Oral Immunization with Escherichia coli Nissle 1917 Expressing SARS-CoV-2 Spike Protein Induces Mucosal and Systemic Antibody Responses in Mice.

As of October 2022, the COVID-19 pandemic continues to pose a major public health conundrum, with increased rates of symptomatic infections in vaccinated individuals. An ideal vaccine candidate for the prevention of outbreaks should be rapidly scalable, easy to administer, and able to elicit a potent mucosal immunity. Towards this aim, we proposed an engineered Escherichia coli (E. coli) Nissle 1917 (EcN) strain with SARS-CoV-2 spike protein (SP)-coding plasmid, which was able to expose SP on its cellular surface by a hybridization with the adhesin involved in diffuse adherence 1 (AIDA1). In this study, we presented the effectiveness of a 16-week intragastrically administered, engineered EcN in producing specific systemic and mucosal immunoglobulins against SARS-CoV-2 SP in mice. We observed a time-dependent increase in anti-SARS-CoV-2 SP IgG antibodies in the sera at week 4, with a titre that more than doubled by week 12 and a stable circulating titre by week 16 (+309% and +325% vs. control; both p < 0.001). A parallel rise in mucosal IgA antibody titre in stools, measured via intestinal and bronchoalveolar lavage fluids of the treated mice, reached a plateau by week 12 and until the end of the immunization protocol (+300, +47, and +150%, at week 16; all p < 0.001 vs. controls). If confirmed in animal models of infection, our data indicated that the engineered EcN may be a potential candidate as an oral vaccine against COVID-19. It is safe, inexpensive, and, most importantly, able to stimulate the production of both systemic and mucosal anti-SARS-CoV-2 spike-protein antibodies.

Experiment and numerical investigation of inhalable particles and indoor environment with ventilation system.

After the outbreak of COVID-19, the indoor environment has become particularly important in closed spaces, being a common concern in environmental science and public health, and of great significance for the building environment. To improve the indoor air quality and control the spread of viruses, the analysis of inhalable particles in indoor environments is critical. In this research, we study standards focused on inhalable particles and indoor environmental quality, as well as analyzing the movement and diffusion of indoor particles. Based on our analysis, we conduct an experimental study to determine the distribution of indoor inhalable particles of different sizes before and after diffusion under the conditions of underfloor air distribution. Furthermore, the mathematical modeling method is adopted to simulate the indoor flow field, particle trajectories, and pollutant dispersion process. The k-ε two-equation model is applied as the turbulence model in the numerical simulation, while the Lagrangian discrete phase model is adopted to trace the motion of particles and analyze the distribution characteristics of indoor particles. The results demonstrate that fine particles (i.e., those with size less than 0.5 µm) have a significant impact on the indoor particle concentration, while coarse particles (i.e., with size above 2.5 µm) have a greater influence on the total mass concentration of indoor particles. Small-sized particles can easily follow the airflow and diffuse to upper parts of the room. Overall, the effects of indoor particles on indoor air quality, including the potential threat of aerosol transmission of respiratory infectious diseases, are non-negligible. Application of the presented research can contribute to improving the health-related aspects of the building environment.

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.

Colchicine prophylaxis is associated with fewer gout flares after COVID-19 vaccination.

OBJECTIVES: COVID-19 vaccination often triggers a constellation of transitory inflammatory symptoms. Gout is associated with several comorbidities linked to poor outcomes in COVID-19, and gout flares can be triggered by some vaccinations. We analysed the risk of gout flares in the first 3 months after COVID-19 vaccination with inactivated virus, and whether colchicine can prevent gout flares following post-COVID-19 vaccination. METHODS: A clinical delivery population-based cross-sectional study was conducted in the Gout Clinic at the Affiliated Hospital of Qingdao University between February and October 2021. Study participants were selected using a systematic random sampling technique among follow-up patients with gout. We collected data, including vaccinations and potential risk factors, using a combination of interviews, health QR codes and medical records. Logistic regression was used to adjust for covariates. RESULTS: We enrolled 549 gout participants (median age 39 years, 84.2% vaccinated). For the 462 patients who received COVID-19 vaccine, 203 (43.9%) developed at least one gout flare in the 3 months after vaccination. Most of these flares were experienced within 1 month after the first (99/119 (83.2%)) or second (70/115 (60.9%)) dose of vaccine. Compared with unvaccinated participants, COVID-19 vaccination was associated with higher odds of gout flare within 3 months (adjusted OR 6.02; 95% CI 3.00 to 12.08). Colchicine use was associated with 47% less likelihood of postvaccine gout flare. CONCLUSION: COVID-19 vaccination was associated with increased odds of gout flare, which developed mainly in month 1 after each vaccine dose, and was negatively associated with colchicine prophylaxis.

