Electrical Detection Assay Based on Programmable Nucleic Acid Probe for Efficient Single-Nucleotide Polymorphism Identification.

The large-scale pandemic and fast evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have triggered an urgent need for an efficient and sensitive on-site nucleic acid testing method with single-nucleotide polymorphism (SNP) identification capability. Here, we report a multiplexed electrical detection assay based on a paperclip-shaped nucleic acid probe (PNprobe) functionalized field-effect transistor (FET) biosensor for highly sensitive and specific detection and discrimination of SARS-CoV-2 variants. The three-stem structure of the PNprobe significantly amplifies the thermodynamic stability difference between variant RNAs that differ in a single-nucleotide mutation. With the assistance of combinatorial FET detection channels, the assay realizes simultaneously the detection and identification of key mutations of seven SARS-CoV-2 variants, including nucleotide substitutions and deletions at single-nucleotide resolution within 15 min. For 70 simulated throat swab samples, the multiplexed electrical detection assay shows an identification accuracy of 97.1% for the discrimination of SARS-CoV-2 variants. Our designed multiplexed electrical detection assay with SNP identification capability provides an efficient tool to achieve scalable pandemic screening.

A Review of Extracellular Vesicles in COVID-19 Diagnosis, Treatment, and Prevention.

The 2019 novel coronavirus disease (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is ongoing, and has necessitated scientific efforts in disease diagnosis, treatment, and prevention. Interestingly, extracellular vesicles (EVs) have been crucial in these developments. EVs are a collection of various nanovesicles which are delimited by a lipid bilayer. They are enriched in proteins, nucleic acids, lipids, and metabolites, and naturally released from different cells. Their natural material transport properties, inherent long-term recycling ability, excellent biocompatibility, editable targeting, and inheritance of parental cell properties make EVs one of the most promising next-generation drug delivery nanocarriers and active biologics. During the COVID-19 pandemic, many efforts have been made to exploit the payload of natural EVs for the treatment of COVID-19. Furthermore, strategies that use engineered EVs to manufacture vaccines and neutralization traps have produced excellent efficacy in animal experiments and clinical trials. Here, the recent literature on the application of EVs in COVID-19 diagnosis, treatment, damage repair, and prevention is reviewed. And the therapeutic value, application strategies, safety, and biotoxicity in the production and clinical applications of EV agents for COVID-19 treatment, as well as inspiration for using EVs to block and eliminate novel viruses are discussed.

Predicting the impact of the COVID-19 pandemic on globalization.

The COVID-19 pandemic has significantly influenced the global economy, international travel, global supply chains, and how people interact, and subsequently affect globalization in coming years. In order to understand the impact of COVID-19 on globalization and provide potential guidance to policymakers, the present study predicted the globalization level of the world average and 14 specific countries in scenarios with and without COVID-19 based on a new Composite Indicator method which contains 15 indicators. Our results revealed that the world average globalization level is expected to decrease from 2017 to 2025 under the scenario without COVID-19 by -5.99%, while the decrease of globalization under the COVID-19 scenario is predicted to reach -4.76% in 2025. This finding implies that the impact of COVID-19 on globalization will not be as severe as expected in 2025. Nevertheless, the downward trend of globalization without COVID-19 is due to the decline of the Environmental indicators, whereas the decline under the COVID-19 scenario is attributed to Economic aspects (almost -50%). The impact of COVID-19 on globalization varies across individual countries. Among the countries investigated, COVID-19 had a positive impact on the globalization of Japan, Australia, the United States, the Russian Federation, Brazil, India and Togo. In contrast, the globalization in the United Kingdom, Switzerland, Qatar, Egypt, China and Gabon are expected to decrease. The variation of impact induced by COVID-19 on those countries is attributed to the weighting of economic, environmental and political aspects of globalization is different across these countries. Our results can help governments take suitable measures to balance economic, environmental and political policies, which may better support their decision-making.

A bibliometric analysis of chronic obstructive pulmonary disease and COVID-19.

