Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine (preprint)

As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity to protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains the same mRNA backbone as the original BNT162b2 vaccine, modified by the incorporation of XBB.1.5-specific sequence changes in the encoded prefusion-stabilized SARS-CoV-2 spike protein (S(P2)). Biophysical characterization of Omicron XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation that adopts a flexible and predominantly open one-RBD-up state, with high affinity binding to the human ACE-2 receptor. When administered as a 4th dose in BNT162b2-experienced mice, the monovalent Omicron XBB.1.5 vaccine elicited substantially higher serum neutralizing titers against pseudotyped viruses of Omicron XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 and HV.1 sublineages and the phylogenetically distant BA.2.86 lineage than the bivalent Wild Type + Omicron BA.4/5 vaccine. Similar trends were observed against Omicron XBB sublineage pseudoviruses when the vaccine was administered as a 2-dose primary series in naive mice. Strong S-specific Th1 CD4+ and IFN{gamma}+ CD8+ T cell responses were also observed. These findings, together with prior experience with variant-adapted vaccine responses in preclinical and clinical studies, suggest that the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine is anticipated to confer protective immunity against dominant SARS-CoV-2 strains. ONE-SENTENCE SUMMARYThe monovalent Omicron XBB.1.5-adapted BNT162b2 mRNA vaccine encodes a prefusion-stabilized spike immunogen that elicits more potent neutralizing antibody responses against homologous XBB.1.5 and other circulating sublineage pseudoviruses compared to the bivalent Wild Type + Omicron BA.4/5 BNT162b2 vaccine, thus demonstrating the importance of annual strain changes to the COVID-19 vaccine.

COVID-19 Symptoms and Immunotherapy in People with Multiple Sclerosis: An Analysis of the COVID-19 in MS Global Data Sharing Initiative Dataset (preprint)

OBJECTIVESTo analyze the symptoms and severity of coronavirus disease 2019 (COVID-19) in people with multiple sclerosis (pwMS) on immunotherapy using data from the COVID-19 in multiple sclerosis (MS) Global Data Sharing Initiative dataset provided by PhysioNet. METHODSThe open-access COVID-19 in MS Global Data Sharing Initiative dataset was obtained through credentialed access using PhysioNet. The variables analyzed included body mass index (BMI), symptoms of COVID-19, age, current use of disease-modifying therapy (DMT), efficacy of DMT, comorbidities, hospitalization status, and type of MS. A linear regression analysis was completed. Data analysis and visualization were completed using STATA v1.5, R-Studio v1.1.447, Python v3.8, and its associated libraries, including NumPy, Pandas, and Matplotlib. RESULTSA total of 1141 participants were included in the analysis. 904 women and 237 men were diagnosed with MS. Among the pwMS included in the study; 208 (19.54%) had a suspected infection with COVID-19 and only 49 (5.25%) were confirmed. Any COVID-19 symptom was present in 360 individuals. The commonly reported DMT agents included dimethyl fumarate (12.71%) and fingolimod (10.17%). 101 in total (8.85%) reported not using any DMT. Factors associated with hospitalization and/or admission to the ICU included having any comorbidity (p = 0.01), neuromuscular disorder (p = 0.046), hypertension (p = 0.005), chronic kidney disease (p < 0.001), and immunodeficiency (p = 0.003). The type of MS, the duration of the disease, and high-efficacy DMT therapy did not have a statistically significant influence on hospitalization. CONCLUSIONThis study underscores the importance of comorbidities, especially neuromuscular disorders, hypertension, chronic kidney disease (CKD), and immunodeficiencies, as possible prognostic indicators for worse outcomes of COVID-19 in pwMS. On the contrary, the type of MS, the duration of the disease, and the efficacy of disease-modifying therapy did not significantly affect the severity of the symptoms of COVID-19 in this cohort.