A protein vaccine with Alum/c-GAMP/poly(I:C) rapidly boosts robust immunity against SARS-CoV-2 and variants of concern.

Adjuvants are important components in vaccines to increase the immunogenicity of proteins and induce optimal immunity. In this study, we designed a novel ternary adjuvant system Alum + c-GAMP + poly(I:C) with STING agonist 3,3'-c-GAMP (c-GAMP) and TLR3 agonist poly(I:C) co-adsorbed on the conventional adjuvant aluminum gel (Alum), and further constructed an S1 protein vaccine. Two doses of vaccination with the ternary adjuvant vaccine were sufficient to induce a balanced Th1/Th2 immune response and robust humoral and cellular immunity. Additionally, the ternary adjuvant group had effective neutralizing activity against live virus SARS-CoV-2 and pseudovirus of all variants of concern (alpha, beta, gamma, delta and omicron). These results indicate that the ternary adjuvants have a significant synergistic effect and can rapidly trigger potent immune responses; the combination of the ternary adjuvant system with S1 protein is a promising COVID-19 vaccine candidate.

MPLA-Adjuvanted Liposomes Encapsulating S-Trimer or RBD or S1, but Not S-ECD, Elicit Robust Neutralization Against SARS-CoV-2 and Variants of Concern.

Safe and effective vaccines are the best method to defeat worldwide SARS-CoV-2 and its circulating variants. The SARS-CoV-2 S protein and its subunits are the most attractive targets for the development of protein-based vaccines. In this study, we evaluated three lipophilic adjuvants, monophosphoryl lipid A (MPLA), Toll-like receptor (TLR) 1/2 ligand Pam3CSK4, and α-galactosylceramide (α-GalCer), in liposomal and nonliposomal vaccines. The immunological results showed that the MPLA-adjuvanted liposomal vaccine induced the strongest humoral and cellular immunity. Therefore, we further performed a systematic comparison of S-trimer, S-ECD, S1, and RBD as antigens in MPLA-adjuvanted liposomes and found that, although these four vaccines all induced robust specific antibody responses, only S-trimer, S1, and RBD liposomes, but not S-ECD, elicited potent neutralizing antibody responses. Moreover, RBD, S-trimer, and S1 liposomes effectively neutralized variants (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results provide important information for the subunit vaccine design against SARS-CoV-2 and its variants.

Profiling COVID-19 Genetic Research: A Data-Driven Study Utilizing Intelligent Bibliometrics.

The COVID-19 pandemic constitutes an ongoing worldwide threat to human society and has caused massive impacts on global public health, the economy and the political landscape. The key to gaining control of the disease lies in understanding the genetics of SARS-CoV-2 and the disease spectrum that follows infection. This study leverages traditional and intelligent bibliometric methods to conduct a multi-dimensional analysis on 5,632 COVID-19 genetic research papers, revealing that 1) the key players include research institutions from the United States, China, Britain and Canada; 2) research topics predominantly focus on virus infection mechanisms, virus testing, gene expression related to the immune reactions and patient clinical manifestation; 3) studies originated from the comparison of SARS-CoV-2 to previous human coronaviruses, following which research directions diverge into the analysis of virus molecular structure and genetics, the human immune response, vaccine development and gene expression related to immune responses; and 4) genes that are frequently highlighted include ACE2, IL6, TMPRSS2, and TNF. Emerging genes to the COVID-19 consist of FURIN, CXCL10, OAS1, OAS2, OAS3, and ISG15. This study demonstrates that our suite of novel bibliometric tools could help biomedical researchers follow this rapidly growing field and provide substantial evidence for policymakers' decision-making on science policy and public health administration.

Phytotherapics in COVID19: Why palmitoylethanolamide?

