Coronavirus pathogenesis in mice explains the SARS-CoV-2 multi-organ spread by red blood cell hitch-hiking (preprint)

SARS-CoV-2 infection causes a multisystemic disease that affects numerous organs beyond the respiratory system. Thus, it is well known that COVID-19 is associated with a wide range of hematological disorders; however, it remains unclear how the SARS-CoV-2 virus is able to navigate from tissue to tissue. In this work, we performed a comprehensive analysis of the pleiotropic effects of a prototypical coronavirus in its natural host, the validated preclinical model of murine hepatitis virus (MHV). Throughout this study we compared our results with the real-world data from COVID-19 patients (including autopsies). Thus, the presence of viral RNA was only detected in less than 25% of the human serum samples, whereas all had multiple positive nasal swabs for SARS-CoV-2. Notably, we found viral RNA not only in lungs, but also in heart and kidney of deceased COVID-19 patients. Subsequently, we investigated the association between viral organotropism and clinical manifestations employing the MHV murine model. Results from RT-qPCR and viral infectivity showcased the presence of viral RNA and infectious particles in multiple organs including liver, lung, brain, heart, kidney, spleen and pancreas, and even the blood of infected mice. Surprisingly, when comparing plasma and red blood cells (RBCs)-enriched fraction, higher viral load levels were detected in RBCs, with decreased RBC count, and hematocrit and hemoglobin levels in infected mice. Next, we treated infected mice with hemin triggering more aggressive symptoms. Strikingly, when combining hemin treatment with chloroquine (a compound that known to interact with the heme group and induces a conformational change in its structure) the infection and its clinical manifestations were distinctly attenuated. Computational docking suggested that heme is able to bind to MHV Spike protein in a similar way to the one, experimentally observed for SARS-CoV-2. Overall, our results lead to a global perspective of COVID-19 beyond the canonical focus on the respiratory system, and strongly support the multi-organ extent of coronavirus infection through specific interactions with RBC hemoproteins.

Authenticity in industrial heritage tourism sites: Local community perspectives

Our research addresses the perceived authenticity by the local community, as a means of enhancing Industrial Heritage Tourism. It aims to explore the influence of perceived authenticity in the future intentions of the local community, concerning a heritage tourism destination. Data was collected from Sao Joao da Madeira residents, Portugal, and the sample consisted of 389 respondents. The statistical technique applied was the structural equation model (SEM). Our findings suggest that perceived heritage plays a significant role in residents' attitudes towards tourism development support, their own participation ideals, and their attachment to the place. These findings will contribute to both practical and theoretical research, as they aim to enhance current knowledge on residents' perceived authenticity, being an understudied approach;furthermore, it offers a valuable opportunity to consider residents in the management and planning of an industrial tourism destination. This study analyses the outcomes of the obtained results. Additionally, it presents the main limitations, suggests future lines of research, and provides practical and theoretical data for both public and private entities, aiming at future improvements in the development of industrial heritage tourism.

¿What did we learn from Convalescent plasma treatment in a COVID-19 patient two-time kidney transplanted? A case report from the viral and immune response evolution perspective (preprint)

Background: COVID-19, an infectious disease caused by SARS-CoV-2 virus, can provoke a vast range of clinical manifestations, ranging from asymptomatic to potentially life-threatening complications. At the beginning, convalescent plasma therapy has been proposed as an effective alternative to treat severe cases. The aim of this study was to follow over time a two-time renal transplanted COVID-19 severe patient treated with convalescent plasma from an immunological and virologic perspective.Case presentation: A 42-year-old female patient, two-time kidney transplanted was hospitalized with COVID-19. Due to worsening of respiratory symptoms, she was admitted to the intensive care unit where she received two doses of convalescent plasma. Conclusion: We analyzed the dynamics of viral load in nasopharyngeal swab, saliva and tracheal aspirate samples, before and after convalescent plasma transfusion. Pro-inflammatory cytokines and antibody titers were also measured in serum samples. A post-treatment decrease in viral load was observed to be sharp in saliva and nasopharyngeal swab samples, and slight in tracheal aspirate samples. Furthermore, we evidenced an increase of antibody titers post transfusion, accompanied with a decrease of several cytokines responsible of the cytokine storm.

