Research progress of nasal mucosal immunization vaccine against COVID-19

Respiratory mucosal immune system is the body's first line of defense against infection. Since the outbreak of novel coronavirus disease 2019 (COVID-19) in 2019, nasal mucosal immune vaccine, with its ability to induce cellular, humoral and mucosal triple immune responses, has become a research hotspot. This article focuses on novel coronavirus, with an understanding of its structure and pathogenesis, a brief introduction to the immune mechanism of nasal mucosa, a summary of the different types of nasal mucosal immune vaccines and their clinical research, aiming to provide some theoretical reference for the development of new vaccines, and exploration of the best methods and strategies to combat COVID-19.

Direct Quantitation of SARS-CoV-2 Virus in Urban Ambient Air via a Continuous-Flow Electrochemical Bioassay.

Airborne SARS-CoV-2 virus surveillance faces challenges in complicated biomarker enrichment, interferences from various non-specific matters and extremely low viral load in the urban ambient air, leading to difficulties in detecting SARS-CoV-2 bioaerosols. This work reports a highly specific bioanalysis platform, with an exceptionally low limit-of-detection (≤1 copy m-3 ) and good analytical accordance with RT-qPCR, relying on surface-mediated electrochemical signaling and enzyme-assisted signal amplification, enabling gene and signal amplification for accurate identification and quantitation of low doses human coronavirus 229E (HCoV-229E) and SARS-CoV-2 viruses in urban ambient air. This work provides a laboratory test using cultivated coronavirus to simulate the airborne spread of SARS-CoV-2, and validate that the platform could reliably detect airborne coronavirus and reveal the transmission characteristics. This bioassay conducts the quantitation of real-world HCoV-229E and SARS-CoV-2 in airborne particulate matters collected from road-side and residential areas in Bern and Zurich (Switzerland) and Wuhan (China), with resultant concentrations verified by RT-qPCR.

The role of air pollution in fetal origins of childhood allergy: Challenges and opportunities

Allergic disease is still a serious global public health problem, affecting 30-40% of world population. The rapid increase in prevalence indicates gene-by-environment interaction, in which epigenetics may be the underlying mechanism. We reviewed recent epidemiological studies about the association between prenatal exposure to air pollution and childhood allergies. On the other hand, we reviewed the evidence that maternal exposure to air pollution caused epigenetic alterations that changed the gene expression or transcription in offspring. We further discussed the challenges of the global warming and COVID-19 to the childhood allergies especially in developing countries, and suggested the opportunities to prevention or control by early intervention, immunotherapy, and epigenetic therapy.

From inflammation to degeneration – Enlarged perivascular spaces and glymphatic clearance in neuropsychiatric long-COVID syndrome

Neuropsychiatric symptoms, such as executive dysfunction, fatigue and depression, are highly prevalent and severely incapacitating among Long- and Post-COVID patients (Schou et al., 2021), to the point where some are unable to resume their jobs and even their daily lives. While the prognosis of these patients remains elusive, cognition worsens over time in many of them (Lu et al., 2020). Perivascular inflammation in the brain, as a consequence of the blood-brain barrier damage caused by SARS-CoV-2 (Yang et al., 2020), is one of the mechanisms of ongoing systemic and intracerebral inflammation proposed to contribute to these long-lasting symptoms. We thus investigated two surrogate measurements of glymphatics, enlarged perivascular spaces in T1-w magnetic resonance imaging and three-dimensional propagation of cardiorespiratory pulsations in ultrafast magnetic resonance encephalography (Barghoorn et al., 2021), in 60 neuropsychiatric long-COVID patients, 30 healthy COVID-19 survivors and 30 never-infected healthy controls. We provide evidence of EPVS burden being associated with cognitive impairment and cardiorespiratory pulsations slightly varying among these groups. We hypothesize glymphatic clearance dysfunction might be a way for post-COVID to transition into a neurodegenerative disorder.

Visual policy narrative messaging improves COVID-19 vaccine uptake.

In the face of vaccine hesitancy, public health officials are seeking more effective risk communication approaches to increase vaccination rates. We test the influence of visual policy narratives on COVID-19 vaccination behavior through a panel survey experiment conducted in early 2021 (n = 3,900) and then 8 weeks later (n = 2,268). We examine the effects of three visual policy narrative messages that test the narrative mechanism of character selection (yourself, your circle, and your community) and a nonnarrative control on COVID-19 vaccine behavior. Visual risk messages that use narratives positively influence COVID-19 vaccination through serial mediation of affective response to the messages and motivation to get the COVID-19 vaccination. Additionally, character selection matters, as messages focusing on protecting others (i.e. your circle and your community) perform stronger than those of yourself. Political ideology moderated some of the effects, with conservative respondents in the nonnarrative control condition having a higher probability of vaccination in comparison to the protect yourself condition. Taken together, these results suggest that public health officials should use narrative-based visual communication messages that emphasize communal benefits of vaccinations.

