Research projects

The objective is to carry out a clinical-epidemiological study as broad as possible in nursing homes in Albacete province to analyze the clinical, sociodemographic, functional, cognitive, nutritional and geriatric syndromes characteristics of the COVID-19, identify factors predisposing to infection and health outcomes specifics of this high-risk population. Initially, it will be held in the "Vasco Núñez de Balboa", "Paseo de La Cuba", "Vital Parque", "Alcabala" and "Alábega" nursing homes, although it could be expanded to other residences. In total, it is planned to include around 1,000 residents. A follow-up will be carried out at 3 and 6 months to collect clinical, epidemiological and economic outcome variables in collaboration with the Department of economic analysis of UCLM (Toledo). The study will be carried out at the Geriatrics Service of Albacete.

The objective of this study is to determine the protective efficacy of mefloquine prophylaxis against placebo in close contacts of people with COVID-19. For this, 200 contacts of people in close contact with patients will be selected infected with COVID-19 and who will be randomly assigned to one or the other arm of the study and they must follow the indicated administration regimen (one tablet per week).

Spanish multicenter epidemiological study based on the registration of cases of pregnant women with COVID 19 in Spain. Objective: the knowledge of the influence of COVID 19 on gestations and childbirth in our country. 77 Associated centers at the time of preparing this document. Data protection law compliant database This is a prospective observational registry study of pregnant women suspected of having a SARS-CoV-2 infection at any time during pregnancy with positive test results for SARS-CoV -2. Follow-up up to two weeks after delivery. Start date March 2020. End March 2021 € 43,000 is requested to create its own database, exploit it and communicate the results.

There is an urgent need to evaluate commonly used drugs with potential efficacy for COVID-19. This protocol evaluates the efficacy of various antiviral treatments in patients with severe SARS-CoV-2 pneumonia regarding mortality, length of the hospital stays and reception of ventilation or intensive care. The study design is an open and randomized clinical trial, allowing to add / remove treatment arms while the trial is in progress. This study complements the Solidarity trial promoted by WHO and will provide additional and valuable information.

SARS-CoV-2 uses the angiotensin-2 converting enzyme (ACE2) to penetrate cells and replicate. Certain drugs are known to increase the expression of ACE2 and may facilitate the entry of the virus and promote the severity of the infection. We intend to conduct an epidemiological case-control study, taking as cases patients hospitalized by COVID-19 in participating hospitals (subclassified by severity) and primary care population controls extracted from the BIFAP database and paired with cases by age (exact), sex and index date. Information on prescribed drugs and comorbidities will be extracted from the hospital and BIFAP clinical records and the adjusted Odds Ratio will be computed using conditioned logistic regression models. Information from non-hospitalized mild COVID-19+ cases will be assessed as an alternative series of controls (1:1 ratio).

Patients with COVID-19 disease have a very high risk of short and long-term cardiovascular adverse events, including death from cardiovascular causes. We propose an epidemiological surveillance study to determine the rate of adverse cardiovascular events (cardiovascular death, myocardial infarction, cardiovascular accident, cardiac arrhythmias) = at the time of infection, 30 days, 6 and 12 months, in patients confirmed by COVID- 19. In addition, to determine the relationship between the use of drugs that inhibit the angiotesin 2 converting enzyme, angiotesin 2 receptor blockers and non-steroidal anti-inflammatory drugs in the presentation of severe or fatal cases by COVID-19, through a case-control study. We will develop tools for early warning, prediction and risk stratification of cardiovascular adverse events in patients with COVID-19 Through a web page, immediate dissemination of the information generated and open use of the tools developed will be made.

Various cell lines (eg Vero or Calu-3) express in their cell membrane the ACE2 protein, involved in the union with the S trimmer of SARS-CoV-2, and also has proteolytic activities for the activation of the same protein, two of the hypothetical requirements for the entry of the virus into a human host. Therefore, those substances that can diminish the role of ACE2 or the activity of proteases of the guest on protein S, could be used for the treatment of the infection. Thus, i) commercial drug libraries authorized for use in humans and ii) antisense oligonucleotides with peptide vehicles will be used as condidate molecules as a new therapeutic approach.

We have developed and patented a methodology that allows to synthesise protein micro (MS) or nanospheres (NS) containing any protein of interest by tagging them with a tag called IC. These MS function as vaccines in the absence of adjuvants and the integrated proteins fold perfectly, allowing quaternary structures and even enzymatic reactions. In this project we intend to generate microspheres containing the S1 domain of protein S or the M or N proteins of SARS-Cov-2 and characterize in a mouse model the immune response they induce when administered intranasally or intramuscular. The methodology is already developed in the baculovirus expression systems, mammalian cells and bacteria, and will adapt to the yeast system for fast implementation in human vaccines.

The project aims to discover Mpro protease inhibitors of the SARS-CoV-2 virus by repositioning drugs as new antiviral agents. This will be done using computer-assisted drug design methods. The process includes the preparation of the target structure by molecular dynamics, molecular screening using a molecular anchorage algorithm and calculation of the free binding energy of the best ligands. Databases of molecules approved as therapeutic agents and natural products will be used for virtual screening. The final result will be an affinity sorted list of various molecules that can be tested in vitro.

The aim is to apply our already recognised knowledge in the establishment of computer models based on new membrane computing techniques in order to develop a multi-parametric and multi-hierarchical model for the prediction of the effect of interventions on the COVID-19 epidemic. The model allows introducing ranges of values at multiple levels (e.g., ages, contact rates, contact times, transmission rates, transmission protection measures and effects of possible therapeutic agents) and observing how the modification of each or several factors simultaneously influences the epidemiological trend of the disease. The purpose is to assist in decision-making for the establishment of on-demand interventions for specific scenarios.

The main objective of the study is to evaluate in-hospital mortality, need for mechanical ventilation in Intensive Care Units, or need for rescue dose of tocilizumab in patients with confirmed infection by COVID-19 in treatment with hydroxychloroquine and azithromycin combined with non-tocilizumab. The study will compare 2 branches, standard of care, control branch; vs. tocilizumab treatment, experimental arm.

Convalescent plasma Therapy (PC, administration of fresh plasma from immunized donors) is used in viral acute respiratory infections. Given the SARS-CoV-2 pandemic, this study proposes to carry out a randomized trial in non-severe subjects hospitalized for COVID-19 with PC vs "standard of care" (according to WHO guidelines), in more than 20 hospitals, in coordination with the transfusion centres and the CNM-ISCIII. In this study, all participating patients will receive the standard treatment provided according to the current treatment protocols for coronavirus disease. In addition to this treatment, each patient will be randomly assigned to receive additional treatment with convalescent plasma transfusion (CP; blood plasma from patients who have been cured of coronavirus), or continue with standard treatment but without adding transfusion.

Currently there are no methods to detect and visualize the presence of the SARS-CoV-2 on material surfaces. This project aims to design, develop and evaluate a prototype of a portable device (using existing optical technologies combined with artificial intelligence) for rapid and contactless detection of contaminated areas in surfaces. To do so, this project will: i) combine multispectral images in the optical range (ultraviolet to thermal infrared) and terahertz, ii) use optical analysis methods computational, interferometry and holography, iii) integrate information through intelligence artificial, and iv) carry out laboratory tests and in contaminated and clean environments.

We are conducting a rapid, multi-national collaboration that aims to identify psychological and cultural factors that may be relevant to the virus spread and its imminent social and material consequences. The online survey includes brief measures to assess topic-relevant beliefs, fears, hopes, and frustrations, predictors of self-containment and social distancing, attitudes toward policies, reasoning, and behavioral self-reports. The survey has a built-in longitudinal component as well as a broader data science mission involving metadata. This is an unfunded, citizen-scientist initiative comprised of 40+ colleagues (and counting). The goal of of group is to publish reports suggesting to policy makers the most promising avenues to thwart the spread of the virus.

The objective of this study is to evaluate the effect of 48-hour treatment with inhaled sevoflurane on arterial oxygenation, assessed by PaO2/FiO2 on day two, in patients with ARDS-CoVid19. The effects of sevoflurane on pro-inflammatory cytokine levels (Tumor Necrosis Factor [TNF] alpha, Alveolar and plasma IL-1beta, IL-6, IL-8) during ARDS-CoVid19 and the mortality at day 30 will also be addressed. It is a multicentre, national, randomized 1:1 ratio, controlled, parallel, open study. Patients in their first 24 hours of admission to the UCC and after being diagnosed with ARDS, they will be randomized to receive sevoflurane as a sedative or standard sedation with propofol.