At present, googling the search terms "COVID-19" and "Functional foods" yields nearly 500,000,000 hits, witnessing the growing interest of the scientific community and the general public in the role of nutrition and nutraceuticals during the COVID-19 pandemic. Many compounds have been proposed as phytotherapics in the prevention and/or treatment of COVID-19. The extensive interest of the general public and the enormous social media coverage on this topic urges the scientific community to address the question of whether which nutraceuticals can actually be employed in preventing and treating this newly described coronavirus-related disease. Recently, the Canadian biotech pharma company "FSD Pharma" received the green light from the Food and Drug Administration to design a proof-of-concept study evaluating the effects of ultramicronized palmitoylethanolamide (PEA) in COVID-19 patients. The story of PEA as a nutraceutical to prevent and treat infectious diseases dates back to the 1970s where the molecule was branded under the name Impulsin and was used for its immunomodulatory properties in influenza virus infection. The present paper aims at analyzing the potential of PEA as a nutraceutical and the previous evidence suggesting its anti-inflammatory and immunomodulatory properties in infectious and respiratory diseases and how these could translate to COVID-19 care.

Mass SARS-CoV-2 molecular and serological screening of medical staff and patients in Hangzhou, China: no evidence of RNA detection, low seroprevalence, and limited exposure risk in the hospital setting.

BACKGROUND: To assess and limit the SARS-CoV-2 exposure risk from symptomless individuals in the hospital setting, molecular and serological screening of staff and patients attending a tertiary hospital in China was conducted. METHODS: SARS-CoV-2 RNA was tested by quantitative RT-PCR. Anti-SARS-CoV-2 IgM and IgG were screened initially with two lateral flow immunoassays (LFIs) and further confirmed with three chemiluminescence immunoassays (CLIAs). The assay performance was assessed using archived samples from 32 confirmed COVID-19 cases and 80 healthy individuals. RESULTS: Between April 24 and May 8, 2020, 16,043 subjects (7,392 medical staff, 4,714 inpatients, 1,209 chaperones, 1,705 outpatients, and 1,023 fever clinic patients) were screened. No subject tested positive for viral RNA. Seventy-three (0.46%) tested positive for IgM or IgG on the initial LFI screening, of whom 63 were investigated with CLIAs: 2 (0.01%) were confirmed as seroreactive and 18 (0.11%) were indeterminate. Unconfirmed seroreactivity was significantly more frequent in fever clinic patients. The CLIAs showed similar (95.0-100%) IgM or IgG specificity but higher IgG sensitivity (93.75-96.88% vs. 31.25-81.25%) than the LFIs. The confirmed seropositive cases included a previously discharged COVID-19 patient and an undiagnosed symptomless patient showing detectable IgM and IgG over 35 days of follow-up. No transmission was evidenced within the corresponding family cluster. CONCLUSIONS: Low SARS-CoV-2 prevalence and limited exposure risk were observed. Seroprevalence varied between 0.012% and 0.12% according to the testing algorithm and the confirmation criteria used, indicating that quality standards for serological tests are needed. Protective immunity in asymptomatic COVID-19 patients who recovered needs to be investigated further, but the associated risk of transmission appeared limited.

Effect of COVID-19 on hospital visits in Ningbo, China: an interrupted time-series analysis.

OBJECTIVE: Unprecedented rigorous public health measures were implemented during the coronavirus disease 2019 (COVID-19) epidemic, but it is still unclear how the intervention influenced hospital visits for different types of diseases. We aimed to evaluate the impact of the intervention on hospital visits in Yinzhou District, Ningbo, Zhejiang province, China. METHODS: We conducted an interrupted time-series analysis from 1 January 2017 to 6 September 2020 based on the Yinzhou Health Information System in Ningbo, Zhejiang province. The beginning of the intervention was on 23 January 2020, and thus, there were 160 weeks before the intervention and 32 weeks after the implementation of the intervention. Level changes between expected and observed hospital visits in the post-intervention period were estimated using quasi-Poisson regression models. RESULTS: Compared with the expected level, there was an estimated decrease of -22.60% (95% confidence interval (CI): -27.53%, -17.36%) in the observed total hospital visits following the intervention. Observed hospital visits for diseases of the respiratory system were found to be decreased dramatically (-62.25%; 95% CI: -65.62%, -58.60%). However, observed hospital visits for certain diseases were estimated to be increased, including diseases of the nervous system (+11.17%; 95% CI: +3.21%, +19.74%); diseases of pregnancy, childbirth and the puerperium (+27.01%; 95% CI: +17.89%, +36.85%); certain conditions originating in the perinatal period (+45.05%; 95% CI: +30.24%, +61.56%); and congenital malformation deformations and chromosomal abnormalities (+35.50%; 95% CI: +21.24%, +51.45%). CONCLUSIONS: Our findings provided scientific evidence that cause-specific hospital visits evolve differently following the intervention during the COVID-19 epidemic.

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections.

