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1.
Eur J Gastroenterol Hepatol ; 33(3): 319-324, 2021 03 01.
Article Dans Anglais | MEDLINE | ID: covidwho-20235516

Résumé

Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.


Sujets)
COVID-19/prévention et contrôle , Endoscopie gastrointestinale , Gastro-entérologues , Prévention des infections , Transmission de maladie infectieuse du patient au professionnel de santé/prévention et contrôle , Transmission de maladie infectieuse du professionnel de santé au patient/prévention et contrôle , Maladies du foie/thérapie , Types de pratiques des médecins , COVID-19/immunologie , COVID-19/transmission , Prise de décision clinique , Techniques d'aide à la décision , Endoscopie gastrointestinale/effets indésirables , Humains , Sujet immunodéprimé , Maladies du foie/diagnostic , Maladies du foie/immunologie , Santé au travail , Sécurité des patients , Appréciation des risques , Facteurs de risque
2.
BMC Health Serv Res ; 23(1): 527, 2023 May 23.
Article Dans Anglais | MEDLINE | ID: covidwho-20243647

Résumé

BACKGROUND: The unprecedented increase in the nurses' workload is one of the issues affecting the quality and safety of patient care in the Intensive Care Units (ICUs). The electronic nursing handover can share sufficient, relevant, and necessary data about patients with greater efficiency and accuracy and prevent their information from being deleted. Therefore, this study aimed to determine and compare the effect of the Electronic Nursing Handover System (ENHS) on patient safety in General ICU and COVID-19 ICU. METHOD: This is a quasi-experimental study conducted during an 8-month period from 22 to 2021 to 26 June 2022 using a test-retest design. A total of 29 nurses working in the General and COVID-19 ICUs participated in this study. Data were collected using a five-part questionnaire consisting of demographic information, handover quality, handover efficiency, error reduction, and handover time. Data analysis was conducted in IBM SPSS Statistics for Windows, version 26 (IBM Corp., Armonk, N.Y., USA) using the chi-squared test, paired t-test, and Analysis of Covariance (ANCOVA). RESULTS: The results showed that the mean scores of handover quality and efficiency, reduction of clinical error, and handover time in the electronic handover were significantly higher than those obtained in the paper-based method. The results showed that the mean score of patient safety in the COVID-19 ICU was 177.40 ± 30.416 for the paper-based handover and 251.40 ± 29.049 for the electronic handover (p = .0001). Moreover, the mean score of patient safety in the general ICU was 209.21 ± 23.072 for the paper-based handover and 251.93 ± 23.381 for the electronic one (p = .0001). CONCLUSION: The use of ENHS significantly improved the quality and efficiency of shift handover, reduced the possibility of clinical error, saved handover time, and finally increased patient safety compared to the paper-based method. The results also showed the positive perspectives of ICU nurses toward the positive effect of ENHS on the patient safety improvement.


Sujets)
COVID-19 , Transfert de la prise en charge du patient , Humains , Sécurité des patients , Électronique , Unités de soins intensifs
3.
West J Emerg Med ; 23(4): 570-578, 2022 Jul 11.
Article Dans Anglais | MEDLINE | ID: covidwho-20237020