To date, only anecdotal cases of COVID-19 have been described in HIV-infected persons. This supports the hypothesis that antiretroviral drugs may have some protective effect against SARS-CoV-2 infection. In order to have reliable information about the incidence of symptomatic or asymptomatic SARS-CoV-2 infection, we intend to carry out a retrospective study within the scope of the Spanish AIDS Research Network Cohort (CoRIS). Objectives: (i) to describe the frequency and epidemiological and clinical characteristics of patients with COVID-19 in CoRIS, as well as the prognostic factors of intensive care requirement, use of mechanical ventilation, duration of admission and mortality; and (ii) to study the prevalence of antibodies against SARS-CoV-2 by determining IgG and IgM antibodies by ELISA

The aim of this project is to determine the risk factors, prognosis and short and long-term outcomes (6 months and one year) of patients with COVID-19 admitted to Spanish ICUs. The second objective is the study of epigenetics and essential predictive enrichment biomarkers to help individualize treatment based on the altered biological pathways in each patient. The clinical data will be analysed with artificial intelligence.

The proposed project aims to develop a set of mathematical models to quantify in real time the new unreported cases of COVID-19 in Spain, by Autonomous Communities or other areas of interest. The estimates provided by these models will be used to study the dynamics of the disease based on the application of compartmentalised epidemiological models (type SIR, SEIR, SIRS, etc.) that will make it possible to estimate, more precisely, the associated mortality and morbidity. Similarly, these estimates will be used to carry out an exhaustive analysis of the cost-effectiveness in different realistic action scenarios, both from the point of view of public management and from that of social management, which will be able to help in the decision-making process in the area of the national public health system and also within each Spanish Autonomous Community, in order to deal with the present pandemic and in future similar situations.

Although some clinical characteristics (advanced age, high fever, high SOFA score) and inflammatory response (IL-6, PC-R, D-dimer) have been described, the reasons why certain patients with COVID-19 develop severe disease, presenting dyspnea and hypoxemia in the first 7 days and rapid progression to ARDS, multi-organ failure and death, continue to be an enigma. The main objective of the present project is to determine the dynamic transcriptomic profile of adult patients hospitalized by COVID-19 and to characterize the subgroup that develops severe disease (ARDS). Secondary objectives are to establish a gene signature capable of basally discriminating the group that will develop ARDS and contribute to the phylogeny of the virus.

The project addresses the preparation of colorimetric sensors based on nanoparticles and oligonucleotides, which allow the detection of the virus by changing the colour of a solution, or the presence of colour in a nitrocellulose strip. The system will be implemented at 3 different amplification systems in order to reduce the use of highly specialized equipment and reagents to a minimum: 1) in RT-PCR, avoiding the use of quantitative RT-PCR, 2) in amplification isothermal, avoiding the use of PCR in general, and 3) in non-enzymatic amplification, avoiding the use of enzymes. The processes developed are industrially scalable, and are expected to acquire rapidly the ability at IMDEA Nanoscience to produce 5,000 sensors based on nanoparticles.

There is a growing pressure to understand the transmission patterns of SARS-CoV-2. As a new emergent virus, we have important gaps in the epidemiology of its infection. Those gaps translate also to limited understanding on who is infectious and for how long and how is connected to clinical outcome. Here we propose several objectives that involve combining viral genome data to epidemiological, clinical information to address those gaps. We will obtain viral complete genome sequences and epidemiological data and combine to (1) inform public health measures by revealing highways of transmission; (2) identify when an individual is infectious; (3) identify early warnings of local spread; (4) viral diversity connected to immune, drug and diagnostic; (5) complement current diagnostic approaches, and (6) identify the connection to adverse clinical outcomes. To this end, we have put together a nation-wide group of infectious disease, genomics, bioinformaticians and clinical researchers from more than 30 institutions.

Airborne transmission of pathogens is a virtually unexplored area due to low concentration of microbial biomass in the air and the lack of sensitive tools for its study. The objective of the project is to study the transmission of SARS-CoV-2 by air in the hospital environment. For this we will use airborne virus capture equipment developed in A. Alcamí's laboratory and already installed in the Hospital La Paz to monitor the presence of SARS-CoV-2. To improve the studies of virus transmission, new faster and more sensitive detection methods will be developed than currently available methods and cutting-edge technologies to detect SARS-CoV2 in the air in real time. The project is structured in 3 objectives: (1) Monitor the prevalence of SARS-CoV2 in different hospital areas (ICU, wards waiting, emergency, rest staff, pediatrics, neonates) (2) Optimize the rapid detection of viruses, by using nanoparticles that identify Genomic RNA and viral proteins (3) Optimize the LIF (laser-induced fluorescence) methodology, a new technology that It will allow to identify SARS-CoV2 particles in real time in the air.

Our objective is to produce an effective vaccine against SARS-CoV-2 as follows: Vaccine 1: This vaccine named MVA-COVID-19(S) will express the full-length S protein of SARS-CoV-2 and is directed to generate in an organism neutralizing antibodies to prevent infection and virus spread. This vaccine is ongoing in our laboratory and expected to have the candidate during April-May 2020 to be used for preclinical studies during June-July 2020. Vaccine 2: This vaccine named MVA-COVID-19(S-E-M) will express three proteins of SARS-CoV-2 (S, E and M) in the form of VLPs and is directed to trigger neutralizing antibodies and T cell (CD4+ and CD8+) immune responses, with the goal to produce long-term control of virus infection. This vaccine will be generated along May-September 2020 to initiate the preclinical studies in October-December 2020.

Following WHO guidelines, it has been announced that new tests will soon be used much faster, but also more inaccurate diagnoses that can lead to false positives and negatives. In this sense, since genetic material of coronavirus has been found in serum exosomes and HIV-1 in exosomes of urine of infected persons here we suggest to perform, the diagnostic tests on the urine exosomes, plasma and saliva of patients at different times of the study, to detect it more reliably and early.

Molecular study using the NGS to obtain the genome sequences of the SARS-CoV-2 virus of the positive cases identified at the Elche General Hospital. With the data obtained, a molecular epidemiological analysis of the genetic variation of the virus in this Hospital from the beginning of the outbreak to the end of it can be carried out. In addition, these sequences will contribute to increase the genomic sequences of this virus in the global databases that will allow the realization of epidemiological studies at both national and global levels. With the information generated, the clinical data of patients affected by SARS-CoV-2, infection can be put into context and it will be possible to identify whether there is a relationship or a cluster of the virus with higher prevalence or worse prognosis in our Hospital.

The SARS-COV-2 coronavirus, similar to other viruses in the same family, has the ability to affect the nervous system. This neuroinvasive ability has been attributed a potential prognostic value because it is related to respiratory failure in infected patients. On the other hand, in a retrospective review of 214 cases attended during the epidemic outbreak in Wuhan, symptoms attributable to both CNS and PNS are described in a relevant percentage. Based on these data, we hypothesize that the neurological involvement in the acute phase and in the medium or long term may condition the prognosis and quality of life in patients who have survived the infection. The objective of this project is the clinical, biological and molecular characterization of neurological involvement in a prospective cohort of SARS-CoV-2 infection survivors.

The aim of this project is to study the innate and acquired immune response in patients diagnosed with SARS-CoV-2, by monitoring the cellular and humoral components of the innate and adaptive immune response in blood and their correlation with clinical severity. This panel is similar to the one used in the clinical characterization of immunocompromised patients and can be applied immediately to the management of patients with COVID-19.

There are few serological tests against SARS-CoV-2 and none that can be performed in solution. The proposed assay allows to detect antibodies (Ab) and / or virus from serum or plasma, without processing and to identify directly Abs that compete the virus / receptor interaction (according to affinity and epitope). It will also allow identifying patients that have Abs blocking the virus / receptor interaction (whose serum can be used in therapy). We will use samples from infected patients to identify coding sequences of variable regions of Abs with sufficient affinity to block the virus / receptor interaction and we will develop Chimeric antigen receptor (CAR) for the destruction of infected cells. We will also develop regulatory CARs to specifically block the immune system, in those cases where it is responsible but also, regulatory CARs to specifically block the immune system, in those cases where it is responsible of the pathogenesis of serious infections. Based on existing developments, we proposed the proof of concept of a nano sensor, which allows the analysis of samples and data collection by the general public using a smartphone.

The STOP-Coronavirus project aims to analyse in an integrated and multidisciplinary way the impact that various factors (clinical presentation, immunological markers, therapeutic strategies, host and virus genomics, and bioethical and socio-economic considerations) have on the evolution and prognosis of COVID-19. A prospective multicenter cohort of patients diagnosed with COVID-19 will be established. In parallel, the immune response to SARS-CoV-2, genetic markers of host susceptibility, the complexity of the SARS-CoV-2 mutant spectrum and the socio-economic and bioethical impact of COVID-19 will be characterized. Clinical analysis will be complemented by a nested cohort of immunosuppressed patients and by the assessment of COVID-19 response to antiviral and immunomodulatory treatment. Ultimately, this project will guide and individualize the clinical and therapeutic approach of COVID-19 and mitigate the health and social impact of the pandemic

Given the speed with which we can sequence the genomes of new RNA viruses, developing therapies directed against them, rather than against viral proteins, would accelerate the development of efficient therapies. In this project, we will generate and validate, in cell culture and in mouse models, circular RNAs (cRNAs) that hybridize and interfere with essential structures of the SARS-CoV-2 genome and inactivate it. The selection of resistances is highly improbable given the conservation of the target sequences and the interference on several regions simultaneously. Our previous success with cRNAs that inhibit the replication of other RNA (+) viruses, and the existence of already clinical RNA-based therapies and nebulization delivery systems, support the feasibility of our proposal.