Bacteremia during COVID-19 pandemic in a tertiary hospital in Spain Bacteriemia durante la pandemia de COVID-19 en un hospital terciario de España

Introduction The reasons for the decrease in blood cultures were investigated and the rate and aetiology of bacteremia and contaminated blood cultures collected from COVID and non-COVID patients were assessed. Methods We performed a retrospective analysis in a tertiary hospital in Spain during the COVID period from 4th March 2020 to 21st June 2020. Results The number of blood cultures processed was 5313, representing 22.7% and 18.8% of decrease compared to the same months of 2019 and 2018, respectively (p = 0.173). The rate of bacteremia was 1.2% higher among COVID-patients than among non-COVID patients (p < 0.001). COVID patients had a higher proportion of nosocomial bacteremia (95.5%) than non-COVID patients (30.5%) (p < 0.001). In COVID-positive patients, the contamination rate was 12.3% vs 5.7% in non-COVID patients (p < 0.001). Conclusion There was a decrease in the number of blood cultures collected during the COVID period compared to previous years. Bacteremia in COVID patients was mainly nosocomial and catheter-related.

Covid 19: Eating behavior changes related to individual and household factors during the COVID-19 lockdown in Spain

Objetive: To analyze the influence of individual and household factors on eating behavior (EB) and other determinants related to eating during the home lockdown in the Covid-19 pandemic. Method: Online survey (April 17 to May 10, 2020) to collect sociodemographic information, health, and various EB attitudes. Statistical analysis of the factors: country, setting, sex, BMI classification, lockdown period, a household with children under 15 years, nutritional needs, age groups, type and size household, monthly income, and religion. Results: 1055 households participated. 75% have modified their eating habits, with differences due to being overweight or obese in the person surveyed (p <0.05). Changes in EB and other lifestyles are influenced by household structure (p <0.001) and the effects that the pandemic has had on the economy of families (p <0.001). Compared to those who do not have them, households with children tend to plan much more meals, spend more time eating, seek a healthier diet, increase the number of daily meals, and look more at labeling. In contrast, people who live alone have worsened the hourly routines of the main meals. Conclusions: Confinement has modified eating behavior differently depending on the individual and domestic factors analyzed.Alternate abstract: Objetivo: Analizar la influencia de factores individuales y del hogar sobre el comportamiento alimentario (CA), y otros determinantes relacionados con la alimentación, durante el confinamiento domiciliario en la pandemia por Covid-19. Método: Encuesta online (17 abril al 10 de mayo de 2020) para recopilar información sociodemográfica, de salud y diversas actitudes del CA. Análisis estadístico sobre los factores: país, ámbito, sexo, IMC, tiempo de confinamiento, hogar con menores de 15 años, necesidades nutricionales, grupos de edad, tipo y tamaño del hogar, ingresos y religión. Resultados: Participaron 1055 hogares. El 75% ha modificado sus hábitos alimentarios, con diferencias por sobrepeso u obesidad de la persona encuestada (p<0.05). Los cambios en el CA y otros estilos de vida están influenciados por la estructura del hogar (p<0.001) y los efectos que la pandemia ha tenido sobre la economía de las familias (p<0.001). Los hogares que tienen hijos/as, respecto a los que no los tienen, tienden a planificar mucho más las comidas, dedicar más tiempo a la alimentación, procuran una alimentación más saludable, incrementan el número de comidas diarias y miran más el etiquetado. Por el contrario, las personas que viven solas han empeorado las rutinas horarias de las principales comidas. Conclusiones: El confinamiento ha modificado de manera diferenciada el comportamiento alimentario en función de los factores individuales y domésticos analizados.

Empoderamiento de mujeres participantes del programa de alivio a la pobreza Emprendiendo una Vida Mejor en Honduras: análisis cualitativo (Empowerment of Women Beneficiaries of a Poverty-alleviation Program in Honduras: A Qualitative Analysis) (preprint)