Résumé

INTRODUCTION: Unvaccinated emergency medical services (EMS) personnel are at increased risk of contracting coronavirus disease 2019 (COVID-19) and potentially transmitting the virus to their families, coworkers, and patients. Effective vaccines for the severe acute respiratory syndrome coronavirus 2 virus exist; however, vaccination rates among EMS professionals remain largely unknown. Consequently, we sought to document vaccination rates of EMS professionals and identify predictors of vaccination uptake. METHODS: We conducted a cross-sectional survey of North Carolina EMS professionals after the COVID-19 vaccines were widely available. The survey assessed vaccination status as well as beliefs regarding COVID-19 illness and vaccine effectiveness. Prediction of vaccine uptake was modeled using logistic regression. RESULTS: A total of 860 EMS professionals completed the survey, of whom 74.7% reported receiving the COVID-19 vaccination. Most respondents believed that COVID-19 is a serious threat to the population, that they are personally at higher risk of infection, that vaccine side effects are outweighed by illness prevention, and the vaccine is safe and effective. Despite this, only 18.7% supported mandatory vaccination for EMS professionals. Statistically significant differences were observed between the vaccinated and unvaccinated groups regarding vaccine safety and effectiveness, recall of employer vaccine recommendation, perceived risk of infection, degree of threat to the population, and trust in government to take actions to limit the spread of disease. Unvaccinated respondents cited reasons such as belief in personal health and natural immunity as protectors against infection, concerns about vaccine safety and effectiveness, inadequate vaccine knowledge, and lack of an employer mandate for declining the vaccine. Predictors of vaccination included belief in vaccine safety (odds ratio [OR] 5.5, P=<0.001) and effectiveness (OR 4.6, P=<0.001); importance of vaccination to protect patients (OR 15.5, P=<0.001); perceived personal risk of infection (OR 1.8, P=0.04); previous receipt of influenza vaccine (OR 2.5, P=0.003); and sufficient knowledge to make an informed decision about vaccination (OR 2.4, P=0.024). CONCLUSION: In this survey of EMS professionals, over a quarter remained unvaccinated for COVID-19. Given the identified predictors of vaccine acceptance, EMS systems should focus on countering misinformation through employee educational campaigns as well as on developing policies regarding workforce immunization requirements.


Sujets)
Vaccins contre la COVID-19 , COVID-19 , Services des urgences médicales , Personnel de santé , Vaccination , COVID-19/prévention et contrôle , Vaccins contre la COVID-19/administration et posologie , Vaccins contre la COVID-19/effets indésirables , Vaccins contre la COVID-19/ressources et distribution , Études transversales , Prise de décision , Personnel de santé/psychologie , Personnel de santé/statistiques et données numériques , Enquêtes de santé , Humains , Vaccins antigrippaux/administration et posologie , Caroline du Nord , Santé au travail , Sécurité des patients , Vaccination/législation et jurisprudence , Vaccination/psychologie , Vaccination/statistiques et données numériques
4.
BMC Emerg Med ; 23(1): 56, 2023 05 26.
Article Dans Anglais | MEDLINE | ID: covidwho-20240541

Résumé

BACKGROUND: During the first weeks of the outbreak of the coronavirus disease 2019 (COVID-19), the North Denmark emergency medical services authorised paramedics to assess patients suspected of COVID-19 at home, and then decide if conveyance to a hospital was required. The aim of this study was to describe the cohort of patients who were assessed at home and their outcomes in terms of subsequent hospital visits and short-term mortality. METHODS: This was a historical cohort study in the North Denmark Region with consecutive inclusion of patients suspected of COVID-19 who were referred to a paramedic's assessment visit by their general practitioner or an out-of-hours general practitioner. The study was conducted from 16 March to 20 May 2020. The outcomes were the proportion of non-conveyed patients who subsequently visited a hospital within 72 hours of the paramedic's assessment visit and mortality at 3, 7 and 30 days. Mortality was estimated using a Poisson regression model with robust variance estimation. RESULTS: During the study period, 587 patients with a median age of 75 (IQR 59-84) years were referred to a paramedic's assessment visit. Three of four patients (76.5%, 95% CI 72.8;79.9) were non-conveyed, and 13.1% (95% CI 10.2;16.6) of the non-conveyed patients were subsequently referred to a hospital within 72 hours of the paramedic's assessment visit. Within 30 days from the paramedic's assessment visit, mortality was 11.1% [95% CI 6.9;17.9] among patients directly conveyed to a hospital and 5.8% [95% CI 4.0;8.5] among non-conveyed patients. Medical record review revealed that deaths in the non-conveyed group had happened among patients with 'do-not-resuscitate' orders, palliative care plans, severe comorbidities, age ≥ 90 years or nursing home residents. CONCLUSIONS: The majority (87%) of the non-conveyed patients did not visit a hospital for the following three days after a paramedic's assessment visit. The study implies that this newly established prehospital arrangement served as a kind of gatekeeper for the region's hospitals in regard to patients suspected of COVID-19. The study also demonstrates that implementation of non-conveyance protocols should be accompanied by careful and regular evaluation to ensure patient safety.


