Viral and host factors associated with SARS-CoV-2 disease severity in Georgia, USA (preprint)

While SARS-CoV-2 vaccines have shown strong efficacy, their suboptimal uptake combined with the continued emergence of new viral variants raises concerns about the ongoing and future public health impact of COVID-19. We investigated viral and host factors, including vaccination status, that were associated with SARS-CoV-2 disease severity in a setting with low vaccination rates. We analyzed clinical and demographic data from 1,957 individuals in the state of Georgia, USA, coupled with viral genome sequencing from 1,185 samples. We found no difference in disease severity between individuals infected with Delta and Omicron variants among the participants in this study, after controlling for other factors, and we found no specific mutations associated with disease severity. Compared to those who were unvaccinated, vaccinated individuals experienced less severe SARS-CoV-2 disease, and the effect was similar for both variants. Vaccination within 270 days before infection was associated with decreased odds of moderate and severe outcomes, with the strongest association observed at 91-270 days post-vaccination. Older age and underlying health conditions, especially immunosuppression and renal disease, were associated with increased disease severity. Overall, this study provides insights into the impact of vaccination status, variants/mutations, and clinical factors on disease severity in SARS-CoV-2 infection when vaccination rates are low. Understanding these associations will help refine and reinforce messaging around the crucial importance of vaccination in mitigating the severity of SARS-CoV-2 disease.

Sovereign default network and currency risk premia.

We construct a sovereign default network by employing high-dimensional vector autoregressions obtained by analyzing connectedness in sovereign credit default swap markets. We develop four measures of centrality, namely, degree, betweenness, closeness, and eigenvector centralities, to detect whether network properties drive the currency risk premia. We observe that closeness and betweenness centralities can negatively drive currency excess returns but do not exhibit a relationship with forward spread. Thus, our developed network centralities are independent of an unconditional carry trade risk factor. Based on our findings, we develop a trading strategy by taking a long position on peripheral countries' currencies and a short position on core countries' currencies. The aforementioned strategy generates a higher Sharpe ratio than the currency momentum strategy. Our proposed strategy is robust to foreign exchange regimes and the coronavirus disease 2019 pandemic.

Gastric outlet obstruction caused by heterotopic pancreas in a patient with alcohol use disorder.

INTRODUCTION AND IMPORTANCE: Heterotopic Pancreas (HP) is defined by the presence of pancreatic tissue in an anatomically distinct location from the main pancreas. While often clinically silent, it may present symptomatically. If located in the gastric antrum, HP may cause gastric outlet obstruction (GOO). The objective of this paper is to present a rare case of HP in the gastric antrum causing GOO. CASE PRESENTATION: Herein, we report a 43-year-old man who presented with abdominal pain and non-bilious emesis in the setting of COVID-19 infection and alcohol consumption. During the initial workup, computed-tomography (CT) was non-specific but demonstrated GOO, concerning for cancer. Cold forceps biopsies taken during esophagogastroduodenoscopy (EGD) confirmed benign HP. Since the patient was symptomatic from gastric outlet compression, he underwent resection via laparoscopic distal gastrectomy and Billroth II gastrojejunostomy. At 1-month postoperative follow-up, the patient recovered uneventfully. We hypothesized that GOO by HP in this case may have been associated with cumulative effects of alcohol consumption and COVID-19 infection on the ectopic tissue. CLINICAL DISCUSSION: HP is rare and difficult to diagnose preoperatively. When located in gastric antrum, HP can cause GOO, mimicking gastric malignancy. Combination of EGD/EUS, biopsy/FNA, and surgical resection are necessary to definitively make the diagnosis. Finally, it is important to consider that heterotopic pancreatitis or structural changes in HP may occur due to classic pancreatic stressors like alcohol and viral infections. CONCLUSION: HP may cause GOO presenting with non-bilious emesis and abdominal pain, mistaken for malignancy on CT imaging.

