Prospects and Challenges in Developing mRNA Vaccines for Infectious Diseases and Oncogenic Viruses.

mRNA vaccines have emerged as an optimistic technological platform for vaccine innovation in this new scientific era. mRNA vaccines have dramatically altered the domain of vaccinology by offering a versatile and rapid approach to combating infectious diseases and virus-induced cancers. Clinical trials have demonstrated efficacy rates of 94-95% in preventing COVID-19, and mRNA vaccines have been increasingly recognized as a powerful vaccine platform. Although mRNA vaccines have played an essential role in the COVID-19 pandemic, they still have several limitations; their instability and degradation affect their storage, delivery, and over-all efficiency. mRNA is typically enclosed in a transport mechanism to facilitate its entry into the target cell because it is an unstable and negatively charged molecule. For instance, mRNA that is given using lipid-nanoparticle-based vaccine delivery systems (LNPs) solely enters cells through endocytosis, establishing an endosome without damaging the cell membrane. The COVID-19 pandemic has accelerated the development of mRNA vaccine platforms used to treat and prevent several infectious diseases. This technology has the potential to change the future course of the disease by providing a safe and effective way to combat infectious diseases and cancer. A single-stranded genetic sequence found in mRNA vaccines instructs host cells to produce proteins inside ribosomes to elicit immunological responses and prepare the immune system to fight infections or cancer cells. The potential applications of mRNA vaccine technology are vast and can lead to the development of a preferred vaccine pattern. As a result, a new generation of vaccinations has gradually gained popularity and access to the general population. To adapt the design of an antigen, and even combine sequences from different variations in response to new changes in the viral genome, mRNA vaccines may be used. Current mRNA vaccines provide adequate safety and protection, but the duration of that protection can only be determined if further clinical research is conducted.

A measles-vectored vaccine candidate expressing prefusion-stabilized SARS-CoV-2 spike protein brought to phase I/II clinical trials: protection of African green monkeys from COVID-19 disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged at the end of 2019 and is responsible for the largest human pandemic in 100 years. Thirty-four vaccines are currently approved for use worldwide, and approximately 67% of the world population has received a complete primary series of one, yet countries are dealing with new waves of infections, variant viruses continue to emerge, and breakthrough infections are frequent secondary to waning immunity. Here, we evaluate a measles virus (MV)-vectored vaccine expressing a stabilized prefusion SARS-CoV-2 spike (S) protein (MV-ATU3-S2PΔF2A; V591) with demonstrated immunogenicity in mouse models (see companion article [J. Brunet, Z. Choucha, M. Gransagne, H. Tabbal, M.-W. Ku et al., J Virol 98:e01693-23, 2024, https://doi.org/10.1128/jvi.01693-23]) in an established African green monkey model of disease. Animals were vaccinated with V591 or the control vaccine (an equivalent MV-vectored vaccine with an irrelevant antigen) intramuscularly using a prime/boost schedule, followed by challenge with an early pandemic isolate of SARS-CoV-2 at 56 days post-vaccination. Pre-challenge, only V591-vaccinated animals developed S-specific antibodies that had virus-neutralizing activity as well as S-specific T cells. Following the challenge, V591-vaccinated animals had lower infectious virus and viral (v) RNA loads in mucosal secretions and stopped shedding virus in these secretions earlier. vRNA loads were lower in these animals in respiratory and gastrointestinal tract tissues at necropsy. This correlated with a lower disease burden in the lungs as quantified by PET/CT at early and late time points post-challenge and by pathological analysis at necropsy.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the largest human pandemic in 100 years. Even though vaccines are currently available, countries are dealing with new waves of infections, variant viruses continue to emerge, breakthrough infections are frequent, and vaccine hesitancy persists. This study uses a safe and effective measles vaccine as a platform for vaccination against SARS-CoV-2. The candidate vaccine was used to vaccinate African green monkeys (AGMs). All vaccinated AGMs developed robust antigen-specific immune responses. After challenge, these AGMs produced less virus in mucosal secretions, for a shorter period, and had a reduced disease burden in the lungs compared to control animals. At necropsy, lower levels of viral RNA were detected in tissue samples from vaccinated animals, and the lungs of these animals lacked the histologic hallmarks of SARS-CoV-2 disease observed exclusively in the control AGMs.

Review: N1-methyl-pseudouridine (m1Ψ): Friend or foe of cancer?

