UDCA May Promote COVID-19 Recovery: A Cohort Study with AI-Aided Analysis (preprint)

To investigate the impact of ursodeoxycholic acid (UDCA) treatment on the clinical outcome of mild and moderate COVID-19 cases, a retrospective analysis was conducted to evaluate the efficacy of UDCA on patients diagnosed with COVID-19 during the peak of the Omicron outbreak in China. This study presents promising results, demonstrating that UDCA significantly reduced the time to Body Temperature Recovery after admission and a higher daily dose seems to be associated with a better outcome without observed safety concerns. We also introduced VirtualBody, a physiologically plausible artificial neural network model, to generate an accurate depiction of the drug concentration-time curve individually, which represented the absorption, distribution, metabolism, and excretion of UDCA in each patient. It exhibits exceptional performance in modeling the complex PK-PD profile of UDCA, characterized by its endogenous and enterohepatic cycling properties, and further validates the effectiveness of UDCA as a treatment option from the drug exposure-response perspective. Our work highlights the potential of UDCA as a novel treatment option for periodic outbreaks of COVID-19 and introduces a new paradigm for PK-PD analysis in retrospective studies to provide evidence for optimal dosing strategies.

Seeing the forest and the trees: Holistic view of social distancing on the spread of COVID-19 in China.

The human social and behavioral activities play significant roles in the spread of COVID-19. Social-distancing centered non-pharmaceutical interventions (NPIs) are the best strategies to curb the spread of COVID-19 prior to an effective pharmaceutical or vaccine solution. This study investigates various social-distancing measures' impact on the spread of COVID-19 using advanced global and novel local geospatial techniques. Social distancing measures are acquired through website analysis, document text analysis, and other big data extraction strategies. A spatial panel regression model and a newly proposed geographically weighted panel regression model are applied to investigate the global and local relationships between the spread of COVID-19 and the various social distancing measures. Results from the combined global and local analyses confirm the effectiveness of NPI strategies to curb the spread of COVID-19. While global level strategies allow a nation to implement social distancing measures immediately at the beginning to minimize the impact of the disease, local level strategies fine tune such measures based on different times and places to provide targeted implementation to balance conflicting demands during the pandemic. The local level analysis further suggests that implementing different NPI strategies in different locations might allow us to battle unknown global pandemic more efficiently.

Comprehensive investigation of pathway enrichment methods for functional interpretation of LC-MS global metabolomics data.

BACKGROUND: Global or untargeted metabolomics is widely used to comprehensively investigate metabolic profiles under various pathophysiological conditions such as inflammations, infections, responses to exposures or interactions with microbial communities. However, biological interpretation of global metabolomics data remains a daunting task. Recent years have seen growing applications of pathway enrichment analysis based on putative annotations of liquid chromatography coupled with mass spectrometry (LC-MS) peaks for functional interpretation of LC-MS-based global metabolomics data. However, due to intricate peak-metabolite and metabolite-pathway relationships, considerable variations are observed among results obtained using different approaches. There is an urgent need to benchmark these approaches to inform the best practices. RESULTS: We have conducted a benchmark study of common peak annotation approaches and pathway enrichment methods in current metabolomics studies. Representative approaches, including three peak annotation methods and four enrichment methods, were selected and benchmarked under different scenarios. Based on the results, we have provided a set of recommendations regarding peak annotation, ranking metrics and feature selection. The overall better performance was obtained for the mummichog approach. We have observed that a ~30% annotation rate is sufficient to achieve high recall (~90% based on mummichog), and using semi-annotated data improves functional interpretation. Based on the current platforms and enrichment methods, we further propose an identifiability index to indicate the possibility of a pathway being reliably identified. Finally, we evaluated all methods using 11 COVID-19 and 8 inflammatory bowel diseases (IBD) global metabolomics datasets.

A Versatile Biomimic Nanotemplating Fluidic Assay for Multiplex Quantitative Monitoring of Viral Respiratory Infections and Immune Responses in Saliva and Blood.