Sujets)
COVID-19 , Services des urgences médicales , Humains , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Paramédicaux , Études de cohortes , COVID-19/épidémiologie , Services des urgences médicales/méthodes , Sécurité des patients
5.
Rev Lat Am Enfermagem ; 31: e3861, 2023.
Article Dans Anglais, Portugais, Espagnol | MEDLINE | ID: covidwho-20236068

Résumé

OBJECTIVE: to evaluate nursing professionals and patient safety culture during the professional performance in the care of suspected or infected patients with COVID-19. METHOD: a cross-sectional study carried out with 90 professionals from critical care units of two teaching hospitals. An instrument for sociodemographic characterization and health conditions was used, in addition to the constructs "Nursing professional and patient safety" and the Hospital Survey on Patient Safety Culture. Univariate analyzes were performed between the diagnosis of COVID-19 and the characteristics of Nursing professionals, applying Kendell's correlation between the constructs. RESULTS: the COVID-19 diagnosis presented a significant statistical difference between nursing professionals that worked for more than six years at the critical care unit (p=0.020) and the items of the construct "Nursing professional and patient safety" regarding the doubts about how to remove the personal protective equipment (p=0.013) and safety flow (p=0,021). The dimensions 2 (p=0.003), 3 (p=0.009), 4 (p=0.013), 6 (p<0.001), and 9 (p=0.024) of the Hospital Survey on Patient Safety Culture were associated with the accomplishment of training. CONCLUSION: a higher professional nursing experience time was associated with non-infection by COVID-19. The perception of the safety culture of the patient was related to the accomplishment of training.


Sujets)
COVID-19 , Humains , COVID-19/épidémiologie , Dépistage de la COVID-19 , Études transversales , Pandémies , Sécurité des patients , Soins de réanimation
6.
Issues Ment Health Nurs ; 44(5): 437-452, 2023 May.
Article Dans Anglais | MEDLINE | ID: covidwho-20233563

Résumé

Violence against nurses is a disturbing trend in healthcare that has reached epidemic proportions globally. These violent incidents can result in physical and psychological injury, exacerbating already elevated levels of stress and burnout among nurses, further contributing to absenteeism, turnover, and intent to leave the profession. To ensure the physical and mental well-being of nurses and patients, attention to the development of strategies to reduce violence against nurses must be a priority. Caring knowledge-rooted in the philosophy of care-is a potential strategy for mitigating violence against nurses in healthcare settings. We present what caring knowledge is, analyze its barriers to implementation at the health system and education levels and explore potential solutions to navigate those barriers. We conclude how the application of models of caring knowledge to the nurse-patient relationship has the potential to generate improved patient safety and increased satisfaction for both nurses and patients.


Sujets)
Épuisement professionnel , Infirmières et infirmiers , Personnel infirmier hospitalier , Violence au travail , Humains , Personnel infirmier hospitalier/psychologie , Violence/psychologie , Épuisement professionnel/prévention et contrôle , Sécurité des patients , Satisfaction professionnelle , Enquêtes et questionnaires , Violence au travail/prévention et contrôle , Violence au travail/psychologie , Renouvellement du personnel
7.
Br J Nurs ; 32(11): 522-525, 2023 Jun 08.
Article Dans Anglais | MEDLINE | ID: covidwho-20233550

Résumé

The World Health Organization (2019) has determined that patient safety is a global public health challenge. In UK clinical areas, policies and procedures are in place for the safe prescribing and delivery of blood and blood product transfusions, yet patient safety incidences continue. Undergraduate nurse education and training may provide the underlying knowledge to practitioners, while postgraduate standalone training sessions support skill development. However, over time, without regular experience, competence will diminish. Nursing students may have little exposure to transfusion practice and COVID-19 may have exacerbated this challenge with a reduction in placement availability. The use of simulation to support theory with follow-up and ongoing drop-in training sessions may help to inform practitioners and improve patient safety in the management and delivery of blood and blood product transfusion.


