offered to people encountering AE are suggested.

Alterations in bile acids as metabolic signatures in the patients with human adenovirus type 7 infection.

Objectives: The changes in metabolism by human adenovirus (HAdV) infection was unclear. The potential mechanism of HAdV-7 causing acute respiratory tract infection was explored. Methods: Totally 35 patients with HAdV-7 infection, 32 asymptomatic cases with HAdV-7 and 14 healthy controls were enrolled from an outbreak of HAdV-7 in the army. The serum samples were analyzed by untargeted and targeted metabolomics. The effects of differential metabolites were verified on HAdV-7 replication in an A549 cell line. Results: The untargeted metabolomics analysis revealed more significant changes in the classes of sphingolipids, polyketides, glycerolipids, fatty acyls, and carboxylic acids and their derivatives in the patients with HAdV-7 than in healthy controls. Two key metabolic pathways of secondary and primary bile acid biosynthesis were noted from pathway enrichment analysis. Targeted metabolomics analysis showed that the levels of unconjugated bile acids in the patients were significantly lower, while the levels of glyco- and tauro- conjugated bile acids in patients and asymptomatic cases were higher than those in the healthy controls. The profiles of cytokines and peripheral lymphocyte subsets obviously varied at different levels of bile acids, with significant differences after HAdV-7 infection. A cell verification test demonstrated that the replication of HAdV-7 significantly reduced when GCDCA and TCA were added. Conclusion: Bile acids inhibited HAdV-7 replication in vitro. Alterations in bile acids was metabolic signatures of HAdV-7 infected subjects, and our results suggested bile acids might play protective roles against HAdV-7 infection.

An achromatic colorimetric nanosensor for sensitive multiple pathogen detection by coupling plasmonic nanoparticles with magnetic separation.

Rapid screening of multiple pathogens will greatly improve the efficiency of pandemic prevention and control. Colorimetric methods exhibit the advantages of convenience, portability, low cost, time efficiency, and free of sophisticated instruments, yet usually have difficulties in simultaneous detection and suffer from monotonous color changes with low visual resolution and sensitivity. Hence, coupled three kinds of plasmonic nanoparticles (NPs) with magnetic separation, we developed an achromatic colorimetric nanosensor with highly enhanced visual resolution for simultaneous detection of SARS-CoV-2, Staphylococcus aureus, and Salmonella typhimurium. The achromatic nanosensor was composed of SARS-CoV-2-targeting red gold NPs, S. aureus-targeting yellow silver NPs and S. typhimurium-targeting blue silver triangle NPs mixed as black color. In the detection, three corresponding magnetic probes were added into the above mixture. In the presence of a target pathogen, it would be recognized and combined with corresponding colored reporters and magnetic probes to form sandwich complexes, which were removed by magnetic separation, and the sensor changed from black to a chromatic color (the color of the reporters remained in supernatant). Consequently, different target pathogen induced different color. For example, SARS-CoV-2, S. aureus, and S. typhimurium respectively produced green, purple, and orange. While coexistence of S. aureus and S. typhimurium produced red, and coexistence of S. aureus and SARS-CoV-2 produced blue, etc. Therefore, by observing the color change or measuring the absorption spectra, multiple pathogen detection was achieved conveniently. Compared with most colorimetric sensors, this achromatic nanosensor involved rich color change, thus significantly enhancing visual resolution and inspection sensitivity. Therefore, this sensor opened a promising avenue for efficient monitoring and early warning of food safety and quality.

Human antibody BD-218 has broad neutralizing activity against concerning variants of SARS-CoV-2.

As SARS-CoV-2 variants of concern (VOC) reduce the effectiveness of existing anti-COVID therapeutics, it is increasingly critical to identify highly potent neutralizing antibodies (nAbs) that bind to conserved regions across multiple variants, especially beta, delta, and omicron variants. Using single-cell sequencing with biochemical methods and pseudo-typed virus neutralization experiments, here we report the characterization of a potent nAb BD-218, identified from an early screen of patients recovering from the original virus. We have determined the cryo-EM structure of the BD-218/spike protein complex to define its epitope in detail, which revealed that BD-218 interacts with a novel epitope on the receptor-binding domain (RBD) of the spike protein. We concluded that BD-218 is a highly effective and broadly active nAb against SARS-CoV-2 variants with promising potential for therapeutic development.

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020.