Due to the health emergency created by SARS-CoV-2, the virus that causes the COVID-19 disease, the rapid implementation of a new vaccine technology was necessary. mRNA vaccines, being one of the cutting-edge new technologies, attracted significant interest and offered a lot of hope. The potential of these vaccines in preventing admission to hospitals and serious illness in people with comorbidities has recently been called into question due to the vaccines' rapidly waning immunity. Mounting evidence indicates that these vaccines, like many others, do not generate sterilizing immunity, leaving people vulnerable to recurrent infections. Additionally, it has been discovered that the mRNA vaccines inhibit essential immunological pathways, thus impairing early interferon signaling. Within the framework of COVID-19 vaccination, this inhibition ensures an appropriate spike protein synthesis and a reduced immune activation. Evidence is provided that adding 100 % of N1-methyl-pseudouridine (m1Ψ) to the mRNA vaccine in a melanoma model stimulated cancer growth and metastasis, while non-modified mRNA vaccines induced opposite results, thus suggesting that COVID-19 mRNA vaccines could aid cancer development. Based on this compelling evidence, we suggest that future clinical trials for cancers or infectious diseases should not use mRNA vaccines with a 100 % m1Ψ modification, but rather ones with the lower percentage of m1Ψ modification to avoid immune suppression.

Knowledge, attitudes, and practices toward COVID-19 and its prevention among medical and dental students in an educational institution in Telangana.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged as a global pandemic, threatening millions of lives worldwide. Everyone was overwhelmed by the plethora of information from different sources, creating confusion, misconceptions, and panic in the community. AIMS: This study aimed to estimate the knowledge, attitudes, and practices (KAP) among medical and dental students toward COVID-19 and to identify factors influencing them. MATERIALS AND METHODS: A cross-sectional study was conducted among undergraduate students enrolled in MBBS and BDS courses, and KAP scores were calculated using a self-administered questionnaire. The statistical analysis was done by unpaired t test and one-way analysis of variance. RESULTS: MBBS students had higher KAP scores when compared with BDS students. Knowledge gaps were discovered in the areas of COVID-19 transmission through blood, World Health Organization (WHO)-designated variants of concern, disinfectant usage, and mandatory vaccination. A majority (91.33%) of the students had a positive attitude toward COVID-19. Better knowledge and practice scores were significantly associated with vaccinated students and those who trusted government website resources. CONCLUSION: Curriculum modifications and creative teaching strategies can fill the lacunae in the KAP scores. Medical and dental students, as torchbearers of the healthcare fraternity, can play a critical role in raising awareness during public health emergencies.

Re-inventing protection in a post-pandemic world: A new aerodynamic endonasal filtration technology.

Is there a "missing device" for respiratory personal protection? Does it exist an easy-to-use device, allowing extensive use in everyday settings by the population, maximizing tolerability and low visual and physical invasiveness protecting from a wide range of threats including airborne pathogens, hence including the particle range of fine and ultrafine particles? Looking at the recent past, in the urgency of finding ready-to-use solutions for the respiratory protection of the population during the outbreak of the SARS-CoV-2 pandemic, devices for occupational safety have been used, such as filtering face masks. These are devices intended for workers operating during work shifts in environments characterized by potential high risk, known a priori, often directly sensible; this makes wearers motivated to tolerate discomfort for a given period to face a localized risk, and safety managers determined to supervise compliance with usage specifications. Their use by general population has implied known shortcomings, such as weak compatibility with relational work and activities, low tolerability during prolonged use, low compliance with the proper use of the device, all of this lessening actual protection. The need for a new perspective has emerged, targeting effectiveness in whole daily life, rather than punctual efficacy. Nasal filters are promising candidates to protect individuals throughout the day during the most varied activities, but they lack a systematic definition as a device and as a product; it follows that the high complexity needed to reach an effective performance envelop is generally underestimated. By reviewing available literature, the present paper draws on the experience from the pandemic and infers systematic product specifications and characterization methods for a new, effective personal respiratory protection device; these specifications are compared with the stringent constraints associated with the endonasal applications and, based on air filtration state of the art, quantifies the need for technology disruption and outlining possible new development paths.

Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported at the end of 2019 as a worldwide health concern causing a pandemic of unusual viral pneumonia and many other organ damages, which was defined by the World Health Organization as coronavirus disease 2019 (COVID-19). The pandemic is considered a significant threat to global public health till now. In this review, we have summarized the lessons learnt during the emergence and spread of SARS-CoV-2, including its prototype and variants. The overall clinical features of variants of concern (VOC), heterogeneity in the clinical manifestations, radiology and pathology of COVID-19 patients are also discussed, along with advances in therapeutic agents.