The coronavirus disease 2019 (COVID-19) outbreak became the worst epidemic in decades. Since its inception, COVID-19 has had a dramatic impact on chronic obstructive pulmonary disease (COPD) patients. This study explores explore the current status, hot spots, and research frontiers of COVID-19 and COPD based on a bibliometric approach. The Web of Science Core Collection was used to search the literature related to COPD and COVID-19, and VOSviewer and CiteSpace software were applied to analyze the distribution characteristics, research hotspots, and research frontiers of literature in related fields and to map the scientific knowledge domains. A total of 816 valid publications were included, among which USA, China, and England are the core countries/regions publishing related literature, and the research institutions are concentrated in Huazhong University of Science and Technology (18 papers), University College London (17 papers), and Imperial College London (16 papers). Guan WJ is the most prolific author with the most articles. The journals with the most publications are PLOS ONE, JOURNAL OF CLINICAL MEDICINE, and FRONTIERS IN MEDICINE. The main research hotspots in this field are clinical features, disease management, and mechanism research. By constructing COPD and COVID-19 research network diagrams, we reveal the hot spots, frontiers, and development trends of relevant research fields, which provide a reference for subsequent researchers to quickly grasp the current status of related research fields.

Temporal dynamics of SARS-CoV-2 genome mutations that occurred in vivo on an aircraft.

We analyzed variations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome during a flight-related cluster outbreak of coronavirus disease 2019 (COVID-19) in Shenzhen, China, to explore the characteristics of SARS-CoV-2 transmission and intra-host single nucleotide variations (iSNVs) in a confined space. Thirty-three patients with COVID-19 were sampled, and 14 were resampled 3-31 days later. All 47 nasopharyngeal swabs were deep sequenced. iSNVs and similarities in the consensus genome sequence were analyzed. Three SARS-CoV-2 variants of concern, Delta (n=31), Beta (n=1), and C.1.2 (n=1), were detected among the 33 patients. The viral genome sequences from 30 Delta-positive patients had similar SNVs; 14 of these patients provided two successive samples. Overall, the 47 sequenced genomes contained 164 iSNVs. Of the 14 paired (successive) samples, the second samples (T2) contained more iSNVs (median: 3; 95% confidence interval [95%CI]: 2.77-10.22) than did the first samples (T1; median: 2; 95%CI: 1.63-3.74; Wilcoxon test, P=0.021). 38 iSNVs were detected in T1 samples, and only seven were also detectable in T2 samples. Notably, T2 samples from two of the 14 paired samples had additional mutations than the T1 samples. The iSNVs of the SARS-CoV-2 genome exhibited rapid dynamic changes during a flight-related cluster outbreak event. Intra-host diversity increased gradually with time, and new site mutations occurred in vivo without a population transmission bottleneck. Therefore, we could not determine the generational relationship from the mutation site changes alone.

Fireworks explosion boosted Harris Hawks optimization for numerical optimization: Case of classifying the severity of COVID-19.

Harris Hawks optimization (HHO) is a swarm optimization approach capable of handling a broad range of optimization problems. HHO, on the other hand, is commonly plagued by inadequate exploitation and a sluggish rate of convergence for certain numerical optimization. This study combines the fireworks algorithm's explosion search mechanism into HHO and proposes a framework for fireworks explosion-based HHo to address this issue (FWHHO). More specifically, the proposed FWHHO structure is comprised of two search phases: harris hawk search and fireworks explosion search. A search for fireworks explosion is done to identify locations where superior hawk solutions may be developed. On the CEC2014 benchmark functions, the FWHHO approach outperforms the most advanced algorithms currently available. Moreover, the new FWHHO framework is compared to four existing HHO and fireworks algorithms, and the experimental results suggest that FWHHO significantly outperforms existing HHO and fireworks algorithms. Finally, the proposed FWHHO is employed to evolve a kernel extreme learning machine for diagnosing COVID-19 utilizing biochemical indices. The statistical results suggest that the proposed FWHHO can discriminate and classify the severity of COVID-19, implying that it may be a computer-aided approach capable of providing adequate early warning for COVID-19 therapy and diagnosis.