The last pandemic exposed critical gaps in monitoring and mitigating the spread of viral respiratory infections at the point-of-need. A cost-effective multiplexed fluidic device (NFluidEX), as a home-test kit analogous to a glucometer, that uses saliva and blood for parallel quantitative detection of viral infection and body's immune response in an automated manner within 11 min is proposed. The technology integrates a versatile biomimetic receptor based on molecularly imprinted polymers in a core-shell structure with nano gold electrodes, a multiplexed fluidic-impedimetric readout, built-in saliva collection/preparation, and smartphone-enabled data acquisition and interpretation. NFluidEX is validated with Influenza A H1N1 and SARS-CoV-2 (original strain and variants of concern), and achieves low detection limit in saliva and blood for the viral proteins and the anti-receptor binding domain (RBD) Immunoglobulin G (IgG) and Immunoglobulin M (IgM), respectively. It is demonstrated that nanoprotrusions of gold electrodes are essential for the fine templating of antibodies and spike proteins during molecular imprinting, and differentiation of IgG and IgM in whole blood. In the clinical setting, NFluidEX achieves 100% sensitivity and 100% specificity by testing 44 COVID-positive and 25 COVID-negative saliva and blood samples on par with the real-time quantitative polymerase chain reaction (p < 0.001, 95% confidence) and the enzyme-linked immunosorbent assay.

Pandemic and prejudice: Results from a national survey experiment

Do health and economic shocks exacerbate prejudice towards racial/ethnic minority groups? We investigate this question in the wake of the COVID-19 pandemic by collecting nationally representative survey data with an embedded experiment. Results show that priming COVID-19 salience has an immediate impact: compared to the control group, respondents in the treatment group reported increased prejudice towards East Asian and Hispanic colleagues. East Asians in the treatment group faced higher prejudicial responses from Americans living in counties with higher COVID-19 infections and those who lost jobs due to COVID-19, and fewer prejudicial responses in counties with a higher concentration of Asians. These results point to the salience of COVID-19 fueled health and economic insecurities in shaping prejudicial attitudes, specifically towards East Asians. County-level socioeconomic factors did not moderate the increased prejudicial attitudes toward Hispanics in the workplace. These findings highlight a dimension of prejudice, intensified during the pandemic, which has been largely underreported and therefore missing from the current discourse on this important topic. (PsycInfo Database Record (c) 2022 APA, all rights reserved)

A C-terminal glutamine recognition mechanism revealed by E3 ligase TRIM7 structures.

The E3 ligase TRIM7 has emerged as a critical player in viral infection and pathogenesis. However, the mechanism governing the TRIM7-substrate association remains to be defined. Here we report the crystal structures of TRIM7 in complex with 2C peptides of human enterovirus. Structure-guided studies reveal the C-terminal glutamine residue of 2C as the primary determinant for TRIM7 binding. Leveraged by this finding, we identify norovirus and SARS-CoV-2 proteins, and physiological proteins, as new TRIM7 substrates. Crystal structures of TRIM7 in complex with multiple peptides derived from SARS-CoV-2 proteins display the same glutamine-end recognition mode. Furthermore, TRIM7 could trigger the ubiquitination and degradation of these substrates, possibly representing a new Gln/C-degron pathway. Together, these findings unveil a common recognition mode by TRIM7, providing the foundation for further mechanistic characterization of antiviral and cellular functions of TRIM7.

Role of Traditional Chinese Medicine in Treating Severe or Critical COVID-19: A Systematic Review of Randomized Controlled Trials and Observational Studies.

