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.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies: relationship with COVID-19 diagnosis, symptoms, smoking, and method of transmission.

Aims: The study of SARS-CoV-2 antibodies in the population is a crucial step towards overcoming the COVID-19 pandemic. Seroepidemiological studies allow an estimation of the number of people who have been exposed to the virus, as well as the number of people who are still susceptible to infection. Methods: In total, 13 560 people from Arganda del Rey, Madrid (Spain) were assessed between January and March 2021 for the presence of IgG antibodies, using rapid tests and histories of symptoms compatible with COVID-19. Results: 24.2% of the participants had IgG antibodies and 9% had a positive COVID-19 diagnosis. Loss of smell/taste was the most discriminating symptom of the disease. The main transmitters of infection were found to be household members. Unexpectedly, in smokers, the incidence of positive COVID-19 diagnoses was significantly lower. Additionally, it was found that there was a discrepancy between COVID-19 diagnosis and the presence of IgG antibodies. Conclusions: Rapid anti-IgG tests are less reliable in detecting SARS-CoV-2 infection at an individual level, but are functional in estimating SARS-CoV-2 infection rates at an epidemiological level. The loss of smell/taste is a potential indicator for establishing COVID-19 infection.

A comparative NMR-based metabolomics study of lung parenchyma of severe COVID‑19 patients (preprint)

The COVID-19 pandemic was the leading cause of mortality due to a single infectious agent in 2020 and 2021. The fatality rate for individuals admitted to the ICU for this condition was over 60%. A metabolomic analysis based on nuclear magnetic resonance was performed on patients who died in the ICU due COVID-19 and other fatal respiratory diseases. Although there is information on metabolic signatures in COVID-19 patients' serum and plasma, little is known about the infection site in the lungs. We found statistically significant differences between metabolites related to energy metabolism and inflammatory processes, revealing a unique metabolic profile. 

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

On the Use of Augmented Reality to Reinforce the Learning of Power Electronics for Beginners

This study aims to develop and evaluate an Augmented Reality (AR) application to teach power electronics to beginners. For this purpose, two topics were presented: The first was the design of a series-connected Resistance–Inductor–Capacitor (RLC) circuit in AR, the space-state equations of which were analyzed in an interactive way, and its assembly in a virtual protoboard to analyze the voltage and currents as measured by an oscilloscope. The second presented topic in AR was about Bidirectional Direct Current (DC)–DC converters, known as Buck–Boost;the aim was to study their behavior when energy is exchanged between two systems, usually photovoltaic panels, electric vehicles, and storage systems. The attitudes of the students towards the AR application was significantly better than those towards traditional teaching. The measurements of the developed skills indicated better cognitive performance when using AR technology. The designed AR tool was used in an industry course to explore the students’ opinions, who provided valuable feedback.

The Cognitive and Psychiatric Subacute Impairment in severe Covid-19. (preprint)

Background: Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Methods: : Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A Principal Component Analysis extracted the main independent characteristics of the syndrome. Results: : 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Conclusion: Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

Changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19 pandemic in Spain (preprint)

Background: We aimed to examine main changes in health behaviors, mental and physical health among older adults under severe lockdown restrictions during the COVID-19. Methods: We used prospective data from 3041 participants in four cohorts of community-dwelling individuals aged [≥]65 years in Spain. Data were obtained using validated questionnaires through a pre-pandemic face-to-face interview and a telephone interview conducted between weeks 7 to 15 after the beginning the COVID-19 lockdown. Lineal or multinomial, as appropriate, regression models with adjustment for the main confounders were used to assess changes in the outcome variables from the pre-pandemic to the confinement period, and to identify their associated factors. Results: On average, the confinement was not associated with a deterioration in lifestyle risk factors (smoking, alcohol intake, diet or weight), except for a decreased physical activity and increased sedentary time, which reversed with the end of confinement. However, chronic pain worsened, and moderate declines in mental health, that did not seem to reverse after restrictions were lifted, were observed. Several subgroups of individuals were at increased risk of developing unhealthier lifestyles or mental health decline with confinement: (i)-males (for physical activity and sedentariness), (ii)-those with greater social isolation (for diet, physical activity, mental health), (iii)-feelings of loneliness (for diet, sleep quality, mental health), (iv)-poor housing conditions (for diet, physical activity, TV viewing time), (v)-unhealthy sleep duration (for physical activity and sedentariness), and (vi-worse overall health or chronic morbidities (for physical activity, screen time, mental health). On the other hand, previously having a greater adherence to the Mediterranean diet and doing more physical activity protected older adults from developing unhealthier lifestyles with confinement. Conclusions: The lockdown during the first wave of the COVID-19 in Spain, which was one of the most restrictive in Europe, only led to minor average changes in health behaviors among older adults. However, mental health was moderately affected. If another lockdown were imposed on this or future pandemics, public health programs should specially address the needs of older individuals with male sex, greater social isolation, poor housing conditions and chronic morbidities, because of their greater vulnerability to the enacted movement restrictions