The Bivalent COVID-19 Booster Immunization after Three Doses of Inactivated Vaccine Augments the Neutralizing Antibody Response against Circulating Omicron Sublineages.

A fourth dose of a COVID-19 vaccine has been recommended by a number of authorities due to waning immunity over time and the emergence of immune-escaping variants. Here, we evaluated the safety and immunogenicity of the bivalent BV-01-B5 or V-01D-351 or the prototype V-01 for heterologous boosting in three-dose inactivated COVID-19 vaccine (ICV) recipients, in comparison with ICV homologous boosting. One pilot study (NCT05583357) included 20 participants randomized at 1:1, either receiving V-01D-351 or CoronaVac. The other one (NCT05585567) recruited 36 participants randomized at 2:1, either receiving BV-01-B5 or V-01, respectively. BV-01-B5, V-01D-351, and V-01 were safe and well-tolerated as heterologous booster shots after three doses of ICV, with adverse reactions predominantly being mild and moderate in severity, similar to the safety profile of ICV boosters. The bivalent V-01D-351 and BV-01-B5 and prototype V-01 booster demonstrated remarkable cross-reactive immunogenicity against the prototype and multiple emerging variants of concern (VOCs), with the geometric mean ratio (versus CoronaVac) in particular being 31.3 (500 vs. 16), 12.0 (192 vs. 16) and 8.5 (136 vs.16) against BA.4/5 14 days after the booster, respectively. Taken together, the modified bivalent-formulation V-01 boosters induced robust neutralizing responses against multiple Omicron sublineages, better than V-01 and remarkably superior to ICV booster, without compromising the safety and tolerability.

Safety, Efficacy, and Immunogenicity of Varying Types of COVID-19 Vaccines in Children Younger Than 18 Years: An Update of Systematic Review and Meta-Analysis.

Vaccination is one of the most effective measures for children as the epidemic progresses. However, there is a significant research gap in the meta-analysis of the COVID-19 vaccines for children younger than 18 years. This study is a comprehensive review of different COVID-19 vaccines. Published articles were retrieved from PubMed, Embase, and the Cochrane Library. Twelve randomized controlled trials (RCTs) of COVID-19 vaccines were included in the review until 21 October 2022. Most local and systemic adverse reactions were predominantly mild to moderate in severity and disappeared quickly after different types of vaccines. The subunit vaccine had the highest safety. The significant risk was lower in the subunit vaccine group after the initial (RR 1.66, 95% CI 1.26-2.17, p = 0.0003) and booster vaccination (RR 1.40, 95% CI 1.02-1.92, p = 0.04). Younger children had a more outstanding safety profile in the mRNA and inactivated vaccine groups. The humoral immune response was proportional to the number of doses in the inactivated and the adenovirus vaccine groups, and the strength of immunogenicity was negatively correlated with age in the inactivated vaccine. The mRNA and the subunit vaccines provided satisfactory prevention against COVID-19, especially seven days after the booster dose. However, more research and longer-term follow-up are needed to assess the duration of immune responses, efficacy, and safety.

A Machine Learning-Based Risk Prediction Model for Post-Traumatic Stress Disorder during the COVID-19 Pandemic.