Background: The coronavirus disease 2019 (COVID-19) continues to spread globally. Due to the higher risk of mortality, the treatment of severe or critical patients is a top priority. Traditional Chinese medicine (TCM) treatment has played an extremely important role in the fight against COVID-19 in China; a timely evidence summary on TCM in managing COVID-19 is crucial to update the knowledge of healthcare for better clinical management of COVID-19. This study aimed to assess the effects and safety of TCM treatments for severe/critical COVID-19 patients by systematically collecting and synthesizing evidence from randomized controlled trials (RCTs) and observational studies (e.g., cohort). Methods: We searched nine databases up to 19th March 2022 and the reference lists of relevant publications. Pairs of reviewers independently screened studies, extracted data of interest, and assessed risk of bias. We performed qualitative systematic analysis with visual presentation of results and compared the direction and distribution of effect estimates for each patient's important outcome. We performed sensitivity analyses to observe the robustness of results by restricting analysis to studies with low risk of bias. Results: The search yielded 217,761 records, and 21 studies (6 RCTs and 15 observational studies) proved eligible. A total of 21 studies enrolled 12,981 severe/critical COVID-19 patients with a mean age of 57.21 years and a mean proportion of men of 47.91%. Compared with usual supportive treatments, the effect estimates of TCM treatments were consistent in direction, illustrating that TCM treatments could reduce the risk of mortality, rate of conversion to critical cases, and mechanical ventilation, and showed significant advantages in shortening the length of hospital stay, time to viral clearance, and symptom resolution. The results were similar when we restricted analyses to low-risk-bias studies. No serious adverse events were reported with TCM treatments, and no significant differences were observed between groups. Conclusion: Encouraging evidence suggests that TCM presents substantial advantages in treating severe/critical COVID-19 patients. TCM has a safety profile that is comparable to that of conventional treatment alone. TCMs have played an important role in China's prevention and treatment of COVID-19, which sets an example of using traditional medicine in preventing and treating COVID-19 worldwide.

Spherical neutralizing aptamer suppresses SARS-CoV-2 Omicron escape.

Recently, the SARS-CoV-2 Omicron has spread very quickly worldwide. Several studies have indicated that the Omicron variant causes a substantial evasion of the humoral immune response and the majority of existing SARS-CoV-2 neutralizing antibodies. Here we address this challenge by applying a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction of Omicron receptor binding domain (RBD) and host Angiotensin-Converting Enzyme 2 (ACE2). With the synergetic blocking strategy based on multivalent multisite aptamer binding and steric hindrance by the size-matched gold scaffold, the SNAP conjugate tightly binds to Omicron RBD with a dissociation constant of 13.6 pM, almost completely blocking the infection of Omicron pseudovirus with a half-maximal inhibitory concentration of 35.9 pM. Overall, the SNAP strategy not only fills the gap of the humoral immune evasion caused by clustered mutations on Omicron, but also provides a clue for the development of new broad neutralizing reagents against future variants.

Non-targeted metallomics through synchrotron radiation X-ray fluorescence with machine learning for cancer screening using blood samples.

Cancer is the leading cause of death in many countries. The development of new methods for early screening of cancers is highly desired. Targeted metallomics has been successfully applied in the screening of cancers through quantification of elements in the matrix, which is time consuming and requires combined techniques for the quantification due to the large elemental difference in the matrix. This work proposed a non-targeted metallomics (NTM) approach through synchrotron radiation based X-ray fluorescence (SRXRF) and machine learning algorithms (MLAs) for the screening of cancers. One hundred serum samples were collected from cancer patients who were confirmed by pathological examination with 100 matched serum samples from healthy volunteers. The serum samples were studied with SRXRF and the spectra from both groups were directly clarified through MLAs, which did not require the quantification of elements. The NTM approach through SRXRF and MLAs is fast (5s for data collection for one sample) and accurate (over 96% accuracy) for cancer screening. Besides, this approach can also identify the most affected elements in cancer samples like Ca, Zn and Ti as we found, which may shed lights on the drug development for cancer treatment. This NTM approach can also be applied through commercially available XRF instruments or ICP-TOF-MS with MLAs. It has the potential for the screening and prediction of other diseases like COVID-19 and neurodegenerative diseases in a high throughput and least invasive way.

Pandemic and prejudice: Results from a national survey experiment.