Influencia de la pandemia por Covid 19 en el trasplante de órganos

En el mes de Diciembre (2019) se diagnosticó la infección viral que tuvo una rápida expansión. En el mes de Junio (2020) solo en 188 países fueron diagnosticados 35 millones de pacientes. Desgraciadamente en nuestro país los resultados de la atención a los enfermos (diagnostico, aislamiento, atención), fue peor que en otros muchos (Alemania, Italia, Corea, Taiwán, Grecia, Portugal, Francia, Japón y otros). 778 pacientes trasplantados sufrieron la infección, de ellos, 249 en la Comunidad de Madrid. La donación de órganos se redujo rápidamente debido a que las áreas de hospitalización, UCI, quirófanos, actividad hospitalaria en general hubo de dedicarse al tratamiento de los enfermos infectados. Hubo de asumir la reducción de trasplantes de riñón, hígado, corazón, pulmón, en casi el 90% de las cifras correspondientes a los dos años anteriores (en el mes de abril 0%), en el periodo marzo-Julio 2020. No se permitió el trasplante con donante vivo,” Split” o "Cluster”. Solo en la Comunidad de Madrid se realizaron 37 trasplantes menos en 2020 que en 2019. Los motivos de este descenso fue la reducción de camas en UCI, de posibilidades de utilización de quirófanos, menor número de facultativos, enfermeras, personal sanitario en general (861.112 infectados, de los cuales 36.000 eran sanitarios, con una mortalidad global de 36.000). Nuevos protocolos, formas de tratamiento, vacunación, hicieron posible volver a la cifra de trasplantes realizados entre 2018-2019.Alternate : On 31 December 2019 COVID-19 Viral infection was diagnoses. On june 2020 only in 188 countries 33 millons of infected people were detected. Unfortunately in Spain the results of the treatment has been worse than in Germany, Italy, Corea, Taiwan., Grece, Portugal, France, Japan, and others. 778 transplanted patients were infected. 249 of them in Madrid area. Organ donation was reduced. National Organization of Organ Trasplantation diminished donation, and transplantation of kidney, liver, heart, lung close to 90% (in april, 0%) from march to july 2020. Living rolated or split, and cluster trasplantation was not permited. In Madrid area, on 2020 were done 37 transplantation less than in 2019 the causes of that were the reduction of UCI beds, time in the OR, reduction of doctors and nurses. 861.112 infected people, 32.992 died and from the total number of patients, 36.000 were included as, doctors, nurses and other related with health care areas new protocols, hospitals, intensive care areas, etc were established along 2020 going back to the previous results obtained during 2018-2019.

Changes in adult trauma at a level 1 trauma center before and during the COVID-19 pandemic.

Background: Prior research has shown the COVID-19 pandemic is associated with changes in ED volumes, trauma caseloads and distribution of disease. Objectives: We aim to characterize the impact of the COVID-19 pandemic at a diverse, high-volume Level 1 trauma center in the US. Methods: We performed a retrospective review of our institutional trauma registry at our center from 2018 through 2021 to study changes before and after COVID-19. We established March 14 - December 31 as the study period of interest for each year. We analyzed the data with descriptive statistics and created Poisson regression models to determine the estimated percentage year-to-year changes. Results: Total number of trauma cases increased with each subsequent year from 2018 (N â€‹= â€‹4605) to 2021 (N â€‹= â€‹7331) (total N â€‹= â€‹23,727). In general, the proportion of Black or African American patients increased over time (2018: 19.2%, 2021: 23.0%). The proportion of patients insured by Medicaid (8.0% vs 10.5%) and Medicare (26.5% vs 32.8%) increased from 2018 to 2021. Comparing 2019 to 2020, we found increases in violent traumas: GSW (+88.6%, 95% CI 63.8%-117.2%) and stabbings (+39.6%, 95% CI 8.1%-80.3%). Trauma patient ED LOS decreased from 300 â€‹min (67-400 IQR) in 2018 to 249 â€‹min in 2021 (104-510 IQR). Conclusion: This analysis identified increased trauma volumes, especially violent trauma (GSW, stabbing, other penetrating). There was a greater proportion of Black/African American patients and those insured with Medicare or Medicaid during the pandemic. TED LOS decreased over time while ED mortality and hospital LOS remained stable.

