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.

[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.

Impact of Vaccination in the Rate of COVID-19 Staff Infection in an Acute Inpatient Rehabilitation Facility.

ABSTRACT: This brief report summarizes the comparative experience of an inpatient rehabilitation facility dealing with two episodes of COVID-19 infection, one before and one after the availability of vaccination, which was deployed to staff. The experience exemplifies the high rate of infection and potential for asymptomatic presentation of COVID-19 as well as the protective advantage of the vaccine for healthcare workers in this report. With a significant reduction in the rate of infection, from nearly 30% before vaccination to only 2.5% after vaccination. The data presented should serve as an encouragement for vaccination across all populations.

Protectins PCTR1 and PD1 Reduce Viral Load and Lung Inflammation During Respiratory Syncytial Virus Infection in Mice.

Viral pneumonias are a major cause of morbidity and mortality, owing in part to dysregulated excessive lung inflammation, and therapies to modulate host responses to viral lung injury are urgently needed. Protectin conjugates in tissue regeneration 1 (PCTR1) and protectin D1 (PD1) are specialized pro-resolving mediators (SPMs) whose roles in viral pneumonia are of interest. In a mouse model of Respiratory Syncytial Virus (RSV) pneumonia, intranasal PCTR1 and PD1 each decreased RSV genomic viral load in lung tissue when given after RSV infection. Concurrent with enhanced viral clearance, PCTR1 administration post-infection, decreased eosinophils, neutrophils, and NK cells, including NKG2D+ activated NK cells, in the lung. Intranasal PD1 administration post-infection decreased lung eosinophils and Il-13 expression. PCTR1 increased lung expression of cathelicidin anti-microbial peptide and decreased interferon-gamma production by lung CD4+ T cells. PCTR1 and PD1 each increased interferon-lambda expression in human bronchial epithelial cells in vitro and attenuated RSV-induced suppression of interferon-lambda in mouse lung in vivo. Liquid chromatography coupled with tandem mass spectrometry of RSV-infected and untreated mouse lungs demonstrated endogenous PCTR1 and PD1 that decreased early in the time course while cysteinyl-leukotrienes (cys-LTs) increased during early infection. As RSV infection resolved, PCTR1 and PD1 increased and cys-LTs decreased to pre-infection levels. Together, these results indicate that PCTR1 and PD1 are each regulated during RSV pneumonia, with overlapping and distinct mechanisms for PCTR1 and PD1 during the resolution of viral infection and its associated inflammation.

Tobacco use, tuberculosis and Covid-19: A lethal triad.

Smoking, TB and Covid-19 are high prevalence entities with public health consequences. All three of them have a possible complex interaction at cellular level. Smoking behavior makes it difficult to maintain infection control measures. Smoking is known to increase TB infection and also adversely affect treatment outcomes in TB. There is also upcoming evidence which suggests that smoking and TB increase the risk of severe Covid-19 symptoms. Simple infection control measures like, social distancing, cough etiquette, isolation, hand hygiene, quarantine, use of masks etc. play a pivotal role in prevention of these diseases. There is need of strengthening of the public health policies and incorporation of the Covid-19 safety awareness measures into the various national programmes.

Design of optical cavity for air sanification through ultraviolet germicidal irradiation.

The transmission of airborne pathogens represents a major threat to worldwide public health. Ultraviolet light irradiation can contribute to the sanification of air to reduce the pathogen transmission. We have designed a compact filter for airborne pathogen inactivation by means of UVC LED sources, whose effective irradiance is enhanced thanks to high reflective surfaces. We used ray-tracing and computational fluid dynamic simulations to model the device and to maximize the performance inside the filter volume. Simulations also show the inhibition of SARS-Cov-2 in the case of high air fluxes. This study demonstrates that current available LED technology is effective for air sanification purposes.

Monoclonal Antibodies vs COVID-19: Eduardo Ojito-Magaz MS General Director, Molecular Immunology Center.