Associations between movement behaviors and emotional changes in toddlers and preschoolers during early stages of the COVID-19 pandemic in Chile (preprint)

BackgroundThere is limited evidence about emotional and behavioral responses in toddlers and preschoolers during the coronavirus disease (COVID-19) pandemic, particularly in Latin America. ObjectiveTo assess associations between changes in movement behaviors (physical activity, screen time and sleeping) and emotional changes in toddlers and preschoolers during early stages of the pandemic in Chile. MethodsA cross-sectional study conducted from March 30th to April 27th, 2020. Main caregivers of 1-to 5-year-old children living in Chile answered an online survey that included questions about sociodemographic characteristics, changes in the childs emotions and behaviors, movement behaviors and caregivers stress during the pandemic. Multiple linear regressions were used to assess the association between different factors and emotional changes in toddlers and preschoolers. ResultsIn total, 1727 caregivers provided complete data on emotional changes for children aged 2.9{+/-}1.36 years old, 47.9% girls. A large proportion of toddlers and preschoolers in Chile experienced emotional and behavioral changes. Most caregivers reported that children were more affectionate (78.9%), more restless (65.1%), and more frustrated (54.1%) compared with pre-pandemic times. Apart from changes in movement behaviors, factors such as child age, caregivers age and stress, and residential area (urban/rural) were consistently associated with changes in emotions and behaviors. ConclusionThe pandemic substantially affected the emotions and behaviors of toddlers and preschoolers in Chile. Mental health promotion programs should consider multilevel approaches in which the promotion of movement behaviors and support for caregivers should be essential pieces for future responses.

PostCOVID mental health

This letter discusses mental health situation post-COVID. The SARS-CoV2 (COVID-19) pandemic is a current challenge for the healthcare systems of the world. From a descriptive point of view, there are several classifications of the healthcare needs derived from COVID-19, through which the consequences of the pandemic could be studied or analyzed. In a few weeks, COVID-19 has put in check the health systems' capacity throughout the world, with almost 3 million people infected, more than 200,000 deaths and 850,000 patients recovered. A very important fact to take into account, is that it has occurred in a limited space of time, which has been a unique stress test for the health systems across the world, which have had to adjust in a record time, in order to absorb all demand and meet the needs of the population. The second wave has to do with to the health care needs of the general population for reasons other than COVID-19, which begin to appear after the withdrawal of the first wave. There are needs related to chronic conditions and the temporary withdrawal of continuity care programs, mostly patients who, during this time, have lowered their self-care protocols, often limited by the confinement circumstances. The last wave is the most specific of mental health problems. It is a longitudinal and cumulative wave. From a conceptual perspective, WHO defines health as the balance between physical, social and psychological well-being. There is no doubt that the deployment of health care resources to approach COVID-19 is being memorable. (PsycInfo Database Record (c) 2021 APA, all rights reserved)

Practices and Behaviors During the COVID-19 Pandemic in Patients With Rheumatoid Arthritis Who Attended Previously to An Educational Program. A Cross-Sectional Study (preprint)

Background: To describe the practices and behaviors of patients with rheumatoid arthritis (RA) who attend to a face-to-face education program, during the quarantine of the COVID-19 pandemic. Methods: Patients who attended previously a face-to-face education program, responded to a telephonic survey in July 2020. The survey included questions about their practices related to the COVID-19 pandemic, SARS-Cov-2 symptoms, adherence to rheumatoid arthritis treatment, virtual rheumatology consultancy compliance and, the influence of news on their adherence. Results: A total of 260 patients participated in a survey. In July 2020 88% of patients had accessed a telemedicine-based and 12% a face-to-face rheumatology consultation. 3.5% of patients reported having been less adherent to pharmacological therapy due to information received through media or social networks. In general patients had been compliant with COVID-19 prevention recommendations.  Only one patient was positive for SARS-CoV-2 and reported only flu symptoms without any complications. Patients highlighted the necessity to have information and education about the relationship between rheumatoid arthritis, its treatment, and COVID-19. Conclusions: An educational program is a helpful tool to maintain high adherence rates to the RA treatment despite of the new challenges associated to the pandemic; Patient-centered education programs should continue to address the patient's concerns and beliefs about their disease and COVID-19.