Analysis of the impact of the COVID-19 pandemic on psychotropic drug use

Background and ImportanceThe COVID-19 disease, declared a pandemic in March 2020, radically changed people's way of life. The health risk, the measures of the state of alarm and its impact at social and economic level have exposed the population to a threat to their psychological well-being.Aim and ObjectivesTo analyse the relationship between COVID-19 and changes in the trend of psychotropic drug consumption.Material and MethodsDescriptive drug utilisation study which included 665,222 inhabitants. This population is distributed in an urban (UA) (275,990 inhabitants) and rural, peri-urban (RA) (389,232 inhabitants) area. The study period was January 2018 to December 2021. Data were obtained from the database of dispensed and billed prescriptions. The unit used was the Defined Daily Dose (DDD) and the main variable was the DDD per 1000 inhabitants and day (DHD). The therapeutic groups studied were benzodiazepines (N05BA, N05CA, N05CF) and antidepressants (N06AB, N06AX), according to the Anatomical Therapeutic Chemical Classification System (ATC). Mann–Whitney test was used for statistical analysis.ResultsThe group of drugs with the greatest increase in consumption was benzodiazepines, followed by antidepressants, the latter being higher in the 2nd and 4th quarter of 2020, coinciding with the first and second wave and higher in rural areas. In antipsychotic dispensations, a slight increase was only observed in the metropolitan area (p<0,05). During the year 2021, the rates of benzodiazepines were decreasing, ending the year at values similar to pre-pandemic rates. In contrast, the increase in antidepressant use was sustained during 2021.-DHD 2nd Quarter:BENZODIAZEPINESUA: 2018:86.71;2019: 83.58;2020:86.16;2021:81.71RA:2018:88.97;2019: 88.95;2020:97.63;2021:87.85ANTIDEPRESSANTSUA:2018:38,79;2019:39,73;2020:40,16;2021 41,38RA:2018:44.76;2019:45.58;2020:48.49;2021:47.85-DHD 4th QuarterBENZODIAZEPINESUA: 2018: 84.67;2019: 83.15;2020: 87.60;2021: 82.00RA: 2018: 88.42;2019: 89.97;2020: 97.38;2021: 87.84ANTIDEPRESSANTSUA: 2018: 38.73;2019: 39.72;2020: 40.99;2021: 43.14RA: 2018: 45.12;2019: 46.24;2020: 48.91;2021: 49.19It was only statistically significant the increase in the consumption of antidepressants (P=0.019) in the periods 2020-2021vs 2018-2019.Conclusion and RelevanceThe uncertainty in the first months of the pandemic, bereavement, isolation and the effects of the economic crisis may have favoured an increase in the consumption of antidepressants and benzodiazepines. It would be necessary to reorient clinical practice strategies, promoting the appropriate and safe use of these drugs in the primary and hospital care setting.References and/or AcknowledgementsConflict of InterestNo conflict of interest.

Longitudinal and Quantitative Fecal Shedding Dynamics of SARS-CoV-2, Pepper Mild Mottle Virus and CrAssphage (preprint)

Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79x10^6 gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1x10^5 gc/mg-dw and 1.86x10^3 gc/mg-dw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates.

