Multimodal Molecular Imaging Reveals Tissue-Based T Cell Activation and Viral RNA Persistence for Up to Two Years Following COVID-19 (preprint)

The etiologic mechanisms of post-acute medical morbidities and unexplained symptoms (Long COVID) following SARS-CoV-2 infection are incompletely understood. There is growing evidence that viral persistence and immune dysregulation may play a major role. We performed whole-body positron emission tomography (PET) imaging in a cohort of 24 participants at time points ranging from 27 to 910 days following acute SARS-CoV-2 infection using a novel radiopharmaceutical agent, [18F]F-AraG, a highly selective tracer that allows for anatomical quantitation of activated T lymphocytes. Tracer uptake in the post-acute COVID group, which included those with and without Long COVID symptoms, was significantly higher compared to pre-pandemic controls in many anatomical regions, including the brain stem, spinal cord, bone marrow, nasopharyngeal and hilar lymphoid tissue, cardiopulmonary tissues, and gut wall. Although T cell activation tended to be higher in participants imaged closer to the time of the acute illness, tracer uptake was increased in participants imaged up to 2.5 years following SARS-CoV-2 infection. We observed that T cell activation in spinal cord and gut wall was associated with the presence of Long COVID symptoms. In addition, tracer uptake in lung tissue was higher in those with persistent pulmonary symptoms. Notably, increased T cell activation in these tissues was also observed in many individuals without Long COVID. Given the high [18F]F-AraG uptake detected in the gut, we obtained colorectal tissue for in situ hybridization SARS-CoV-2 RNA and immunohistochemical studies in a subset of participants with Long COVID symptoms. We identified cellular SARS-CoV-2 RNA in rectosigmoid lamina propria tissue in all these participants, ranging from 158 to 676 days following initial COVID-19 illness, suggesting that tissue viral persistence could be associated with long-term immunological perturbations.

La economía social responsable y los Objetivos de Desarrollo Sostenible frente a la crisis post-COVID-19: la voz de las personas expertas

El objetivo del trabajo es conocer las aportaciones que pueden realizar la economía social y de la responsabilidad social corporativa en la búsqueda de soluciones a la crisis sanitaria y económica actual, con el fin de evitar sus efectos más traumáticos. Para ello, se analizan las variaciones que pueden producirse en tres escenarios: en las organizaciones sociales y responsables, en los cambios de valores en concordancia con los Objetivos de Desarrollo Sostenible (ODS), y en las transformaciones hacia nuevos modelos económicos y de empresa. De este modo, se revisan los elementos favorables existentes, como el papel de las empresas contra los efectos de la pandemia, el importante consenso internacional existente -los Diez Principios del Pacto Mundial y los 17 ODS- y la mayor conciencia colectiva sobre la importancia de lo público y de los riesgos del planeta. La principal contribución del trabajo es plantear posibles estrategias frente a la crisis, tanto a nivel macro como micro, sobre la base de que esta inédita situación recoge y estimula elementos preexistentes que ahora toman nuevas dimensiones. Desde el punto vista metodológico, estas propuestas se generan en un debate donde se entrecruzan la literatura académica, los ejemplos de actuaciones empresariales, el resultado de encuestas y, de forma destacada, la técnica de recopilación documental y análisis del discurso de personas expertas en la materia. Entre los hallazgos y conclusiones cabe destacar la mayor sensibilidad hacia lo público y la sostenibilidad, como elementos de desarrollo, y más receptividad hacia un nuevo paradigma empresarial.Alternate :The objective of the work is to know the contributions that the social economy and corporate social responsibility can make in the search for solutions to the current health and economic crisis, in order to avoid its most traumatic effects. To this end, we analyze the variations that can occur in three scenarios: in social and responsible organizations, in the changes of values in accordance with the Sustainable Development Goals (SDGs), and in the transformation towards new economic and business models. In this way, the existing favorable elements are reviewed, such as the role of companies against the effects of the pandemic, the important existing international consensus -the Ten Principles of the Global Compact and the 17 SDGs- and the increased collective awareness of the importance of the public and the risks of the planet. The main contribution of the work is to propose possible strategies against the crisis, both at the macro and micro levels, on the basis that this unprecedented situation collects and stimulates pre-existing elements that now take on new dimensions. Methodologically, these proposals are generated in a debate where academic literature, examples of business actions, the results of surveys and in a outstanding way, the technique of documentary compilation and analysis of the discourse of experts in the field. Among the findings and conclusions, we should highlight the greater sensitivity towards the public and sustainability, as an element of development, and more receptivity towards a new business paradigm.