Do health and economic shocks exacerbate prejudice towards racial/ethnic minority groups? We investigate this question in the wake of the COVID-19 pandemic by collecting nationally representative survey data with an embedded experiment. Results show that priming COVID-19 salience has an immediate impact: compared to the control group, respondents in the treatment group reported increased prejudice towards East Asian and Hispanic colleagues. East Asians in the treatment group faced higher prejudicial responses from Americans living in counties with higher COVID-19 infections and those who lost jobs due to COVID-19, and fewer prejudicial responses in counties with a higher concentration of Asians. These results point to the salience of COVID-19 fueled health and economic insecurities in shaping prejudicial attitudes, specifically towards East Asians. County-level socioeconomic factors did not moderate the increased prejudicial attitudes toward Hispanics in the workplace. These findings highlight a dimension of prejudice, intensified during the pandemic, which has been largely underreported and therefore missing from the current discourse on this important topic.

Preparation of different fragments of SARS-co V-2 urine protein and its application in fluorescent layer system

Expression and purification of different fragments of the new coronavirus nucleocapsid (N) protein, establish a new coronavirus total antibody fluorescence immunochromatographic method and evaluate the influence of different protein fragments on the method. Using bioinformatics technology to analyze, synthesize, express and purify the N protein sequence, prepare different N protein fragments;use 1-ethyl-(3-dimethylaminopropyl) carbodiimide (1-( 3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) method of fluorescent microspheres coupled with antigen was established to establish a sandwich fluorescence chromatography antibody detection method, and the performance was evaluated respectively. In the prepared 4 N protein fragments, the full-length N protein (N419) is preferably coated, and N412 is labeled with 0.5mol/L NaCl as the optimal combination;the 91-120th amino acid (N412) of the N-terminus of the N antigen is deleted It can reduce 87.5% of non-specific interference;the linear range is 0.312-80U/L, the lowest detection limit is 0.165U/L, and the accuracy is above 95%. The fluorescence immunochromatographic detection method for total antibodies of the new coronavirus established by pairing the N protein fragments has a total coincidence rate of 98% compared with the Guangzhou Wanfu test strip. The improvement provides experimental basis and reference.

Spherical Neutralizing Aptamer Inhibits SARS-CoV-2 Infection and Suppresses Mutational Escape.

New neutralizing agents against SARS-CoV-2 and associated mutant strains are urgently needed for the treatment and prophylaxis of COVID-19. Herein, we develop a spherical cocktail neutralizing aptamer-gold nanoparticle (SNAP) to block the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 and host ACE2. With the multivalent aptamer assembly as well as the steric hindrance effect of the gold scaffold, SNAP exhibits exceptional binding affinity against the RBD with a dissociation constant of 3.90 pM and potent neutralization against authentic SARS-CoV-2 with a half-maximal inhibitory concentration of 142.80 fM, about 2 or 3 orders of magnitude lower than that of the reported neutralizing aptamers and antibodies. More importantly, the synergetic blocking strategy of multivalent multisite binding and steric hindrance ensures broad neutralizing activity of SNAP, almost completely blocking the infection of three mutant pseudoviruses. Overall, the SNAP strategy provides a new direction for the development of antivirus agents against SARS-CoV-2 and other emerging coronaviruses.

[Preparation of different fragments of SARS-CoV-2 N protein and its application in fluorescence chromatography].