Background: The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China. Method: From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes. Result: A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world. Conclusions: The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

Predicting the Hate: A GSTM Model based on COVID-19 Hate Speech Datasets

COVID-19 crisis has been accompanied by copious hate speeches widespread on social media. It reinforces the fragmentation of the world, resulting in more significant racial discrimination and distrust between people, leading to crimes, and injuring individuals spiritually or physically. Hate speech is hard to crack for a global recovery in the post-epidemic era. Conducting with Twitter datasets, this paper aims to find the key indicators that influence the trend of hate speech, then builds a Gaussian Spatio-Temporal Mixture (GSTM) model for trends prediction based on the pre-analysis. Findings show that in the early period, the participation of influential users is closely related to the emergence of sentiment peaks, and the interval time is around one week. After hate speech waves up, the indicator of total exposure becomes more critical, suggesting that grass-root release influences at this stage. Compared with three classical time-series predicting models, the GSTM model shows better peak prediction ability and lower residual mean. This work enriches the approaches of predicting unknown but foreseeable hate speeches accompanied by future pandemics.

Molecular Epidemiology of Herpangina Children in Tongzhou District, Beijing, China, During 2019-2020

Background The changing pattern of pathogen spectrum causing herpangina in the time of coronavirus disease 2019 (COVID-19) pandemic was unknown. The purpose of this study was to investigate the changes on the molecular epidemiology of herpangina children during 2019-2020 in Tongzhou district, Beijing, China. Method From January 2019 to December 2020, children diagnosed with herpangina were recruited by the staff from Tongzhou Center for Disease Control and Prevention (CDC) in Beijing. Viral RNA extraction from pharyngeal swabs was used for enterovirus (EV) detection and the complete VP1 gene was sequenced. The phylogenetic analysis was performed based on all VP1 sequences for EV genotypes. Result A total of 1,331 herpangina children were identified during 2019-2020 with 1,121 in 2019 and 210 in 2020, respectively. The predominant epidemic peak of herpangina children was in summer and autumn of 2019, but not observed in 2020. Compared to the number of herpangina children reported in 2019, it decreased sharply in 2020. Among 129 samples tested in 2019, 61 (47.3%) children were detected with EV, while 22.5% (20/89) were positive in 2020. The positive rate for EV increased since June 2019, peaked at August 2019, and decreased continuously until February 2020. No cases were observed from February to July in 2020, and the positive rate of EV rebounded to previous level since August 2020. Four genotypes, including coxsackievirus A6 (CV-A6, 9.3%), CV-A4 (7.8%), CV-A10 (2.3%) and CV-A16 (10.1%), were identified in 2019, and only three genotypes, including CV-A6 (9.0%), CV-A10 (6.7%) and CV-A16 (1.1%), were identified in 2020. The phylogenetic analysis showed that all CV-A6 strains from Tongzhou located in Group C, and the predominant strains mainly located in C2-C4 subgroups during 2016-2018 and changed into C1 subgroup during 2018-2020. CV-A16 strains mainly located in Group B, which consisting of strains widely distributed around the world. Conclusions The predominant genotypes gradually shifted from CV-A16, CV-A4 and CV-A6 in 2019 to CV-A6 in 2020 under COVID-19 pandemic. Genotype-based surveillance will provide robust evidence and facilitate the development of public health measures.

Drivers of CO2 Emissions: A Debt Perspective.

CO2 emissions and debt accumulation are twin threats to sustainable development. To fill the gap that few studies can untangle the reasons behind CO2 emissions from the debt perspective, we illustrate debt can cause CO2 emissions through various channels. We then examined how debt-based drivers impact emission trajectories. We use the logarithmic mean Divisia index (LMDI) method to decompose the emission changes into five factors. We make decomposition analyses between different country groups to identify their respective characteristics. Further, to investigate the potential financial crisis impacts, we consider the full period 2001-2019 and two sub-periods (pre- and post-2008). The results show that the gross domestic product (GDP) is always the biggest contributor to emissions, whose effect on advanced economies saw a bigger decrease after 2008 than that on emerging economies. Debt-GDP is second only to GDP in contributing to emissions. It has a similar impact on emissions before and after 2008 for advanced economies, while it rockets after 2008 for emerging economies. Private debt financing of fossil fuels is the prominent inhibitor for both economies, especially for emerging economies. It has a stronger mitigation impact after 2008 than before for emerging economies, while has the opposite change for advanced economies. Debt structure and fossil CO2 intensity have relatively smaller effects on emissions. The crisis is an opportunity to promote low-carbon development. Since the COVID-19 pandemic is analogous to the 2008 crisis in terms of debt level and emission change, we provide recommendations for emission mitigation in the post-pandemic context.

Willingness and SARS-CoV-2 Vaccination Coverage among Healthcare Workers in China: A Nationwide Study.