Humoral Response After Successive Doses of Mrna Vaccine Against Sars-Cov-2 in Stable Kidney Transplant Recipients

BACKGROUND AND AIMS The poor humoral response after vaccination against SARS-CoV-2 in kidney transplant (KT) patients led to the approval of a third dose. Recent data show an increase in the antibody titer, although lower than in the general population. Our aim is to analyze the humoral immune response after the third dose a mRNA vaccine against SARS-CoV-2 and the evolution of the antispike antibody (antiS) titers in KT recipients. METHOD We performed a prospective cohort study of stable KT patients from our center who received three doses of a mRNA vaccine from March to November 2021. KT recipients with less than 6 months after transplantation and with active oncological or hematologic disease were excluded. We determined antiS titers (Abbott SARS‐CoV‐2 IgG chemiluminescent microparticle immunoassay) at baseline, one month after the second dose and one month after the third one. We compared those KT patients who seroconverted with 2 and with 3 doses of vaccine and those who did not seroconvert. To identify risk factors for no seroconversion, a logistic regression analysis was carried out. RESULTS We included 83 KT. Mean age was 59.3 years and 62.7% were male. The median time from KT to the first vaccine dose was 94 months and between the second and third dose median time was 4 months. Seroconversion rate was 63.8% after 2 doses and 85.5% after the third one (P  < 0.001). Twelve KT did not develop antibodies (Table 1). Patients who did not seroconvert were older (P = 0.047), had a worse renal function (P = 0.009) and had fewer lymphocytes than those that developed antibodies (0.013). Besides, they almost half of them received a KT from a non-heart-beating donor (P = 0.026) and were treated with thymoglobulin in the 2 years prior to the vaccine more frequently (P = 0.007). In patients who seroconverted after 2 doses, we observed a 10-fold increase in the antiS titer after the third vaccine (82 [34–350] UI/mL versus 814 [205–2415] UI/mL;P  < 0.001). No patients had neither acute rejection nor serious adverse effects. In the multivariable analysis advanced age, a worse kidney function and recent treatment with thymoglobulin were risk factors for no seroconversion (Table 1). CONCLUSION The third dose of a mRNA vaccine against SARS-CoV-2 significantly increased the seroconversion rate and the antiS titers in stable KT patients. Advanced age, poorer kidney function and immunosuppressive treatment are risk factors for no seroconversion.

Impact of Pre-Existing Chronic Viral Infection and Reactivation on the Development of Long COVID (preprint)

ABSTRACT The presence and reactivation of chronic viral infections such as Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV) have been proposed as potential contributors to Long COVID (LC), but studies in well-characterized post-acute cohorts of individuals with COVID-19 over a longer time course consistent with current case definitions of LC are limited. In a cohort of 280 adults with prior SARS-CoV-2 infection, we observed that LC symptoms such as fatigue and neurocognitive dysfunction at a median of 4 months following initial diagnosis were independently associated with serological evidence of recent EBV reactivation (early antigen-D [EA-D] IgG positivity) or high nuclear antigen IgG levels, but not with ongoing EBV viremia. Evidence of EBV reactivation (EA-D IgG) was most strongly associated with fatigue (OR 2.12). Underlying HIV infection was also independently associated with neurocognitive LC (OR 2.5). Interestingly, participants who had serologic evidence of prior CMV infection were less likely to develop neurocognitive LC (OR 0.52) and tended to have less severe (>5 symptoms reported) LC (OR 0.44). Overall, these findings suggest differential effects of chronic viral co-infections on the likelihood of developing LC and predicted distinct syndromic patterns. Further assessment during the acute phase of COVID-19 is warranted. SUMMARY The authors found that Long COVID symptoms in a post-acute cohort were associated with serological evidence of recent EBV reactivation and pre-existing HIV infection when adjusted for participant factors, sample timing, comorbid conditions and prior hospitalization, whereas underlying CMV infection was associated with a decreased risk of Long COVID.