Different fragments of SARS-CoV-2 nucleocapsid (N) protein were expressed and purified, and a fluorescence immunochromatography method for detection of SARS-CoV-2 total antibody was established. The effect of different protein fragments on the performance of the method was evaluated. The N protein sequence was analyzed by bioinformatics technology, expressed in prokaryotic cell and purified by metal ion affinity chromatography column. Different N protein fragments were prepared for comparison. EDC reaction was used to label fluorescence microsphere on the synthesized antigen to construct sandwich fluorescence chromatography antibody detection assay, and the performance was systemically evaluated. Among the 4 prepared N protein fragments, the full-length N protein (N419) was selected as the optimized coating antigen, N412 with 0.5 mol/L NaCl was used as the optimal combination; deleting 91-120 amino acids from the N-terminal of N412 reduced non-specific signal by 87.5%. the linear range of detection was 0.312-80 U/L, the limit of detection was 0.165 U/L, and the accuracy was more than 95%. A fluorescence immunochromatographic detection method for analysis of SARS-CoV-2 total antibody was established by pairing N protein fragments. The detection result achieved 98% concordance with the commercially available Guangzhou Wanfu test strip, which is expected to be used as a supplementary approach for detection of SARS-CoV-2. The assay could also provide experimental reference for improving the performance of COVID-19 antibody detection reagents.

American Attitudes Toward COVID-19: More Trumpism Than Partisanship

We investigate how support for President Donald Trump, beyond partisanship, guided Americans’ attitudes toward COVID-19. This speaks to not just how “Trumpism” and the Trump administration’s handling of the pandemic influenced public attitudes but to the larger issue of how Trump’s hold on voters within and beyond the Republican Party provides further evidence that leaders surpass the role of parties in influencing public opinion. Using longitudinal data with individual fixed-effects, we find that from the start of the pandemic, support for Trump above and beyond partisanship drove public attitudes capturing skepticism toward COVID-19, fears of personal vulnerability, compliance with public-safety measures, and viewing the pandemic in racist terms. Between March and August 2020, this gulf in attitudes between Trump voters and non-supporters, and between Republicans and Democrats, widened;the widening was more pronounced between Trump voters and non-supporters. Trump’s influence on Independents and non-voters also grew over the same period. While the use of terms like “China virus” was related to partisanship and support for Trump, we find an increase in awareness across groups that these terms were racist.

The Role of Imaging in the Detection and Management of COVID-19: A Review.

Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly around the world, resulting in a massive death toll. Lung infection or pneumonia is the common complication of COVID-19, and imaging techniques, especially computed tomography (CT), have played an important role in diagnosis and treatment assessment of the disease. Herein, we review the imaging characteristics and computing models that have been applied for the management of COVID-19. CT, positron emission tomography - CT (PET/CT), lung ultrasound, and magnetic resonance imaging (MRI) have been used for detection, treatment, and follow-up. The quantitative analysis of imaging data using artificial intelligence (AI) is also explored. Our findings indicate that typical imaging characteristics and their changes can play crucial roles in the detection and management of COVID-19. In addition, AI or other quantitative image analysis methods are urgently needed to maximize the value of imaging in the management of COVID-19.

Occurrence and Distribution of Disinfection Byproducts in Domestic Wastewater Effluent, Tap Water, and Surface Water during the SARS-CoV-2 Pandemic in China.

Intensified efforts to curb transmission of the Severe Acute Respiratory Syndrome Coronavirus-2 might lead to an elevated concentration of disinfectants in domestic wastewater and drinking water in China, possibly resulting in the generation of numerous toxic disinfection byproducts (DBPs). In this study, the occurrence and distribution of five categories of DBPs, including six trihalomethanes (THMs), nine haloacetic acids (HAAs), two haloketones, nine nitrosamines, and nine aromatic halogenated DBPs, in domestic wastewater effluent, tap water, and surface water were investigated. The results showed that the total concentration level of measured DBPs in wastewater effluents (78.3 µg/L) was higher than that in tap water (56.0 µg/L, p = 0.05), followed by surface water (8.0 µg/L, p < 0.01). Moreover, HAAs and THMs were the two most dominant categories of DBPs in wastewater effluents, tap water, and surface water, accounting for >90%, respectively. Out of the regulated DBPs, none of the wastewater effluents and tap water samples exceeded the corresponding maximum guideline values of chloroform (300 µg/L), THM4 (80 µg/L), NDMA (100 ng/L), and only 2 of 35 tap water samples (67.6 and 63.3 µg/L) exceeded the HAA5 (60 µg/L) safe limit. HAAs in wastewater effluents showed higher values of risk quotient for green algae. This study illustrates that the elevated use of disinfectants within the guidance ranges during water disinfection did not result in a significant increase in the concentration of DBPs.