Outcomes of vaccinated versus unvaccinated COVID-19 patients in Israel during the Omicron and Delta waves—A retrospective cohort study / Resultados de pacientes con COVID-19 vacunados vs. no vacunados en Israel durante las olas de ómicron y delta: Un estudio de cohorte retrospectivo

Introduction Initiation of global vaccination significantly reduced the morbidity and mortality of COVID-19. During the Omicron wave, approximately 70% of the Israeli adult population was fully vaccinated, but the efficacy of the vaccine was questioned. Methods We conducted a retrospective cohort study of all adult patients admitted to the COVID-19 departments in Rabin Medical Center, during the Delta wave and the Omicron wave. Patients were matched in the 2 waves using the inverse probability of treatment weighting (IPTW) method and risk for mechanical ventilation and 30-day all-cause mortality was assessed. Results Vaccination had a significant effect on 30-day mortality in the Delta and Omicron waves with adjusted OR of 0.35 (0.17–0.70) and 0.5 (0.27–0.95) respectively. Nonetheless, the rate of mechanical ventilation was similar between the groups with OR of 0.75 (0.52–1.09) and 0.64 (0.40–1.01). Vaccination status did not change the length of admission in both waves. Conclusion We observed a decreased risk for 30-day mortality among vaccinated patients during the Delta and Omicron waves in Israel. This association, even though consistent, was of a lesser magnitude during the Omicron wave (AU)

Introducción La iniciación de la vacunación global redujo significativamente la morbilidad y la mortalidad de la COVID-19. Durante la ola de ómicron, aproximadamente 70% de la población adulta israelí estaba completamente vacunada, pero se cuestionó la eficacia de la vacuna. Métodos Realizamos un estudio de cohorte retrospectivo de todos los pacientes adultos ingresados en los departamentos de COVID-19 en el Centro Médico Rabin, durante las olas de delta y ómicron. Los pacientes fueron emparejados en las dos olas utilizando el método de ponderación inversa de probabilidad de tratamiento (IPTW) y se evaluó el riesgo de ventilación mecánica y la mortalidad por todas las causas a los 30 días. Resultados La vacunación tuvo un efecto significativo en la mortalidad a los 30 días en las olas de delta y ómicron con odds ratio (OR) ajustadas de 0,35 (0,17-0,70) y 0,5 (0,27-0,95), respectivamente. Sin embargo, la tasa de ventilación mecánica fue similar entre los grupos con OR de 0,75 (0,52-1,09) y 0,64 (0,40-1,01). El estado de vacunación no cambió la duración del ingreso en ambas olas.Conclusión Observamos un menor riesgo de mortalidad a los 30 días entre los pacientes vacunados durante las olas de delta y ómicron en Israel. Esta asociación, aunque constante, fue de menor magnitud durante la ola de ómicron (AU)

[Surgical treatment of COVID-19 patients during the pandemic]. / Opyt khirurgicheskogo lecheniya patsientov s COVID-19 v period pandemii.

OBJECTIVE: To analyze the results of emergency surgery in COVID-19 patients with viral pneumonia. MATERIAL AND METHODS: A retrospective study included 75 COVID-19 patients who underwent emergency surgical interventions. Comorbidities included cardiac diseases, nonspecific lung diseases, type 2 diabetes, kidney diseases, overweight, and cancer. Various combinations of these diseases were also noted. RESULTS: We carried out emergency surgeries for abdominal, thoracic, soft tissue and venous diseases. Postoperative mortality was 42.6%. The best results were obtained after minimally invasive interventions without mechanical ventilation. Extended surgery with mechanical ventilation was followed by fast progression of pneumonia according to clinical and CT data. CONCLUSION: Surgical interventions undoubtedly worsen prognosis of treatment in patients with COVID-19. Emergency minimally invasive surgery without mechanical ventilation can reduce the risk of unfavorable outcomes in patients with viral pneumonia, especially in case of concomitant cancer and other severe comorbidities.

Impacto del periodo de confinamiento por la pandemia COVID-19 en España sobre la salud y la atención recibida por los niños, niñas y jóvenes con discapacidad originada en la infancia / The impact of COVID-19 lockdown on the health and care of children and adolescents with a childhood-onset disability