Impact of COVID-19 Lockdown on Wildlife-Vehicle Collisions in NW of Spain

Wildlife–vehicle collisions (WVCs) in many places have a significant impact on wildlife management and road safety. The COVID-19 lockdown enabled the study of the specific impact that traffic has on these events. WVC variation in the Asturias and Cantabria regions (NW of Spain) because of the COVID-19 lockdown reached a maximum reduction of −64.77% during strict confinement but it was minimal or nonexistent during 'soft';confinement. The global average value was −30.22% compared with the WVCs registered in the same period in 2019, but only −4.69% considering the average throughout the period 2010–2019. There are huge differences between conventional roads, where the traffic reduction was greater, and highways, where the traffic reduction was lesser during the COVID-19 lockdown. The results depend on the season, the day of the week and the time of day, but mainly on the traffic reduction occurring. The results obtained highlight the need to include the traffic factor in WVC reduction strategies.

User Perception of New E-Health Challenges: Implications for the Care Process

Establishing new models of health care and new forms of professional health-patient communication are lines of development in the field of health care. The onset of the COVID-19 pandemic has accelerated the evolution of information systems and communication platforms to guarantee continuity of care and compliance with social distancing measures. Our objective in this article was, firstly, to know the expectations of patients treated in the healthcare processes “cervical cancer” and “pregnancy, childbirth and puerperium” regarding online access to their clinical history and follow-up in the care process. Secondly, we analyzed times involved in the cervical cancer process to find points of improvement in waiting times when digital tools were used for communication with the patient. A descriptive cross-sectional study was carried out on 120 women included in any of the aforementioned processes using a hetero-administered questionnaire. The analysis of times was carried out using the Business Intelligence tool Biwer Analytics®. Patients showed interest in knowing their results before the appointment with the doctor and would avoid appointments with their doctor if the right conditions were met. Most recognized that this action would relieve their restlessness and anxiety. They were highly interested in receiving recommendations to improve their health status. It was estimated that there was room for improvement in the times involved in the care process, which could be shortened by 34.48 days if communication of results were through digital information access technologies. This would favor the optimization of time, resources and user perception.

[18F]FDG PET/CT in Short-Term Complications of COVID-19: Metabolic Markers of Persistent Inflammation and Impaired Respiratory Function (preprint)

Evaluation of the usefulness of [18F]FDG-PET/CT in the short-term follow-up of patients admitted for COVID-19 pneumonia and to explore the association of findings with clinical prognostic markers. Prospective study included 20 patients admitted to hospital with COVID-19 pneumonia between November 2020 and March 2021. Clinical and laboratory test findings were gathered at admission, 48-72h post-admission, and 2-3 months post-discharge. [18F]FDG-PET/CT and respiratory function tests were performed at 2-3 months post-discharge. Lung volumes (TLC), spirometry (FVC, FEV1), lung diffusion capacity for carbon monoxide (DLCO), and respiratory muscle strength were measured. PET/CT images were qualitatively and semi-quantitatively interpreted. Volumetric [18F]FDG-PET/CT results were correlated with laboratory test and respiratory parameters. Eleven [18F]FDG-PET/CT (55%) were positive. The main finding was hypermetabolic lymphade-nopathy in the mediastinum (90.9%). SUVpeak of the target mediastinum lesion was correlated with neutrophil and lymphocyte counts. Eleven (55%) patients had impaired respiratory function, most frequently a reduced DLCO (35%). SUVpeak was positively correlated with %predict-ed-DLCO values. Pulmonary TLG was negatively correlated with %predicted-DLCO and TLC values. In the short-term follow-up of patients hospitalized for COVID-19 pneumonia, [18F]FDG-PET/CT findings revealed significant detectable inflammation in lungs and mediastinal lymph nodes that correlated with pulmonary function impairment in more than half of the patients.

