Informing the need for a SARS-CoV-2 booster based upon the immune response among young healthy adults to variants circulating during late 2023 (preprint)

COVID-19 remains a global public health challenge due to ongoing emergence of new immune-evasive SARS-CoV-2 variants, heterogeneous immunity, poor education campaigns, and suboptimal surveillance. In this cross-sectional study, we evaluated the adaptive immune responses in US active-duty service members who completed a COVID-19 primary vaccine series to 3 previously dominant variants (Ancestral, Delta, BA.5) and compared them to 3 variants currently circulating (XBB.1.5, EG.5, and BA.2.86). Analyses were performed based upon time (within or beyond 12 months) and type (vaccine or infection) of most recent exposure. Significant reduction was observed in binding antibodies, neutralization antibodies, memory B cells, and CD8+ T cells against current circulating variants compared to previous dominant variants. The reduction in antibody response was more pronounced in those whose most recent exposure, regardless if vaccination or infection, was greater than 12 months from study enrollment. In contrast, the CD4+ T cell response was largely consistent across all tested variants. Our study did not show that the type exposure in the last 12 months was a significant factor in determining the magnitude of immune responses. However, the antibody responses to circulating variants were decreased among participants who received the bivalent booster compared to those with an infection in the past 12 months, potentially due to immunological imprinting of the Ancestral strain. Administration of the new XBB.1.5-based booster is likely to enhance cross-reactive humoral immune responses against current SARS-CoV-2 circulating strains.

Current Status and Associated Factors of Health Information Literacy Among the Community Elderly in Central China in the COVID-19 Pandemic: A Cross-Sectional Study.

Purpose: COVID-19 posed a threat to the public's physical and mental health, and under outbreak control, the opportunities to go outside of the elderly have been reduced and making it more difficult to access health information and detrimental to their health management. This study aims to assess the current status of health information literacy (HIL) among older adults in the community in the context of COVID-19 and to identify its associated factors. Methods: A cross-sectional survey was conducted from April to July, 2021, for which 617 community elderly members were recruited in Chenzhou, China. Data were collected through a general information questionnaire, The Chinese residents' HIL self-rated scale and a reliability evaluation form. Results: The average score of HIL was 75.87 ± 9.85, and after processed by the 100-point system, we found 84.12% (519/617) of the participants scored less than 60 points, which indicates that the overall level of HIL among the community elderly is low. Multiple linear regression showed that age, gender, education, annual family Income, living arrangement, and chronic disease status (ß = -0.341, -0.296, 0.384, 0.327, 0.296, 0.356, respectively; all P < 0.001) were significantly associated with the level of HIL found among the community elderly, out of which education was the most important associated factor. Conclusion: The overall HIL level among the community elderly was low in Central China during the COVID-19 pandemic. Our results further prove the need for tailor-made health education programs for this group, with particular attention paid to the low-educated and low-income among them. Those measures must highlight on three aspects of health information search, evaluation, and application skills to offer useful experiences that improve the HIL level of the elderly and strengthen their ability to cope with emerging public health events.

Short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer

Background The aim of this study was to explore the short-term safety and immunogenicity of inactivated and peptide-based SARS-CoV-2 vaccines in patients with endocrine-related cancer (ER). Methods Eighty-eight patients with ER cancer and 82 healthy controls who had completed a full course of inactivated or peptide-based SARS-CoV-2 vaccines were recruited. Adverse events (AEs) were recorded. Responses to receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs) and RBD+ memory B cells (MBCs) were evaluated. Results Approximately 26.14% (23/88) of patients with ER cancer reported AEs within 7 days, which was comparable to that reported by healthy controls (24.39%, 20/82). Both the overall seroprevalence of anti-RBD-IgG and NAbs was obviously lower in the cancer group (70.45% vs. 86.59%, P < 0.05;69.32% vs. 82.93%, P < 0.05, respectively). Anti-RBD-IgG and NAbs titers exhibited similar results, and dropped gradually over time. Patients with ongoing treatment had an attenuated immune response, especially in patients receiving active chemotherapy. The frequency of overall RBD+ MBCs was similar between the two groups, but the percentage of active MBCs was remarkably reduced in patients with ER cancer. Unlike antibody titers, MBCs responses were relatively constant over time. Conclusion Inactivated and peptide-based COVID-19 vaccines were well tolerated, but with lower immunogenicity for ER cancer patients. More intensive antibody monitoring and timely booster immunization is recommended for patients with ER cancer presenting disordered subpopulations of RBD+ MBCs.

