Novel insight into the underlying dysregulation mechanisms of immune cell-to-cell communication by analyzing multitissue single-cell atlas of two COVID-19 patients.

How does SARS-CoV-2 cause lung microenvironment disturbance and inflammatory storm is still obscure. We here performed the single-cell transcriptome sequencing from lung, blood, and bone marrow of two dead COVID-19 patients and detected the cellular communication among them. Our results demonstrated that SARS-CoV-2 infection increase the frequency of cellular communication between alveolar type I cells (AT1) or alveolar type II cells (AT2) and myeloid cells triggering immune activation and inflammation microenvironment and then induce the disorder of fibroblasts, club, and ciliated cells, which may cause increased pulmonary fibrosis and mucus accumulation. Further study showed that the increase of T cells in the lungs may be mainly recruited by myeloid cells through ligands/receptors (e.g., ANXA1/FPR1, C5AR1/RPS19, and CCL5/CCR1). Interestingly, we also found that certain ligands/receptors (e.g., ANXA1/FPR1, CD74/COPA, CXCLs/CXCRs, ALOX5/ALOX5AP, CCL5/CCR1) are significantly activated and shared among lungs, blood and bone marrow of COVID-19 patients, implying that the dysregulation of ligands/receptors may lead to immune cell's activation, migration, and the inflammatory storm in different tissues of COVID-19 patients. Collectively, our study revealed a possible mechanism by which the disorder of cell communication caused by SARS-CoV-2 infection results in the lung inflammatory microenvironment and systemic immune responses across tissues in COVID-19 patients.

3044 Cases reveal important prognosis signatures of COVID-19 patients.

Critical patients and intensive care unit (ICU) patients are the main population of COVID-19 deaths. Therefore, establishing a reliable method is necessary for COVID-19 patients to distinguish patients who may have critical symptoms from other patients. In this retrospective study, we firstly evaluated the effects of 54 laboratory indicators on critical illness and death in 3044 COVID-19 patients from the Huoshenshan hospital in Wuhan, China. Secondly, we identify the eight most important prognostic indicators (neutrophil percentage, procalcitonin, neutrophil absolute value, C-reactive protein, albumin, interleukin-6, lymphocyte absolute value and myoglobin) by using the random forest algorithm, and find that dynamic changes of the eight prognostic indicators present significantly distinct within differently clinical severities. Thirdly, our study reveals that a model containing age and these eight prognostic indicators can accurately predict which patients may develop serious illness or death. Fourthly, our results demonstrate that different genders have different critical illness rates compared with different ages, in particular the mortality is more likely to be attributed to some key genes (e.g. ACE2, TMPRSS2 and FURIN) by combining the analysis of public lung single cells and bulk transcriptome data. Taken together, we urge that the prognostic model and first-hand clinical trial data generated in this study have important clinical practical significance for predicting and exploring the disease progression of COVID-19 patients.

Knowledge mapping of COVID-19 and dentistry: A bibliometric analysis.

Background: COVID-19 has a significant impact on dental medicine. The present study aims to overview dental-related research on COVID-19 by visual mapping method. Methods: We analyzed the publications in the "Dentistry Oral Surgery Medicine" category in the Web of Science core collection. On June 10, 2022, we conducted an advanced search using the items TS = ("Novel coronavirus 2019" or "COVID 19" or "Coronavirus disease 2019" or "2019-nCOV" or "SARS-CoV-2" or "coronavirus-2") and WC = ("Dentistry Oral Surgery medicine") to screen publications in the dental field that focus on COVID-19 or SARS-CoV-2. The contributions of authors, journals, institutions, and countries were described using Microsoft Excel 2010 and VOSviewer. The keywords co-occurring analysis and references analysis were visualized using VOSviewer and CiteSpace. Results: A total of 1,732 papers were identified between 2020 and 2022. The United States, the United Kingdom, and Brazil were three major contributors to this field. Univ São Paulo (Brazil) ranked first with 55 publications in this field. Martelli Junior, Hercilio from Universidade Jose do Rosario Vellano (Brazil) was the most prolific author with 19 publications. Oral Diseases and British Dental Journal were the two most productive journals. The central topics were dental practice and infection control, oral manifestation related to COVID-19, dental education and online learning, teledentistry, and mental health problems. Conclusion: The growth rate of publications regarding dental research on COVID-19 has risen sharply. Research topics shifted from "Dental practice and infection control, oral manifestation related to COVID-19" in 2020 to "Dental education and online learning, teledentistry, mental health problems," which are three important research topics for the future.