Aspectos claves de la Neumología y Cirugía Torácica sometidos a debate en la era COVID-19

Resumen La Sociedad Española de Neumología y Cirugía Torácica (SEPAR), celebró a finales del año 2020 la segunda edición del Foro de Presidentes de las Sociedades Científicas Autonómicas de Neumología y Cirugía Torácica de España. A lo largo de dicha sesión se abordaron cinco mesas de debate con temas de especial relevancia para el desarrollo de la Neumología y la Cirugía Torácica en España. La primera de ellas se dedicó a comentar los principales resultados del Año SEPAR 2020-21. Por la Calidad del Aire. Cambio Climático y Salud. La segunda mesa analizó las evidencias existentes sobre la prescripción de fármacos antifibróticos en la Patología intersticial asociada a colagenopatías. La tercera mesa se centró en el análisis del abordaje multidisciplinar de la COVID-19 y su visión como una oportunidad de desarrollo y liderazgo para la Neumología. La cuarta mesa valoro la Integración de las UCRIs en los Servicios de Neumología. Y la quinta mesa fue dedicada a la cirugía torácica Cirugía Torácica y durante la misma se estudiaron las diferencias regionales en los plazos de intervención para el Cáncer de Pulmón. Además, de valorar la integración de la Cirugía Torácica en las sociedades regionales.

Human Rights in the Least Developed Countries of Asia: An Index for Quantifying Sustainable Development Goal 3 (Good Health and Wellbeing).

This paper aims to measure disparities among the variables associated with Sustainable Development Goal (SDG) 3 defined by the United Nations (UN) in the least developed countries (LDCs) of Asia. In the terms of the UN Conference on Trade and Development, LDCs are countries with profound economic and social inequalities. The indicator was constructed using a set of variables associated with SDG3: Good Health and Wellbeing. Applying Pena's DP2 distance method to the most recent data available (2018) enables regional ordering of Asia's LDCs based on the values of these variables. The index integrates socioeconomic variables that permit examination of the impact of each individual indicator to determine territorial disparities in terms of the partial indicators of SDG3. "Maternal education," "Proportion of women who make their own informed decisions regarding sexual relations, contraceptive use, and reproductive health care," and "Gender parity index in primary education" are the most important variables in explaining spatial disparities in good health and wellbeing in the LDCs of Asia.

Patients With Hereditary Angioedema Do Not Develop More Severe COVID-19 but SARS-CoV-2 Infection May Trigger Attacks: 66 Cases (preprint)

Purpose: Hereditary angioedema (HAE) is a rare genetic disease with hyperactivated contact and kallikrein-kinin systems leading to bradykinin (BK) release and edema. SARS-CoV-2 infection results in inflammatory exacerbation. C1 inhibitor (C1-INH) deficiency could aggravate clinical outcomes, with HAE patients at a greater risk of adverse outcomes of COVID-19, however, data are still limited. Our aim was to characterize the course and severity of COVID-19 in patients with HAE.MethodsLatin American HAE reference centers evaluated SARS-CoV-2 infection in this population. Patients with confirmed diagnosis of HAE with (HAE-C1-INH) or without C1-INH deficiency (HAE-nC1-INH) were included. HAE symptomatology and the course of COVID-19 were characterized with the application of a questionnaire. Results66 patients from 10 countries (HAE-C1-INH 80,3%; HAE-nC1-INH 19.6%) were reported with SARS-CoV-2 infection. Comorbidities were absent in 69.7% of the patients and obesity present in 12.1%. Attacks occurred in 45.5% of patients with HAE during SARS-CoV-2 infection. Long term prophylaxis was reported in 52% (34/66) of HAE patients. Complete cure was observed in 61 patients (92.4%), pulmonary sequelae in 4 and death in one HAE-C1-INH patient. The cause of death was septic shock secondary to bacterial pulmonary coinfection. Disease progression was not impacted by sex, therapy or type of HAE (p = 0.803). ConclusionAttacks occurred in almost half of HAE patients suggesting that SARS-CoV-2 infection is a trigger. HAE did not represent a risk factor for a worse outcome of COVID-19, even in use of androgens.

