IL-37 possesses both anti-inflammatory and antiviral effects against Middle East respiratory syndrome coronavirus infection.

BACKGROUND: The aim was to elucidate the function of IL-37 in middle east respiratory syndrome coronavirus (MERS-CoV) infection, thereby providing a novel therapeutic strategy for managing the clinical treatment of inflammatory response caused by respiratory virus infection. METHODS: We investigated the development of MERS by infecting hDPP4 mice with hCoV-EMC (107 TCID50 [50% tissue culture infectious dose]) intranasally. We infected A549 cells with MERS-CoV, which concurrently interfered with IL-37, detecting the viral titer, viral load, and cytokine expression at certain points postinfection. Meanwhile, we administered IL-37 (12.5 µg/kg) intravenously to hDPP4 mice 2 h after MERS-CoV-2 infection and collected the serum and lungs 5 days after infection to investigate the efficacy of IL-37 in MERS-CoV infection. RESULTS: The viral titer of MERS-CoV-infected A549 cells interfering with IL-37 was significantly reduced by 4.7-fold, and the viral load of MERS-CoV-infected hDPP4 mice was decreased by 59-fold in lung tissue. Furthermore, the administration of IL-37 suppressed inflammatory cytokine and chemokine (monocyte chemoattractant protein 1, interferon-γ, and IL-17A) expression and ameliorated the infiltration of inflammatory cells in hDPP4 mice. CONCLUSION: IL-37 exhibits protective properties in severe pneumonia induced by MERS-CoV infection. This effect is achieved through attenuation of lung viral load, suppression of inflammatory cytokine secretion, reduction in inflammatory cell infiltration, and mitigation of pulmonary injury.

Infection with SARS-CoV-2 can cause pancreatic impairment.

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of diabetes. Herein, we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates (NHPs) models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 patients. Multi-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and humans. Minor and limited phenotypic and histopathological changes were observed in adult models. Systemic proteomics and metabolomics results indicated metabolic disorders, mainly enriched in insulin resistance pathways, in infected adult NHPs, along with elevated fasting C-peptide and C-peptide/glucose ratio levels. Furthermore, in elder COVID-19 NHPs, SARS-CoV-2 infection causes loss of beta (ß) cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis, activation of α-SMA and aggravated fibrosis consisting of lower collagen in serum, an increase of pancreatic inflammation and stress markers, ICAM-1 and G3BP1, along with more severe glycometabolic dysfunction. In contrast, vaccination maintained glucose homeostasis by activating insulin receptor α and insulin receptor ß. Overall, the cumulative risk of diabetes post-COVID-19 is closely tied to age, suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

WeChat official accounts' posts on medication use of 251 community healthcare centers in Shanghai, China: content analysis and quality assessment.

Background: The dissemination of online health information (OHI) on medication use via WeChat Official Accounts (WOAs) is an effective way to help primary care practitioners (PCPs) address drug-related problems (DRPs) in the community. Although an increasing number of primary care institutions in China have published WOA posts on medication use, their content and quality have not yet been assessed. Objective: This study aimed to explore the general features and content of WOA posts on medication use published by community healthcare centers (CHCs) in Shanghai, China and to assess their quality of content. It also aimed to explore the factors associated with the number of post views. Methods: From June 1 to October 31, 2022, two coauthors independently screened WOA posts on medication use published throughout 2021 by the CHCs in Shanghai. Content analysis was performed to analyze their general features (format, length, and source, etc.) and content (types of medicines and diseases). The QUEST tool was used to assess the quality of the posts. We compared the differences among posts published by CHCs in central urban areas and suburban areas, and used multiple linear regression to explore the factors associated with the number of post views. Results: A total of 236 WOAs of interest published 37,147 posts in 2021, and 275 (0.74%) of them were included in the study. The median number of post views was 152. Thirty percent of the posts were reviewed by the CHCs' staff before publication and only 6% provided information on PCPs' consultations. The most commonly mentioned medicines and diseases in the posts were Chinese patent medicines (37.1%) and respiratory diseases (29.5%). The posts frequently provided information on indications (77%) and usage (56%) but rarely on follow-up (13%) and storage (11%). Of the posts, 94.9% had a total QUEST score < 17 (full score = 28). The median number of post views and total post quality scores did not significantly differ among the CHCs in central urban and suburban areas. In the multiple linear regression model, the number of post views was associated with scores of complementarity (B = 56.47, 95% CI 3.05, 109.89) and conflict of interest (B = -46.40, 95% CI -56.21, -36.60). Conclusion: The quantity and quality of WOA posts on medication use published by CHCs in China need improvement. The quality of posts may partially impact the dissemination effect, but intrinsic causal associations merit further exploration.

Comparison of the replication and neutralization of different SARS-CoV-2 Omicron subvariants in vitro.