Business intelligence for the visualization and data analysis of Telepharmacy activity indicators in a hospital pharmacy service scorecard

Objective: The consolidation of Telepharmacy during the COVID-19 pandemic has raised the need for managing large volumes of real-time activity data through data analysis. The aim of this project was to design a dynamic, user-friendly, customizable scorecard in a hospital pharmacy service for the visualization and analysis of Telepharmacy activity indicators through the use of advanced business intelligence technology. Method: The software tool was developed by a multidisciplinary team between April and May 2021, driven from the hospital pharmacy service. Once the Telepharmacy indicators of interest were established, datasets were extracted from raw databases (administrative databases, Telepharmacy database, outpatient dispensing software, drug catalogues) through data analysis. The different data sources were integrated in a scorecard using PowerBI®. The criteria for processing missing and duplicated data were defined, and data pre-processing, normalization and transformation were performed. Once the pilot scorecard was validated by different profiles of users, the structure was designed for the panels to automatically update as databases were updated. Results: Design and implementation of a scorecard of Telepharmacy activity: general descriptive panel (demographic profile of patients, count and delivery conditions, program and medical service);geolocation of destination;pharmacological profile;relative analysis of patients involved in the Telepharmacy program with respect to the total of outpatients. In the last updating as of January 2022, data from 16, 000 dispensations to more than 4, 000 patients had been collected. This means that 21.93% of outpatients had benefited at some time point from the Telepharmacy service. Filters enable the visualization of timeline progress and patient characterization, and measure Telepharmacy activity by program. Conclusions: The processing of large Telemedicine datasets from various sources through Business Intelligence in a hospital pharmacy service makes it possible to synthesize information, generate customized reports, and visualize information in a dynamic and attractive format. The application of this new technology will help us improve strategic clinical and management decision making. © 2022 Grupo Aula Medica S.L.. All rights reserved.

EE-7978. Implementación de la campaña de vacunación frente a COVID-19 en un hospital de tercer nivel

Gestionar la campaña de vacunación COVID-19 siguiendo las recomendaciones vigentes de las autoridades sanitarias nacionales y autonómicas en un hospital de tercer nivel. Métodos: Se formó el Comité de Vacunación_COVID-19 del hospital (Direcciones: Médica, Enfermería y Planificación;Servicios: Medicina Preventiva, Farmacia, Admisión, Pediatría). Reuniones semanales. Se organizó: a) diseño/implementación de circuitos de vacunación;b) gestión de citas;c) gestión de recursos;d) cuadro de mando. Resultados: Inicialmente se organizaron 2 circuitos de vacunación: los pacientes con condiciones de alto riesgo (inicio de vacunación: 12/04/2021) y población en general (ciudadanos por grupo de edad) (inicio de vacunación: 10/04/2021). La Unidad de Vacunación-Servicio de Medicina Preventiva (UV-MPRE) participa activamente en la coordinación del proceso y se encarga de la elaboración de cartelería (preparación de vacunas ARNm, según ficha técnica;la elaboración del procedimiento de trabajo: FEA de guardia en los circuitos;el registro normalizado de uso de viales/incidencias y coordinación de guardias FEA en ambos circuitos de vacunación). En 2021, se realizaron 231 turnos de vacunación entre los 2 circuitos. En una segunda etapa se organizó la vacunación COVID-19 de los pacientes de alto riesgo y las dosis de recuerdo según las recomendaciones vigentes mediante la citación en UV-MPRE (parte de interconsulta);(2021: se vacunaron 1.937 pacientes en UV-MPRE). Para la gestión de los pacientes citados en UV-MPRE, se crearon 5 agendas con prestaciones específicas (según el número de dosis y la marca comercial, inicialmente para una pauta homóloga) (tabla 1). Para el seguimiento/cumplimiento de la pauta vacunal de los pacientes vacunados UV-MPRE se creó en la historia clínica electrónica el proceso: COVID19-vacunación y un localizador de pacientes con vacunación COVID-19 incompleta (2021: 3.741 procesos: COVID19-Vacunación). La UV-MPRE también se encarga de: registrar vacunas administradas en el Registro Unificado de Vacunación (RUV);resolver las incidencias en el RUV a requerimiento de los interesados;resolver dudas relacionadas con las vacunas COVID-19 y la estrategia de vacunación;la emisión del certificado COVID-19 digital-UE (vacunación/recuperación): 1.127 durante 2021.Unlabelled Image Conclusiones: La participación del hospital en el despliegue de la estrategia de vacunación COVID-19 y el abordaje multidisciplinario en su organización, ha permitido una mejor adaptación al contexto, integrar la gestión de riesgos, una buena coordinación interprofesional logrando una mayor eficiencia en los resultados y la calidad en la atención al paciente.