Analysis of Emergency Remote Education in COVID-19 Crisis Focused on the Perception of the Teachers

This descriptive study intends to identify the satisfaction perception among the teachers of the Universidad del Valle de México (UVM) concerning the use of the Microsoft Teams platform in the transition from traditional model (face-to-face) to 100% online education [Emergency Remote Teaching (ERT)]. The proposal aims to determine the perspectives of teachers regarding the use of the Microsoft Teams platform during the crisis caused by COVID-19. UVM has 6938 full-time teachers and part-time teachers who collaborated in educational programs during January-June 2020 in the 33 campuses of UVM. And an instrument was developed and applied using finite population sampling, UVM perspective of teachers, which was distributed via Google Forms. The feasibility of the data collection instrument was determined by the Cronbach’s Alpha coefficient, with a result of 0.926. The data collection period was aligned with the first isolation period: 23 March to 20 April. The results in the perception of teacher satisfaction in the different sections of the instrument established an agreement in the answers (very satisfied or satisfied) regarding values that were higher than 60% in terms of satisfaction using the equipment. The analysis of the data collected was performed to verify the proposed hypothesis with the R version 4.0 software. A G-test was performed with the Logverosimilitude coefficient to test whether the categorical variables were independent (qualitative variables that are not defined continuously). The Krammer coefficient of association was then calculated to measure the correlation.

Validation of a Rapid Antigen Test as a Screening Tool for SARS-CoV-2 Infection in Asymptomatic Populations. Sensitivity, Specificity and Predictive Values (preprint)

Background: Early diagnosis of SARS-CoV-2 infection is essential to reduce disease spread. Rapid antigen tests have not been sufficiently evaluated in asymptomatic patients to be used as massive population screening tools.Methods: Head-to-head evaluation of Roche rapid antigen test as a SARS-CoV-2 screening tool in asymptomatic adults from a semi-closed community. Sensitivity, specificity and predictive values were calculated using RT-PCR as reference method . Findings: Roche-rapid test was performed on 2542 asymptomatic adults in a community with a SARS-CoV-2 incidence of 1.93%. It showed a sensitivity of 71.43% (IC 95%: 56.74 – 83.42) and a specificity of 99.68% (IC 95%: 99.37 - 99.86). Positive Predictive Value was 81.4 (IC95% 66.6 – 91.61) and Negative Predictive Value was 99.44 (IC 95% 99.06 – 99.69). Test sensitivity was related to viral load, with higher sensitivity in RT-PCR Ct values under 25 (93.75%, IC 95%: 71.96 – 98.93), that dropped to 29.41% (IC 95%: 10.31- 55.96) in RT-PCR Ct values above 25. Interpretation: This study demonstrates that rapid antigen tests are less effective in asymptomatic population, and therefore are not useful for widespread testing, due to the potential false-negative results and their consequences.Funding: This research received no external funding. Roche Diagnostics S.L. provided the rapid antigen tests required for the study.Declaration of Interest: None to declare. Ethical Approval: Approved by the University of Navarra Ethics committee

IN-HOSPITAL CONTINUATION WITH ANGIOTENSIN RECEPTOR BLOCKERS IS ASSOCIATED WITH A LOWER MORTALITY RATE THAN CONTINUATION WITH ANGIOTENSIN CONVERTING ENZYME INHIBITORS IN COVID-19 PATIENTS A RETROSPECTIVE COHORT STUDY (preprint)

Background: Several studies have reported a reduced risk of death associated with the inpatient use of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) in COVID-19 patients, but have been criticized for incurring in several types of bias. Also, most studies have pooled ACEIs and ARBs as if they were a unique group, overlooking their pharmacological differences. We aimed to assess whether the in-hospital continuation of ARBs and ACEIs, in regular users of these drugs, was associated with a reduced risk of death as compared to their discontinuation and also to compare head-to-head ARBs with ACEIs. Methods: Adult patients with a PCR-confirmed diagnosis of COVID-19 requiring admission during March, 2020 were consecutively selected from 7 hospitals in Madrid, Spain. Among them, we identified outpatient users of ACEIs/ARBs and divided them in two cohorts depending on treatment discontinuation/continuation at admission. Then, they were followed-up until discharge or in-hospital death. An intention-to-treat survival analysis was carried out and hazard ratios (HRs) and their 95%CI were computed through a Cox regression model adjusted for propensity scores of discontinuation and controlled by potential mediators. Results: Out of 625 ACEI/ARB users, 340(54.4%) discontinued treatment. The in-hospital mortality rates were 27.6% and 27.7% in discontinuation and continuation cohorts, respectively (HR=1.01; 95%CI:0.70-1.46). No difference in mortality was observed between ARB and ACEI discontinuation (28.6% vs. 27.1%, respectively), while a significantly lower mortality rate was found among patients who continued with ARBs (20.8%,N=125) as compared to those who continued with ACEIs (33.1%,N=136; p=0.03). The head-to-head comparison (ARB vs. ACEI continuation) yielded an adjusted HR of 0.52 (95%CI:0.29-0.93), being especially notorious among males (HR=0.34; 95%CI:0.12-0.93), subjects older than 74 years (HR=0.46; 95%CI:0.25-0.85), and patients with obesity (HR=0.22; 95%CI:0.05-0.94), diabetes (HR=0.36; 95%CI:0.13-0.97) and heart failure (HR=0.12; 95%CI:0.03-0.97). Conclusions: Among regular users of ARBs admitted for COVID-19, the in-hospital continuation with them was associated with an improved survival, while this was not observed with ACEIs. Regular users of ARBs should continue with this treatment if admitted for COVID-19, unless medically contraindicated. In admitted ACEI users, a switching to ARBs should be considered, especially among high-risk patients.