Sujets)
COVID-19 , Formation au diplôme infirmier (USA) , Infirmières et infirmiers , Humains , Transfusion sanguine , Formation au diplôme infirmier (USA)/méthodes , Sécurité des patients , Compétence clinique
10.
BMC Health Serv Res ; 23(1): 483, 2023 May 13.
Article Dans Anglais | MEDLINE | ID: covidwho-2319919

Résumé

BACKGROUND: During the COVID-19 pandemic, health care had to find new ways to care for patients while reducing infection transmission. The role of telemedicine role has grown exponentially. METHODS: A questionnaire on experiences and satisfaction was sent to the staff of the Head and Neck Center of Helsinki University Hospital and to otorhinolaryngology patients treated remotely between March and June 2020. Additionally, patient safety incident reports were examined for incidents involving virtual visits. RESULTS: Staff (response rate 30.6%, (n = 116)) opinions seemed to be quite polarized. In general, staff felt virtual visits were useful for select groups of patients and certain situations, and beneficial in addition to face-to-face visits, not instead of them. Patients (response rate 11.7%, (n = 77)) gave positive feedback on virtual visits, with savings in time (average 89 min), distance travelled (average 31.4 km) and travel expenses (average 13.84€). CONCLUSIONS: While telemedicine was implemented during the COVID-19 pandemic to ensure patient treatment, its usefulness after the pandemic must be examined. Evaluation of treatment pathways is critical to ensure that quality of care is upheld while new treatment protocols are introduced. Telemedicine offers the opportunity to save environmental, temporal, and monetary resources. Nonetheless, the appropriate use of telemedicine is essential, and clinicians must be offered the option to examine and treat patients face-to-face.


Sujets)
COVID-19 , Télémédecine , Humains , COVID-19/épidémiologie , Pandémies , Sécurité des patients , Télémédecine/méthodes , Satisfaction des patients
11.
13.
BMC Med Educ ; 23(1): 235, 2023 Apr 12.
Article Dans Anglais | MEDLINE | ID: covidwho-2293236

Résumé

Identifying systems failures and contributing to a safety culture is the Association of American Colleges (AAMC's) thirteenth Entrustable Professional Activity (EPA). While most curricula teach Patient Safety (PS) and Quality Improvement (QI) principles, student participation in live QI/PS activities remains limited. This workshop enabled late Clerkship phase students to apply these Health Systems Science (HSS) principles to real adverse patient event cases through team-based simulation.This 3-h capstone included both a didactic review of QI, PS, and TeamSTEPPS® tools and an experiential component where student-led interactive small group discussions were augmented by resident and faculty preceptors. Collaboratively, students composed an adverse patient event report, conducted a Root Cause Analysis (RCA) during role-play, and proposed error prevention ideas after identifying systems problems. In April 2020, the in-person workshop became fully virtual due to the COVID-19 pandemic.A statistically significant increase in ability to identify Serious Safety Events, Escalation Chain of Command, and define a Plan-Do-Study-Act (PDSA) cycle was observed. Comfort with RCA increased from 48 to 87% and comfort with TeamSTEPPS® principles increased from 68% to 85.5%This novel capstone provided students with the tools to synthesize HSS concepts through problem-solving processes and recognize EPA 13's importance. Their increased capability to identify appropriate chain of command, escalate concerns, and recognize serious adverse patient events also has training and practice readiness implications.