The main objective of this study is to describe the influence of pregnancy on COVID-19 infection, as well as the influence of COVID-19 (and its treatment) on pregnancy, the fetus and the newborn. It is a descriptive, longitudinal, observational, multicenter study involving 8 hospitals to be conducted between April 2020 and March 2021. An electronic data collection notebook (REDCap) will be designed where data will be entered anonymously. Pregnant women infected by SARS-CoV-2 will be included, microbiological samples will be collected and processed (PCR-SARS-CoV-2 in a deferred way) from the mother and newborn and clinical data related to the patient, the infection, her treatment and complications, pregnancy and complications, delivery and newborn.

Patients infected with SARS-CoV-2 virus are characterized by a high degree of inflammation and dysregulation of the specific T response. We have found that the hypoxia and oxidative stress suffered by these patients activate the inflammation complex. This complex also has effects on pyroptosis and on the production of IFN type l. On the other hand, the inflammatory condition of the patient will directly condition the specific T-response. In short, understanding the inflammatory state in patients provides information relevant to the evolution of the pathology. This project proposes as an object to study the effect of drugs collected in this clinical trial in patients with COVID-19, in the activation of inflammation and its effect on inflammation and T-response. These data associated with patient evolution are crucial to classify responders and viral avoidance mechanisms.

Although SARS-CoV-2 and other coronaviruses are primarily transmitted directly between individuals during epidemic phases, the permanence of the virus in the environment has the potential to cause new outbreaks despite mitigation efforts. SARS-CoV-2 was detected in hospital wastewater in China and it was shown that the viral particles could remain infective long enough to pose a risk. We will investigate the potential for environmental transmission of the virus under our country's specific conditions. To do this we will first focus on the analysis of wastewater treatment plants and the release of the virus via the gut. We will also study the stability of the virus, as well as its presence in other environments, such as common surfaces like plastics, stainless steel or glass. This will provide valuable information for the management of the epidemic.

The present study aims to identify an early marker in blood that will allow the anticipation of the developmentof ARDS in patients with COVID-19. We will perform, for a week, daily blood draws on a cohort of 100 patients currently admitted to the Hospital HM Sanchinarro with confirmed or suspected diagnosis of COVID-19. In these samples we will determine a broad cytokine panel (LUMINEX) correlating, in a prospective way, the analytical results with the development of severe ARDS. Using computer algorithms we will establish the determinations that best predict the appearance of this complication. The analysis will focus on proteins included in the portfolio of commercial companies that produce, on an industrial scale, diagnostic kits by ELISA. Thus, the markers found will be immediately available in any health care center in the country. In parallel, we will study the interindividual genetic variability and the evolution of viral load in these cases. In a second phase we will develop more precise and patentable multiplex kits.

The purpose of this project is to design and test in preclinical studies a new vaccine against SARS-CoV-2. The overall objective: 1. In a first step, to test a new mRNA vaccine candidate encoding SARS-CoV-2 epitopes selected through a bioinformatic approach and co-formulated with nanoparticles (mRNA-CoV2) in vitro and in vivo to assess the potential to induce SARS-CoV-2-specific immune responses. 2. In a second step, to test if a prime-boost strategy with mRNA-CoV-2 prime and MVA-CoV2 boost induce higher immune responses as compared with mRNA-CoV2 alone.

The objectives of the COVID-19-EII study are 1) to describe the incidence and characteristics of SARS-CoV-2 infection in the ENEIDA cohort of IBD patients during the epidemic period and 2) to understand the course of the disease and its immunosuppressive and comorbidity treatment.

Infection with SARS-CoV-2 virus ranges from asymptomatic forms to very severe bilateral pneumonias that often result in the death of the patient. Microbiome and virome are altered in a large number of pathologies, but their involvement in this process is unknown, although it is possible that both are involved in the different clinical severity of the patient. Therefore, the study of the microbiome and the virome should be carried out by means of a bioinformatic and statistical analysis of the microbial diversity and the taxa present in each of the samples, in order to identify biomarkers of severity of the process that can be used in the best management of the patient.

A SARS-CoV-2 biosecurity vaccine engineering platform will be established, which includes three production procedures. The first will use human cells that secrete virus-like particles (VLPs), through the constitutive expression of SARS-CoV-2 proteins S, M and E. The second will use baculoviral vectors for the expression of these genes on a large scale and to compare the production of VLPs. The third procedure will be based on the production of non-replicative and non-integrative lentiviral particles, pseudotyped with the SARS-CoV-2 protein S and expressing the rest of the structural proteins. These particles will deliver the B and T epitopes to the immune system in a VLP format. BIRB796 will be incorporated into the vaccine preparations to enhance the human T response, since it is a MAPK p38 inhibitor approved for human use and with anti-senescent properties in lymphocytes.

There are no models allowing to unveil the molecular pathways and cellular responses differently regulated upon SARS-CoV-2 infection in human tissues. Organoid technology represents an affordable solution to COVID-19 research. Our consortia is able to infect a plethora of human organoids opening the door for drug screening for COVID19 treatment. These results are part of a present manuscript under review in Cell. Based in our current findings our aim is to understand, identify and target ACE2-SARS-CoV-2 cellular responses exploiting kidney and heart organoids exposed to systemic conditions worsening COVID19 disease (i.e., Diabetes). Using seRNA sequentiation we will unveil unique and common cellular responses upon SARS-CoV-2 infection and use primary cell cultures and retrospective COVID19 necropsies for validation. This approach will identify top ranked pathways differentially regulated upon SARS-CoV-2 infection in control and diabetic backgrounds.

The biological cycle of coronaviruses allows the differentiation between the encapsulated virus and its infection and replication processes. We will develop modular kits that allow on the one hand to determine the presence of the virus and on the other the presence of viral processes involved in the infection and the determination of those variables that may be relevant in the development of the disease (viral and human). The kits will be based on isothermal amplification and by rapid PCR of the regions of interest and their rapid detection (15-30 minutes the presence of the virus, available in 1 - 2 months). In a second kit-module, from these amplified and those of interest in relation to the patient, will be generated libraries to be sequenced using Nanopore systems. This second part of the study will allow know the virus strain and the patient variables that are relevant to the disease, performing a report based on the available data and including other clinical variables of interest.

This trial aims to assess the effect of hydroxychloroquine (HCQ) in reducing viral load and preventing SARS-CoV-2 infection in pregnant women. The proposed clinical trial will help improving the care and reduce the risk of poor pregnancy outcomes of women infected with SARS-CoV-2 in this and in future epidemics. By reducing the viral load of infected pregnant women, this trial will also have an impact on the reduction of the spread of the virus, both vertical and horizontal transmission. As the results from other trials testing the hydroxychloroquine (HCQ) may not be extrapolated to pregnant women given the special features of the pregnancy status, this clinical research is urgently needed.

In the race to find a COVID-19 vaccine, gene-based approaches are the leading choice with some already ongoing clinical trials. However, the major challenge of this technology is the extreme sensitivity and the very low cellular uptake of the gene material that triggers the hosts' immune response, which hampers their potential. To overcome this limitation, we have developed a synthetic platform for the rapid screening of peptide amphiphiles with potential as gene delivery vehicles. The application of this approach allowed the identification of a candidate with a remarkable (one order of magnitude in vitro) improvement in delivery efficiency and cellular toxicity compared to typical commercial reagents. Remarkably, this candidate has also recently proven highly active for in vivo delivery of mRNA in mice, which suggests that it can be an excellent non-viral vector for the formulation of mRNA vaccines with a boosted potency, due to the uptake enhancement provided by this conceptually-new delivery vector.

This study aims to generate knowledge about the populations of immune cells responsible for infection control, in order to understand the kinetics and magnitude of the immune response during COVID-19 disease. This knowledge can identify biomarkers that contribute to: 1) identifying which patients are most likely to experience respiratory failure requiring admission and respiratory support treatment in intensive care units, 2) monitoring the evolution of the infection and 3) exploring new therapeutic interventions. All of this not only seeks to contribute to the personalised treatment according to the profile and immunological response of each patient, but it will also reduce the stress on the health system by being able to predict in advance which patients may develop more serious clinical pictures and therefore plan and optimize the use of the resources available by the health system.

The implications of the COVID-19 pandemic on pregnancy are not well known. Severe maternal infection may be associated with premature delivery or impaired fetal growth. Maternal hypoxia could have consequences on neurodevelopment and on the fetal heart. On the other hand, there are no data on the impact of COVID-19 infection by trimester. Our aim is to analyze the perinatal outcome and the risk of growth retardation, abnormalities at the level of neurosonography or fetal echocardiography in women with COVID-19, as well as associated factors (severe maternal infection, hypoxemia, gestational age at infection). The expected results can be very useful in advising on possible fetal risks, improving the care and experience of pregnancy.