Could lockdown increase the incidence of eating disorders?

Introduction Spanish Governmen declared state of emergency in March 2020 to prevent coronavirus COVID-19 from spreading. During September and October 2020, at Child and Adolescent Psychiatry Unit we have attended patients who presented altered eating behaviors whose onset was during lockdown. We report a series of seven cases of adolescent girls between the ages of 11 and 16, who had no previous history of mental illness. During lockdown, they have presented restriction of food and increased physical exercise, with weight loss. Some of these patients have also presented food binges and purging behaviors. Objectives Review the impact of lockdown on eating behavior, specially on weight loss. Methods Literature review of scientific papers searching in Pubmed. Results There are articles that study the variations in eating habits and exercise ocurred during confinement. Most focus on two trends: on the one hand, increased intake and the tendency to a more sedentary life;on the other hand, the worsening of people with a previous diagnosis of eating disorder. However, there is a third trend for which there are few studies: the new appearance of restrictive eating behaviors, together with increased physical exercise, bingeing and purging. This is the case of the patients we present. These studies describe as a possible cause of these alterations that confinement is a novel situation, which generates stress, social isolation, boredom, anxiety and a feeling of loneliness, which can influence self-concept and eating behaviors. Conclusions Lockdown has favored a change in eating habits and exercise. More studies are needed on new-onset eating disorders.

COVID-19 pandemic in a mental health ward: inpatient admissions, use of mechanical restraint and aggressions (preprint)

Background. To analyze the impact of the COVID-19 pandemic on mental health hospital admissions, the use of mechanical restraint and number of aggressions to the staff. Methods. Outcomes in the period from March 14, 2020–December 31, 2020 were compared to the same period in 2019. A multivariate logistic regression analysis was carried out to compare the risk of mechanical restraint during admissions in the two periods, controlling for potential confounding variables. Results. There was a 30.7% reduction in the number of inpatient admissions with significant changes in the profiles of the patients admitted. There were no differences in the risk of restraint and aggressions. Violence was less frequent as a reason for restraint in the pandemic period, while agitation increased. Conclusions. The COVID-19 pandemic has had a significant impact on the functioning of the hospitalization ward. Measures introduced during pandemic did not seem to have a meaningful effect on mechanical restraint procedures or violent behavior towards the staff.

Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study (preprint)

The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset.

Predictive factors of six-week mortality in critically ill patients with SARS-CoV-2: A multicenter prospective study Factores predictivos de la mortalidad a las seis semanas en pacientes críticos con SARS-CoV-2: estudio multicéntrico prospectivo

Objective The objective of the study is to identify the risk factors associated with mortality at six weeks, especially by analyzing the role of antivirals and munomodulators. Design Prospective descriptive multicenter cohort study. Setting 26 Intensive care units (ICU) from Andalusian region in Spain. Patients or participants Consecutive critically ill patients with confirmed SARS-CoV-2 infection were included from March 8 to May 30. Interventions None. Variables Variables analyzed were demographic, severity scores and clinical condition. Support therapy, drug and mortality were analyzed. An univariate followed by multivariate Cox regression with propensity score analysis was applied. Results 495 patients were enrolled, but 73 of them were excluded for incomplete data. Thus, 422 patients were included in the final analysis. Median age was 63 years and 305 (72.3%) were men. ICU mortality: 144/422 34%;14 days mortality: 81/422 (19.2%);28 days mortality: 121/422 (28.7%);6-week mortality 152/422 36.5%. By multivariable Cox proportional analysis, factors independently associated with 42-day mortality were age, APACHE II score, SOFA score at ICU admission >6, Lactate dehydrogenase at ICU admission >470 U/L, Use of vasopressors, extrarenal depuration, %lymphocytes 72 h post-ICU admission <6.5%, and thrombocytopenia whereas the use of lopinavir/ritonavir was a protective factor. Conclusion Age, APACHE II, SOFA > value of 6 points, along with vasopressor requirements or renal replacement therapy have been identified as predictor factors of mortality at six weeks. Administration of corticosteroids showed no benefits in mortality, as did treatment with tocilizumab. Lopinavir/ritonavir administration is identified as a protective factor.