Spanish Abstract: En el año 2018, el gobierno hondureño inició la implementación del programa Emprendiendo una Vida Mejor (EVM), enfocado en reducir la pobreza extrema de hogares rurales en tres departamentos del país. Este programa está basado en el enfoque de graduación, que ha probado resultados efectivos en reducir la pobreza en varias dimensiones. El diseño, la implementación y el seguimiento del programa estuvieron acompañados por un ejercicio de evaluación que incluyó tanto análisis cuantitativo como cualitativo. En este documento se presentan los principales resultados del análisis cualitativo, con un enfoque especial en el empoderamiento de las mujeres participantes. Incluye las percepciones de las mujeres receptoras del programa como de sus compañeros y explora los efectos en acceso a recursos, agencia e impacto en varias dimensiones. Los resultados señalan mejoras en el empoderamiento de las mujeres participantes en aspectos relacionados con la toma de decisiones productivas, domésticas, financieras y de movilización, así como en cambios en el uso del tiempo en actividades domésticas y productivas. Adicionalmente, encontramos mejoras en ingresos, seguridad alimentaria del hogar, activos y actividad productiva, y cambios sustantivos en autoestima, confianza, y la capacidad de establecer metas y definir estrategias para alcanzarlas. El programa EVM otorgó resiliencia a los hogares receptores para enfrentar los efectos de la pandemia causada por el Covid y el confinamiento al que obligó.English Abstract: The Honduran government launched the Emprendiendo una Vida Mejor (EVM) program in 2018. Based on the graduation approach, which has proven effective in reducing poverty in several dimensions, EVM was designed to reduce extreme poverty among rural households in three of the country's departments. Its design, implementation, and monitoring were coupled with an evaluation exercise that included quantitative and qualitative analysis. This paper presents the main results of the qualitative analysis, focusing on the empowerment of women participants. It investigates the perceptions of both women program recipients and their spouses and explores the effects on access to resources, agency, and impact in several dimensions. The results indicate that the women participants are more empowered in aspects related to productive, domestic, and mobility-related decision-making, as well as in terms of changes in their use of time in domestic and productive activities. We also found improvements in income, household food security, assets and productive activity, and substantive changes in self-esteem, confidence, and the ability to set goals and define strategies to achieve them. The EVM program provided resilience to recipient households to cope with the effects of the Covid pandemic and the confinement it enforced.

Emergence and spread of a B.1.1.28-derived lineage with Q675H and Q677H Spike mutations in Uruguay (preprint)

Uruguay was able to control the viral dissemination during the first nine months of the SARS-CoV-2 pandemic. Unfortunately, towards the end of 2020, the number of daily new cases exponentially increased. We previously identified a B.1.1.28 sublineage carrying mutations Q675H+Q677H in the viral Spike, with local transmission in Rocha, a department bordering Brazil. To understand whether these B.1.1.28+Q675H+Q677H sequences were part of an emergent SARS-CoV-2 lineage broadly disseminated in Uruguay, herein we analyzed the country-wide genetic diversity of viruses between November, 2020 and April, 2021. Our findings support that B.1.1.28+Q675H+Q677H probably arose around November 2020, in Montevideo, Uruguay's capital department. This clade spread to other Uruguayan departments, with evidence of further local transmission clusters. It also spread to the USA and Spain. The Q675H and Q677H mutations are in the proximity of the polybasic cleavage site at the S1/S2 boundary and also arose independently in many SARS-CoV-2 lineages circulating worldwide. Although in Uruguay the B.1.1.28+Q675H+Q677H lineage was dominated by the VOC P.1 since April 2021, the monitoring of the concurrent emergence of Q675H+Q677H in VOIs and/or VOCs should be of worldwide interest.

Implementation of a qPCR assay coupled with genomic surveillance for real-time monitoring of SARS-CoV-2 variants of concern. (preprint)

We developed a genomic surveillance program for real-time monitoring of SARS-CoV-2 variants of concern in Uruguay. Here, we present the first results, including the proposed qPCR-VOC method, the general workflow and the report of the introduction and community transmission of the VOC P.1 in Uruguay in multiple independent events.