Cuba has five COVID-19 vaccines in clinical trials and is on track to receive emergency use authorization from the country's regulatory agency to begin mass vaccination with two of those candidates: Abdala and SOBERANA 02. Results from phase 1 and 2 trials of these vaccines, the first developed and produced in Latin America, have been encouraging, both in terms of safety and immunogenicity. The ongoing phase 3 trials will continue to look at safety, together with efficacy; parallel intervention studies involving over a million people in Havana will begin generating data on effectiveness. Coordination between Cuba's biotechnology sector and its public health system-particularly throughout the different levels of primary care-to control and treat COVID-19 is a cornerstone of the Cuban strategy and one that could serve as a blueprint for future pandemics. Another Cuban product, itolizumab, is showing positive results mitigating cytokine release syndrome (CRS) in COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Developed in collaboration with Biocon (India), itolizumab is administered under an expanded access program to treat vulnerable populations in Cuba. Marshaling complementary capacities of dozens of institutions belonging to BioCubaFarma-the country's biotech conglomerate-and developing therapies, vaccines and medical technologies together, is another cornerstone of Cuba's strategy to combat COVID-19 and improve population health. The Molecular Immunology Center (CIM) is a key player in this strategy. Founded in 1992, CIM is a powerhouse in monoclonal antibody research and production, with 6 registered products and 22 in the pipeline. Known for several novel therapeutic cancer treatments, CIM has over two decades' experience producing complex recombinant proteins in mammalian cells on an industrial scale. Once Cuba's Innovation Committee (convened in January 2020 as part of the National COVID-19 Prevention & Control Plan) determined Cuban researchers would pursue protein subunit vaccine candidates, they turned to CIM to produce the required receptor-binding domain (RBD) of the SARS-CoV-2 spike protein, among other responsibilities. CIM's General Director, Dr Eduardo Ojito-Magaz, is a chemical engineer and holds a master's degree in biotechnology. He spoke with MEDICC Review just days before 1.7 million Havana residents began participating in the country's largest intervention study with the COVID-19 vaccines his center helped make possible.

Association of Tracheostomy With Outcomes in Patients With COVID-19 and SARS-CoV-2 Transmission Among Health Care Professionals: A Systematic Review and Meta-analysis.

Importance: Approximately 5% to 15% of patients with COVID-19 require invasive mechanical ventilation (IMV) and, at times, tracheostomy. Details regarding the safety and use of tracheostomy in treating COVID-19 continue to evolve. Objective: To evaluate the association of tracheostomy with COVID-19 patient outcomes and the risk of SARS-CoV-2 transmission among health care professionals (HCPs). Data Sources: EMBASE (Ovid), Medline (Ovid), and Web of Science from January 1, 2020, to March 4, 2021. Study Selection: English-language studies investigating patients with COVID-19 who were receiving IMV and undergoing tracheostomy. Observational and randomized clinical trials were eligible (no randomized clinical trials were found in the search). All screening was performed by 2 reviewers (P.S. and M.L.). Overall, 156 studies underwent full-text review. Data Extraction and Synthesis: We performed data extraction in accordance with Meta-analysis of Observational Studies in Epidemiology guidelines. We used a random-effects model, and ROBINS-I was used for the risk-of-bias analysis. Main Outcomes and Measures: SARS-CoV-2 transmission between HCPs and levels of personal protective equipment, in addition to complications, time to decannulation, ventilation weaning, and intensive care unit (ICU) discharge in patients with COVID-19 who underwent tracheostomy. Results: Of the 156 studies that underwent full-text review, only 69 were included in the qualitative synthesis, and 14 of these 69 studies (20.3%) were included in the meta-analysis. A total of 4669 patients were included in the 69 studies, and the mean (range) patient age across studies was 60.7 (49.1-68.8) years (43 studies [62.3%] with 1856 patients). We found that in all studies, 1854 patients (73.8%) were men and 658 (26.2%) were women. We found that 28 studies (40.6%) investigated either surgical tracheostomy or percutaneous dilatational tracheostomy. Overall, 3 of 58 studies (5.17%) identified a small subset of HCPs who developed COVID-19 that was associated with tracheostomy. Studies did not consistently report the number of HCPs involved in tracheostomy. Among the patients, early tracheostomy was associated with faster ICU discharge (mean difference, 6.17 days; 95% CI, -11.30 to -1.30), but no change in IMV weaning (mean difference, -2.99 days; 95% CI, -8.32 to 2.33) or decannulation (mean difference, -3.12 days; 95% CI, -7.35 to 1.12). There was no association between mortality or perioperative complications and type of tracheostomy. A risk-of-bias evaluation that used ROBINS-I demonstrated notable bias in the confounder and patient selection domains because of a lack of randomization and cohort matching. There was notable heterogeneity in study reporting. Conclusions and Relevance: The findings of this systematic review and meta-analysis indicate that enhanced personal protective equipment is associated with low rates of SARS-CoV-2 transmission during tracheostomy. Early tracheostomy in patients with COVID-19 may reduce ICU stay, but this finding is limited by the observational nature of the included studies.