Thrombotic and bleeding complications in patients with chronic lymphocytic leukemia and COVID-19: A study of ERIC, the European Research Initiative on CLL (preprint)

Background: Patients with chronic lymphocytic leukemia (CLL) may be more susceptible to COVID-19 related poor outcomes, including thrombosis and death, due to the advanced age, the presence of comorbidities, and the disease and treatment-related immune deficiency. In this retrospective multicenter study, conducted by ERIC, the European Research Initiative on CLL, we assessed the risk of thrombosis and bleeding in patients with CLL affected by severe COVID-19.Methods: The study included patients from 79 centers across 22 countries. Data collection was conducted between April and May 2021.Results: A total of 793 patients from 79 centers were included in the study with 593 being hospitalized (74.8%). Among these, 518 were defined as having severe COVID: 162 were admitted to the ICU while 356 received oxygen supplementation outside the ICU. Most patients (90%) were receiving thromboprophylaxis. During COVID-19 treatment, 8.8% developed a thromboembolic event, while 4.8% experienced bleeding. Thrombosis developed in 20.5% of patients who were not receiving thromboprophylaxis, but only in 8.1% of patients who were on thromboprophylaxis. Bleeding episodes were more frequent in patients receiving intermediate/therapeutic versus prophylactic doses of low-molecular-weight heparin (LWMH) (11.1% vs. 4.2%, respectively) and in elderly. In multivariate analysis, peak D-dimer level was a poor prognostic factor for thrombosis occurrence (OR=1.020, 95%CI 1.006‒1.033), while thromboprophylaxis use was protective (OR=0.194, 95%CI 0.061‒0.614). Age and LMWH intermediate/therapeutic dose administration were prognostic factors in multivariate model for bleeding (OR=1.055, 95%CI 1.013-1.103 and OR=2.490, 95%CI 1.044-5.935, respectively). Conclusions: Patients with CLL affected by severe COVID-19 are at a high risk of thrombosis if thromboprophylaxis is not used, but also at increased risk of bleeding under the LMWH intermediate/therapeutic dose administration.  

SARS-CoV-2 ORF8 encoded protein contains a histone mimic, disrupts chromatin regulation, and enhances replication (preprint)

SARS-CoV-2 emerged in China at the end of 2019 and caused the global pandemic of COVID-19, a disease with high morbidity and mortality. While our understanding of this new virus is rapidly increasing, gaps remain in our understanding of how SARS-CoV-2 can effectively suppress host cell antiviral responses. Recent work on other viruses has demonstrated a novel mechanism through which viral proteins can mimic critical regions of human histone proteins. Histone proteins are responsible for governing genome accessibility and their precise regulation is critical for the ability of a cell to control transcription and respond to viral threats. Here, we show that the protein encoded by ORF8 (Orf8) in SARS-CoV-2 functions as a histone mimic of the ARKS motif in histone 3. Orf8 is associated with chromatin, binds to numerous histone-associated proteins, and is itself acetylated within the histone mimic site. Orf8 expression in cells disrupts multiple critical histone post-translational modifications (PTMs) including H3K9ac, H3K9me3, and H3K27me3 and promotes chromatin compaction while Orf8 lacking the histone mimic motif does not. Further, SARS-CoV-2 infection in human cell lines and postmortem patient lung tissue cause these same disruptions to chromatin. However, deletion of the Orf8 gene from SARS-CoV-2 largely blocks its ability to disrupt host-cell chromatin indicating that Orf8 is responsible for these effects. Finally, deletion of the ORF8 gene affects the host-cell transcriptional response to SARS-CoV-2 infection in multiple cell types and decreases the replication of SARS-CoV-2 in human induced pluripotent stem cell-derived lung alveolar type 2 (iAT2) pulmonary cells. These findings demonstrate a novel function for the poorly understood ORF8-encoded protein and a mechanism through which SARS-CoV-2 disrupts host cell epigenetic regulation. Finally, this work provides a molecular basis for the finding that SARS-CoV-2 lacking ORF8 is associated with decreased severity of COVID-19.