Facile and Unplugged Surface Plasmon Resonance Biosensor with NIR-Emitting Perovskite Nanocomposites for Fast Detection of SARS-CoV-2.

The emergence of the coronavirus disease 2019 (COVID-19) pandemic prompted researchers to develop portable biosensing platforms, anticipating to detect the analyte in a label-free, direct, and simple manner, for deploying on site to prevent the spread of the infectious disease. Herein, we developed a facile wavelength-based SPR sensor built with the aid of a 3D printing technology and synthesized air-stable NIR-emitting perovskite nanocomposites as the light source. The simple synthesis processes for the perovskite quantum dots enabled low-cost and large-area production and good emission stability. The integration of the two technologies enabled the proposed SPR sensor to exhibit the characteristics of lightweight, compactness, and being without a plug, just fitting the requirements of on-site detection. Experimentally, the detection limit of the proposed NIR SPR biosensor for refractive index change reached the 10-6 RIU level, comparable with that of state-of-the-art portable SPR sensors. In addition, the bio-applicability of the platform was validated by incorporating a homemade high-affinity polyclonal antibody toward the SARS-CoV-2 spike protein. The results demonstrated that the proposed system was capable of discriminating between clinical swab samples collected from COVID-19 patients and healthy subjects because the used polyclonal antibody exhibited high specificity against SARS-CoV-2. Most importantly, the whole measurement process not only took less than 15 min but also needed no complex procedures or multiple reagents. We believe that the findings disclosed in this work can open an avenue in the field of on-site detection for highly pathogenic viruses.

Opinion and Sentiment Analysis of Palliative Care in the Era of COVID-19.

During the COVID-19 pandemic, the value of palliative care has become more evident than ever. The current study quantitatively investigated the perceptions of palliative care emerging from the pandemic experience by analyzing a total of 26,494 English Tweets collected between 1 January 2020 and 1 January 2022. Such an investigation was considered invaluable in the era of more people sharing and seeking healthcare information on social media, as well as the emerging roles of palliative care. Using a web scraping method, we reviewed 6000 randomly selected Tweets and identified four themes in the extracted Tweets: (1) Negative Impact of the Pandemic on Palliative Care; (2) Positive Impact of the Pandemic on Palliative Care; (3) Recognized Benefits of Palliative Care; (4) Myth of Palliative Care. Although a large volume of Tweets focused on the negative impact of COVID-19 on palliative care as expected, we found almost the same volume of Tweets that were focused on the positive impact of COVID-19 on palliative care. We also found a smaller volume of Tweets associated with myths about palliative care. Using these manually classified Tweets, we trained machine learning (ML) algorithms to automatically classify the remaining tweets. The automatic classification of Tweets was found to be effective in classifying the negative impact of the COVID-19.

Health maintenance through home-based interventions for community-dwelling older people with sarcopenia during and after the COVID-19 pandemic: A systematic review and meta-analysis.

BACKGROUND: The COVID-19 pandemic has greatly impacted people's lifestyles and changed the delivery of health interventions, especially interventions for community-dwelling older people with sarcopenia. OBJECTIVE: To summarize the components and explore the effectiveness of home-based interventions for improving sarcopenia and other health-related outcomes among community-dwelling older people with sarcopenia. DESIGN: Systematic review and meta-analysis. METHODS: The Cochrane Library, Scopus, EMBASE, Web of Science, CINAHL, Medline (via PubMed), and PsycINFO were searched for relevant papers published from January 1, 2010 to March 29, 2022. Only papers written in English were included. The modified version of Cochrane's risk-of-bias tool was used to assess the risks of bias in the included studies. The template for intervention description and replication checklist was used to summarize the intervention components. The mean difference (MD) or standard mean difference with a 95 % confidence interval (CI) was used to determine the effect size of studies using the same or different measuring methods. Random-effects models were in meta-analyses to pool the effects of home-based interventions on the included outcomes. RESULTS: After detailed screening and exclusion, 11 randomized controlled trials including 1136 older people with sarcopenia were included in our analyses. Three categories of home-based interventions were identified: exercise interventions, nutritional interventions, and combined exercise and nutritional interventions. The overall analysis of the outcomes (e.g., appendicular skeletal muscle mass index, lean mass, body fat mass, handgrip strength, and gait speed), showed that the effects of home-based exercise interventions were inconclusive. Compared with passive controls, home-based exercise interventions significantly improved knee extension strength (MD = 0.56 kg, 95 % CI: 0.09, 1.03, p = 0.020) and reduced the time required to complete the Timed Up and Go Test (MD = -1.41 s, 95 % CI: -2.28, -0.54, p = 0.001). Home-based nutritional interventions were effective in improving appendicular skeletal muscle mass (MD = 0.25 kg, 95 % CI: 0.02, 0.49, p = 0.030), gait speed (MD = 0.06 m/s, 95 % CI: 0.03, 0.09, p = 0.0001), and quality of life in terms of both the physical component summary (MD = 13.54, 95 % CI: 0.73, 26.34, p = 0.040) and mental component summary scores (MD = 8.69, 95 % CI: 2.98, 14.41, p = 0.003). CONCLUSION: Home-based exercise interventions have the potential to improve muscle strength and physical function, while home-based nutritional interventions are effective in increasing muscle mass, physical function, and quality of life. Both of these can be applied at home during and after the COVID-19 pandemic to alleviate sarcopenia and improve health-related outcomes in community-dwelling older people.