A Comparative Study of Severe and Critical Influenza B in Children in the 2021-2022 Winter Season.

Introduction: Influenza B viruses are less common than influenza A viruses in most seasons and cause relatively milder forms of infection that are less studied. We witnessed a dominance of influenza B in Shijiazhuang, China, in the 2021-2022 winter season. In this study, we comparatively investigated the severe and critical influenza B in pediatric patients. Methods: Children who were hospitalized from December 2021 to January 2022 and diagnosed with influenza B were included in this study. Those who tested positive for COVID-19 were excluded. Demographic data, clinical features, underlying medical conditions, laboratory testing results, and treatment outcomes were retrieved and analyzed retrospectively. Disease severity was classified as severe or critical according to Chinese expert consensus on diagnosis and treatment of influenza in children. Results: A significantly greater proportion of patients with critical influenza had extra-pulmonary complications and bacterial coinfections. Children with critical influenza B had substantially higher levels of procalcitonin and lactate dehydrogenase, a markedly higher neutrophil percentage and a significantly lower CD4+ lymphocyte percentage. Conclusion: Our findings suggest that, to effectively manage critical influenza B, therapeutic regimens should consist of organ-specific supportive care, antibiotic application if bacterial coinfection is present, and anti-inflammatory and immune-boosting treatments.

Pandemic Risk Perception, Vaccine Efficacy Awareness, and Preventive Behaviors of Chinese Residents: A Study Based on the Influence of COVID-19 Vaccine News Media Coverage (preprint)

Methods: : Adults aged between 18- and 58-years-old completed an online survey reporting how they gathered the media information sources of COVID-19 vaccine any relation their risk perception, vaccine efficacy and preventive behaviors in COVID-19 pandemic. We finally got 995 valid questionnaires. Results: Results showed that traditional and social media Information sources is both significantly and positively influenced on people’s COVID-19 preventive behaviors, with a stronger effect from the former. COVID-19 contact risk perception and vaccine efficacy awareness of media audiences partly mediates their relationship. 92.6% of the audience pay more attention to COVID-19 vaccine-related information. People believe more in the news information of the mainstream media of COVID-19 pandemic. 67.2% of the audience were most frequently exposed to state-controlled news media, 63.6% of the audience were most frequently exposed to Weibo. Conclusions: Although developing an effective vaccine for human immunity has long been determined as the main defensive strategy against this global pandemic, but under the background of rapid COVID-19 virus mutation, people’s daily preventive behavior is more important. Media organizations should shoulder more social responsibilities, embed the health concept of COVID-19 vaccination into the values and cultural order of the whole society, find and shape the common meaning space, and make it produce internal coupling and value identification.

Equation Chapter 0 Section 1 category-specific EPU indices, macroeconomic variables and stock market return predictability

This paper mainly investigates whether the category-specific EPU indices have predictability for stock market returns. Empirical results show that the content of category-specific EPU can significantly predict the stock market return, no matter the individual category-specific EPU index or the principal component of category-specific EPU indices. In addition, the information of category-specific EPU indices can also have higher economic gains than traditional macroeconomic variables, even considering the trading cost and different investor risk aversion coefficients. During different forecasting windows, multi-period forecast horizons and the COVID-19 pandemic, we find the information contained in category-specific EPU indices can have better performances than that of the macroeconomic variables. Our paper tries to provide new evidence for stock market returns based on category-specific EPU indices.

ROS-responsive polymer nanoparticles with enhanced loading of dexamethasone effectively modulate the lung injury microenvironment.