Ephedrae Herba: A Review of Its Phytochemistry, Pharmacology, Clinical Application, and Alkaloid Toxicity.

Ephedrae Herba (Ephedra), known as "MaHuang" in China, is the dried straw stem that is associated with the lung and urinary bladder meridians. At present, more than 60 species of Ephedra plants have been identified, which contain more than 100 compounds, including alkaloids, flavonoids, tannins, sugars, and organic phenolic acids. This herb has long been used to treat asthma, liver disease, skin disease, and other diseases, and has shown unique efficacy in the treatment of COVID-19 infection. Because alkaloids are the main components causing toxicity, the safety of Ephedra must be considered. However, the nonalkaloid components of Ephedra can be effectively used to replace ephedrine extracts to treat some diseases, and reasonable use can ensure the safety of Ephedra. We reviewed the phytochemistry, pharmacology, clinical application, and alkaloid toxicity of Ephedra, and describe prospects for its future development to facilitate the development of Ephedra.

Changes in Parental Attitudes Toward COVID-19 Vaccination and Routine Childhood Vaccination During the COVID-19 Pandemic: Repeated Cross-sectional Survey Study.

BACKGROUND: It was reported that one in four parents were hesitant about vaccinating their children in China. Previous studies have revealed a declining trend in the vaccine willingness rate in China. There is a need to monitor the level of parental vaccine hesitancy toward routine childhood vaccination and hesitancy toward the COVID-19 vaccine during the ongoing COVID-19 pandemic. OBJECTIVE: This study aims to assess changes in trends of parental attitudes toward routine childhood vaccines and COVID-19 vaccinations across different time periods in China. METHODS: Three waves of cross-sectional surveys were conducted on parents residing in Wuxi City in Jiangsu Province, China from September to October 2020, February to March 2021, and May to June 2021. Participants were recruited from immunization clinics. Chi-square tests were used to compare the results of the three surveys, controlling for sociodemographic factors. Binary and multivariable logistic regression analysis was used to examine factors related to parental vaccine hesitancy and COVID-19 vaccine willingness. RESULTS: Overall, 2881, 1038, and 1183 participants were included in the survey's three waves. Using the Vaccine Hesitancy Scale, 7.8% (225/2881), 15.1% (157/1038), and 5.5% (65/1183) of parents showed hesitancy to childhood vaccination (P<.001), and 59.3% (1709/2881), 64.6% (671/1038), and 92% (1088/1183) of parents agreed to receive a COVID-19 vaccine themselves in the first, second, and third surveys, respectively (P<.001). In all three surveys, "concerns about vaccine safety and side effects" was the most common reason for refusal. CONCLUSIONS: There has been an increasing acceptance of COVID-19 vaccination in Wuxi City, China. Effective interventions are needed to mitigate public concerns about vaccine safety.

International student perceptions of online medical education during the COVID-19 epidemic.

This study aimed to investigate how international students enrolled on medical and surgical bachelor's degree programs (MBBS) in China perceived online medical education course, compared to native Chinese students during the Covid-19 pandemic. The perceptions of 38 MBBS and 31 Chinese sophomores were surveyed using the Chaoxing platform. The international student group's mean satisfaction with online teaching was 2.737 on a 5-point scale, much lower than the Chinese students' mean score of 4.355 (p < 0.05). Similarly, the international students expressed less satisfaction than the Chinese learners with other aspects of the course, including the teacher's level, at 3.964 ± 0.818 versus 4.445 ± 0.548 (p < 0.05); curriculum organization, at 3.651 ± 0.848 versus 4.333 ± 0.568 (p < 0.05); and self-learning level, at 3.634 ± 0.996 versus 3.686 ± 0.949 (p > 0.05), respectively. There were also noteworthy differences between the progress made by the international students in Chinese language learning, which was positively correlated with satisfaction with teaching on the online medical education (p < 0.05). The results suggest that, while online teaching was a necessary response to the Covid-19 pandemic, satisfaction with this mode of education is lower among international students than their Chinese counterparts.

Safety and Immunogenicity of Inactivated COVID-19 Vaccines Among People Living with HIV in China.