Introducción Durante el periodo inicial del confinamiento por la COVID-19 se tomaron una serie de medidas de restricción que modificaron el día a día de la población. En este estudio se buscó conocer el impacto de este periodo en la salud física y mental de niños y jóvenes con discapacidad originada en la infancia, y de sus familias, y describir los cambios que se produjeron en el acceso a la educación y a los servicios de salud. Material y métodos Se realizó un estudio analítico observacional y transversal. Los datos se obtuvieron mediante una encuesta electrónica a través de una plataforma online realizada por la Academia Europea de Discapacidad Infantil. La encuesta incluyó preguntas sobre cuatro bloques temáticos: características sociodemográficas y de salud, impacto del confinamiento en la salud y bienestar, acceso a la educación y a los servicios de salud. Resultados Se obtuvieron 145 respuestas. El 45,5% de los niños y jóvenes eran totalmente dependientes. Se percibió un impacto sobre su salud física (54,5%), mental (47,6%) y sobre ambas (32%), mayores niveles de estrés (68,3%) y problemas de sueño (41,4%), así como una sobrecarga muy elevada en el 84,8% de los progenitores, sobre todo en familias de niños con mayor nivel de dependencia (p<0,001). El 55% de los niños y jóvenes no recibieron ningún tratamiento durante este periodo, ni siquiera remoto. Conclusiones El confinamiento afectó en gran medida la salud física y mental, así como a los servicios recibidos por los niños y jóvenes con discapacidad y sus familias (AU)

Introduction During the initial period of COVID-19 lockdown, restriction measures modified the day-to-day life of the population. This study sought to know the impact of this period on the physical and mental health of children and young people with disabilities originating in childhood, and their families, and to describe the changes that occurred in access to education and health services. Material and methods An observational and cross-sectional analytical study was carried out. The data were obtained by means of an electronic survey through an online platform carried out by the European Academy of Childhood Disability. The survey included questions on four thematic blocks: sociodemographic and health characteristics, impact of lock down on health and well-being, and access to education and health services. Results One hundred and forty-five responses were obtained. 45.5% of the children and young people were totally dependent. There was an impact on their physical (54.5%), mental health (47.6%) and both (32%), higher levels of stress (68.3%), and sleep problems (41.4%), as well as a high burden in 84.8% of parents, especially in families of children with a higher level of dependency (P=.00). 55% of children and young people did not receive any treatment during this period, not even remotely. Conclusions COVID lock down period greatly affected physical and mental health, as well as the services for children and young people with disabilities and their families (AU)

Fall of viral and bacterial pneumonia hospitalizations following COVID-19 pandemic mitigation strategies: a central Italian Region retrospective study.

Community-Acquired Pneumonia (CAP) represents one of the first causes of hospitalization and death in the elderly all over the world and weighs heavily on public health system. Since the beginning of the COVID-19 (CoronaVirus Disease-19) pandemic, everybody's behavior was forced to change, as the result of a global lockdown strategy and the obligation of using personal protection equipment (PPE). We aimed to evaluate how the mitigation strategies adopted to fight SARS-CoV-2 (Severe Acute Respiratory Coronavirus Syndrome 2) infection have influenced hospitalizations due to CAP in two different Local Health Boards (LHBs) of central Italy. We considered two main periods of observation: before and after the national start of lockdown, in two Abruzzo's LHBs. We analyzed 19,558 hospital discharge records of bacterial and viral CAP. Excluding SARS-CoV2 infection, a significant decrease in CAP hospitalizations was observed. Through the analysis of Diagnosis Related Group (DRG) values, we highlighted a significant saving of founds for the Regional Health Service. The enactment of social distancing measures to contain COVID-19 spread, brought down admissions for bacterial and viral pneumonia. Our study emphasizes that costs for hospitalizations due to CAP could be drastically reduced by mask wearing and social distancing.

Farmacovigilancia de las vacunas frente a COVID-19 en farmacias comunitarias. Resultados tras la primera dosis / Pharmacovigilance of vaccines against COVID-19 in community pharmacies. Results with the first dose