Background: The SARS-CoV-2 vaccine has been widely rolled out globally in the general populations. However, specific data on vaccination confidence, willingness or coverage among health care workers (HCWs) has been less reported. Methods: A cross-sectional online survey was conducted to specify the basic data and patterns of vaccination confidence, willingness and coverage among HCWs nationwide. Results: In total, 2386 out of 2583 (92.4%) participants were enrolled for analysis, and the rates of confidence in vaccine, professional institutes and government were 75.1%, 85.2% and 85.4%, respectively. The overall vaccination coverage rate was 63.6% which was adjusted as 82.8% for participants under current medical conditions or having contraindications. Confidence in vaccine safety was shown to be the most related factor to willingness among doctors, nurses, medical technicians and hospital administrators, while confidence in vaccine effectiveness as well as trust in government played the key role in formulating public health employees' willingness. 130 (7.1% of 1833) participants reporting willingness still not been vaccinated regardless of contraindications. Multivariate analysis among willingness participants showed that males, aged over 30 years, public health employees and higher vaccination confidence had significantly higher vaccination rates with ORs (95% confidence intervals) as 1.64 (1.08-2.49), 3.14 (2.14-4.62), 2.43 (1.46-4.04) or 2.31 (1.24-4.33). Conclusions: HCWs' confidence, willingness and coverage rates to the vaccine were generally at high levels. Heterogeneity among HCWs should be considered for future vaccination promotion strategies. The population's confidence in vaccination is not only the determinant to their willingness, but also guarantees their actual vaccine uptake.

Neurological manifestations in COVID-19 patients and their application in predicting fatal disease: A retrospective cohort study.

BACKGROUND: To explore the development of central nervous system (CNS) symptoms and clinical application in predicting the clinical outcomes of SARS-COV-2 patients. METHODS: A retrospective cohort study was performed on the hospitalized patients with SARS-COV-2 recruited from four hospitals in Hubei Province, China from 18 January to 10 March 2020. The patients with CNS symptoms were determined. Data regarding clinical symptoms and laboratory tests were collected from medical records. RESULTS: Of 1268 patients studied, 162 (12.8%) had CNS symptoms, manifested as unconsciousness (71, 5.6%), coma (69, 5.4%), dysphoria (50, 3.9%), somnolence (34, 2.7%) and convulsion (3, 0.2%), which were observed at median of 14 (interquartile range 9-18) days after symptom onset and significantly associated with older age (OR = 5.71, 95% confidence interval [CI] 2.78-11.73), male (OR = 1.73, 95% CI 1.22-2.47) and preexisting hypertension (OR = 1.78, 95% CI 1.23-2.57). The presence of CNS symptoms could be predicted by abnormal laboratory tests across various clinical stages, including by lymphocyte counts of <0.93 × 109/L, LDH≥435 U/L and IL-6≥28.83 pg/L at 0-10 days post disease; by lymphocyte count<0.86 × 109/L, IL-2R ≥ 949 U/L, LDH≥382 U/L and WBC≥8.06 × 109/L at 11-20 days post disease. More patients with CNS symptoms developed fatal outcome compared with patients without CNS symptoms (HR = 33.96, 95% CI 20.87-55.16). CONCLUSION: Neurological symptoms of COVID-19 were related to increased odds of developing poor prognosis and even fatal infection.

A systematic meta-analysis of immune signatures in patients with COVID-19.

Currently severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been on the rise worldwide. Predicting outcome in COVID-19 remains challenging, and the search for more robust predictors continues. We made a systematic meta-analysis on the current literature from 1 January 2020 to 15 August 2020 that independently evaluated 32 circulatory immunological signatures that were compared between patients with different disease severity was made. Their roles as predictors of disease severity were determined as well. A total of 149 distinct studies that evaluated ten cytokines, four antibodies, four T cells, B cells, NK cells, neutrophils, monocytes, eosinophils and basophils were included. Compared with the non-severe patients of COVID-19, serum levels of Interleukins (IL)-2, IL-2R, IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor α were significantly up-regulated in severe patients, with the largest inter-group differences observed for IL-6 and IL-10. In contrast, IL-5, IL-1ß and Interferon (IFN)-γ did not show significant inter-group difference. Four mediators of T cells count, including CD3+ T, CD4+ T, CD8+ T, CD4+ CD25+ CD127- Treg, together with CD19+ B cells count and CD16+ CD56+ NK cells were all consistently and significantly depressed in severe group than in non-severe group. SARS-CoV-2 specific IgA and IgG antibodies were significantly higher in severe group than in non-severe group, while IgM antibody in the severe patients was slightly lower than those in the non-severe patients, and IgE antibody showed no significant inter-group differences. The combination of cytokines, especially IL-6 and IL-10, and T cell related immune signatures can be used as robust biomarkers to predict disease severity following SARS-CoV-2 infection.