Recent Advances in the Molecular Design and Delivery Technology of mRNA for Vaccination Against Infectious Diseases.

Vaccines can prevent many millions of illnesses against infectious diseases and save numerous lives every year. However, traditional vaccines such as inactivated viral and live attenuated vaccines cannot adapt to emerging pandemics due to their time-consuming development. With the global outbreak of the COVID-19 epidemic, the virus continues to evolve and mutate, producing mutants with enhanced transmissibility and virulence; the rapid development of vaccines against such emerging global pandemics becomes more and more critical. In recent years, mRNA vaccines have been of significant interest in combating emerging infectious diseases due to their rapid development and large-scale production advantages. However, their development still suffers from many hurdles such as their safety, cellular delivery, uptake, and response to their manufacturing, logistics, and storage. More efforts are still required to optimize the molecular designs of mRNA molecules with increased protein expression and enhanced structural stability. In addition, a variety of delivery systems are also needed to achieve effective delivery of vaccines. In this review, we highlight the advances in mRNA vaccines against various infectious diseases and discuss the molecular design principles and delivery systems of associated mRNA vaccines. The current state of the clinical application of mRNA vaccine pipelines against various infectious diseases and the challenge, safety, and protective effect of associated vaccines are also discussed.

An emissions inventory using flight information reveals the long-term changes of aviation CO2 emissions in China

The low-carbon development of air transport industry is of great significance for China to achieve the commitment of carbon peak and carbon neutrality goals. In order to improve the basic data of aviation CO2 emissions, this study continuously collected full flight information in China from January 2017 to December 2020, and established a flight information database and an aircraft-engine parameter database. On the basis of IPCC's Tier 3B accounting method, this study established a long-term aviation CO2 emissions inventory of China from 2017 to 2020 by calculating and accumulating CO2 emissions of each flight. And aviation CO2 emissions of various provinces and cities in China were calculated combined with spatial allocation method. The results showed that aviation CO2 emissions in China was 104.1, 120.1, 136.9, and 88.3 Mt in 2017, 2018, 2019, and 2020, respectively, with annual growth rates of 15.4%, 14.0%, and −35.3% in 2018, 2019, and 2020, respectively. Affected by the COVID-19 pandemic, aviation CO2 emissions in all 31 provinces and 93% of cities decreased in 2020 compared with 2019. China is in the stage of rapid development of air transport industry, and aviation fossil energy consumption and CO2 emissions have continued to grow in recent years.

Recent Advances in the Molecular Design and Delivery Technology of mRNA for Vaccination Against Infectious Diseases

Vaccines can prevent many millions of illnesses against infectious diseases and save numerous lives every year. However, traditional vaccines such as inactivated viral and live attenuated vaccines cannot adapt to emerging pandemics due to their time-consuming development. With the global outbreak of the COVID-19 epidemic, the virus continues to evolve and mutate, producing mutants with enhanced transmissibility and virulence;the rapid development of vaccines against such emerging global pandemics becomes more and more critical. In recent years, mRNA vaccines have been of significant interest in combating emerging infectious diseases due to their rapid development and large-scale production advantages. However, their development still suffers from many hurdles such as their safety, cellular delivery, uptake, and response to their manufacturing, logistics, and storage. More efforts are still required to optimize the molecular designs of mRNA molecules with increased protein expression and enhanced structural stability. In addition, a variety of delivery systems are also needed to achieve effective delivery of vaccines. In this review, we highlight the advances in mRNA vaccines against various infectious diseases and discuss the molecular design principles and delivery systems of associated mRNA vaccines. The current state of the clinical application of mRNA vaccine pipelines against various infectious diseases and the challenge, safety, and protective effect of associated vaccines are also discussed.

How Mortality Salience and Self-Construal Make a Difference: An Online Experiment to Test Perception of Importance of COVID-19 Vaccines in China.