On how COVID-19 has affected radiation therapy treatments

Purpose or Objective: Cancer diagnostics and surgery have been disrupted by the response of health care services to the coronavirus disease pandemic. With the COVID-19 irruption in 2020, some radiotherapy treatments were omitted, delayed, changed intent or shifted to a hypofractionated scheme. The purpose of this study is to investigate the effect, direct or indirect, that COVID-19 has had on radiotherapy treatments in comparison with previous years. Materials and Methods: All treatments from 2018 (1521), 2019 (1498) and 2020 (1613) were analysed. Treatments were separated into two categories regarding treatment intent: curative or palliative. Moreover curative treatments were classified by site or pathology: H&N, lung, rectum, prostate, breast, central nervous system (CNS), gynaecological, SBRT and other sites. Percentage of hypofractionated treatments per year (for those with curative intent) was also taken into account. Results: Regarding treatment intent, we have found that the number of palliative treatments was similar to previous years: 38% in 2020, 37 % in 2018 and 35% in 2019. Figure I shows the percentage of hypofractionated treatments. During 2020 there were 10% hypofractionated treatments more than 2019, which is more than a threefold increase compared to the growth between 2018 and 2019 (3%). (Figure Presented) Conclusion: On one side, reasons related directly or indirectly with COVID-19 do not had an effect on the treatment intent in our department: similar number of palliative treatments was reported during 2020. On the other side, the use of hypofractionated schemes was accelerated during the pandemic, following national and international recommendations. This has allowed reducing treatment time bringing more comfort to the patients. To resume, it is difficult to assess whether the pandemic had a negative effect on cancer treatments based on treatment intent. Deeper analysis of cancer staging could reveal a different result related to collateral damage to the pandemic.

The Input–Output Method for Calculating the Carbon Footprint of Tourism: An Application to the Spanish Tourism Industry

The tourism sector is one of the most affected by COVID-19 pandemic. The global shutting down of non-essential sectors and the maintained global mobility restrictions have led to the industry’s partial closure worldwide. Tourism could play a leading role as the driver for achieving the sustainable development goals (SDG) and as an engine of wealth generation and cultural preservation. However, the negative impacts on the environment have to be considered when shaping the forthcoming and refurbished post-pandemic tourism industry of the future. In this chapter, we propose an environmentally extended input–output model to estimate the tourism carbon footprint to assess the sustainability of the tourism industry and applied it to tourism in Spain. This modelling allows for identifying direct and indirect emissions hot spots along the complex and intricate global value chains. The main results show how while Spain’s tourism contribution to GDP accounts for 12.3%, its carbon footprint accounts for 15% of the Spanish total emissions, which is above the global average (8%). In global terms, 29% of the total carbon footprint is imported, so it is, directly or indirectly, embodied in the global production chains. It is concentrated in some close European Union countries, China, BRIIAT, and the United States. Sectorally, the Spanish tourism carbon footprint is concentrated in some sectors where emissions are mostly domestic (air transport, land transport, or retail trade). © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Phylogenomics and population genomics of SARS-CoV-2 in Mexico reveals variants of interest (VOI) and a mutation in the Nucleocapsid protein associated with symptomatic versus asymptomatic carriers (preprint)