In this project we intend to make a rapid approach to the state of lymphocyte populations and the inflammation process in COVID-19 positive patients with and without symptoms versus COVID-19 negative patients. With the hypothesis that immunosenescence is playing a role in the susceptibility to be infected, the studies will be performed in different age ranges (30-40 / 40-50 /50-60 / over 60). In the case of COVID-19 positive patients, immunosenescence and inflammation profiles at the time of diagnosis will be correlated with the clinical variables of monitoring the disease in search of prognostic markers in the evolution.

In this project we will investigate, using highly sensitive immune assays, the development of short and long-lasting immunity, both humoral and cellular, specific against SARS-CoV-2, at the time of infection and at different time points afterwards up to 24 months in previously healthy individuals, patients with relevant co-morbidities, solid organ transplant patients receiving chronic immunosuppression and patients with malignancies receiving chemotherapy.

Because COVID19 spectrum of disease range from asymptomatic disease to severe lung injury leading to death, we aim to exploit extreme clinical phenotypes of COVID-19 disease to identify mechanisms that can be leveraged to improve outcomes and to identify predictors of adverse outcomes. Because the clear correlation between clinical outcomes and age, we plan to recruit individuals across a broad range of age, including pediatric populations, reflecting the broad range of COVID19 disease severity. We will interrogate targeted biological pathways (i.e., ACE2 expression and polymorphisms, antiviral responses and innate and adaptive immunity) and untargeted pathways using plasma metabolomics and enzymolomics. These parameters will be correlated with the clinical phenotype and with virologic measures of CoVID19 using multiparametric data integration through a bioinformatic approach.

Patients with chronic inflammatory arthritis (CIA) have an increased risk of infections due to both dysregulation of the immune system and immunosuppressive treatment. Preliminary evidence in our service indicates a lower rate of transmission by SARS-CoV-2 in patients with CIA receiving immunosuppressive treatment than that reported for the general population (<1%). This is a cross-sectional study of a very well-characterized cohort of N = 1,175 patients with CIA receiving treatment with selective immunosuppressants (ISS), both adult and pediatric, followed systematically in a third-level university hospital. Epidemiological and clinical data will be obtained from the electronic clinical history, the shared clinical history of Catalonia and through a telephone survey. The prevalence and clinical expression of COVID-19 in these patients will be determined, which will allow establishing clinical practice recommendations with great scientific and social impact.

No information exists regarding COVID-19 in solid organ transplant recipients (SOTR). Besides, treatment is challenging as drug interactions might have an important impact on drug toxicity, graft dysfunction and rejection and probably outcome is adverse. No specific recommendations regarding COVID-19 exist. Objectives: to better understand the incidence, risk factors, clinical manifestations and outcome of COVID19 in SOTR. The results obtained will allow us to gain insight on the need of antiviral treatment, on the strategy for complications surveillance, on how to adjust the immunosuppressant therapy and on the level of care in which each patient should be treated. Design: Multicenter prospective study of consecutive cases of COVID-19 in SOTR. There will be a clinical follow-up of the patients included in this study to observe possible complications and survival rate.

We will fight SARS-CoV2 by using massive high-performance computing. Thanks to the recently published X-Ray structures, we will unveil the physico-chemical properties of the viral spike protein, those of the human ACE2 receptor and those of the complex they form to permit virus to infect cells and spread. This information, well implemented with knowledge-based bioinformatics techniques, will help us to understand the mechanism of viral entrance into the cell and what are the "next evolutionary moves" of the CoV family. Unbiased tajectories along with extensive free-energy calculation would help to identify new "druggable spots" (not detectable by crystallography). On this knowledge, we will start a drug discovery effort (of commercially available drugs first) to inhibit the interaction between the virus and the human host, hence impeding virus internalization and spread.

The project investigates the role of NK cells in the susceptibility and prognosis of SARS-CoV-2 infection (COVID-19). In patients with mild (n=100) and severe (n=100) disease, the genotype (PCR-SSO-Luminex) and expression in NK cells (12-fluorescence cytometry) of KIR/ligand HLA-I interactions that regulate the education and function of these cells and determine their effectiveness against viral infections will be analysed. The data will be compared with 600 healthy controls of known genotype. The results will help to optimize health resources and avoid collapse by facilitating: 1) increased protection efforts in more susceptible people (health professionals, law enforcement, families of patients, etc.); and 2) anticipate anti-viral and anti-inflammatory therapies to the appearance of the most severe symptoms in susceptible patients.

COVID-19 disease challenges the capacity of national health systems. The course of the disease differs from other pneumonias known to date. The main objective of this project is to derive and validate a prognostic score (COVID-19) Severity Index [CSI] from a multicenter database on patients with COVID-19 pneumonia with prognostic variables of severity at admission to predict ICU requirement and death. A retrospective, multicenter study of adult patients with COVID-19 pneumonia requiring hospitalization in hospitals throughout Spain will be conducted (it is estimated that some 4,000 pneumonias will be recruited).

In this project we hypothesize that patients infected with SARS-CoV-2 virus who are carriers of an aging immune system, determined by the presence of small clones of B cells circulating in peripheral blood and the secondary immunodeficiency associated with this condition, would develop a more severe disease and would evolve worse due to their inability to recognize new antigens. To this end, we propose: 1) to explore the presence of B-lymphoid clones (LBMlo) in the blood of infected patients admitted to the Hospital Universitario de Salamanca; 2) to study the status of their immune system, using innovative tools developed by the research group that allow the identification in blood of >250 different populations of immune cells; 3) to relate the above data with the clinical characteristics of the patients; and 4) to identify parameters related to an aging immune system that will provide a solid basis for prognostic stratification and clinical validation.

It is currently unknown whether the minority of poorly progressing cases of COVID-19 are due to an excess or defect in the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological scenarios in which this infection develops. Objective: To generate algorithms to stratify patients according to the immunological risk profile applicable to the analysis of clinical trials with immunomodulars in progress or in the future and, specifically, to support therapeutic strategies. Modules 1) daily collection and analysis of parameters of inflammation, coagulation, immunology and microbiology as well as biochemistry in relation to the origins of the samples and the demographic data of the patients, evolutionary follow-up and progressive assessment of the most predictive indices; 2) Measurement in 120 patients of the level of 18 cytokines and 32 lymphocyte populations; 3) Generation of prognostic algorithm and therapeutic orientation; 4) Identification of activated response pathways. Support modules include generating sample collections, clinical data extraction, and statistical analysis.

The aim of this project is to determine the efficacy of the intravenous infusion of Defibrotide to reduce mortality in patients with SARS-CoV-2 infection with clinical status grade 4 (Hospitalized patients requiring oxygen therapy), grade 5 (Hospitalized patients requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both) or grade 6 (Hospitalized patients requiring extracorporeal membrane oxygenation or invasive mechanical ventilation), according to the WHO classification.

After the epidemic of severe acute respiratory syndrome due to coronavirus (SARS-CoV), many of the people who survived developed residual pulmonary fibrosis (PF). Autopsies of these COVID-19 patients showed the presence of pulmonary fibrosis at different stages of infection. Risk of PF was highest in the elderly, and was correlated with clinical severity and duration of disease. On the other hand, dysregulation of the inflammatory response was observed in lung biopsies, with levels of certain proinflammatory cytokines in serum being especially elevated. Also, infection SARS-CoV-2 induces overactivation of the TGF pathway leading to pulmonary fibrosis. The goals of this projects are: 1) to improve the knowledge about the physiopathology of SARS-CoV-2; 2) to determine if in the people infected with SARS-CoV-2 who required admission for further lung damage persists a "inflammatory microenvironment" that could lead to residual lung injury, 3) assess the correlation between expression of cytokines, chemokines and serum/sputum growth factors and the respiratory function tests and the walking test.

Approximately 14% of patients infected with SARS-CoV-2 present severe clinical symptoms and 5% require critical care, causing an overload on the health system. In this context, the use of predictive models to identify the most vulnerable subjects becomes a priority objective. Using data collected from electronic health records, this project aims to: 1) build survival and classification algorithms to estimate patient risk; and 2) based on the treatments administered to the patients, using causal inference models, quantifying the effectiveness of the drugs according to the characteristics of the patients.

It is currently not known whether the minority of poorly evolving cases of COVID-19 are due to an excess or defect in the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological/virological scenarios in which this infection develops. The objective of this project is to generate algorithms/indices to stratify patients by the immunological/virological risk profile applicable to the analysis of ongoing or future clinical trials with immunomodulators. Methods: 1) Capture of parameters of inflammation, coagulation, immunology and microbiology as well as general analysis in relation to the origins of the samples, demographic data and clinical evolution; 2) Measurement in 120 patients of the level of 16 cytokines and 32 lymphocyte populations for: 3) the generation of prognostic and therapeutic orientation algorithms from 2; 4) detailed identification by Nanostring® transcriptomics of the immune response pathways activated in 40 patients and thus confirm/improve the algorithm generated in 3.