To better understand why Chinese residents' COVID-19 perceptions of the importance of vaccination change dramatically over time, this research used an online lab-like experiment to test the antecedents of individuals' perception of the importance of COVID-19 vaccines. We find that participants who view themselves as separate from others (i.e. independent self-construal) perceive COVID-19 vaccines as more important than Hepatitis B vaccines (i.e. control group), regardless of how salient mortality is for them. In contrast, among participants who view themselves as a part of their social groups (i.e. interdependent self-construal), awareness of death (i.e. mortality salience) plays a moderating role. Specifically, when mortality is salient, COVID-19 vaccines are considered more important than Hepatitis B vaccines; when morality is not salient, vaccine type does not make a difference on perceptions of vaccine importance.

Cellular and humoral immune response to SARS-CoV-2 vaccination and booster dose in immunosuppressed patients: An observational cohort study.

BACKGROUND: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response. METHODS: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naïve individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination. RESULTS: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P < 0.001), sphingosine 1-phsophate (S1P) receptor modulators (P < 0.001), mycophenolate (P = 0.002), and B cell lymphoma (P = 0.004); those associated with low cellular response rates included S1P receptor modulators (P < 0.001) and mycophenolate (P < 0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination. CONCLUSIONS: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

Network Pharmacology and Comparative Transcriptome Reveals Biotargets and Mechanisms of Curcumol Treating Lung Adenocarcinoma Patients With COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has led to 4,255,892 deaths worldwide. Although COVID-19 vaccines are available, mutant forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have reduced the effectiveness of vaccines. Patients with cancer are more vulnerable to COVID-19 than patients without cancer. Identification of new drugs to treat COVID-19 could reduce mortality rate, and traditional Chinese Medicine(TCM) has shown potential in COVID-19 treatment. In this study, we focused on lung adenocarcinoma (LUAD) patients with COVID-19. We aimed to investigate the use of curcumol, a TCM, to treat LUAD patients with COVID-19, using network pharmacology and systematic bioinformatics analysis. The results showed that LUAD and patients with COVID-19 share a cluster of common deregulated targets. The network pharmacology analysis identified seven core targets (namely, AURKA, CDK1, CCNB1, CCNB2, CCNE1, CCNE2, and TTK) of curcumol in patients with COVID-19 and LUAD. Clinicopathological analysis of these targets demonstrated that the expression of these targets is associated with poor patient survival rates. The bioinformatics analysis further highlighted the involvement of this target cluster in DNA damage response, chromosome stability, and pathogenesis of LUAD. More importantly, these targets influence cell-signaling associated with the Warburg effect, which supports SARS-CoV-2 replication and inflammatory response. Comparative transcriptomic analysis on in vitro LUAD cell further validated the effect of curcumol for treating LUAD through the control of cell cycle and DNA damage response. This study supports the earlier findings that curcumol is a potential treatment for patients with LUAD and COVID-19.

Spatio-Temporal Heterogeneity of the Relationships Between PM2.5 and Its Determinants: A Case Study of Chinese Cities in Winter of 2020.

Fine particulate matter (PM2.5) poses threat to human health in China, particularly in winter. The pandemic of coronavirus disease 2019 (COVID-19) led to a series of strict control measures in Chinese cities, resulting in a short-term significant improvement in air quality. This is a perfect case to explore driving factors affecting the PM2.5 distributions in Chinese cities, thus helping form better policies for future PM2.5 mitigation. Based on panel data of 332 cities, we analyzed the function of natural and anthropogenic factors to PM2.5 pollution by applying the geographically and temporally weighted regression (GTWR) model. We found that the PM2.5 concentration of 84.3% of cities decreased after lockdown. Spatially, in the winter of 2020, cities with high PM2.5 concentrations were mainly distributed in Northeast China, the North China Plain and the Tarim Basin. Higher temperature, wind speed and relative humidity were easier to promote haze pollution in northwest of the country, where enhanced surface pressure decreased PM2.5 concentrations. Furthermore, the intensity of trip activities (ITAs) had a significant positive effect on PM2.5 pollution in Northwest and Central China. The number of daily pollutant operating vents of key polluting enterprises in the industrial sector (VOI) in northern cities was positively correlated with the PM2.5 concentration; inversely, the number of daily pollutant operating vents of key polluting enterprises in the power sector (VOP) imposed a negative effect on the PM2.5 concentration in these regions. This work provides some implications for regional air quality improvement policies of Chinese cities in wintertime.