The impact of the COVID-19 pandemic on pediatric operations: a retrospective study of Chinese children.

BACKGROUND: The aim of this study was to quantify the impact of coronavirus disease 2019 (COVID-19) on pediatric operations, and establish preoperative, intraoperative, and postoperative protocols to improve the pediatric operations. METHODS: We here compare the number of patients who underwent surgery in Chongqing Medical University Affiliated Children's Hospital during the pandemic (January 23-March 11), after the pandemic (March 12-April 30), after our measures were put in place (May 1-May 21), and the equivalent period in 2019. RESULT: During the COVID-19 pandemic, 62.68% fewer patients underwent surgery than during the homologous period of time 1 year earlier (P < 0.01). After the COVID-19 pandemic, the number of orchidopexy cases increased significantly from 175.14 to 504.57 per week (P < 0.01). The large number of patients that accrued in our hospital may have increased the risk of COVID-19 transmission. In response, hospitals and clinics have made protocols and reorganized healthcare facilities (e.g., performing nucleic acid tests (NAT), adding adequate personal protective equipment (PPE)) from May 1, 2020. After the measures were implemented, the number of operations performed remained stable and comparable to the pre-pandemic period. COVID-19 RNA detection was performed in 5104 cases and there were no new confirmed cases in our hospital. CONCLUSION: This outbreak of COVID-19 has affected not only individuals with COVID-19 but also patients seeking surgical operations. Understanding the present situation helps clinicians provide a high level of treatment to all children.

Epidemiological parameters of COVID-19 and its implication for infectivity among patients in China, 1 January to 11 February 2020.

BackgroundThe natural history of disease in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remained obscure during the early pandemic.AimOur objective was to estimate epidemiological parameters of coronavirus disease (COVID-19) and assess the relative infectivity of the incubation period.MethodsWe estimated the distributions of four epidemiological parameters of SARS-CoV-2 transmission using a large database of COVID-19 cases and potential transmission pairs of cases, and assessed their heterogeneity by demographics, epidemic phase and geographical region. We further calculated the time of peak infectivity and quantified the proportion of secondary infections during the incubation period.ResultsThe median incubation period was 7.2 (95% confidence interval (CI): 6.9‒7.5) days. The median serial and generation intervals were similar, 4.7 (95% CI: 4.2‒5.3) and 4.6 (95% CI: 4.2‒5.1) days, respectively. Paediatric cases < 18 years had a longer incubation period than adult age groups (p = 0.007). The median incubation period increased from 4.4 days before 25 January to 11.5 days after 31 January (p < 0.001), whereas the median serial (generation) interval contracted from 5.9 (4.8) days before 25 January to 3.4 (3.7) days after. The median time from symptom onset to discharge was also shortened from 18.3 before 22 January to 14.1 days after. Peak infectivity occurred 1 day before symptom onset on average, and the incubation period accounted for 70% of transmission.ConclusionThe high infectivity during the incubation period led to short generation and serial intervals, necessitating aggressive control measures such as early case finding and quarantine of close contacts.

A High-Throughput, Multi-Index Isothermal Amplification Platform for Rapid Detection of 19 Types of Common Respiratory Viruses Including SARS-CoV-2.

Fast and accurate diagnosis and the immediate isolation of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are regarded as the most effective measures to restrain the coronavirus disease 2019 (COVID-19) pandemic. Here, we present a high-throughput, multi-index nucleic acid isothermal amplification analyzer (RTisochip™-W) employing a centrifugal microfluidic chip to detect 19 common respiratory viruses, including SARS-CoV-2, from 16 samples in a single run within 90 min. The limits of detection of all the viruses analyzed by the RTisochip™-W system were equal to or less than 50 copies·µL-1, which is comparable to those of conventional reverse transcription polymerase chain reaction. We also demonstrate that the RTisochip™-W system possesses the advantages of good repeatability, strong robustness, and high specificity. Finally, we analyzed 201 cases of preclinical samples, 14 cases of COVID-19-positive samples, 25 cases of clinically diagnosed samples, and 614 cases of clinical samples from patients or suspected patients with respiratory tract infections using the RTisochip™-W system. The test results matched the referenced results well and reflected the epidemic characteristics of the respiratory infectious diseases. The coincidence rate of the RTisochip™-W with the referenced kits was 98.15% for the detection of SARS-CoV-2. Based on these extensive trials, we believe that the RTisochip™-W system provides a powerful platform for fighting the COVID-19 pandemic.