The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients as currently seen in coronavirus disease 2019 (COVID-19). There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to lung to reduce the burden of high doses of medications and attenuate inflammatory cells and pathways. Herein, we prepared dexamethasone-loaded ROS-responsive polymer nanoparticles (PFTU@DEX NPs) by a modified emulsion approach, which achieved high loading content of DEX (11.61 %). DEX was released faster from the PFTU@DEX NPs in a ROS environment, which could scavenge excessive ROS efficiently both in vitro and in vivo. The PFTU NPs and PFTU@DEX NPs showed no hemolysis and cytotoxicity. Free DEX, PFTU NPs and PFTU@DEX NPs shifted M1 macrophages to M2 macrophages in RAW264.7 cells, and showed anti-inflammatory modulation to A549 cells in vitro. The PFTU@DEX NPs treatment significantly reduced the increased total protein concentration in BALF of ALI mice. The delivery of PFTU@DEX NPs decreased the proportion of neutrophils significantly, mitigated the cell apoptosis remarkably compared to the other groups, reduced M1 macrophages and increased M2 macrophages in vivo. Moreover, the PFTU@DEX NPs had the strongest ability to suppress the expression of NLRP3, Caspase1, and IL-1ß. Therefore, the PFTU@DEX NPs could efficiently suppress inflammatory cells, ROS signaling pathways, and cell apoptosis to ameliorate LPS-induced ALI. STATEMENT OF SIGNIFICANCE: The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients. There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to modulate the inflammatory disorder and suppress the expression of ROS and inflammatory cytokines. The inhaled PFTU@DEX NPs prepared through a modified nanoemulsification method suppressed the activation of NLRP3, induced the polarization of macrophage phenotype from M1 to M2, and thereby reduced the neutrophil infiltration, inhibited the release of proteins and inflammatory mediators, and thus decreased the acute lung injury in vivo.

Toward Combatting COVID-19: A Risk Assessment System.

The coronavirus disease 2019 (COVID-19) has rapidly become a significant public health emergency all over the world since it was first identified in Wuhan, China, in December 2019. Until today, massive disease-related data have been collected, both manually and through the Internet of Medical Things (IoMT), which can be potentially used to analyze the spread of the disease. On the other hand, with the help of IoMT, the analysis results of the current status of COVID-19 can be delivered to people in real time to enable situational awareness, which may help mitigate the disease spread in communities. However, current accessible data on COVID-19 are mostly at a macrolevel, such as for each state, county, or metropolitan area. For fine-grained areas, such as for each city, community, or geographical coordinate, COVID-19 data are usually not available, which prevents us from obtaining information on the disease spread in closer neighborhoods around us. To address this problem, in this article, we propose a two-level risk assessment system. In particular, we define a "risk index." Then, we develop a risk assessment model, called MK-DNN, by taking advantage of the multikernel density estimation (MKDE) and deep neural network (DNN). We train MK-DNN at the macrolevel (for each metro area), which subsequently enables us to obtain the risk indices at the microlevel (for each geographic coordinate). Moreover, a heuristic validation method is further designed to help validate the obtained microlevel risk indices. Simulations conducted on real-world data demonstrate the accuracy and validity of our proposed risk assessment system.

The Predictive Value of Myoglobin for COVID-19-Related Adverse Outcomes: A Systematic Review and Meta-Analysis.

Objective: Cardiac injury is detected in numerous patients with coronavirus disease 2019 (COVID-19) and has been demonstrated to be closely related to poor outcomes. However, an optimal cardiac biomarker for predicting COVID-19 prognosis has not been identified. Methods: The PubMed, Web of Science, and Embase databases were searched for published articles between December 1, 2019 and September 8, 2021. Eligible studies that examined the anomalies of different cardiac biomarkers in patients with COVID-19 were included. The prevalence and odds ratios (ORs) were extracted. Summary estimates and the corresponding 95% confidence intervals (95% CIs) were obtained through meta-analyses. Results: A total of 63 studies, with 64,319 patients with COVID-19, were enrolled in this meta-analysis. The prevalence of elevated cardiac troponin I (cTnI) and myoglobin (Mb) in the general population with COVID-19 was 22.9 (19-27%) and 13.5% (10.6-16.4%), respectively. However, the presence of elevated Mb was more common than elevated cTnI in patients with severe COVID-19 [37.7 (23.3-52.1%) vs.30.7% (24.7-37.1%)]. Moreover, compared with cTnI, the elevation of Mb also demonstrated tendency of higher correlation with case-severity rate (Mb, r = 13.9 vs. cTnI, r = 3.93) and case-fatality rate (Mb, r = 15.42 vs. cTnI, r = 3.04). Notably, elevated Mb level was also associated with higher odds of severe illness [Mb, OR = 13.75 (10.2-18.54) vs. cTnI, OR = 7.06 (3.94-12.65)] and mortality [Mb, OR = 13.49 (9.3-19.58) vs. cTnI, OR = 7.75 (4.4-13.66)] than cTnI. Conclusions: Patients with COVID-19 and elevated Mb levels are at significantly higher risk of severe disease and mortality. Elevation of Mb may serve as a marker for predicting COVID-19-related adverse outcomes. Prospero Registration Number: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020175133, CRD42020175133.