Sujets)
COVID-19 , Internat et résidence , Humains , Amélioration de la qualité , Sécurité des patients , Pandémies , COVID-19/prévention et contrôle , Programme d'études
14.
JAMA ; 329(14): 1149-1150, 2023 04 11.
Article Dans Anglais | MEDLINE | ID: covidwho-2292146

Résumé

This Viewpoint discusses the need for clinicians to be involved in every stage of the development of patient safety interventions in order to not only improve patient care, but also maximize the interventions' effectiveness and ensure clinician well-being and buy-in.


Sujets)
Personnel de santé , Sécurité des patients , Satisfaction des patients , , Conception universelle , Humains , Personnel de santé/psychologie , Personnel de santé/normes
15.
Int J Qual Health Care ; 34(3)2022 Aug 30.
Article Dans Anglais | MEDLINE | ID: covidwho-2303322

Résumé

BACKGROUND: Health service administrators are continually investigating new ways to improve the safety and quality of health services. A positive and powerful relationship between employee engagement and patient safety has been suggested in the research literature, and steps can be taken by employers to enhance engagement to improve the safety of health services, particularly considering the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: The aim of this review was to explore the current literature on the impact of employee engagement on patient safety. METHODS: A review of peer-reviewed literature relating to the impact of employee engagement on patient safety within health services between January 2015 and May 2021 was conducted using Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline Complete, Scopus, Health Business Elite and Business Source Ultimate databases. A search of grey literature using the Bielefeld Academic Search Engine database was also completed. RESULTS: Of relevant articles, 3693 were identified, of which 15 studies were included in this review. Ten articles measured employee engagement using existing, validated tools, whereas patient safety was most frequently assessed through surveys seeking staff member's perceptions of safety or the quality of care they provide. Overall, there appeared to be a positive correlation between employee engagement and patient safety, but the strength of the relationship varied. CONCLUSION: Anecdotal accounts of improving employee engagement and improving patient safety abound, and the evidence reviewed appears in agreement. However, research into the impact of employee engagement on patient safety is in its early stages. As health service managers consider the best use of funding to support safe and high-quality care, evidence to support the positive impact employee engagement has on patient safety may be useful in managing the fallout from the COVID-19 pandemic.


Sujets)
COVID-19 , Sécurité des patients , COVID-19/épidémiologie , Humains , Pandémies , Qualité des soins de santé , Engagement dans le travail
16.
J Nurs Care Qual ; 38(3): 264-271, 2023.
Article Dans Anglais | MEDLINE | ID: covidwho-2263815

Résumé

BACKGROUND: Reporting a near-miss event has been associated with better patient safety culture. PURPOSE: To examine the relationship between patient safety culture and nurses' intention to report a near-miss event during COVID-19, and factors predicting that intention. METHODS: This mixed-methods study was conducted in a tertiary medical center during the fourth COVID-19 waves in 2020-2021 among 199 nurses working in COVID-19-dedicated departments. RESULTS: Mean perception of patient safety culture was low overall. Although 77.4% of nurses intended to report a near-miss event, only 20.1% actually did. Five factors predicted nurses' intention to report a near-miss event; the model explains 20% of the variance. Poor departmental organization can adversely affect the intention to report a near-miss event. CONCLUSIONS: Organizational learning, teamwork between hospital departments, transfers between departments, and departmental disorganization can affect intention to report a near-miss event and adversely affect patient safety culture during a health crisis.