Understanding the evolution of SARS-CoV-2 virus in various regions of the world during the Covid19 pandemic is of the utmost importance to help mitigate the effects of this devastating disease. We describe the phylogenomic and population genetic patterns of the virus in Mexico during the pre-vaccination stage, including asymptomatic carriers. A RT-qPCR screening and phylogenomics reconstructions directed a sequence/structure analysis of the Spike glycoprotein, revealing mutation of concern E484K in genomes from central Mexico, in addition to the nationwide prevalence of the imported variant 20C/S:452R (B.1.427/9). Overall, the detected variants in Mexico show mutations in the N-terminal domain (i.e., R190M), in the receptor-binding motif (i.e., T478K, E484K), within the S1-S2 subdomains (i.e., P681R/H, T732A), and at the basis of the protein, V1176F, raising concerns about the lack of phenotypic and clinical data available for the postulated variants of interest (VOIs) 20B/478K.V1 and P.3. Moreover, the population patterns of Single Nucleotide Variants (SNVs) from symptomatic and asymptomatic carriers sampled with a self-sampling scheme, revealed a bimodal distribution of polymorphisms in all three sampled localities from central Mexico, and confirmed the presence of several fixed variants, mostly from the 241T-3037T-14408T-23403G haplotype common in Asia. Despite gene flow among Mexican localities, we found differences in both the allelic frequencies among localities and the allelic imbalance of the mutation S194L of the nucleocapsid protein between symptomatic and asymptomatic carriers. Our results highlight the dual role of Spike and Nucleocapsid proteins in adaptive evolution of SARS-CoV-2 to their hosts and provide a baseline for specific follow-up of mutations of concern during the vaccination stage in Mexico. IMPACT STATEMENTFollowing self-sampling, screening of mutations of concern, and a combined phylogenomic and population genetics pipeline, we reveal the occurrence of two variants of interest with mutations in the Spike protein, P.3 (B.1.1.28.3) and 20B/478K.V1 (B.1.1.222, recently named B.1.1.519) in Mexico during the pre-vaccination stage, plus a mutation in the Nucleocapsid protein, S194L, that associates only with symptomatic patients versus asymptomatic carriers in the population investigated. Our research can aid epidemiological genomics efforts during the vaccination stage in Mexico by contributing with a combined analytical platform and information about variants within different genetic backgrounds. DATA SUMMARYThe Mexstrain-Nextstrain data can be found at: http://www.ira.cinvestav.mx/ncov.evol.mex.aspx. Data generated and used in this study is provided as supplementary Tables: Table S1. Self-sampling performance validation data generated in 58 volunteers. Table S2. Metadata of SARS-CoV-2 genomes generated and investigated. Table S3. Complete dataset of the population genomics analysis of SARS-CoV-2.

Teachers and students opinions about a comprehensive online program in medicine during COVID-19 lockdown

Introduction: The COVID-19 crisis led to the closure of the country's universities in March 2020, with total interruption of face-to-face activity. To dealt with last 2019/20 semester in lockdown, our Faculty of Medicine implemented a joint training program totally online with a «self-regulatory» teaching approach. This study presents the opinions of teachers and students. Methods: The educational characteristics of the online Program for COVID-19 (POLAC), for 1st and 2nd year of medicine, structuring and organization of the intervention and academic results, have been described in other work. This study through online surveys explores the opinions of teachers and students. Two researchers coded the open-ended responses obtained thematically and independently, classifying them into categories. Results: The 8 teachers involved and a variable number of student by subject responded, receiving 234 questionnaires (17%). The students highlight as positive the optimization of the teaching resources used, the usefulness of the online tools, especially self-assessments and the doubts management system. The development of practical sessions and lack of face-to-face learning are highlighted as negative aspects of the Program. Dedication of teachers received positive and negative remarks. Teachers highlight the empowerment of the student's autonomy and the usefulness of online tools but also the additional need to be presence. Conclusion: Globally, the positive and negative comments are in line with the strengths and weaknesses of both online teaching and «self-regulatory» teaching approaches. More robust design studies are needed to verify the true scope of these results. © 2021 Elsevier España, S.L.U.