Purpose: Vaccination reduces the incidence of severe COVID-19 and death and effectively limits viral spread. Concerns have been raised about COVID-19 vaccine responses in the large population of HIV-infected patients. This study aims to explore the safety and immunogenicity of the inactivated COVID-19 vaccine in people living with HIV (PLWH). Patients and Methods: All participants in this study already had their second dose of an inactivated COVID-19 vaccine at least 14 days earlier, without a history of SARS-CoV-2 infection. The primary safety outcomes were the incidence of adverse reactions and changes in CD4+ T-cell counts. SARS-CoV-2 IgG and neutralizing antibody responses to the D614G variant and delta variant were measured for immune response assessment. Results: Forty-seven HIV-infected patients and 18 healthy donors (HDs) were enrolled in this study. Adverse reactions were mild or self-limiting and were reported in 19.1% of HIV-infected patients. Most PLWH developed antibody responses against the inactivated COVID-19 vaccine. The longitudinal analysis of antibody responses in PLWH (median interval between detection and complete vaccination, 59 days) showed that antibodies were maintained for at least three months, though their titers were reduced. However, the antibody-positive rates in PLWH were significantly lower than those in HDs. Additionally, compared to HDs (Geomean titers (GMT) of 165 for D614G and GMT of 72 for delta), the neutralizing antibody titers against the two variants in PLWH (GMT of 43 for D614G and GMT 13 for delta) were decreased significantly (p = 0.018 and p < 0.001, respectively). HIV-infected patients with CD4+T-cell counts ≤350 cells/µL appeared to exhibit a poor antibody response to inactivated vaccination. Conclusion: Inactivated COVID-19 vaccines appear to be efficacious in PLWH. However, antibody responses in HIV-infected patients are inferior to those in healthy individuals, especially PLWH with lower CD4+T-cell counts.

Inhibitor screening using microarray identifies the high capacity of neutralizing antibodies to Spike variants in SARS-CoV-2 infection and vaccination.

Rationale: Mutations of SARS-CoV-2, which is responsible for coronavirus disease 2019 (COVID-19), could impede drug development and reduce the efficacy of COVID-19 vaccines. Here, we developed a multiplexed Spike-ACE2 Inhibitor Screening (mSAIS) assay that can measure the neutralizing effect of antibodies across numerous variants of the coronavirus's Spike (S) protein simultaneously. Methods: The SARS-CoV-2 spike variant protein microarrays were prepared by printing 72 S variants onto a chemically-modified glass slides. The neutralization potential of purified anti-S antibodies and serum from convalescent COVID-19 patients and vaccinees to S variants were assessed with the mSAIS assay. Results: We identified new S mutations that are sensitive and resistant to neutralization. Serum from both infected and vaccinated groups with a high titer of neutralizing antibodies (NAbs) displayed a broader capacity to neutralize S variants than serum with low titer NAbs. These data were validated using serum from a large vaccinated cohort (n = 104) with a tiled S peptide microarray. In addition, similar results were obtained using a SARS-CoV-2 pseudovirus neutralization assay specific for wild-type S and five prevalent S variants (D614G, B.1.1.7, B.1.351, P.1, B.1.617.2), thus demonstrating that high antibody diversity is associated with high NAb titers. Conclusions: Our results demonstrate the utility of the mSAIS platform in screening NAbs. Moreover, we show that heterogeneous antibody populations provide a more protective effect against S variants, which may help direct COVID-19 vaccine and drug development.

Difference in Amyloid Load Between Single Memory Domain and Multidomain Subjective Cognitive Decline: A Study from the SILCODE.

BACKGROUND: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer's disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. OBJECTIVE: We aim to explore the difference in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. METHODS: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. RESULTS: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. CONCLUSION: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.

Using an extended protection motivation theory to explain vaccine hesitancy: a cross-sectional study among Chinese adults.