Comparison of viral RNA-host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2.

In contrast to the extensive research about viral protein-host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection, few studies have examined interactions between host factors and viral RNAs (vRNAs). Here, we profiled vRNA-host protein interactomes for three RNA virus pathogens (SARS-CoV-2, Zika, and Ebola viruses) using ChIRP-MS. Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection. In particular, SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation. Our interactome-informed drug repurposing efforts identified several FDA-approved drugs (e.g., Cepharanthine) as broad-spectrum antivirals in cells and hACE2 transgenic mice. A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant. Thus, our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA-host protein interactome perspective.

Construction of Optimal SERS Hotspots Based on Capturing the Spike Receptor-Binding Domain (RBD) of SARS-CoV-2 for Highly Sensitive and Specific Detection by a Fish Model.

It is highly challenging to construct the best SERS hotspots for the detection of proteins by surface-enhanced Raman spectroscopy (SERS). Using its own characteristics to construct hotspots can achieve the effect of sensitivity and specificity. In this study, we built a fishing mode device to detect the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at low concentrations in different detection environments and obtained a sensitive SERS signal response. Based on the spatial resolution of proteins and their protein-specific recognition functions, SERS hotspots were constructed using aptamers and small molecules that can specifically bind to RBD and cooperate with Au nanoparticles (NPs) to detect RBD in the environment using SERS signals of beacon molecules. Therefore, two kinds of AuNPs modified with aptamers and small molecules were used in the fishing mode device, which can specifically recognize and bind RBD to form a stable hotspot to achieve high sensitivity and specificity for RBD detection. The fishing mode device can detect the presence of RBD at concentrations as low as 0.625 ng/mL and can produce a good SERS signal response within 15 min. Meanwhile, we can detect an RBD of 0.625 ng/mL in the mixed solution with various proteins, and the concentration of RBD in the complex environment of urine and blood can be as low as 1.25 ng/mL. This provides a research basis for SERS in practical applications for protein detection work.

Bacteriostatic Potential of Melatonin: Therapeutic Standing and Mechanistic Insights.

Diseases caused by pathogenic bacteria in animals (e.g., bacterial pneumonia, meningitis and sepsis) and plants (e.g., bacterial wilt, angular spot and canker) lead to high prevalence and mortality, and decomposition of plant leaves, respectively. Melatonin, an endogenous molecule, is highly pleiotropic, and accumulating evidence supports the notion that melatonin's actions in bacterial infection deserve particular attention. Here, we summarize the antibacterial effects of melatonin in vitro, in animals as well as plants, and discuss the potential mechanisms. Melatonin exerts antibacterial activities not only on classic gram-negative and -positive bacteria, but also on members of other bacterial groups, such as Mycobacterium tuberculosis. Protective actions against bacterial infections can occur at different levels. Direct actions of melatonin may occur only at very high concentrations, which is at the borderline of practical applicability. However, various indirect functions comprise activation of hosts' defense mechanisms or, in sepsis, attenuation of bacterially induced inflammation. In plants, its antibacterial functions involve the mitogen-activated protein kinase (MAPK) pathway; in animals, protection by melatonin against bacterially induced damage is associated with inhibition or activation of various signaling pathways, including key regulators such as NF-κB, STAT-1, Nrf2, NLRP3 inflammasome, MAPK and TLR-2/4. Moreover, melatonin can reduce formation of reactive oxygen and nitrogen species (ROS, RNS), promote detoxification and protect mitochondrial damage. Altogether, we propose that melatonin could be an effective approach against various pathogenic bacterial infections.