Manejo del paciente pediátrico ante sospecha de infección por el nuevo coronavirus SARS-CoV-2 en atención primaria (COVID-19) AEPap-SEIP/AEP-SEPEAP

No disponible

Teaching Challenges in COVID-19 Scenery: Teams Platform-Based Student Satisfaction Approach

At the onset of the crisis caused by COVID-19, the Mexican education system chose to join the global context and suspend face-to-face classes for all educational levels. For the continuity of educational processes, a transition from a traditional educational model (face-to-face) to emergency remote teaching (ERT) was made through virtual learning platforms and learning management system (LMS) schemes. Universidad del Valle de Mexico (UVM), in a collaboration agreement with Microsoft Co., chose to use Teams to continue its educational process. In this work, we intend to identify the factors that can be taken into account regarding the level of student satisfaction in the teaching-learning process in ERT using Teams, and validate the established educational strategy. Statistical analysis was carried out to analyze the academic environment for these scenario changes while considering knowledge assessment, and competencies achievement. A combined sampling method was applied with convenience and statistical analysis. The main results established significant percentages, where more than 60% of the students surveyed were manifested in the use of the teams and the organization of the class sessions by the teachers, and the activities developed. Using the Cronbach"s Alpha coefficient, the reliability of the data collection instruments was determined. The correlations of each of the survey questions were calculated to determine the relationship between themselves and the total answers, giving results similar to those obtained through data science tools. Taking advantage of the situation, data science tools were applied to compare the results with obtained values from RapidMiner software in the correlation of factors in of 0.440, 0.384, 0.246, 0.048 and 0.384.

Recomendaciones sobre reanimación cardiopulmonar en pacientes con sospecha o infección confirmada por SARS-CoV-2 (COVID-19). Resumen ejecutivo

Resumen La pandemia por SARS-CoV-2 ha generado nuevos escenarios que requieren modificaciones de los protocolos habituales de reanimación cardiopulmonar. Las guías clínicas vigentes sobre el manejo de la parada cardiorrespiratoria no incluyen recomendaciones para situaciones aplicables a este contexto. Por ello, el Plan Nacional de Reanimación Cardiopulmonar de la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias, en colaboración con el Grupo Español de RCP Pediátrica y Neonatal y con el programa de Enseñanza de Soporte Vital en Atención Primaria de la Sociedad Española de Medicina Familiar y Comunitaria, ha redactado las siguientes recomendaciones, que están divididas en cinco partes que tratan los principales aspectos para cada entorno asistencial. En este artículo se presenta un resumen ejecutivo de las mismas. The SARS-CoV-2 pandemic has created new scenarios that require modifications to the usual cardiopulmonary resuscitation protocols. The current clinical guidelines on the management of cardiorespiratory arrest do not include recommendations for situations that apply to this context. Therefore, the National Cardiopulmonary Resuscitation Plan of the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC), in collaboration with the Spanish Group of Pediatric and Neonatal CPR and with the Teaching Life Support in Primary Care program of the Spanish Society of Family and Community Medicine (SEMFyC), have written these recommendations, which are divided into five parts that address the main aspects for each healthcare setting. This article consists of an executive summary of them.