Comparative susceptibility of SARS-CoV-2, SARS-CoV, and MERS-CoV across mammals.

Exploring wild reservoirs of pathogenic viruses is critical for their long-term control and for predicting future pandemic scenarios. Here, a comparative in vitro infection analysis was first performed on 83 cell cultures derived from 55 mammalian species using pseudotyped viruses bearing S proteins from SARS-CoV-2, SARS-CoV, and MERS-CoV. Cell cultures from Thomas's horseshoe bats, king horseshoe bats, green monkeys, and ferrets were found to be highly susceptible to SARS-CoV-2, SARS-CoV, and MERS-CoV pseudotyped viruses. Moreover, five variants (del69-70, D80Y, S98F, T572I, and Q675H), that beside spike receptor-binding domain can significantly alter the host tropism of SARS-CoV-2. An examination of phylogenetic signals of transduction rates revealed that closely related taxa generally have similar susceptibility to MERS-CoV but not to SARS-CoV and SARS-CoV-2 pseudotyped viruses. Additionally, we discovered that the expression of 95 genes, e.g., PZDK1 and APOBEC3, were commonly associated with the transduction rates of SARS-CoV, MERS-CoV, and SARS-CoV-2 pseudotyped viruses. This study provides basic documentation of the susceptibility, variants, and molecules that underlie the cross-species transmission of these coronaviruses.

Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution.

The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution, we show that the ACE can be selectively inhibited by ACE2 to prevent cleavage of angiotensin I, even when the concentration of ACE is more than 30-fold higher than that of ACE2. We also show that the activity of ACE2 for cleaving angiotensin peptides is clearly suppressed by the spike protein of SARS-CoV-2. This leads to the relaxation of ACE and the increased probability of accumulation of the principal effector angiotensin II. The spike protein of the SARS-CoV-2 Delta variant is demonstrated to have a much greater impact on the crosstalk than the wild type.

Determinants of voluntary compliance: COVID-19 mitigation.

During the pre-vaccine period, the success of containing the spread of COVID-19 depends upon how communities respond to non-pharmaceutical mitigation policies such as social distancing, wearing of masks, retail and dining constraints, crowd limitation, and shelter-in-place orders. Of these policies, shelter-in-place and social distancing are of central importance. By using county-level mobility data as a measure of a community's voluntary compliance with social distancing policies, this study found that counties who received strong state social distancing policy directives and who had a high pro-social character showed lower mobility on retail and recreation mobility and grocery and pharmacy mobility (better social distancing) after states reopened from shelter-in-place orders. Counties that experienced a longer duration of shelter-in-place orders showed higher mobility (less social distancing), implying that the duration of the shelter-in-place order deteriorated social distancing response after reopening. This may be because reopening sent a "safe" signal to these counties or resulted in a response to the pent-up demand inducing higher mobility. The results indicate that implementing shelter-in-place and social distancing policies to slow down the transmission of COVID-19 were not necessarily effective in motivating a county to reduce mobility voluntarily. A county's pro-social character and the duration of shelter-in-place order should be considered when designing COVID-19 mitigation policies.

The Impact of the COVID-19 Pandemic on Kidney Transplant Candidate Waitlist Status across Demographic and Geographic Groups: A National Analysis of UNOS STAR Data.