An online platform will be created to register cases of patients with previous heart failure or family heart disease in which SARS-CoV-19 infection is confirmed. It will be an anonymized registry that will be accessed with a username and password through the web and will include basic demographic data, previous diagnoses, symptoms, previous treatments and during the episode, necessary interventions during admission and events. A common database will be generated from which the grouped data can be displayed and the corresponding statistical analyzes performed. The data will be available from the beginning of the project to the health authorities and to the participants in the registry. The registry will remain active for at least 2 years in order to collect data retrospectively from patients under previous follow-up in consultations, and to incorporate information on evolution and complications in the short and medium term.

The aim is to establish the association and impact between COVID-19 infection and chronic treatment with ACEI or ARAII, in terms of a torpid-fatal clinical course. These drugs increase the expression of ACE2, the vehicle of entry to target cells in acute respiratory syndrome by SARS CoV-2. The aim is to establish the relationship between viral load and genetic predisposition by identifying polymorphisms and their expression linked to this enzyme, related to diseases such as: diabetes, hypertension, and stroke and their treatments; trying to develop clinical trials to identify more efficient therapies in a population with high mortality.

The pathways of a pathogen into our body is based on the breakdown of our physiological barriers. In In the case of the respiratory tract, the epithelium is one of the first barriers that the human body presents. The viral transfer of This epithelium has two alternatives: 1) the paracellular space, which would involve disassembling the tight junctions and adherents between neighboring cells, and 2) performing an intracellular transport process, taking the virus for their benefit intracellular traffic routes. This project aims to 1 study how the virus enters our body through the epithelial cells of the human airways. On the other hand the release of new viruses to the lumen of the pathways Respiratory may be due to virus exocytosis. This process would require the use of the secretory pathways they use. cells naturally. This project in its objective 2 will study the exocytosis of SARS-CoV2 in epithelial cells of the human airways. In addition, the development of Objective 1 and 2 will conclude with the development of two platforms for screening, allowing to search for drugs that block the entry or exit of the virus directly into epithelia of the respiratory tract.

We seek to inhibit the cellular entry of the coronavirus by administering large amounts of soluble (non-cell bound) viral receptor (ACE2) to act as a "decoy". We will inactivate by directed mutagenesis the carboxypeptidase activity of ACE2, without removing the catalytic Zn2+ with possible structural functions and without interfering with the stability of the protein or its interaction with the viral spicule, and we will produce it using baculovirus/insect cells (system that we use routinely). We will purify wild or mutant ACE2 by affinity chromatography exploiting an artificial eliminable label. We will prove that the mutant forms of ACE2 are catalytically inactive, stable, and that they bind to the binding region of the viral protein S. We will evaluate in cell cultures (collaboration with Jesús Rodríguez Díaz, Dept. of Microbiology, Hospital Clínico-University of Valencia) the potency of the mutated forms to inhibit the infection of viral inocula. We will determine (crystallography or cryoEM) structures of ACE mutant complexes/S binding domain.

Objectives: 1.-Create risk stratification scales for poor evolution of patients infected with SARS-CoV-19, and evolutionary profile of patients; 2.-Assess effectiveness of treatment and diagnostic tests; 3-Evaluation of accessibility, equity, variability and costs. Methods: Information extracted manually / automatically from the electronic medical history of parameters such as epidemiological history, onset of symptoms, clinical manifestations, tests performed, treatments and evolution up to 3 months after discharge. Statistical analysis: using classic survival models, logistic regression, generalized linear models, and also analysis using artificial intelligence techniques that assess the risk of poor evolution. Health care costs are valued. Decision making applications will be derived as a product.

There are significant inconsistencies and lack of evidence on the effect of treatment with antihypertensive drugs of the ACEI and / or ARAII type and some NSAIDs and this could be a risk factor for severity and even mortality due to COVID-19. This favors rumors and errors in information, which can negatively affect Public Health and decision-making. Therefore, with this study we intend to assess whether previous consumption of certain medications (ACE inhibitors, ARAII) conditions a greater susceptibility to SARS-CoV-2 infection; and to identify those treatments received before and after infection that are associated with a better evolution and greater survival. For this, population records from Galicia will be used, using the HEXIN big data platform.

The risk of patients with COVID19 increases with age as does the redox status and the inflammatory component. The hypothesis of this study is that in COVID19 patients there is an inflammatory profile associated with the severity of the disease that evolves depending on the patient's ability to stabilize their redox status. The objectives of this study are to perform a clinical biological and molecular characterization of Covid19 disease and to establish one of the innovative therapeutic targets and biomarkers of prognostic clinical activity. and even death that can significantly reduce the mortality trend that currently our country is suffering.

It is essential to design antivirals capable of simultaneously inhibiting various coronaviruses, thus introducing a series of molecules that can act as the first line of shock in mutations of SARS-CoV-2 and in future pandemics. For this, it is essential to locate targets with high similarity, structurally well characterized, and perform virtual screening of millions of compounds, task that is only possible with the massive use of supercomputing. With this objective, we have formed a team with extensive experience in development and massive application of software in pharmacological studies, as well as chemical synthesis and medical chemistry. Selected compounds and synthesized will be tested in different projects already underway (to which we will transfer the molecules): the Grifols-IrsiCaixa consortium and the UK's national synchrotron centre, Diamond.

Control of SARS-CoV-2 infection is based on the development of an immune response effective against the virus and in the development and maintenance of memory T-lymphocytes that can be activated if the virus reappears. The generation of memory T-lymphocytes is also necessary to ensure the effectiveness of vaccination strategies. Using cellular techniques (ELISPOT, flow cytometry) we will study the characteristics of the immune response in patients who have resolved the infection, regardless of its clinical manifestations. In addition, we will analyze the evolution of the infection and immune response in patients with chronic inflammatory diseases to study whether immunosuppressive treatments (biological or pharmacological) may have had some positive impact or negative, in the course of the infection and in the establishment of the immunological memory.

At the present time, COVID-19 has generated the greatest public health crisis, putting the health system at serious risk of collapse. Thus, in mid-March it was necessary to resort to the national state of emergency and impose a house confinement that will continue until at least mid-April, with a high probability of extension. During this time, all the services of our hospitals, and especially the emergency and intensive care services, are fully restored, exceeding 100% of the existing capacity. In this chaos, tents and pavilions are being set up to serve the increasing number of patients with mild, moderate or severe symptoms of the disease. Furthermore, the prognosis, as well as the clinical presentation, is highly variable, with no empirical evidence to corroborate these differences. In this project we want to stratify the infected population according to different stages of fragility, tempting to study the difference in evolution as well as in the use of hospital resources.

The aim of this project is to determine if patients with confirmed SARS-CoV-2 infection, treated with drugs that increase the expression of angiotensin-converting enzyme 2 (ACE2, ARBs and / or NSAIDs) are more at risk of poor evolution of the disease (pneumonia, ARDS and cardiac involvement), mortality or hospital admission than patients not treated with these drugs. A retrospective study of all patients with confirmed SARS-CoV-2 virus infection in Alava is proposed. All patients with confirmed infection will be followed up from the first contact with the health system until its resolution (test negative) or death, if applicable. The data will precede the electronic clinical history of each patient.

The ultimate goal of this proposal is to develop a genetically modified mouse, capable of being infected by the SARS-CoV-2 virus. We propose two models. The first consists of a knock-in model in which the murine Ace2 gene is replaced by the coding sequence of its human counterpart. We know that Ace2 knockout mice develop phenotypes that may not be rescued by expression of the human protein. Therefore, and in parallel, we propose the generation of a transgenic model, by means of a BAC that contains all the regulatory sequences of the expression of the murine Ace2 gene, and in which the coding sequence of such gene is replaced by that of the human gene (cDNA). In both models, concomitant with the expression of the human ACE2 protein, the fluorescent protein tdTomatoo will be expressed, in order to easily detect and isolate the cells susceptible to being infected by the SARS-CoVi-2 virus.

The objective of this project is to estimate the effect of sociodemographic characteristics, chronic diseases and other conditions on the risk of infection, hospitalization and severe forms of COVID-19. Methods: The population cohort covered by the Navarre Health Service (640,000 people) will be built from healthcare databases and epidemiological surveillance. Two sub-cohorts will be defined for specific analyzes: institutionalized people (n = 6,000) and health professionals (n = 12,000). The incidence rates of cases with clinical suspicion, infection confirmed by PCR, hospitalizations, ICU admissions, assisted ventilation and mortality will be calculated. Case fatality will also be calculated in confirmed and hospitalized cases. The predictor variables to be evaluated are sex, age, chronic diseases, pregnancy, obesity, hypertension, smoking, functional capacity, socioeconomic level, number of cohabitants, minors in the home and use of services. Antibody seroprevalence will be evaluated in a sample of patients from the sentinel physician network and / or donors.