BACKGROUND: New Omicron subvariants are emerging rapidly from BA.1 to BA.4 and BA.5. Their pathogenicity has changed from that of wild-type (WH-09) and Omicron variants have over time become globally dominant. The spike proteins of BA.4 and BA.5 that serve as the target for vaccine-induced neutralizing antibodies have also changed compared to the previous subvariants, which is likely to cause immune escape and the reduction of the protective effect of the vaccine. Our study addresses the above issues and provides a basis for formulating relevant prevention and control strategies. METHODS: We collected cellular supernatant and cell lysates and measured the viral titers, viral RNA loads, and E subgenomic RNA (E sgRNA) loads in different Omicron subvariants grown in Vero E6 cells, using WH-09 and Delta variants as a reference. Additionally, we evaluated the in vitro neutralizing activity of different Omicron subvariants and compared it to the WH-09 and Delta variants using macaque sera with different types of immunity. RESULTS: As the SARS-CoV-2 evolved into Omicron BA.1, the replication ability in vitro began to decrease. Then with the emergence of new subvariants, the replication ability gradually recovered and became stable in the BA.4 and BA.5 subvariants. In WH-09-inactivated vaccine sera, geometric mean titers of neutralization antibodies against different Omicron subvariants declined by 3.7~15.4-fold compared to those against WH-09. In Delta-inactivated vaccine sera, geometric mean titers of neutralization antibodies against Omicron subvariants declined by 3.1~7.4-fold compared to those against Delta. CONCLUSION: According to the findings of this research, the replication efficiency of all Omicron subvariants declined compared with WH-09 and Delta variants, and was lower in BA.1 than in other Omicron subvariants. After two doses of inactivated (WH-09 or Delta) vaccine, cross-neutralizing activities against various Omicron subvariants were seen despite a decline in neutralizing titers.

Primary care physician responses to requests by older adults for unnecessary drugs: a qualitative study.

BACKGROUND: Unnecessary drug use can cause avoidable harm to older adults and is particularly common in primary care, but how primary care physicians (PCPs) respond to older adult requests for unnecessary drugs has not been well studied. This study is to explore PCPs' responses to requests for unnecessary drugs from older adults, and their influencing factors and potential solutions. METHODS: This qualitative study was conducted through semi-structured, in-depth interviews from January 4 to September 30, 2020 using a grounded theory methodology. A purposive sample of PCPs affiliated with community healthcare centers in Zhejiang Province and Guangdong Province, China were recruited. The face-to-face interviews were audio-recorded, transcribed verbatim, and independently coded by two investigators. Themes surrounding PCPs' responses to requests for unnecessary drugs, their influencing factors and potential solutions were analysed using a constant comparative approach. RESULTS: Of the 23 participants involved in this study, 12 (52%) were women and the mean age was 35 years. PCPs frequently declined older adults' requests for unnecessary drugs through dissuasion, and occasionally rebuffed patients or referred them to another practitioner. PCPs may fulfill requests due to physician acquiescence, patient pressure, or inadequate supervision and support. Participants recommended four potential solutions to improve the quality of prescribing, including developing professional communication skills, enhancing pharmacist-physician collaboration, improving electronic prescription systems, and strengthening prescription management. CONCLUSIONS: PCPs typically deny requests by older adults for unnecessary drugs according to three main patterns, and guidance is necessary to reduce the potential for adverse consequences. Factors contributing to request fulfillment by PCPs require attention, and the potential solutions recommended by participants deserve consideration to improve the service quality of prescribing for older adults in primary care practices.

Safety and protective capability of an inactivated SARS-CoV-2 vaccine on pregnancy, lactation and the growth of offspring in hACE2 mice.

The mass inoculation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine to induce herd immunity is one of the most effective measures to fight COVID-19. The vaccination of pregnant women cannot only avoid or reduce the probability of infectious diseases, but also offers the most effective and direct protection for neonates by means of passive immunization. However, there is no randomized clinical data to ascertain whether the inactivated vaccination of pregnant women or women of childbearing age can affect conception and the fetus. We found that human angiotensin-converting enzyme 2 (hACE2) mice that were vaccinated with two doses of CoronaVac (an inactivated SARS-CoV-2 vaccine) before and during pregnancy exhibited normal weight changes and reproductive performance indices; the physical development of their offspring was also normal. Following intranasal inoculation with SARS-CoV-2, pregnant mice in the immunization group all survived; reproductive performance indices and the physical development of offspring were all normal. In contrast, mice in the non-immunization group all died before delivery. Analyses showed that inoculation of CoronaVac was safe and did not exert any significant effects on pregnancy, lactation, or the growth of offspring in hACE2 mice. Vaccination effectively protected the pregnant mice against SARS-CoV-2 infection and had no adverse effects on the growth and development of the offspring, thus suggesting that inoculation with an inactivated SARS-CoV-2 vaccine may be an effective strategy to prevent infection in pregnant women.