Background and Objectives: The COVID-19 pandemic has caused global public panic, leading to severe mental illnesses, such as post-traumatic stress disorder (PTSD). This study aimed to establish a risk prediction model of PTSD based on a machine learning algorithm to provide a basis for the extensive assessment and prediction of the PTSD risk status in adults during a pandemic. Materials and Methods: Model indexes were screened based on the cognitive-phenomenological-transactional (CPT) theoretical model. During the study period (1 March to 15 March 2020), 2067 Chinese residents were recruited using Research Electronic Data Capture (REDCap). Socio-demographic characteristics, PTSD, depression, anxiety, social support, general self-efficacy, coping style, and other indicators were collected in order to establish a neural network model to predict and evaluate the risk of PTSD. Results: The research findings showed that 368 of the 2067 participants (17.8%) developed PTSD. The model correctly predicted 90.0% (262) of the outcomes. Receiver operating characteristic (ROC) curves and their associated area under the ROC curve (AUC) values suggested that the prediction model possessed an accurate discrimination ability. In addition, depression, anxiety, age, coping style, whether the participants had seen a doctor during the COVID-19 quarantine period, and self-efficacy were important indexes. Conclusions: The high prediction accuracy of the model, constructed based on a machine learning algorithm, indicates its applicability in screening the public mental health status during the COVID-19 pandemic quickly and effectively. This model could also predict and identify high-risk groups early to prevent the worsening of PTSD symptoms.

Predictors of the Public's Aversion to Patients Infected with COVID-19 in China: The Mediating Role of Negative Physiology.

COVID-19 has had a lasting impact on the public's mental health. Understanding the mechanism of the formation of the public's aversion to COVID-19-infected people can not only help eliminate the irrational stigma, rejection, and aversion of the public but also promote the creation of a harmonious and healthy social atmosphere. Based on stimulus-organism-response theory, this study explored the relationships between environmental stimuli, public negative physiology, and aversion responses. A cross-sectional, online-based survey study was conducted in April 2022. A total of 1863 effective questionnaires from respondents of various ages, genders, incomes, and education levels were acquired. Structural equation modeling was used to test the proposed model. The environmental stimuli including the use of social media and the perception of risk communication aggravated the negative physiology of the public, while the public's perception of prevention measures reduced the public's negative physiology during the epidemic. The negative physiology of the public increases the public's aversion responses, including disgust, stigma, and avoidance, toward patients infected with COVID-19. The negative physiology of the public plays a mediating role in the relationship between the environmental stimuli and the public's aversion to patients infected with COVID-19. The emergence of excessive information in social media and strict prevention measures in daily life, as well as the dissemination of a large amount of risk information in pseudo-environments and realistic environments, have all exerted an impact on public sentiment and cognition. In the case of the prolonged spread of the epidemic, the accumulation of negative physiology, such as anxiety, panic, and depression, is more likely to lead to the public's aversion to people with COVID-19.

Risk of adverse outcomes in inflammatory bowel disease patients infected with SARS-CoV-2: a systematic review and meta-analysis.

BACKGROUND: Between people with and without inflammatory bowel disease (IBD), there was no statistically significant difference in the probability of contracting the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). However, the risk of adverse outcomes in IBD patients after virus infection remains unclear. METHODS: Eligible studies conducted from January 1, 2020 to March 17, 2022 were obtained by searching PubMed, Embase, and Web of Science. Information was collected in tables from the included studies. Random-effects and fixed-effects models were used as measures for the pooled estimates. All data were estimated by R version 4.1.3. RESULTS: Twenty-four studies were included. The risk ratio (RR) of adverse outcomes in COVID-19 patients with IBD increased by 32% (RR 1.32; 95% CI 1.06-1.66) relative to COVID-19 patients without IBD. The RR of mortality was higher in COVID-19 patients with IBD from Europe (RR 1.72; 95% CI 1.11-2.67) than in those that were not from Europe (RR 1.00; 95% CI 0.79-1.26; χ2 = 4.67; P = 0.03). Patients with ulcerative colitis were at higher risk of adverse outcomes after SARS-CoV-2 infection than patients with Crohn's disease patients (RR1.38; 95% CI 1.27-1.50). The IBD drugs treatment was associated with the risk of adverse outcomes, the pooled odds ratio (OR) of mesalazine (1.79; 95% CI 1.59-2.02), immunomodulators (1.30; 95% CI 1.10-1.53), and anti-TNF (0.47; 95% CI 0.41-0.53) were assessed. CONCLUSION: COVID-19 patients with IBD had an increased risk of adverse outcomes than those without IBD, whereas anti-TNF treatment might reduce the risk.