Sujets)
COVID-19 , Incident critique en soins de santé , Personnel infirmier hospitalier , Humains , Intention , Enquêtes et questionnaires , Sécurité des patients , Gestion de la sécurité/méthodes , Culture organisationnelle
17.
J Patient Saf ; 19(4): 271-280, 2023 06 01.
Article Dans Anglais | MEDLINE | ID: covidwho-2267262

Résumé

BACKGROUND: The Ministry of Health and Family Welfare has introduced the "National Patient Safety Implementation Framework" to ensure the patient safety at different levels of healthcare delivery system. However, there is limited effort made in evaluating the implementation status of this framework. Hence, we have performed the process evaluation of National Patient Safety Implementation Framework across the public healthcare facilities in Tamil Nadu. METHODS: This was a facility-level survey conducted by research assistants who visited 18 public health facilities across 6 districts of Tamil Nadu, India, for the purpose of documenting the presence of structural support systems and strategies to promote patient safety. We developed a tool for data collection based on the framework. It comprised a total of 100 indicators under the following domains and subdomains: structural support, systems for reporting, workforce, infection prevention and control, biomedical waste management, sterile supplies, blood safety, injection safety, surgical safety, antimicrobial safety, and COVID-19 safety. RESULTS: Only one facility (subdistrict hospital) belonged to the high-performing category with a score of 79.5 on the implementation of patient safety practices. About 11 facilities (4 medical colleges and 7 Government Hospitals) belonging to medium-performing category. The best-performing medical college had a score of 61.5 for patient safety practices. Six facilities (2 medical colleges, 4 Government Hospitals) belonged to low-performing category in terms of patient safety. The least-performing facilities (both subdistrict hospitals) had scores of 29.5 and 26 for patient safety practices, respectively. Because of COVID-19, there was a positive effect on biomedical waste management and infectious disease safety across all facilities. Most performed poor in the domain with structural systems to support quality and efficiency of healthcare and patient safety. CONCLUSIONS: The study concludes that based on the current situation of patient safety practices in public health facilities, it will be difficult to perform full-fledged implementation of patient safety framework by the year 2025.


Sujets)
COVID-19 , Sécurité des patients , Humains , Inde , Recherche opérationnelle , Prestations des soins de santé
18.
BMJ Open Qual ; 12(1)2023 03.
Article Dans Anglais | MEDLINE | ID: covidwho-2254504

Résumé

BACKGROUND: The COVID-19 pandemic necessitated increased synchronous distance education (SDE) in graduate medical education, presenting challenges for Quality Improvement and Patient Safety (QIPS) best practices, which call for integration with daily clinical care and investigation of real patient safety events. OBJECTIVE: To evaluate educational outcomes for QIPS training after conversion of a mature, in-person curriculum to SDE. METHODS: 68 postgraduate year (PGY)-1 residents were surveyed before and after the SDE Culture of Patient Safety training in June 2020, and 59 PGY-2s were administered the Quality Improvement Knowledge Application Tool-Revised (QIKAT-R) before and after the SDE QIPS seminar series in July-August 2020. Values before and after training were compared using sign tests for matched pairs (PGY-1) and Wilcoxon signed-rank tests (PGY-2). RESULTS: 100% (68 of 68) of PGY-1s and 46% (27 of 59) of PGY-2s completed precourse and postcourse surveys. Before the course, 55 PGY-1s (81%) strongly agreed that submitting patient safety event reports are a physician's responsibility, and 63 (93%) did so after (15% increase, p=0.004). For PGY-2s, the median composite QIKAT-R score was 17 (IQR 14.5-20) before and 22.5 (IQR 20-24.5) after the seminars, with a median difference of 4.5 (IQR 1.5-7), a 32% increase in QIPS competency (p=0.001). CONCLUSIONS: Patient safety attitudes and quality improvement knowledge increased after SDE QIPS training at comparable levels to previously published results for in-person training, supporting SDE use in future hybrid curricula to optimise educational value and reach.