Mathematical model optimized for prediction and health care planning for COVID-19 (preprint)

Objective. The COVID-19 pandemic has threatened to collapse hospital and ICU services, and it has affected the care programs for non-COVID patients. The objective was to develop a mathematical model designed to optimize predictions related to the need for hospitalization and ICU admission by COVID-19 patients. Design. Prospective study. Setting. Province of Granada (Spain). Population. Consecutive COVID-19 patients hospitalized, admitted to ICU, recovered and died from March 15 to September 22, 2020. Study variables. The number of patients infected with SARS-CoV-2 and hospitalized or admitted to ICU for COVID-19. Results. The data reported by hospitals was used to develop a mathematical model that reflects the flow of the population among the different interest groups in relation to COVID-19. This tool has allowed us to analyse different scenarios based on socio-health restriction measures, and to forecast the number of people infected, hospitalized and admitted to the ICU until May 2021. Conclusions. The mathematical model is capable of providing predictions on the evolution of the COVID-19 sufficiently in advance as to anticipate the peaks of prevalence and hospital and ICU care demands, and also the appearance of periods in which the care for non-COVID patients could be intensified.

Sociodemographic Predictors of Changes in Physical Activity, Screen Time, and Sleep Among Toddlers and Pre-Schoolers in Chile During the COVID-19 Pandemic (preprint)

The aim was to examine the sociodemographic predictors associated with changes in movement behaviours (physical activity, screen time and sleep) among toddlers and pre-schoolers during the early stages of the coronavirus disease 2019 pandemic in Chile. Caregivers of 1- to 5-year-old children completed an online survey between March 30th and April 27th, 2020. Information about the child's movement behaviours before (retrospectively) and during the pandemic, as well as family characteristics were reported. In total, 3,157 participants provided complete data (mean children age: 3.1±1.38 years). During early stages of the pandemic, time spent in physical activity decreased, recreational screen time and sleep duration increased, and sleep quality declined. Toddlers and pre-schoolers with space to play at home and living in rural areas experienced an attenuated impact of the pandemic restrictions on their physical activity levels, screen time, and sleep quality. Older children, those whose caregivers had a higher educational level, and children living in apartments had greater changes, mainly a decrease in total physical activity and increase in screen time. This study has shown the significant impact of the pandemic restrictions on movement behaviours in toddlers and pre-schoolers in Chile.

COVID-19 in regions with low prevalence and low density of population. An uncertainty dynamic modeling approach. (preprint)

The coronavirus disease 2019 (COVID-19) that emerged in China at the end of 2019 has spread worldwide. In this article, we present a mathematical SEIR model focused on analysing the transmission dynamics of COVID-19, the patients circulating in the hospitals and evaluating the effects of health policies and vaccination on the control of the pandemic. We tested the model using registered cases and population data from the province of Granada (Spain), that represents a population size near 1 million citizens with low density of population and low prevalence. After calibrating the model with the data obtained from 15 March to 22 September 2020, we simulate different vaccination scenarios - including effectiveness and availability date - in order to study the possible evolution of the disease. The results show that: 1) infected will increase until 5.6\% - 7.4\% of the total population over next 3-4 months (2nd wave); 2) vaccination seems not to be enough to face the pandemic and other strategies should be used; 3) we also support the claim of the WHO about the effectiveness of the vaccine, that should be, at least, of 50\% to represent a substantial progress against the COVID-19; 4) after the 2nd wave, the return to normal life should be controlled and gradual to avoid a 3rd wave. The proposed study may be a useful tool for giving insight into the transmission dynamics of SARS-CoV-2 and to design vaccination and health policies.

HIGH VERSUS STANDARD DOSES OF CORTICOSTEROIDS IN COVID-19 PATIENTS WITH AN ACUTE RESPIRATORY DISTRESS SYNDROME: a controlled observational comparative study. (preprint)

INTRODUCTION: Despite the increasing evidence of the benefit of corticosteroids for the treatment of moderate-severe Coronavirus disease 2019 (COVID-19) patients, no data are available about the potential role of high doses of steroids for these patients. METHODS: All consecutive confirmed COVID-19 patients admitted to a single center were selected, including those treated with steroids and an acute respiratory distress syndrome (ARDS). Patients were allocated to the high doses (HD, 250mg/day or more of methylprednisolone) of corticosteroids or the standard doses (SD, 1.5mg/kg/day or more of methylprednisolone) at discretion of treating physician. The primary endpoint was the mortality between both cohorts and secondary endpoints were the risk of need for mechanical ventilation (MV) or death and the risk of developing a severe ARDS. RESULTS: 573 patients were included: 428 (74.7%) men, with a median (IQR) age of 64 (54-73) years. In HD cohort, a worse baseline respiratory situation was observed and male sex, older age and comorbidities were significantly more common. After adjusting by baseline characteristics, HD were associated with a higher mortality than SD (adjusted-OR 2.46, 95% CI 1.58-3.83, p<0.001) and with an increased risk of needing MV or death (adjusted-OR 2.50, p=0.001). Conversely, the risk of developing a severe ARDS was similar between groups. Interaction analysis showed that HD increased mortality exclusively in elderly patients. CONCLUSION: Our real-world experience advises against exceeding 1-1.5mg/kg/day of corticosteroids for severe COVID-19 with an ARDS, especially in older subjects. This reinforces the rationale of modulating rather than suppressing immune responses in these patients.