The chemical mechanism of pestilences or Coronavirus disease 2019 (COVID-19)

Around the end of 2019, a new viral species caused large-scale transmissions and infections, discovered in Wuhan (WHO Emergencies Preparedness, Response, 2020) and subsequently around the world (WHO COVID-19 Disease Dashboard, 2020). Symptoms caused include coughing, shortness of breath, and fever. Around 1% to 5% (Worldometer, 2020) of confirmed infections have resulted in deaths, mainly due to severe respiratory failure (CDC, 2020). Genealogical tree studies of the new virus strains have later revealed them to be phylogenetically intimate relatives of the Severe Acute Respiratory Syndrome Coronavirus, namely (SARS-CoV), first identified in 2003 [1]. This new virus has been named SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV) (Gorbalenya et al., 2020) on February 11th, 2020.

The occurrence and control of waterborne viruses in drinking water treatment: A review.

As the coronavirus disease 2019 continues to spread globally, its culprit, the severe acute respiratory syndrome coronavirus 2 has been brought under scrutiny. In addition to inhalation transmission, the possible fecal-oral viral transmission via water/wastewater has also been brought under the spotlight, necessitating a timely global review on the current knowledge about waterborne viruses in drinking water treatment system - the very barrier that intercepts waterborne pathogens to terminal water users. In this article we reviewed the occurrence, concentration methods, and control strategies, also, treatment performance on waterborne viruses during drinking water treatment were summarized. Additionally, we emphasized the potential of applying the quantitative microbial risk assessment to guide drinking water treatment to mitigate the viral exposure risks, especially when the unregulated novel viral pathogens are of concern. This review paves road for better control of viruses at drinking water treatment plants to protect public health.

Administration Timing and Efficacy of Tocilizumab in Patients With COVID-19 and Elevated IL-6.

BACKGROUND: Tocilizumab (TCZ), an interleukin-6 receptor antibody, has previously been used for treating patients with the coronavirus disease 2019 (COVID-19), but there is a lack of data regarding the administration timing of TCZ. OBJECTIVES: This study aimed to evaluate the timing and efficacy of TCZ in the treatment of patients with COVID-19. METHODS: Laboratory-confirmed patients with COVID-19 with an elevated interleukin-6 (IL-6) level (>10 pg/ml) were offered TCZ intravenously for compassionate use. Clinical characteristics, laboratory tests, and chest imaging before and after the administration of TCZ were retrospectively analyzed. RESULTS: A total of 58 consecutive patients who met the inclusion criteria and with no compliance to the exclusion criteria were included. Of these 58 patients, 39 patients received TCZ treatment, and 19 patients who declined TCZ treatment were used as the control cohort. In the TCZ-treatment group, 6 patients (15.4%) were in mild condition, 16 (41.0%) were in severe condition, and 17 (43.6%) were in critical condition. After TCZ treatment, the condition of 27 patients (69.2%) improved and 12 (30.8%) died. Compared with the improvement group, patients in the death group had higher baseline levels of IL-6 (P = 0.0191) and procalcitonin (PCT) (P = 0.0003) and lower lymphocyte percentage (LYM) (P = 0.0059). Patients receiving TCZ treatment had better prognoses than those without TCZ treatment (P = 0.0273). Furthermore, patients with a baseline IL-6 level of ≥100 pg/ml in the TCZ-treatment group had poorer clinical outcomes than those with an IL-6 level of <100 pg/ml (P = 0.0051). CONCLUSION: The administration of TCZ in an early stage of cytokine storm (IL-6 level < 100 pg/ml) may effectively improve the clinical prognosis of patients with COVID-19 by blocking the IL-6 signal pathway.

In vivo structural characterization of the SARS-CoV-2 RNA genome identifies host proteins vulnerable to repurposed drugs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding of the RNA virus and its interactions with host proteins could improve therapeutic interventions for COVID-19. By using icSHAPE, we determined the structural landscape of SARS-CoV-2 RNA in infected human cells and from refolded RNAs, as well as the regulatory untranslated regions of SARS-CoV-2 and six other coronaviruses. We validated several structural elements predicted in silico and discovered structural features that affect the translation and abundance of subgenomic viral RNAs in cells. The structural data informed a deep-learning tool to predict 42 host proteins that bind to SARS-CoV-2 RNA. Strikingly, antisense oligonucleotides targeting the structural elements and FDA-approved drugs inhibiting the SARS-CoV-2 RNA binding proteins dramatically reduced SARS-CoV-2 infection in cells derived from human liver and lung tumors. Our findings thus shed light on coronavirus and reveal multiple candidate therapeutics for COVID-19 treatment.