The primary goal of this retrospective study is to understand how the COVID-19 pandemic differentially impacted transplant status across race, sex, age, primary insurance, and geographic regions by examining which candidates: (i) remained on the waitlist, (ii) received transplants, or (iii) were removed from the waitlist due to severe sickness or death on a national level. Methods: The trend analysis aggregated by monthly transplant data from 1 December 2019 to 31 May 2021 (18 months) at the transplant center level. Ten variables about every transplant candidate were extracted from UNOS standard transplant analysis and research (STAR) data and analyzed. Characteristics of demographical groups were analyzed bivariately using t-test or Mann-Whitney U test for continuous variables and using Chi-sq/Fishers exact tests for categorical variables. Results: The trend analysis with the study period of 18 months included 31,336 transplants across 327 transplant centers. Patients experienced a longer waiting time when their registration centers in a county where high numbers of COVID-19 deaths were observed (SHR < 0.9999, p < 0.01). White candidates had a more significant transplant rate reduction than minority candidates (-32.19% vs. -20.15%) while minority candidates were found to have a higher waitlist removal rate than White candidates (9.23% vs. 9.45%). Compared to minority patients, White candidates' sub-distribution hazard ratio of the transplant waiting time was reduced by 55% during the pandemic period. Candidates in the Northwest United States had a more significant reduction in the transplant rate and a greater increase in the removal rate during the pandemic period. Conclusions: Based on this study, waitlist status and disposition varied significantly based on patient sociodemographic factors. During the pandemic period, minority patients, those with public insurance, older patients, and those in counties with high numbers of COVID-19 deaths experienced longer wait times. In contrast, older, White, male, Medicare, and high CPRA patients had a statistically significant higher risk of waitlist removal due to severe sickness or death. The results of this study should be considered carefully as we approach a reopening world post-COVID-19, and further studies should be conducted to elucidate the relationship between transplant candidate sociodemographic status and medical outcomes during this era.

Exosome-Based Carrier for RNA Delivery: Progress and Challenges.

In the last few decades, RNA-based drugs have emerged as a promising candidate to specifically target and modulate disease-relevant genes to cure genetic defects. The key to applying RNA therapy in clinical trials is developing safe and effective delivery systems. Exosomes have been exploited as a promising vehicle for drug delivery due to their nanoscale size, high stability, high biocompatibility, and low immunogenicity. We reviewed and summarized the progress in the strategy and application of exosome-mediated RNA therapy. The challenges of exosomes as a carrier for RNA drug delivery are also elucidated in this article. RNA molecules can be loaded into exosomes and then delivered to targeted cells or tissues via various biochemical or physical approaches. So far, exosome-mediated RNA therapy has shown potential in the treatment of cancer, central nervous system disorders, COVID-19, and other diseases. To further exploit the potential of exosomes for RNA delivery, more efforts should be made to overcome both technological and logistic problems.

Machine learning-based integration develops biomarkers initial the crosstalk between inflammation and immune in acute myocardial infarction patients.

Great strides have been made in past years toward revealing the pathogenesis of acute myocardial infarction (AMI). However, the prognosis did not meet satisfactory expectations. Considering the importance of early diagnosis in AMI, biomarkers with high sensitivity and accuracy are urgently needed. On the other hand, the prevalence of AMI worldwide has rapidly increased over the last few years, especially after the outbreak of COVID-19. Thus, in addition to the classical risk factors for AMI, such as overwork, agitation, overeating, cold irritation, constipation, smoking, and alcohol addiction, viral infections triggers have been considered. Immune cells play pivotal roles in the innate immunosurveillance of viral infections. So, immunotherapies might serve as a potential preventive or therapeutic approach, sparking new hope for patients with AMI. An era of artificial intelligence has led to the development of numerous machine learning algorithms. In this study, we integrated multiple machine learning algorithms for the identification of novel diagnostic biomarkers for AMI. Then, the possible association between critical genes and immune cell infiltration status was characterized for improving the diagnosis and treatment of AMI patients.

Regional poverty and infection disease: early exploratory evidence from the COVID-19 pandemic.

This paper examines the role of regional poverty on the COVID-19 pandemic in the USA. It also explores how the effects differ with the concentration of ethnic minorities. We find that poverty is a significant and consistent determinant of higher COVID-19 infections and fatalities. Prevalent poverty areas experienced higher infections due to economic structure that require hypermobility (high mobility and interpersonal interaction)-more physical human to human contact resulting in higher deaths from limited access to health services. These are also regions where minority groups are concentrated. Disproportionate infections and fatalities occurred within the black, Hispanic, and Asian population. Our evidence is robust to state fixed effects that capture local COVID-19 mitigation policies, multi-level hierarchical modeling, spatial autoregressive assessment, and large sets of county-level health, social, and economic factors. This paper contributes to the literature on health and economic disparities and their resulting consequences for infectious diseases.