Sujets)
COVID-19 , Enseignement à distance , Internat et résidence , Humains , Amélioration de la qualité , Sécurité des patients , Pandémies/prévention et contrôle
19.
Trials ; 24(1): 254, 2023 Apr 04.
Article Dans Anglais | MEDLINE | ID: covidwho-2271555

Résumé

The COVID-19 pandemic has had an unprecedented and disruptive impact on people's health and lives worldwide. In addition to burdening people's health in the short-term in the form of infection, illness, and mortality, there has been an enormous negative impact on clinical research. Clinical trials experienced challenges in ensuring patient safety and enrolling new patients throughout the pandemic. Here, we investigate and quantify the negative impact that the COVID-19 pandemic has industry-sponsored clinical trials, both in the USA and worldwide. We find a negative correlation between the severity of the COVID-19 pandemic and clinical trial screening rate, with the relationship being strongest during the first three months of the pandemic compared to the entire duration of the pandemic. This negative statistical relationship holds across therapeutic areas, across states in the USA despite the heterogeneity of responses at the state-level, and across countries. This work has significant implications for the management of clinical trials worldwide in response to the fluctuating severity of COVID-19 moving forward and for future pandemics.


Sujets)
COVID-19 , Humains , Pandémies/prévention et contrôle , SARS-CoV-2 , Sécurité des patients
20.
ACS Biomater Sci Eng ; 9(3): 1656-1671, 2023 03 13.
Article Dans Anglais | MEDLINE | ID: covidwho-2271527

Résumé

As the world braces to enter its fourth year of the coronavirus disease 2019 (COVID-19) pandemic, the need for accessible and effective antiviral therapeutics continues to be felt globally. The recent surge of Omicron variant cases has demonstrated that vaccination and prevention alone cannot quell the spread of highly transmissible variants. A safe and nontoxic therapeutic with an adaptable design to respond to the emergence of new variants is critical for transitioning to the treatment of COVID-19 as an endemic disease. Here, we present a novel compound, called SBCoV202, that specifically and tightly binds the translation initiation site of RNA-dependent RNA polymerase within the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome, inhibiting viral replication. SBCoV202 is a Nanoligomer, a molecule that includes peptide nucleic acid sequences capable of binding viral RNA with single-base-pair specificity to accurately target the viral genome. The compound has been shown to be safe and nontoxic in mice, with favorable biodistribution, and has shown efficacy against SARS-CoV-2 in vitro. Safety and biodistribution were assessed using three separate administration methods, namely, intranasal, intravenous, and intraperitoneal. Safety studies showed the Nanoligomer caused no outward distress, immunogenicity, or organ tissue damage, measured through observation of behavior and body weight, serum levels of cytokines, and histopathology of fixed tissue, respectively. SBCoV202 was evenly biodistributed throughout the body, with most tissues measuring Nanoligomer concentrations well above the compound KD of 3.37 nM. In addition to favorable availability to organs such as the lungs, lymph nodes, liver, and spleen, the compound circulated through the blood and was rapidly cleared through the renal and urinary systems. The favorable biodistribution and lack of immunogenicity and toxicity set Nanoligomers apart from other antisense therapies, while the adaptability of the nucleic acid sequence of Nanoligomers provides a defense against future emergence of drug resistance, making these molecules an attractive potential treatment for COVID-19.


Sujets)
, COVID-19 , Génome viral , Nanomédecine , Nanostructures , Oligoribonucléotides , Acides nucléiques peptidiques , SARS-CoV-2 , SARS-CoV-2/effets des médicaments et des substances chimiques , SARS-CoV-2/génétique , COVID-19/virologie , /effets indésirables , /méthodes , Nanostructures/administration et posologie , Nanostructures/effets indésirables , Nanostructures/usage thérapeutique , Nanomédecine/méthodes , Sécurité des patients , Acides nucléiques peptidiques/administration et posologie , Acides nucléiques peptidiques/effets indésirables , Acides nucléiques peptidiques/pharmacocinétique , Acides nucléiques peptidiques/usage thérapeutique , Oligoribonucléotides/administration et posologie , Oligoribonucléotides/effets indésirables , Oligoribonucléotides/pharmacocinétique , Oligoribonucléotides/usage thérapeutique , Animaux , Souris , Souris de lignée BALB C , Techniques in vitro , Génome viral/effets des médicaments et des substances chimiques , Génome viral/génétique , Distribution tissulaire
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