Human-to-human transmission of Chlamydia psittaci in China, 2020: an epidemiological and aetiological investigation.

BACKGROUND: Chlamydia psittaci can infect a wide range of avian species, occasionally causing psittacosis (also known as parrot fever) in humans. Most human psittacosis cases are associated with close contact with pet birds or poultry. In December, 2020, an outbreak of severe community-acquired pneumonia of unknown aetiology was reported in a hospital in Shandong province, China, and some of the patients' close contacts had respiratory symptoms. Our aims were to determine the causative agent of this epidemic and whether there had been human-to-human transmission. METHODS: For this epidemiological and aetiological investigation study, we enrolled patients who had community-acquired pneumonia confirmed by chest CT at two local hospitals in Shandong Province in China. We collected sputum, bronchoalveolar lavage fluid, and nasopharyngeal swab samples from participants and detected pathogens by surveying for 22 target respiratory microbes using a commercial assay, followed by metagenomic next-generation sequencing, specific nested PCR, and qPCR tests. We excluded individuals who were C psittaci-negative on both tests. We recruited close contacts of the C psittaci-positive patients, and tested nasopharyngeal swabs from the close contacts and samples from ducks from the processing plant where these patients worked. We then integrated the epidemiological, clinical, and laboratory data to reveal the potential chain of transmission of C psittaci that characterised this outbreak. FINDINGS: Between Dec 4 and 29, 2020, we used metagenomic next-generation sequencing and different PCR-based approaches to test 12 inpatients with community-acquired pneumonia, of whom six (50%) were workers at a duck-meat processing plant and two (17%) were unemployed people, who were positive for C psittaci and enrolled in this study. We contacted 61 close contacts of the six patients who worked at the duck-meat processing plant, of whom 61 (100%) were enrolled and tested, and we determined that the community-acquired pneumonia outbreak was caused by C psittaci. Within the outbreak cluster, 17 (77%) of 22 participants had confirmed C psittaci infections and five (23%) of 22 participants were asymptomatic C psittaci carriers. The outbreak had begun with avian-to-human transmission, and was followed by secondary and tertiary human-to-human transmission, which included transmission by several asymptomatic carriers and by health-care workers. In addition, some of the participants with confirmed C psittaci infection had no identified source of infection, which suggested cryptic bacterial transmission. INTERPRETATION: Our study data might represent the first documented report of human-to-human transmission of C psittaci in China. Therefore, C psittaci has the potential to evolve human-to-human transmission via various routes, should be considered an elevated biosecurity and emergent risk, and be included as part of the routine diagnosis globally, especially for high-risk populations. FUNDING: Academic Promotion Programme of Shandong First Medical University, National Science and Technology Major Project, ARC Australian Laureate Fellowship.

Pathogen-host adhesion between SARS-CoV-2 spike proteins from different variants and human ACE2 studied at single-molecule and single-cell levels.

The binding of the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein onto human angiotensin-converting enzyme 2 (ACE2) is considered as the first step for the virus to adhere onto the host cells during the infection. Here, we investigated the adhesion of spike proteins from different variants and ACE2 using single-molecule and single-cell force spectroscopy. We found that the unbinding force and binding probability of the spike protein from Delta variant to the ACE2 were the highest among the variants tested in our study at both single-molecule and single-cell levels. As the most popular variants, the Omicron variants have slightly higher unbinding force to the ACE2 than wild type. Molecular dynamics simulation showed that ACE2-RBD (Omicron BA.1) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations, when compared with Delta variant. In addition, a neutralizing antibody, produced by immunization with wild type spike protein, could effectively inhibit the binding of spike proteins from wild type, Delta and Omicron variants (BA.1 and BA.5) onto ACE2. Our results provide new insight for the molecular mechanism of the adhesive interactions between spike protein and ACE2 and suggest that effective monoclonal antibody can be prepared using wild type spike protein against different variants.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data.