The objective is to evaluate the effectiveness of hydroxychloroquine chemoprophylaxis for healthcare personnel and elderly people in nursing homes: a) on the incidence of secondary cases of SARS-CoV-2 infection in elderly people, and b) on the incidence of SARS-CoV-2 infection in the healthcare personnel themselves. Assess the efficacy of measures to promote infection control. Controlled, randomized, open-label, stepwise cluster study in elderly people and care professionals in 4 autonomous regions using HCQ

Difficulty breathing due to severe pneumonia is by far, the most life-threatening emergency symptoms reported for COVID-19. This is because the SARS-CoV-2 virus accesses host cells via the enzyme ACE2, which is most abundant in the alveolar cells of the lungs. We aim to study SARS-CoV-2 receptor ACE2 to identify the regions/residues critical for an efficient cell entry. We also aim to determine how the genetic variants/polymorphisms of main receptor ACE2 found in Spanish population and different tissues impinge on SARS-CoV-2 infection capacity. This have a clear therapeutic application (e.g. development of ACE2 peptide comprising the critical region as a viral attachment inhibitor and prospective antibody generation) and can be easily transferred to the clinic as it could explain why different patients have a different susceptibility, symptoms, and outcome of COVID-19 depending on the ACE2 polymorphism. Finally in an unprecedented analysis of the COVID-19 disease in human lung epithelium, we will make use of CRISPR/Cas9 to study how ACE2-dependent SARS-CoV-2 infection affects epithelial organization, cells most susceptible to infection and we will confirm the previous findings in a totally translational/bench-to-bedside approach.

The general objective is to analyze the influence of the SARS-CoV-2 viral load on the lower respiratory tract (sputum or invasive samples if its study is indicated), as well as blood and feces as indicators of disseminated disease, as factors associated with development of pneumonia and the evolution of the disease, measured by the need for assisted ventilation and cure or death. Virological variables will be included in an analysis together with demographic variables, comorbidities, and the clinical and radiological characteristics of pneumonia. Also, the sensitivity of the SARS-CoV-2 RT-PCR in nasopharyngeal smears will be evaluated. Finally, the excretion and infectivity of the virus in feces will be determined after the patients are cured.

The project aims to analyze the spatial behavior of transmission of the Covid-19 virus in urban spaces, in order to know where the main sources of infection are located, which are more virulent and evolve at a faster rate, with what factors are related, and what are the key areas of action through anti-contagion measures to stop the spread. We understand that spatial monitoring of contagion at the urban micro-scale level is key to cutting the virus transmission chain. The spatial scope of study is made up of the urban spaces of the province of Malaga, including its capital, an urban area in which results are already being obtained.

Implementation of a combined monitoring system (technological solutions and face-to-face visits) in patients who have overcome a critical episode by COVID-19 to characterize the Post-Intensive Care syndrome and detect early needs for specific treatment or physical and cognitive rehabilitation. The follow-up will be done in person at discharge from the ICU and 12 months after discharge from the ICU, and through the use of mobile applications and telephone calls 1 month, 3 months and 6 months after discharge from the ICU. A diagnostic tree will be developed to detect survivors of critical illness due to COVID-19 who present moderate-severe physical, cognitive and emotional disorders 3 months after discharge from the ICU. These patients will be offered an extraordinary face-to-face visit with a specialist at 6 months.

The aim of this core protocol is to compare the effects on major outcomes in hospital of the local standard of care alone versus the local standard of care plus one of four alternative anti-viral agent (Remdesivir, Chloroquine / OHchloroquine, Lopinavir + Ritonavir or Lopinavir / Ritonavir + Interferon). The primary objective is to provide reliable estimates on any effects of these anti-viral treatments on in-hospital mortality in moderate and in severe COVID and the secondary to assess any effects of these anti-viral treatments on hospital duration and receipt of ventilation or intensive care, and to identify any serious adverse reactions.

This project aims to predict the evolution of the expansion and incidence of COVID-19, solving the main problems that the known models are facing: the disputed reliability of the available data, both due to difficulties in the detection mechanisms and to a probable abundance of asymptomatic infected people. To this end, work is being carried out on three fronts: a) on the basis of compartmental models, which provide systems of differential equations; b) with so-called Empirical Dynamic Modelling, which dispenses with equations, thus eliminating any dependence on the pre-determination of causal agents; and c) through an analysis of the Spanish social network, which will feed back into a) and b). The work in these three blocks will have continuous interconnection.

The objective of this project is to search for risk genomic biomarkers that may predispose to more serious infection, prognostic stratification and / or response genomic biomarkers in patients who have received treatment during infusion. A complete genome association study (GWAS) will be performed in a sample of 7000 Spanish patients and a complete genome sequencing study in a group of selected patients (300), collected by a national and international consortium that includes more than 15 hospitals, complemented by a high-level research group. Clinical data (signs, symptoms, and findings) and personal and epidemiological history will be collected in a common database designed ad hoc for this project. We will thus find genetic / genomic determinants of risk and poor evolution that allow a better stratification of patients and the adaptation and optimization of therapeutic protocols.

Due to the health emergency caused by the outbreak of the COVID-19 pandemic, and in view of a possible scenario of rebound or chronicity of the disease, urges the development of tools that facilitate the detection and follow-up of patients susceptible to infection by the virus SARS-CoV-2. This project aims to generate an alternative, fast and sensitive test for the detection direct from human samples of virus RNA species, in order to simplify the time, costs and experimental complexity required for the current diagnosis of COVID-19. To this end, this proposal contemplates the design of a battery of molecular beacons and the use of scalable fluorimetric analysis through the use of signal amplification by a nicking enzyme (NESA) for the purpose of identification direct, effective and low cost of different species of coronavirus RNA in human samples.

Currently, COVID-19 has generated the greatest public health crisis, putting the health care system at serious risk of collapse. Thus, in mid-March it was necessary to resort to the national state of emergency and impose a house confinement that will continue, at least until mid-April, with a high probability of extension. During this time, the health services have been completely overwhelmed. In this new situation, tents and pavilions are being set up to serve the ever-increasing number of patients with mild, moderate or severe symptoms of the disease, deriving resources from other levels of care. Furthermore, the prognosis, as well as the clinical presentation, is highly variable, and there is no empirical evidence to corroborate these differences. In this project we want to stratify the infected population that does not require hospital admission, its predisposing factors, comorbidity and fragility, as well as to analyze the use of resources in PC in this pandemic in our country.

Objectives: to evaluate the effectiveness of 4 active treatment regimens in monotherapy (hydroxychloroquine, Prednisone, Azithromycin, or Colchicine) vs. placebo in COVID-19 patients with non-pneumonia severe without admission criteria measured as hospital admission or death in the following 2 weeks after start of treatment; assess and compare the safety of treatment guidelines at 28 days and describe changes occurred in the perception of health status at 12 weeks and analyze the impact of various clinical and sociodemographic factors in these potential changes. Design: Clinical trial randomized, multicenter, double-blind, placebo-controlled. N = 1711. Analysis by intention to treat.

The clinical management of COVID-19 patients and the implementation of measures to prevent, alleviate and eventually eradicate the disease will require not only a complete characterization of the structural and biological features of the virus, but also a deep understanding of the molecular intricacies of the virus-host cell interaction. In this project we will carry out comparative studies aimed at identifying viral and host genomic features involved in pathogenicity and disease susceptibility. We will also study the role of cellular proteases involved in SARS-CoV-2 infection and explore their regulatory mechanisms, their endogenous inhibitors and their potential role in aging-associated disease vulnerability. These studies will be complemented with a CRISPR/Cas9-based screening designed to search for new cellular factors involved in the infection process and host response.

It is currently not known whether the minority of poorly evolving cases of COVID-19 are due to an excess or defect in the innate or adaptive immune response or to joint dysregulation. There are tools not yet applied to be able to discern between the various immunological/virological scenarios in which this infection develops. The objective of this project is to generate algorithms/indices to stratify patients by the immunological/virological risk profile applicable to the analysis of ongoing or future clinical trials with immunomodulators. Methods: 1) Capture of parameters of inflammation, coagulation, immunology and microbiology as well as general analysis in relation to the origins of the samples, demographic data and clinical evolution; 2) Measurement in 120 patients of the level of 16 cytokines and 32 lymphocyte populations for: 3) the generation of prognostic and therapeutic orientation algorithms from 2; 4) detailed identification by Nanostring® transcriptomics of the immune response pathways activated in 40 patients and thus confirm/improve the algorithm generated in 3.

At present we do not know if SARS-CoV-2 infection will be able to generate immunological memory at the population level. The presence of immunological T-memory is essential for the control of a new COVID-19 outbreak. Under these premises, this project proposes: 1) To identify the regions of SARS-CoV-2 recognized by the immune T response associated with protection. 2) To determine the time of generation of these responses. 3) To characterize the functionality of T responses associated to SARS-CoV-2 protection. This information is essential to successfully design and evaluate the immunogenicity of a new prototype T vaccine in a second phase. The ultimate goal is to achieve prolonged population protection against SARS-CoV-2 through vaccination.