Objetivos: detección, notificación y seguimiento de sospechas de reacciones adversas (RA) tras la administración de la primera dosis de la vacuna frente a la COVID-19 en usuarios de las farmacias comunitarias y su repercusión sobre la salud y vida diaria. Métodos: diseño: observacional prospectivo. Sujetos: personas vacunadas frente a la COVID-19, mayores de edad, que firmaron el consentimiento informado. Variables: número y porcentaje de participantes que presentaban al menos una RA. Número, tipo y frecuencia de posible reactividad. Repercusión en su vida diaria. El estudio fue aprobado por el CEIm-G (Exp. 2021-007).Resultados: colaboraron 10 farmacias de Pontevedra y 2 de Ourense. 781 casos, 488 (62,5 %) mujeres. Edad 56,8 (DE=17,9) años. 389 (49,8 %) en grupo de riesgo.495 (63,4 %) vacunados, 321 mujeres (65,8 %) y 174 (59,4 %) hombres refirieron al menos una RA: 236 (53,0 %) frente a Comirnaty®, 157 (82,6 %) a Vaxzevria®, 69 (66,3 %) a Spikevax® y 33 (80,5) a Janssen®.Se registraron 1.367 RA, 1,8 por persona vacunada. Las más prevalentes (el % es sobre el total de pacientes): dolor en punto de inyección 375 (48,0 %), cansancio/fatiga 170 (21,8 %), escalofríos 118 (15,1 %), cefalea 117 (15,0 %), dolor muscular 112 (14,3 %) y fiebre 98 (12,5 %). De los 495 encuestados con RA, necesitaron ayuda profesional 77 (15,6 %): del médico de familia 30 (39,0 %), 9 (11,7 %) en servicio de urgencias, 1 (1,3 %) en hospital y 37 (48,1 %) en la farmacia. A 118 (15,1 %) les impidió desarrollar su actividad diaria.Se comunicaron las RA que refirieron 264 vacunados (53,3 %).Conclusiones: el número de vacunados que manifestaron haber sufrido RA fue alto. Dolor en el punto de inyección fue la RA más prevalente. La mitad fueron atendidos en la farmacia. Aunque fueron en general leves, afectaron notablemente a su vida diaria. (AU)

Pathogen evolution, prevention/control strategy and clinical features of COVID-19: experiences from China / 医学前沿

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported at the end of 2019 as a worldwide health concern causing a pandemic of unusual viral pneumonia and many other organ damages, which was defined by the World Health Organization as coronavirus disease 2019 (COVID-19). The pandemic is considered a significant threat to global public health till now. In this review, we have summarized the lessons learnt during the emergence and spread of SARS-CoV-2, including its prototype and variants. The overall clinical features of variants of concern (VOC), heterogeneity in the clinical manifestations, radiology and pathology of COVID-19 patients are also discussed, along with advances in therapeutic agents.

Telerrehabilitación en personas con enfermedad cardiovascular durante el periodo de aislamiento preventivo obligatorio por COVID-19 en Colombia / Telerehabilitation in people with cardiovascular disease during the period of compulsory preventive isolation by COVID-19 in Colombia

Introducción: La enfermedad cardiovascular es una de las principales causas de morbimortalidad a nivel mundial. Como resultado de la pandemia de COVID-19, muchos programas de rehabilitación han pasado a modelos de entrega remota. La telerrehabilitación es una forma de realizar rehabilitación cardiaca mientras se reduce el riesgo de transmisión del COVID-19. Objetivo Describir los efectos de un programa de ejercicio terapéutico en personas con enfermedad cardiovascular que realizan telerrehabilitación, en el periodo de aislamiento preventivo obligatorio por COVID-19. Materiales y métodos Estudio cuasiexperimental, de 6 meses, en personas con enfermedad cardiovascular que ingresaron a un programa de ejercicio terapéutico asistido por tecnología virtual en una clínica de Cali (Colombia). Resultados De 31 personas, 21 eran hombres. La edad promedio fue de 60,48±11,21 años. Se encontraron diferencias significativas al inicio y al final del estudio en las variables de fracción de eyección del ventrículo izquierdo, frecuencia cardiaca, presión arterial, frecuencia respiratoria, índice de masa corporal, perímetro de abdomen, porcentaje de grasa, porcentaje de masa muscular, colesterol, estado de depresión, distancia recorrida, consumo de oxígeno e índice metabólico (MET), con p<0,05. Conclusión Un programa de ejercicio terapéutico en personas con enfermedad cardiovascular que realizan telerrehabilitación resulta eficaz, al alcanzar las metas de tratamiento (AU)

Introduction: Cardiovascular disease is one of the leading causes of morbidity and death globally. As a result of the COVID-19 pandemic, many rehabilitation programs have shifted to remote delivery models. Telerehabilitation is a way to perform cardiac rehabilitation while reducing the risk of COVID-19 transmission. Objective This study aimed to describe the effects of a physical exercise program in persons with cardiovascular disease who performed telerehabilitation in the period of mandatory preventive isolation due to the COVID-19 emergency. Materials and methods This was a quasiexperimental 6-month study of persons with cardiovascular disease who entered a virtual technology-assisted physical exercise program in a clinic in Cali, Colombia. Results Significant differences were found at the beginning and end of the study in the variables of left ventricular ejection fraction, heart rate, blood pressure, respiratory rate, body mass index, abdominal perimeter, percentage of fat, percentage of muscle mass, cholesterol, state of depression, distance traveled, oxygen consumption and metabolic equivalent (METs), showing p-value <0.05. Conclusions A physical exercise program in persons with cardiovascular disease performing telerrehabilitation proves effective in achieving treatment goals (AU)