Barriers to and facilitators of the implementation of pharmacist services in primary care clinics: a scoping review protocol.

INTRODUCTION: Inappropriate medication use is a leading cause of avoidable harm in health systems and is particularly severe in primary care settings. Evidence has shown that the integration of pharmacists into primary care clinics has favourable satisfaction and effectiveness in health outcomes. However, barriers to and facilitators of pharmacist services in these settings have not been comprehensively reviewed. Therefore, this scoping review aims to map and examine the literature available on the barriers to and facilitators of the implementation of pharmacist services in primary care clinics to guide future implementation research. METHODS AND ANALYSIS: This scoping review will be undertaken following the six-stage framework developed by Arksey and O'Malley and be guided by recommendations by Levac et al. Eight electronic databases (PubMed, Embase, Scopus, Web of Science, CINAHL, PsycINFO, CNKI and Wanfang) will be searched. Reference lists and related citations, and grey literature from websites will be searched manually. Available information that has been reported in Chinese or English up to 31 August 2021 will be included. Studies will be selected and screened by two reviewers independently. Findings from the included studies will be extracted by two independent reviewers and supervised by a third reviewer. A content analysis of the findings will be performed using MAXQDA 2020. ETHICS AND DISSEMINATION: Ethical approval will not be required for this scoping review, as all data and information will be obtained from publicly available literature. The findings of this scoping review will be shared with healthcare managers in primary care institutions and health authorities as well as disseminated via publication in a peer-reviewed journal.

Integrated histopathological, lipidomic, and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted on mink farms between minks and humans in many countries. However, the systemic pathological features of SARS-CoV-2-infected minks are mostly unknown. Here, we demonstrated that minks were largely permissive to SARS-CoV-2, characterized by severe and diffuse alveolar damage, and lasted at least 14 days post inoculation (dpi). We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular, hepatobiliary, urinary, endocrine, digestive, and immune systems. The viral protein partially co-localized with activated Mac-2+ macrophages throughout the body. Moreover, we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks, especially at 6 dpi, and were similar to that of patients with severe and fatal COVID-19. Particularly, altered metabolic pathways, abnormal digestion, and absorption of vitamins, lipids, cholesterol, steroids, amino acids, and proteins, consistent with hepatic dysfunction, highlight metabolic and immune dysregulation. Enriched kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage activation. Melatonin, which has significant anti-inflammatory and immunomodulating effects, was significantly downregulated at 6 dpi and displayed potential as a targeted medicine. Our data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients, delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies, vaccine research, and potential biomarkers.

Factors associated with potentially inappropriate prescriptions and barriers to medicines optimisation among older adults in primary care settings: a systematic review.

OBJECTIVE: To identify factors that likely contribute to potentially inappropriate prescriptions (PIPs) among older adults in primary care settings, as well as barriers to medicines optimisation and recommended potential solutions. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Quantitative studies that analysed the factors associated with PIPs among older adults (≥65 years) in primary care settings, and qualitative studies that explored perceived barriers and potential solutions to medicines optimisation for this population. INFORMATION SOURCES: PubMed, EMBASE, Scopus, CINAHL, PsycINFO, Web of Science, CNKI and Wanfang. RESULTS: Of the 13 167 studies identified, 50 were included (14 qualitative, 34 cross-sectional and 2 cohort). Nearly all quantitative studies examined patient-related non-clinical factors (eg, age) and clinical factors (eg, number of medications) and nine studies examined prescriber-related factors (eg, physician age). A greater number of medications were identified as positively associated with PIPs in 25 quantitative studies, and a higher number of comorbidities, physical comorbidities and psychiatric comorbidities were identified as patient-related clinical risk factors for PIPs. However, other factors showed inconsistent associations with the PIPs. Barriers to medicines optimisation emerged within four analytical themes: prescriber related (eg, inadequate knowledge, concerns of adverse consequences, clinical inertia, lack of communication), patient related (eg, limited understanding, patient non-adherence, drug dependency), environment related (eg, lack of integrated care, insufficient investment, time constraints) and technology related (eg, complexity of implementation and inapplicable guidance). Recommended potential solutions were based on each theme of the barriers identified accordingly (eg, prescriber-related factors: incorporating training courses into continuing medical education). CONCLUSIONS: Older adults with more drugs prescribed and comorbidities may have a greater risk of receiving PIPs in the primary care setting, but it remains unclear whether other factors are related. Barriers to medicines optimisation among primary care older adults comprise multiple factors, and evidence-based and targeted interventions are needed to address these difficulties. PROSPERO REGISTRATION NUMBER: CRD42020216258.