The clinical deterioration of SARS-CoV-2 infection would be the result of a combination of virus-induced direct cytopathic effects and immunopathology induced by a cytokine release syndrome associated with the immune response to the virus. The experience that is being acquired in our centers indicates that in the most serious cases the clinical picture is mainly related to the activation of an exaggerated immune response and an uncontrolled inflammatory process, which leads to a multi-organ failure that ends in death. A recent study of 150 confirmed cases of COVID-19 in Wuhan has just identified elevated ferritin and IL-6 as the main predictors of mortality, confirming that the hyperinflammation caused by the response to SARS-CoV-2 would be the main cause of mortality in COVID-19. Our project aims to make an exhaustive study of the patient's immune status: i) establishing an early monitoring of cytokines to guide the targeted and personalized use of biological drugs, in order to rescue patients with a worse evolution from a probable death; ii) studying the immunological factors associated with relative risk, progression and also the development of immunity against the virus.

The registry of SARS-CoV-2 infection in pediatric patients with hemoglobinopathies with clinical severity, such as sickle cell disease (SCD) or thalassemia major (TM), among others and / or splenectomized patients, aims to collect epidemiological information relevant to the surveillance of this risk group; The aim is to study morbidity and mortality in this population in addition to quantifying the resources used by this population during the current epidemic situation (hospitalization rate, treatments used, admission rate in intensive care units, among other markers). from an observational, descriptive, multicenter and ambispective study. This study wants to study the socioeconomic impact and epidemiology of COVID-19 disease in this population group.

The creation of the COVID19 patient cohort and samples associated with the IISGS Biobank in the Vigo health area provides the basis for the study of COVID-19 disease in a standardized and quality way. It will allow the execution of clinical and experimental studies to increase our knowledge and optimize the prevention, diagnosis, clinical follow-up and treatment of patients infected with SARS-COV-2 locally and globally, favoring consortia and study groups with other national centers and for the development of joint research projects. For this, a Coordination Unit of the COVID19-IISGS Cohort and a Scientific-Technical Committee have been created for the evaluation of research projects that require the use of data and samples from the cohort once they have the approval of the Relevant Ethics Committees.

The fight currently taking place in Spain against CoVidl9 has many fronts. One of the most important at a strategic level is the shortage of personal protective equipment (PPE), which has resulted in: 1) a high percentage of infected healthcare professionals, 2) reduction in the number of operating professionals, a high percentage of infected health professionals, 2) reduction in the number of operating professionals, 3) that professionals can spread the infection. Ozone has been used for decades in the treatment and disinfection of water (waste and for public use) and air. At low concentrations it destroys most viruses in a few minutes. If this effect on CoVid19 is confirmed, ozone could be used to: 1) inactivate the virus in PPE and facilitate its rapid reuse and availability for professionals, 2) decrease the number of PPE withdrawal procedures as a risk factor. The basic idea of ​​this project was published, as a comment, in March-2020 in the JAMA magazine.

A prospective cohort study of three groups: (1) COVID-19 cases or close contacts recently isolated or quarantined; (2) healthcare workers; and (3) the general population, including both adults and children/adolescents. Recruitment through epidemiologic surveillance services, hospitals, primary care centers in 6 Spanish Autonomous Communities (groups 1 & 2), a panel survey (group 3 - adults), and snowball sampling through social media (group 3 - children/adolescents). Web-based surveys at baseline and 6-month follow-up assess: current living and employment status; COVID-19 infection status; mental health (post-traumatic stress, panic, depression, anxiety, alcohol use, suicidality; services use); psychological functioning; health and quality of life. Specific modules focus on impact of isolation or quarantine (group 1) and care for COVID-19 patients (group 2). Children/adolescents receive adapted modules. Smartphone-based daily brief surveys among groups 1 & 2 will provide additional assessment of main outcomes in the two weeks following baseline assessment.

Research initiated on the dynamics of growth of the SARS-CoV-2 epidemic will be continued using physical-mathematical epidemiological models. The study will be conducted on official data on the number of patients. The following will be investigated: phases of the epidemic (exponential growth, peak and decline); severity according to peak height and width; growth rate and reproductive number; effect of uncertainty on the number of infected persons. The scientific basis for the design of the most suitable containment strategies according to parameter optimization (not only containment) will be proposed. Simulations will be carried out in different scenarios of the incidence and affected curves, which will help to anticipate control measures, and to understand the risk of importing cases and outbreaks.

Herein we are proposing the use of a low throughput peptide-screening assay to identify peptides that can inhibit SARS-CoV2 virus entry. The rationale is logical, the technology developed to identify these peptides, the feasibility of using peptides inhibitors of viral entry has been tested and proven and the translation of such findings to the clinic (e.g. clinical trials) is practical. Hence, our group is well positioned to tackle the immediate and growing need to develop novel compounds that can treat patients infected with SARS-CoV2. As principal investigator, I have a proven track record in Virology, with a particular emphasis on viral entry and the development and / or identification of compounds that inhibit viral entry. Thus, the proposal outlined below is well within my and my laboratories expertise and capabilities.

One of the symptomatic aspects of COVID19 is the effect of pneumonia. Our group is an expert in image analysis and its treatment for combined use with radiologists. With the resources we have available, we want to help develop a radiological screening system based on artificial intelligence to help identify the severity of the pathology. During the project, the solution's exploitation capacity will be looked for, looking for leading companies in the sector as engines for the acquisition of images.

According to the WHO, hypertension, cardiovascular and chronic respiratory diseases, diabetes, immunosuppression, cancer, along with old age, belong to the specific risk group of people affected by the current COVID-19 pandemic. As we age, our body accumulates senescent cells, which produce harmful effects on the body, and are known to play a causal role in the onset of the diseases listed above. This fact, together with known data, place senescent cells as targets to eliminate or alleviate the symptoms of the infection. The main objective of this project is the specific elimination of senescent cells through the use of senolytics, in order to improve the clinical picture of those affected. The fact that some senolytics are already in the clinical phase, means that their use in patients would be faster. The development of vaccines based on cellular response, is also raised here.

A significant proportion of the SARS-CoV-2 proteome lacks homology with known proteins and appears to have no defined structure. Proteins intrinsically Disordered (IDP) are essential for viral infections, as they hijack human regulatory networks. IDPs are refractory to structural analysis using X-ray crystallography or cryo-electron microscopy. The objective of this project is to characterize the partial structure and dynamics of three disordered proteins and three peptides of the SARS-CoV-2 proteome, for example, the segment that covers residues 962-1021: FGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPWQ. We will use NMR spectroscopy and molecular dynamics, which are the only methods that provide information at the atomic level on IDPs.

The rapid expansion of SARS-CoV-2, a new virus, has caught health systems without adequate therapy. Although the development of a new drug is not feasible in the short term, the solution of reusing drugs with other indications would bring closer the availability of new therapies. Computational approaches have been shown to be faster and cheaper than experimental ones. Among these, those based on mechanistic models, which allow inferring cause-effect relationships, have shown greater effectiveness than traditional solutions such as virtual screening or others. We propose the use of a mechanistic model based on artificial intelligence that has already demonstrated its effectiveness in rare diseases for the reuse of drugs for Covid-19.

1) Análisis de la respuesta inflamatoria mediante perfil de citoquinas en suero relacionadas con señalización de IL-6 para estratificar pacientes, valorar actividad de la enfermedad COVI-19 y seleccionar pacientes donde atenuar la respuesta inflamatoria mediante el bloqueo de IL-6. 2) Análisis de SNPs de los genes que participan en la señalización de IL-6 que puedan explicar reacciones exacerbadas (datos bioinformaticos y datos a obtener con nuestras muestras). 3) Demostrar la importancia de un bloqueo selectivo de IL-6. es decir bloquear sólo el trans-signalling de IL-6 en los pacientes donde exista una respuesta inflamatoria grave con altos niveles de receptor soluble de IL-6 (sIL-6R) y bajos sgp130 (buffer natural del trans-signaling), no se afecta la clásica de IL-6. Esto contrasta con el uso de Tociluzimab, donde se inhiben no se afecta la clásica de IL-6. Esto contrasta con el uso de Tociluzimab, donde se inhiben todas las respuestas de IL-6 con afectación de la señalización clásica regeneradora y de defensa de IL-6 en los procesos de inflamación.

National prospective multicenter study conducted in RECLIP healthcare centers. At least 150 mother-newborn couples with confirmed SARS-CoV2 infection will be tested during pregnancy. Epidemiological, clinical aspects, infection treatments, evolution will be collected. Microbiological studies of SARS-Cov-2 will be carried out in 50 couples in respiratory samples, blood, placenta, urine and feces of the newborn, breast milk, and immunological samples at the time of diagnosis of the pregnant woman and at birth in the newborn. , and prospectively up to 6 months of infant life, aimed at knowing in depth the transmission of the infection as well as the immune response that occurs in these populations against SARS-CoV-2.