Reporte de situación COVID-19 Cuba No. 60 (5 de abril de 2020) / COVID-19 Cuba Situation Report No. 60 (April 5, 2020)

Cuba ya produce lotes monodosis que no contienen tiomersal de los tres candidatos vacunales Soberana contra la COVID-19, de modo que puedan beneficiarse personas que son alérgicas a esta sustancia, y que, en los actuales ensayos clínicos, quedan fuera por esta causa. También con el candidato vacunal Abdala se está trabajando a escala productiva en vacunas que no contendrán tiomersal, para utilizarlas en etapas futuras del desarrollo clínico. El candidato vacunal Mambisa es un spray nasal y el bulbo no contiene esa sustancia.

ÁNCASH: fortaleciendo la respuesta del gobierno nacional y regional a la emergencia por COVID-19 / ANCASH: strengthening the national and regional government response to the COVID-19 emergency

El trabajo en conjunto de la Organización Panamericana de la Salud, el Programa Mundial de Alimentos, el Estado y la sociedad civil ha sido muy valioso. Se estableció una dinámica cercana, fluida y de permanente retroalimentación con la DIRESA Áncash, que permitió que el personal de salud aproveche de la mejor manera la asistencia técnica. El componente tecnológico del proyecto fue innovador y muy útil. La introducción de herramientas tecnológicas, como la Sala de Situación Interactiva y el aplicativo móvil Alerta COVID, han permitido tener información en tiempo real del comportamiento de la enfermedad en la región. Implementar un plan de trabajo con la participación activa de los agentes comunitarios de salud fue determinante, porque reforzaron los mensajes de conductas saludables, la vigilancia sanitaria y fueron el nexo entre la comunidad y el servicio de salud. La entrega de bonos y kits de higiene permitió que la población vulnerable pueda mantener una cuarentena en aislamiento con las necesidades básicas cubiertas.

Rueda de prensa semanal sobre COVID-19: palabras de apertura de la directora, 14 de abril de 2021 / Weekly Press Conference on COVID-19: Opening Remarks from the Director, April 14, 2021

Permítanme comenzar abordando la erupción del volcán La Soufrière en San Vicente y las Granadinas. Quiero señalar que la OPS ha desplegado a cinco expertos en salud pública en San Vicente y las Granadinas, y que estamos respondiendo a la emergencia de forma coordinada con el Ministerio de Salud y con el apoyo de los asociados.

Rueda de prensa semanal sobre COVID-19: palabras de apertura de la directora, 21 de abril de 2021 / Weekly Press Conference on COVID-19: Opening Remarks from the Director, April 21, 2021

En la última semana, se notificaron más de 1,5 millones de nuevos casos de COVID-19 y casi 40.000 muertes a causa del virus en la Región de las Américas.

Rueda de prensa semanal sobre COVID-19: palabras de apertura de la directora, 28 de abril de 2021 / Weekly Press Conference on COVID-19: Opening Remarks from the Director, April 28, 2021

La semana pasada, más de 1,4 millones de personas contrajeron la COVID-19 y más de 36.000 personas murieron a causa del virus en la Región de las Américas. De hecho, de todas las muertes debidas a la COVID-19 notificadas en el mundo la semana pasada, una de cada cuatro se produjo en la Región de las Américas.

Clinical and Economic Effects of Widespread Rapid Testing to Decrease SARS-CoV-2 Transmission.