OBJECTIVES: Selenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). METHOD: An observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. RESULTS: The association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215-4.916) for moderate selenium-deficient counties and 16.002 (14.706-17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061-1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00-8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14-50.16). CONCLUSION: Selenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Green spaces, especially nearby forest, may reduce the SARS-CoV-2 infection rate: A nationwide study in the United States

The coronavirus pandemic is an ongoing global crisis that has profoundly harmed public health. Although studies found exposure to green spaces can provide multiple health benefits, the relationship between exposure to green spaces and the SARS-CoV-2 infection rate is unclear. This is a critical knowledge gap for research and practice. In this study, we examined the relationship between total green space, seven types of green space, and a year of SARS-CoV-2 infection data across 3,108 counties in the contiguous United States, after controlling for spatial autocorrelation and multiple types of covariates. First, we examined the association between total green space and SARS-CoV-2 infection rate. Next, we examined the association between different types of green space and SARS-CoV-2 infection rate. Then, we examined forest–infection rate association across five time periods and five urbanicity levels. Lastly, we examined the association between infection rate and population-weighted exposure to forest at varying buffer distances (100m to 4km). We found that total green space was negative associated with the SARS-CoV-2 infection rate. Furthermore, two forest variables (forest outside park and forest inside park) had the strongest negative association with the infection rate, while open space variables had mixed associations with the infection rate. Forest outside park was more effective than forest inside park. The optimal buffer distances associated with lowest infection rate are within 1,200m for forest outside park and within 600m for forest inside park. Altogether, the findings suggest that green spaces, especially nearby forest, may significantly mitigate risk of SARS-CoV-2 infection.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Early Warning Biomarkers for COVID-19 Progression and Myocardial Injury.

Background: The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods: We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results: Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion: This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.

Interleukin-6 Elevation Is a Key Pathogenic Factor Underlying COVID-19-Associated Heart Rate-Corrected QT Interval Prolongation.

Background: Heart rate-corrected QT interval (QTc) prolongation is prevalent in patients with severe coronavirus disease 2019 (COVID-19) and is associated with poor outcomes. Recent evidence suggests that the exaggerated host immune-inflammatory response characterizing the disease, specifically interleukin-6 (IL-6) increase, may have an important role, possibly via direct effects on cardiac electrophysiology. The aim of this study was to dissect the short-term discrete impact of IL-6 elevation on QTc in patients with severe COVID-19 infection and explore the underlying mechanisms. Methods: We investigated the following mechanisms: (1) the QTc duration in patients with COVID-19 during the active phase and recovery, and its association with C-reactive protein (CRP) and IL-6 levels; (2) the acute impact of IL-6 administration on QTc in an in vivo guinea pig model; and (3) the electrophysiological effects of IL-6 on ventricular myocytes in vitro. Results: In patients with active severe COVID-19 and elevated IL-6 levels, regardless of acute myocardial injury/strain and concomitant QT-prolonging risk factors, QTc was significantly prolonged and rapidly normalized in correlation with IL-6 decrease. The direct administration of IL-6 in an in vivo guinea pig model acutely prolongs QTc duration. Moreover, ventricular myocytes incubated in vitro with IL-6 show evident prolongation in the action potential, along with significant inhibition in the rapid delayed rectifier potassium current (IKr). Conclusion: For the first time, we demonstrated that in severe COVID-19, systemic inflammatory activation can per se promote QTc prolongation via IL-6 elevation, leading to ventricular electric remodeling. Despite being transitory, such modifications may significantly contribute to arrhythmic events and associated poor outcomes in COVID-19. These findings provide a further rationale for current anti-inflammatory treatments for COVID-19, including IL-6-targeted therapies.

A Heterologous V-01 or Variant-Matched Bivalent V-01D-351 Booster following Primary Series of Inactivated Vaccine Enhances the Neutralizing Capacity against SARS-CoV-2 Delta and Omicron Strains.