Priming COVID-19 salience increases prejudice and discriminatory intent against Asians and Hispanics.

Mounting reports in the media suggest that the COVID-19 pandemic has intensified prejudice and discrimination against racial/ethnic minorities, especially Asians. Existing research has focused on discrimination against Asians and is primarily based on self-reported incidents or nonrepresentative samples. We investigate the extent to which COVID-19 has fueled prejudice and discrimination against multiple racial/ethnic minority groups in the United States by examining nationally representative survey data with an embedded vignette experiment about roommate selection (collected in August 2020; n = 5,000). We find that priming COVID-19 salience has an immediate, statistically significant impact: compared to the control group, respondents in the treatment group exhibited increased prejudice and discriminatory intent against East Asian, South Asian, and Hispanic hypothetical room-seekers. The treatment effect is more pronounced in increasing extreme negative attitudes toward the three minority groups than decreasing extreme positive attitudes toward them. This is partly due to the treatment increasing the proportion of respondents who perceive these minority groups as extremely culturally incompatible (Asians and Hispanics) and extremely irresponsible (Asians). Sociopolitical factors did not moderate the treatment effects on attitudes toward Asians, but prior social contact with Hispanics mitigated prejudices against them. These findings suggest that COVID-19-fueled prejudice and discrimination have not been limited to East Asians but are part of a broader phenomenon that has affected Asians generally and Hispanics as well.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms.

Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS) as common life-threatening lung diseases with high mortality rates are mostly associated with acute and severe inflammation in lungs. With increasing in-depth studies of ALI/ARDS, significant breakthroughs have been made, however, there are still no effective pharmacological therapies for treatment of ALI/ARDS. Especially, the novel coronavirus pneumonia (COVID-19) is ravaging the globe, and causes severe respiratory distress syndrome. Therefore, developing new drugs for therapy of ALI/ARDS is in great demand, which might also be helpful for treatment of COVID-19. Natural compounds have always inspired drug development, and numerous natural products have shown potential therapeutic effects on ALI/ARDS. Therefore, this review focuses on the potential therapeutic effects of natural compounds on ALI and the underlying mechanisms. Overall, the review discusses 159 compounds and summarizes more than 400 references to present the protective effects of natural compounds against ALI and the underlying mechanism.

Role of perceived family support in psychological distress for pregnant women during the COVID-19 pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused major public panic in China. Pregnant women may be more vulnerable to stress, which may cause them to have psychological problems. AIM: To explore the effects of perceived family support on psychological distress in pregnant women during the COVID-19 pandemic. METHODS: A total of 2232 subjects were recruited from three cities in China. Through the online surveys, information on demographic data and health status during pregnancy were collected. Insomnia severity index, generalized anxiety disorder 7-item scale, patient health questionnaire-9, somatization subscale of the symptom check list 90 scale, and posttraumatic stress disorder checklist were used to assess the psychological distress. RESULTS: A total of 1015 (45.4%) women reported having at least one psychological distress. The women who reported having inadequate family support were more likely to suffer from multiple psychological distress (≥ 2 psychological distress) than women who received adequate family support. Among the women who reported less family support, 41.8% reported depression, 31.1% reported anxiety, 8.2% reported insomnia, 13.3% reported somatization and 8.9% reported posttraumatic stress disorder (PTSD), which were significantly higher than those who received strong family support. Perceived family support level was negatively correlated with depressive symptoms (r = -0.118, P < 0.001), anxiety symptoms (r = -0.111, P < 0.001), and PTSD symptoms (r = -0.155, P < 0.001). CONCLUSION: Family support plays an important part on pregnant women's mental health during the COVID-19 pandemic. Better family support can help improve the mental health of pregnant women.