In silico analysis and experimental validation to exhibit anti-nasopharyngeal carcinoma effects of plumbagin, an anti-cancer compound.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is publicly known as a malignant tumor. Our previous study reported that plumbagin exhibits potent anti-cancer actions. Nevertheless, more mechanical details of plumbagin against NPC remain unknown. The present study aimed to unmask the core targets/genes and anti-NPC mechanisms involved in the signaling pathways of plumbagin prior to biochemical validation. METHODS: A network pharmacology approach was employed to respective identification of mutual and core targets/genes in plumbagin and/treating NPC. Molecular docking determination was used to identify core target proteins for biochemical validation using human and cell line samples. RESULTS: In total, 60 anti-NPC genes of plumbagin were screened out, and then nine core target genes of plumbagin against NPC were identified accordingly. The enrichment findings revealed detailed biological functions and pharmacological pathways of plumbagin against NPC. Moreover, in silico analysis using molecular docking had determined the core targets for further experimental validation, comprising protein kinase B (AKT1) and sarcoma gene (SRC). In human sample validation, clinical NPC sections showed increased positive expression of AKT1 and SRC. Additionally, plumbagin-treated NPC cells resulted in inactivated protein expression of AKT1 and SRC. CONCLUSION: The re-identified core targets/genes in the molecular docking report may function as plumbagin-related pharmacological targets for treating NPC via experimental validation. Furthermore, additional anti-NPC molecular mechanisms of plumbagin action were disclosed on the basis of enrichment findings. © 2022 Society of Chemical Industry.

Exploration of Q-Marker of Rhubarb Based on Intelligent Data Processing Techniques and the AUC Pooled Method.

Rhubarb, as a traditional Chinese medicine, has several positive therapeutic effects, such as purging and attacking accumulation, clearing heat and purging fire, cooling blood, and detoxification. Recently, Rhubarb has been used in prescriptions for the prevention and treatment of COVID-19, with good efficacy. However, the exploration of effective quantitative approach to ensure the consistency of rhubarb's therapeutic efficacy remains a challenge. In this case, this study aims to use non-targeted and targeted data mining technologies for its exploration and has comprehensively identified 72 rhubarb-related components in human plasma for the first time. In details, the area under the time-concentration curve (AUC)-pooled method was used to quickly screen the components with high exposure, and the main components were analyzed using Pearson correlation and other statistical analyses. Interestingly, the prototype component (rhein) with high exposure could be selected out as a Q-marker, which could also reflect the metabolic status changes of rhubarb anthraquinone in human. Furthermore, after comparing the metabolism of different species, mice were selected as model animals to verify the pharmacodynamics of rhein. The in vivo experimental results showed that rhein has a positive therapeutic effect on pneumonia, significantly reducing the concentration of pro-inflammatory factors [interleukin (IL)-6 and IL-1ß] and improving lung disease. In short, based on the perspective of human exposure, this study comprehensively used intelligent data post-processing technologies and the AUC-pooled method to establish that rhein can be chosen as a Q-marker for rhubarb, whose content needs to be monitored individually.

Reliability and Validity of General Health Questionnaire-12 in Chinese Dental Healthcare Workers During the COVID-19 Pandemic.