BACKGROUND: The value of frequent, rapid testing to reduce community transmission of SARS-CoV-2 is poorly understood. OBJECTIVE: To define performance standards and predict the clinical, epidemiologic, and economic outcomes of nationwide, home-based antigen testing. DESIGN: A simple compartmental epidemic model that estimated viral transmission, portrayed disease progression, and forecast resource use, with and without testing. DATA SOURCES: Parameter values and ranges as informed by Centers for Disease Control and Prevention guidance and published literature. TARGET POPULATION: U.S. population. TIME HORIZON: 60 days. PERSPECTIVE: Societal; costs included testing, inpatient care, and lost workdays. INTERVENTION: Home-based SARS-CoV-2 antigen testing. OUTCOME MEASURES: Cumulative infections and deaths, number of persons isolated and hospitalized, and total costs. RESULTS OF BASE-CASE ANALYSIS: Without a testing intervention, the model anticipates 11.6 million infections, 119 000 deaths, and $10.1 billion in costs ($6.5 billion in inpatient care and $3.5 billion in lost productivity) over a 60-day horizon. Weekly availability of testing would avert 2.8 million infections and 15 700 deaths, increasing costs by $22.3 billion. Lower inpatient outlays ($5.9 billion) would partially offset additional testing expenditures ($12.5 billion) and workdays lost ($14.0 billion), yielding incremental cost-effectiveness ratios of $7890 per infection averted and $1 430 000 per death averted. RESULTS OF SENSITIVITY ANALYSIS: Outcome estimates vary widely under different behavioral assumptions and testing frequencies. However, key findings persist across all scenarios, with large reductions in infections, mortality, and hospitalizations. Costs per death averted are roughly an order of magnitude lower than commonly accepted willingness-to-pay values per statistical life saved ($5 to $17 million). LIMITATIONS: Analysis was restricted to at-home testing. There are uncertainties concerning test performance. CONCLUSION: High-frequency home testing for SARS-CoV-2 with an inexpensive, imperfect test could contribute to pandemic control at justifiable cost and warrants consideration as part of a national containment strategy. PRIMARY FUNDING SOURCE: National Institutes of Health.

Low Doses of Radiation Increase the Immunosuppressive Profile of Lung Macrophages During Viral Infection and Pneumonia.

PURPOSE: Severe pneumonia and acute respiratory distress syndrome (ARDS) have been described in patients with severe coronavirus disease 2019 (COVID-19). Recently, early clinical data reported the feasibility of low doses of radiation therapy (RT) in the treatment of ARDS in patients with severe COVID-19. However, the involved mechanisms remained unknown. METHODS AND MATERIALS: Here, we used airways-instilled lipopolysaccharide (LPS) and influenza virus (H1N1) as murine models of pneumonia, and toll-like receptor (TLR)-3 stimulation in human lung macrophages. RESULTS: Low doses of RT (0.5-1 Gray) decreased LPS-induced pneumonia, and increased the percentage of nerve- and airway-associated macrophages producing interleukin (IL) 10. During H1N1 viral infection, we observed decreased lung tissue damage and immune cell infiltration in irradiated animals. Low doses of RT increased IL-10 production by infiltrating immune cells into the lung. Irradiation of TLR-3 ligand-stimulated human lung macrophages ex vivo increased IL-10 secretion and decreased interferon γ production in the culture supernatant. The percentage of human lung macrophages producing IL-6 was also decreased. CONCLUSIONS: Our data highlight a mechanism by which low doses of RT regulate lung inflammation and skew lung macrophages toward an anti-inflammatory profile. These data provide a preclinical mechanistic support to clinical trials evaluating low doses of RT, such as COVID-19-induced ARDS.

Comunicación de riesgos y participación comunitaria para la localización de contactos en el contexto de la COVID-19 / Risk communication and community engagement for COVID-19 contact tracing: interim guidance

La localización de contactos es un elemento clave del enfoque recomendado por la OMS para controlar la propagación de la COVID-19 e interrumpir las cadenas de transmisión de persona a persona. Si los principios de la comunicación de riesgos y participación comunitaria (CRPC) se incorporan de manera eficaz en las actividades de localización de contactos en el contexto de la COVID-19, se salvaguarda el cumplimiento de las actividades de localización de contactos y se frena o detiene la transmisión de dicha enfermedad, lo cual en última instancia reduce la mortalidad y la enfermedad y mitiga su incidencia negativa en los sistemas de atención de salud y las economías. En este documento se ofrecen orientaciones a las autoridades de salud en todos los niveles para que mejoren la tasa de éxito de la localización de contactos al asegurarse de que las actividades correspondientes se sustenten en los principios, la evidencia y las actividades de CRPC, y se suministran herramientas a los profesionales que participan en dicha localización a fin de asentar sus prácticas en los principios de la CRPC y mejorar igualmente su tasa de éxito.