DMV biogenesis during ß-coronavirus infection requires autophagy proteins VMP1 and TMEM41B.

Upon entering host cells, ß-coronaviruses specifically induce generation of replication organelles (ROs) from the endoplasmic reticulum (ER) through their nonstructural protein 3 (nsp3) and nsp4 for viral genome transcription and replication. The most predominant ROs are double-membrane vesicles (DMVs). The ER-resident proteins VMP1 and TMEM41B, which form a complex to regulate autophagosome and lipid droplet (LD) formation, were recently shown to be essential for ß-coronavirus infection. Here we report that VMP1 and TMEM41B contribute to DMV generation but function at different steps. TMEM41B facilitates nsp3-nsp4 interaction and ER zippering, while VMP1 is required for subsequent closing of the paired ER into DMVs. Additionally, inhibition of phosphatidylserine (PS) formation by siPTDSS1 partially reverses the DMV and LD defects in VMP1 KO cells, suggesting that appropriate PS levels also contribute to DMV formation. This work provides clues to the mechanism of how host proteins collaborate with viral proteins for endomembrane reshaping to promote viral infection.

Safety and immunogenicity of a mosaic vaccine booster against Omicron and other SARS-CoV-2 variants: a randomized phase 2 trial.

An ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of a mosaic-type recombinant vaccine candidate, named NVSI-06-09, as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had administered two or three doses of inactivated vaccine BBIBP-CorV at least 6 months prior to enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. Between May 25 and 30, 2022, 516 adults received booster vaccination with 260 in NVSI-06-09 group and 256 in BBIBP-CorV group. Interim results showed a similar safety profile between two booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 post-booster, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those by BBIBP-CorV. Our findings indicated that a booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against divergent SARS-CoV-2 variants, including Omicron and its sub-lineages.

Response of Algal-Bacterial Regrowth Characteristics to the Hypochlorite in Landscape Ponds Replenished with Reclaimed Water

Sodium hypochlorite was widely used as a supplementary disinfectant in reclaimed water (RW) production during the COVID-19 epidemic. It is well known that the chlorination of RW results in a relatively high bacterial regrowth potential in pipeline systems. However, the algal growth and algal-bacterial interactions would be another concern in RW-replenished surface water with light irradiation. In this study, microcosmic experiments were used to explore the impact of hypochlorite on the algae-bacteria community, including the influence of hypochlorite on algal-bacterial regrowth, microbial community structure, and the specific bacteria that can survive chlorination. Results demonstrated that algal growth potential could be promoted after chlorination of the RW, and bacteria abundance increased along with an increase in algal density, which is probably related to DOM decomposition by chlorine oxidation. Additionally, the characteristics of the bacterial community were altered. It is more likely that phytospheric bacteria will survive chlorination. It was discovered that the secondary risks of chlorine disinfection include the growth of algae in addition to bacterial regeneration, which is an extension of the common perception. As a consequence, when chlorinated reclaimed water is used as a supplement for urban landscape ponds, particular attention should be paid to controlling bio-available organic matter induced by reactive chlorine, as well as the algal bloom, to decrease the risk of pathogen transmission.

Adverse Events Associated with Nirmatrelvir/Ritonavir: A Pharmacovigilance Analysis Based on FAERS.

Nirmatrelvir/ritonavir is approved for the treatment of adults and pediatric patients with mild to moderate COVID-19, but information on adverse events associated with its use is limited. We aim to evaluate adverse events with potential risk for nirmatrelvir/ritonavir using the FDA Adverse Event Reporting System (FAERS). Disproportionality analysis was performed using the reporting odds ratio (ROR) method, and subset analysis based on patient age and gender, as well as sensitivity analysis restricting the type of reporter to healthcare professionals. Nirmatrelvir/ritonavir was the most commonly reported COVID-19 drug, and 87.66% of the outcomes were non-serious. The most frequently reported events were disease recurrence (40.43%), dysgeusia (17.55%), and diarrhea (8.80%). In disproportionality analysis, the use of nirmatrelvir/ritonavir was significantly associated with disease recurrence (ROR: 212.01, 95% CI: 162.85-276.01), whereas no signal of disease recurrence was detected for any other COVID-19 drug. Disease recurrence (ROR: 421.38, 95% CI: 273.60-648.99) was more significant when limiting the reporter type to healthcare professionals. No significant differences in adverse event reports were found based on patient gender or age. Our study confirms that the risk of serious adverse events is low with nirmatrelvir/ritonavir, but its association with disease recurrence should not be ignored.