BACKGROUND: The General Health Questionnaire-12 (GHQ-12) is a widely used instrument to assess mental health status. However, little is known about its applicability in Chinese healthcare workers. This study aimed to evaluate the reliability and validity of the GHQ-12 in Chinese dental healthcare workers. METHODS: Dental healthcare workers participated in the first occupational survey in China conducted by the Chongqing Stomatological Association from February 2021 to March 2021 by filling out GHQ-12. The reliability and validity of GHQ-12 were then tested. RESULTS: A total of 3,020 valid electronic questionnaires were acquired. The positive detection rate of self-reported mental health status was 23.80% (719/3,020). The Cronbach's α coefficient of the GHQ-12 was 0.892, and the Cronbach's α coefficient was 0.877-0.888 after the deletion of individual items, and the split-half reliability was 0.843. The correlation coefficient between the item-total score ranged from 0.465 to 0.762 (P<0.05). The exploratory factor analysis found 2 common factors with a factor load of 0.564-0.818. The confirmatory factor analysis showed that the factor load on the specified items was 0.480-0.790. CONCLUSIONS: The two-factor model of GHQ-12 featured good reliability and validity, which could be used to assess the mental health status of Chinese dental healthcare workers.

Bioinformatics and in-silico findings reveal medical features and pharmacological targets of biochanin A against colorectal cancer and COVID-19.

Severe mortality due to the COVID-19 pandemic resulted from the lack of effective treatment. Although COVID-19 vaccines are available, their side effects have become a challenge for clinical use in patients with chronic diseases, especially cancer patients. In the current report, we applied network pharmacology and systematic bioinformatics to explore the use of biochanin A in patients with colorectal cancer (CRC) and COVID-19 infection. Using the network pharmacology approach, we identified two clusters of genes involved in immune response (IL1A, IL2, and IL6R) and cell proliferation (CCND1, PPARG, and EGFR) mediated by biochanin A in CRC/COVID-19 condition. The functional analysis of these two gene clusters further illustrated the effects of biochanin A on interleukin-6 production and cytokine-cytokine receptor interaction in CRC/COVID-19 pathology. In addition, pathway analysis demonstrated the control of PI3K-Akt and JAK-STAT signaling pathways by biochanin A in the treatment of CRC/COVID-19. The findings of this study provide a therapeutic option for combination therapy against COVID-19 infection in CRC patients.

CRP, SAA, LDH, and DD predict poor prognosis of coronavirus disease (COVID-19): a meta-analysis from 7739 patients.

Understanding factors associated with disease severity and mortality from coronavirus disease (COVID-19) was critical for effective risk stratification. We aimed to investigate the association between biomarkers of clinical laboratory tests, including serum C-reactive protein (CRP), serum amyloid protein (SAA), lactate dehydrogenase (LDH), and D-dimer (DD) and poor prognosis of COVID-19. We have searched many studies on COVID-19 on PubMed (Medline), Web of Science and Cochrane until 1 March 2021. The interest of this study was original articles reporting on laboratory testing projects and outcome of patients with COVID-19 that comprises mortality, acute respiratory distress syndrome (ARDS), need for care in an intensive care unit (ICU), and severe COVID-19. After synthesizing all data, we performed meta-analysis of random effects, and determined mean difference (MD) and standard mean difference at the biomarker level for different disease severity. A total of 7,739 patients with COVID-19 were pooled from 32 studies. CRP was significantly associated with poor prognosis of COVID-19 (SMD = 0.98, 95% CI = (0.85, 1.11), p < .001). Elevated SAA was associated with an increased composite poor outcome in COVID-19 (SMD = 1.06, 95% CI = (0.39, 1.72), p = .002). An elevated LDH was associated with a composite poor outcome (SMD = 1.18, 95% CI = (1.00, 1.36), p < .001). Patients with a composite poor outcome had a higher DD level (SMD = 0.91, 95% CI = (0.79, 1.02), p < .001). This meta-analysis showed that elevated serum CRP, SAA, LDH, and DD were associated with a poor outcome in COVID-19.