BACKGROUND: Vaccine hesitancy was listed as one of the top 10 issues threatening global health in 2019. The objectives of this study were to (a) use an extended protection motivation theory (PMT) with an added trust component to identify predictors of vaccine hesitancy and (b) explore the predictive ability of vaccine hesitancy on vaccination behavior. METHODS: We conducted an online questionnaire from February 9 to April 9, 2021, in China. The target population was Chinese residents aged 18 and over. A total of 14,236 responses were received. Structural equation modeling was used to test the extended PMT model hypotheses. RESULTS: A total of 10,379 participants were finally included in this study, of whom 52.0% showed hesitancy toward vaccination. 2854 (27.5%) participants reported that they got flu shots in the past year, and 2561 (24.7%) participants were vaccinated against COVID-19. 2857 (27.5%) participants engaged in healthcare occupation. The model explained 85.7% variance of vaccine hesitancy. Self-efficacy was the strongest predictor, negatively associated with vaccine hesitancy (ß = -0.584; p < .001). Response efficacy had a negative effect on vaccine hesitancy (ß = -0.372; p < .001), while threat appraisal showed a positive effect (ß = 0.104; p < .001). Compared with non-health workers, health workers showed more vaccine hesitancy, and response efficacy was the strongest predictor (ß = -0.560; p < .001). Vaccine hesitancy had a negative effect on vaccination behavior (ß = -0.483; p < .001), and the model explained 23.4% variance of vaccination behavior. CONCLUSIONS: This study demonstrates that the extended PMT model is efficient in explaining vaccine hesitancy. However, the predictive ability of vaccine hesitancy on vaccination behavior is limited.

Neutralizing SARS-CoV-2 by dimeric side chain-to-side chain cross-linked ACE2 peptide mimetics.

We present the finding of a dimeric ACE2 peptide mimetic designed through side chain cross-linking and covalent dimerization. It has a binding affinity of 16 nM for the SARS-CoV-2 spike RBD, and effectively inhibits the SARS-CoV-2 pseudovirus in Huh7-hACE2 cells with an IC50 of 190 nM and neutralizes the authentic SARS-CoV-2 in Caco2 cells with an IC50 of 2.4 µM. Our study should provide a new insight for the optimization of peptide-based anti-SARS-CoV-2 inhibitors.

Chinese Consensus Report on Family-Based Helicobacter pylori Infection Control and Management (2021 Edition).

OBJECTIVE: Helicobacter pylori infection is mostly a family-based infectious disease. To facilitate its prevention and management, a national consensus meeting was held to review current evidence and propose strategies for population-wide and family-based H. pylori infection control and management to reduce the related disease burden. METHODS: Fifty-seven experts from 41 major universities and institutions in 20 provinces/regions of mainland China were invited to review evidence and modify statements using Delphi process and grading of recommendations assessment, development and evaluation system. The consensus level was defined as ≥80% for agreement on the proposed statements. RESULTS: Experts discussed and modified the original 23 statements on family-based H. pylori infection transmission, control and management, and reached consensus on 16 statements. The final report consists of three parts: (1) H. pylori infection and transmission among family members, (2) prevention and management of H. pylori infection in children and elderly people within households, and (3) strategies for prevention and management of H. pylori infection for family members. In addition to the 'test-and-treat' and 'screen-and-treat' strategies, this consensus also introduced a novel third 'family-based H. pylori infection control and management' strategy to prevent its intrafamilial transmission and development of related diseases. CONCLUSION: H. pylori is transmissible from person to person, and among family members. A family-based H. pylori prevention and eradication strategy would be a suitable approach to prevent its intra-familial transmission and related diseases. The notion and practice would be beneficial not only for Chinese residents but also valuable as a reference for other highly infected areas.

Gut microbiota imbalance in colorectal cancer patients, the risk factor of COVID-19 mortality.

BACKGROUND: COVID-19 pandemic is sweeping across the world. Previous studies have shown that gut microbiota is associated with COVID-19, and operational taxonomic unit (OTU) composed of Blautia genus, Lactobacillus genus, and Ruminococcus genus of Firmicutes is correlated with the severity of COVID-19. Gut microbiota imbalance in colorectal cancer patients may lead to the variation of OTU. RESULTS: Based on the GMrepo database, the gut microbiota of 1374 patients with colorectal neoplasms and 27,329 healthy people was analyzed to investigate the differences in the abundance of microbes between colorectal neoplasms patients and healthy people. Furthermore, We collected feces samples from 12 patients with colorectal cancer and 8 healthy people in Xiangya hospital for metabolomic analysis to investigate the potential mechanisms. Our study showed that the abundance of Blautia and Ruminococcus was significantly increased in colorectal neoplasms, which may increase the severity of COVID-19. The gender and age of patients may affect the severity of COVID-19 by shaping the gut microbiota, but the BMI of patients does not. CONCLUSIONS: Our work draws an initial point that gut microbiota imbalance is a risk factor of COVID-19 mortality and gut microbiota may provide a new therapeutic avenue for colorectal cancer patients.