Immune escape of emerging SARS-CoV-2 variants of concern (VOCs) and waning immunity over time following the primary series suggest the importance and necessity of booster shot of COVID-19 vaccines. With the aim to preliminarily evaluate the potential of heterologous boosting, we conducted two pilot studies to evaluate the safety and immunogenicity of the V-01 or a bivalent V-01D-351 (targeting Delta and Beta strain) booster after 5-7 months of the primary series of inactivated COVID-9 vaccine (ICV). A total of 77 participants were enrolled, with 20 participants in the V-01D-351 booster study, and 27, 30 participants in the age stratified participants of V-01 booster study. The safety results showed that V-01 or V-01D-351 was safe and well-tolerated as a heterologous booster shot, with overall adverse reactions predominantly being absent or mild in severity. The immunogenicity results showed that the heterologous prime-boost immunization with V-01 or bivalent V-01D-351 booster induced stronger humoral immune response as compared with the homologous booster with ICV. In particular, V-01D-351 booster showed the highest pseudovirus neutralizing antibody titers against prototype SARS-CoV-2, Delta and Omicron BA.1 strains at day 14 post boosting, with GMTs 22.7, 18.3, 14.3 times higher than ICV booster, 6.2, 6.1, 3.8 times higher than V-01 booster (10 µg), and 5.2, 3.8, 3.5 times higher than V-01 booster (25 µg), respectively. The heterologous V-01 booster also achieved a favorable safety and immunogenicity profile in older participants. Our study has provided evidence for a flexible roll-out of heterologous boosters and referential approaches for variant-specific vaccine boosters, with rationally conserved but diversified epitopes relative to primary series, to build herd immunity against the ongoing pandemic.

Time trend prediction and spatial–temporal analysis of multidrug-resistant tuberculosis in Guizhou Province, China, during 2014–2020

Background Guizhou is located in the southwest of China with high multidrug-resistant tuberculosis (MDR-TB) epidemic. To fight this disease, Guizhou provincial authorities have made efforts to establish MDR-TB service system and perform the strategies for active case finding since 2014. The expanded case finding starting from 2019 and COVID-19 pandemic may affect the cases distribution. Thus, this study aims to analyze MDR-TB epidemic status from 2014 to 2020 for the first time in Guizhou in order to guide control strategies. Methods Data of notified MDR-TB cases were extracted from the National TB Surveillance System correspond to population information for each county of Guizhou from 2014 to 2020. The percentage change was calculated to quantify the change of cases from 2014 to 2020. Time trend and seasonality of case series were analyzed by a seasonal autoregressive integrated moving average (SARIMA) model. Spatial–temporal distribution at county-level was explored by spatial autocorrelation analysis and spatial–temporal scan statistic. Results Guizhou has 9 prefectures and 88 counties. In this study, 1,666 notified MDR-TB cases were included from 2014–2020. The number of cases increased yearly. Between 2014 and 2019, the percentage increase ranged from 6.7 to 21.0%. From 2019 to 2020, the percentage increase was 62.1%. The seasonal trend illustrated that most cases were observed during the autumn with the trough in February. Only in 2020, a peak admission was observed in June. This may be caused by COVID-19 pandemic restrictions being lifted until May 2020. The spatial–temporal heterogeneity revealed that over the years, most MDR-TB cases stably aggregated over four prefectures in the northwest, covering Bijie, Guiyang, Liupanshui and Zunyi. Three prefectures (Anshun, Tongren and Qiandongnan) only exhibited case clusters in 2020. Conclusion This study identified the upward trend with seasonality and spatial−temporal clusters of MDR-TB cases in Guizhou from 2014 to 2020. The fast rising of cases and different distribution from the past in 2020 were affected by the expanded case finding from 2019 and COVID-19. The results suggest that control efforts should target at high-risk periods and areas by prioritizing resources allocation to increase cases detection capacity and better access to treatment.