The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that target nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

Short-term Changes on Follow-up Chest X-rays of Familial Cluster of COVID-19 Cases.

In this study, we report a familial cluster of cases which included five patients and two close contacts who were confirmed to have coronavirus disease 2019 (COVID-19). These participants had received real-time reverse transcription-polymerase chain reaction (RT-PCR) and chest X-rays (CXRs) before diagnosis. The follow-up CXRs of three patients in the family showed significant progression, with COVID-19 pneumonia, clinically worsening in a short period of time. Therefore, the results of follow-up CXRs in the short-term may be an adjunctive diagnostic method for COVID-19 disease diagnosis and its progression. Key Words: Chest X-ray, COVID-19, RT-PCR, Familial clustering.

A cross-sectional study of the epidemic situation on COVID-19 in Gansu Province, China - a big data analysis of the national health information platform.

BACKGROUND: In December 2019, a pneumonia caused by SARS-CoV-2 emerged in Wuhan, China and has rapidly spread around the world since then. This study is to explore the patient characteristics and transmission chains of COVID-19 in the population of Gansu province, and support decision-making. METHODS: We collected data from Gansu Province National Health Information Platform. A cross-sectional study was conducted, including patients with COVID-19 confirmed between January 23 and February 6, 2020, and analyzed the gender and age of the patients. We also described the incubation period, consultation time and sources of infection in the cases, and calculated the secondary cases that occurred within Gansu for each imported case. RESULTS: We found thirty-six (53.7%) of the patients were women and thirty-one (46.3%) men, and the median ages were 40 (IQR 31-53) years. Twenty-eight (41.8%) of the 67 cases had a history of direct exposure in Wuhan. Twenty-five (52.2%) cases came from ten families, and we found no clear reports of modes of transmission other than family clusters. The largest number of secondary cases linked to a single source was nine. CONCLUSION: More women than men were diagnosed with COVID-19 in Gansu Province. Although the age range of confirmed cases of COVID-19 in Gansu Province covered almost all age groups, most patients with confirmed COVID-19 tend to be middle aged persons. The most common suspected mode of transmission was through family cluster. Gansu and other settings worldwide should continue to strengthen the utilization of big data in epidemic control.

The potential of cannabidiol in the COVID-19 pandemic.

Identifying drugs effective in the new coronavirus disease 2019 (COVID-19) is crucial, pending a vaccine against SARS-CoV2. We suggest the hypothesis that cannabidiol (CBD), a non-psychotropic phytocannabinoid, has the potential to limit the severity and progression of the disease for several reasons:- (a) High-cannabidiol Cannabis sativa extracts are able to down-regulate the expression of the two key receptors for SARS-CoV2 in several models of human epithelia, (b) cannabidiol exerts a wide range of immunomodulatory and anti-inflammatory effects and it can mitigate the uncontrolled cytokine production responsible for acute lung injury, (c) being a PPARγ agonist, it can display a direct antiviral activity and (d) PPARγ agonists are regulators of fibroblast/myofibroblast activation and can inhibit the development of pulmonary fibrosis, thus ameliorating lung function in recovered patients. We hope our hypothesis, corroborated by preclinical evidence, will inspire further targeted studies to test cannabidiol as a support drug against the COVID-19 pandemic. LINKED ARTICLES: This article is part of a themed issue on The Pharmacology of COVID-19. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.21/issuetoc.

Balancing the decomposable behavior and wet tensile mechanical property of cellulose-based wet wipe substrates by the aqueous adhesive.

With the current global outbreak of novel coronaviruses, the fabrication of decomposable wet wipe with sufficient wet strength to meet daily use is promising but still challenging, especially when renewable cellulose was employed. In this work, a decomposable cellulose-based wet wipe substrate is demonstrated by introducing a synthetic N-vinyl pyrrolidone-glycidyl methacrylate (NVP-GMA) adhesive on the cellulose surface. Experimental results reveal that the NVP-GMA adhesive not only significantly facilitates the chemical bonding between cellulose fibers in the wet state, but also increase the surface wettability and water retention. The as-fabricated cellulose-based wet wipe substrate displays a superb water retention capacity of 1.9 times, an excellent water absorption capacity (completely wetted with 0° water contact angle), and a perfect wet tensile index of 3.32 N.m.g-1. It is far better than state-of-the-art wet toilet wipe on the market (non-woven). The prepared renewable and degradable cellulose-based substrate with excellent mechanical strength has potential application prospects in diverse commercially available products such as sanitary and medical wet wipes.