An effective COVID-19 response in South America: the Uruguayan Conundrum (preprint)

Background: South America has become the new epicenter of the COVID-19 pandemic with more than 1.1M reported cases and >50,000 deaths (June 2020). Conversely, Uruguay stands out as an outlier managing this health crisis with remarkable success. Methods: We developed a molecular diagnostic test to detect SARS-CoV-2. This methodology was transferred to research institutes, public hospitals and academic laboratories all around the country, creating a COVID-19 diagnostic lab network. Uruguay also implemented active epidemiological surveillance following the Test, Trace and Isolate (TETRIS) strategy coupled to real-time genomic epidemiology. Results: Three months after the first cases were detected, the number of positive individuals reached 826 (23 deaths, 112 active cases and 691 recovered). The Uruguayan strategy was based in a close synergy established between the national health authorities and the scientific community. In turn, academia rapidly responded to develop national RT-qPCR tests. Consequently, Uruguay was able to perform ~1,000 molecular tests per day in a matter of weeks. The COVID-19 diagnostic lab network performed more than 54% of the molecular tests in the country. This, together with real-time genomics, were instrumental to implement the TETRIS strategy, helping to contain domestic transmission of the main outbreaks registered so far. Conclusions: Uruguay has successfully navigated the first trimester of the COVID-19 health crisis in South America. A rapid response by the scientific community to increase testing capacity, together with national health authorities seeking out the support from the academia were fundamental to successfully contain, until now, the COVID-19 outbreak in the country.

Impact of COVID-19 outbreak on ischemic stroke admissions and in-hospital mortality in North-West Spain.

BACKGROUND AND PURPOSE: Spain has been one of the countries heavily stricken by COVID-19. But this epidemic has not affected all regions equally. We analyzed the impact of the COVID-19 pandemic on hospital stroke admissions and in-hospital mortality in tertiary referral hospitals from North-West Spain. METHODS: Spanish multicenter retrospective observational study based on data from tertiary hospitals of the NORDICTUS network. We recorded the number of patients admitted for ischemic stroke between 30 December 2019 and 3 May 2020, the number of IVT and EVT procedures, and in-hospital mortality. RESULTS: In the study period, 2737 patients were admitted with ischemic stroke. There was a decrease in the weekly mean admitted patients during the pandemic (124 vs. 173, p<0.001). In-hospital mortality of stroke patients increased significantly (9.9% vs. 6.5%, p = 0.003), but there were no differences in the proportion of IVT (17.3% vs. 16.1%, p = 0.405) or EVT (22% vs. 23%, p = 0.504). CONCLUSION: We found a decrease in the number of ischemic stroke admissions and an increase in in-hospital mortality during the COVID-19 epidemic in this large study from North-West Spain. There were regional changes within the network, not fully explained by the severity of the pandemic in different regions.

Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples (preprint)

The pandemic caused by SARS-CoV-2 has triggered an extraordinary collapse of healthcare systems and hundred thousand of deaths worldwide. Following the declaration of the outbreak as a Public Health Emergency of International Concern by the World Health Organization (WHO) on January 30th, 2020, it has become imperative to develop diagnostic tools to reliably detect the virus in infected patients. Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. In addition, these methods have been recommended by the WHO for laboratory diagnosis. Since all these protocols are based on the use of fluorogenic probes and one-step reagents (cDNA synthesis followed by PCR amplification in the same tube), these techniques can be difficult to perform given the limited supply of reagents in low and middle income countries. In the interest of economy, time and availability of chemicals and consumables, the SYBR Green-based detection was implemented to establish a convenient assay. Therefore, we adapted one of WHO recommended Taqman-based one-step real time PCR protocols (from the University of Hong Kong) to SYBR Green. Our results suggest that SYBR-Green detection represents a reliable cost-effective alternative to increase the testing capacity.

Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay (preprint)

BackgroundAfter its emergence in China in December 2019, the new coronavirus disease (COVID-19) caused by SARS-CoV-2, has rapidly spread infecting more than 3 million people worldwide. South America is among the last regions hit by COVID-19 pandemic. In Uruguay, first cases were detected on March 13 th 2020 presumably imported by travelers returning from Europe. MethodsWe performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Then, we applied genomic epidemiology using a global dataset to reconstruct the local spatio-temporal dynamics of SARS-CoV-2. ResultsOur phylogeographic analysis showed three independent introductions of SARS-CoV-2 from different continents. Also, we evidenced regional circulation of viral strains originally detected in Spain. Introduction of SARS-CoV-2 in Uruguay could date back as early as Feb 20th. Identification of specific mutations showed rapid local genetic differentiation. ConclusionsWe evidenced early independent introductions of SARS-CoV-2 that likely occurred before first cases were detected. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region.