Study of the prophylactic activity of trained innate immunity induced by MTBVAC live attenuated vaccine compared to BCG against SARS-CoV2 in the rhesus macaque (Macaca mulatta) model at the Biomedical Primate Research Centre (BPRC) in the Netherlands. The present research is part of the studies that the BPRC is going to start on the protective activity by the increase of trained immunity induced by BCG against SARS-CoV2 by studying the inoculation of BCG vaccine by different routes administration (intradermal, pulmonary and intravenous).

The project aims at the development of a rapid and easy-to-use serological test for the screening of COVID-19 and the differentiation between current and past infections. The addition of fingerpick blood sample and a final immersion of dipstick/addition of substrate is the only required end-user intervention. It is based on the detection of the IgM and IgG antibodies produced by the infected person`s immune system to fight the infection. The assay design will differ from the common format used by numerous manufacturers to eliminate the possibility of false negative results. Gold and carbon nanoparticle labels will be used for visual readout and the specific colour combination on the strips will be related to the presence of specific antibody type. A recombinant COVID-19 antigen will be prepared for the final preparation of prototype tests to be validated using patient blood samples. The assay time will be less than 15 minutes and the production cost will be 1€. The methodology will be disseminated internationally and can be easily implemented globally.

Population-based cohort study, with 4-month retrospective-prospective follow-up (03/03 / 2020-30 / 06/2020), which will include 48,000 people> 60 years from Tarragona (1,500 of them institutionalized). Objectives: (i) to know the real incidence of COVID-19 infection, discriminating according to "confirmed" (PCR +) and / or "suspicious" cases (COVID19-like without PCR confirmation); (ii) identify the frequency of presentation (initial and during the evolution) of symptoms and signs of the disease in both types of patients (confirmed / suspected); (iii) characterize the clinical presentation profile (symptoms and signs) of COVID-19 infection in the population and explore models for predicting low / high risk profiles of complication (sudden worsening, need for hospitalization / ICU, death) based on possible predictive covariates (sex, age, symptoms / signs, comorbidity and previous medication).

Given the uncertainty generated by the health crisis, and based on the large amount of data generated every day on the COVID19 disease, we propose to apply the most modern and reliable techniques for the analysis and prediction of space-time series using / deep-learning / and others. paradigms of artificial intelligence. The objective is to immediately develop predictive systems for infections, admissions, patients in the ICU and deaths by province and autonomous community, along with other magnitudes (logistical, economic, ...) that allow for more effective orientation of the action of the Ministry of Health in this and other crises. In addition, a retrospective analysis is proposed that enables the start date of each focus of the epidemic to be determined a posteriori, as well as visualization tools and dashboards that allow useful knowledge to be extracted and decision-making to be facilitated from the data.

For greater effectiveness and potency, an ideal vaccine should induce both a humoral and a cellular memory response. We have a methodology developed to obtain recombinant vaccinia MVA viruses that simultaneously express two antigens from two separate loci of the genome, without inactivating any virus gene that can attenuate the response. In the case of COVID-19, it seems likely that protein S induces good neutralizing antibodies but a poor cellular response, so we propose to generate vaccine candidates that enhance the T cell response by expressing, in addition to SARS glycoprotein S -CoV-2, the ns1 / 2 or N proteins. These vaccine candidates must be able to induce humoral immunity in addition to cellular immunity against conserved epitopes on intracellular proteins. Once the recombinant viruses have been generated, their immunogenic capacity will be evaluated in mouse models.

Cohort study including 1,000 pregnant women and their 1,000 newborns in the Cantabria community, which will be followed for one year. Determinations of IgG and IgM antiSARS-CoV-2 will be carried out in the mother in the first pregnancy consultation, on the day of delivery and at 6 and 12 months after delivery; in the newborn on the day of birth and at 6 and 12 months. Sociodemographic information and the process of care for pregnancy and childbirth will be collected. At follow-up, somatometry and psychomotor development of the newborn will be evaluated.

Patients with severe COVID-19 develop a cytokine storm syndrome (CTS) that seriously worsens their prognosis. STC is characterized by excessive accumulation of activated macrophages that cause massive release of proinflammatory cytokines. Macrophage depletion in STC development has been reported to decrease lethality in several animal models. Data from our laboratory demonstrate that agonists of the α2-adrenergic receptors prevent the accumulation of neutrophils in the inflammatory focus and preliminary results have prevented the accumulation of neutrophils in the inflammatory focus and preliminary results have shown a similar anti-inflammatory effect in circulating monocytes. . The main objective of this project is to generate the mechanistic rationality that allows to support a2 adrenergic agonists as modulators of monocyte migration to the inflammatory focus, in order to prevent / treat COVID-19 patients who develop an STC.

This project seeks to evaluate, by simulating: (1) analyzing the effect of the spread of new epidemics on a European scale as well as the effectiveness of policies to restrict the movement of individuals; (2) the impact of climatic conditions (both summer and winter) on the spread of the epidemic; (3) the effect of a potential summer and winter) on the spread of the epidemic; (3) the effect of a potential selective vaccination of the population taking into account different levels of vaccine efficacy as well as potential mutations in the virus that decrease the immunity of the group that has already been vaccinated or has suffered from the disease; (4) the efficiency of different measures of social distancing (closing of schools, closing of work or remote work for a percentage of the working class, social isolation, etc.) on the following stages of infection taking into account different possible levels of immunization collective.

Prospective study to be carried out at the Son Espases and Son LLátzer Hospitals in Palma de Mallorca, the objective of which is to identify virological and immunological factors, as well as clinical, radiological and analytical factors, related to severe forms of COVID-19. During the months of April and May 20120, 150 patients diagnosed with mild, severe and moderate COVID-19 (50 patients in each group) will be recruited and peripheral blood measurements will be performed at baseline levels and at 2 weeks of IL1, IL6, IL8, IL10, TNFa and IL2R, from lymphocyte subpopulations and complement study, as well as semiquantitative viral load study in oropharyngeal and peripheral blood and Ac production against SARS-VOC-2. The relationship of these parameters with the epidemiological, clinical and radiological variables of mild, severe and moderate COVID-2 will be analyzed.

Prospective multicenter observational study to characterize the infection in pediatric critically ill patients with SARS-COVID-19. It is an on-line registration through an electronic form in which pediatric ICUs from all over Spain will participate. The registry is promoted and sponsored by the Spanish Society of Care throughout Spain. The registry is promoted and sponsored by the Spanish Society of Pediatric Intensive Care. Demographic, clinical upon admission, epidemiological, diagnostic, therapeutic, microbiological and prognostic variables will be recorded.

MS is an autoimmune disease and its interaction with COVID-19 infection has not yet been studied. This is important for several reasons. 1) COVID-19 infection could modify the evolution of MS 2) MS could alter the response to COVID-19. The evolution of the infection according to the immunomodulatory treatment (TME) received and whether it alters the evolution of the MS has not been studied either. In this we intend to study a) how the SARS-VOC-2 contagion affects the clinical and immunological status of patients with MS based on the characteristics of their MS and the TME they take, b) how MS and treatment with TME influence in the appearance and development of SARS-COV-2 infection and c) if there are beneficial effects of some TME in the evolution of SARS-COV-2 infection or if some drugs used in the treatment of infection could be beneficial for MS treatment.

The effective immune response capacity against a new pathogen will depend primarily on the specific recognition capacity of the naTve T lymphocytes. The reduction of these cells as a consequence of physiological aging or secondary to pathology could be responsible for the inadequate control of infection against SARS-COV-2. In patients with a certain genetic or pathophysiological component, an exaggerated and uncontrolled inflammatory response may occur, perhaps as a compensatory mechanism, which, together with other risk factors, leads to a fatal outcome. Defining the lymphocyte profile that characterizes patients with different degrees of involvement by SARS-CoV-2 will allow predicting those at higher risk of different degrees of involvement by SARS-CoV-2 will allow prediction of those at increased risk of complications or who may not benefit of vaccination once it is available.

Although outbreaks of previous infectious diseases such as SARS have generated mental health problems in affected communities, the health emergency caused by SARS-CoV-2 is reaching an unprecedented impact, bringing health systems like the Spanish one to collapse. The data from China emphasize the importance and urgency of examining the psychosocial impact of COVID-19. This urgency is even greater in the case of people with a higher level of risk, among which are workers of sanitary devices. Given the magnitude of this public health problem and the exposure to the pandemic and its derivatives suffered by healthcare workers, this prospective, multi-center, 12-month follow-up cohort study identifies stressors and protective factors, in order to inform health policies immediately.

SARS-CoV-2 depends on microtubules for its internalization and release process, therefore microtubules can be an effective target to stop its replication. since they are involved in important cellular processes essential for growth and proliferation, essential for viral replication. Tools are available to visualize the movement of microtubular transporters bound to viral model peptides and thus assess their response to minuscule concentrations of drugs as well as the world's largest library of drugs directed against tubulin. A screening of the library will be performed in the evaluation system developed looking for drugs that inhibit this transport and viral replication at tolerable doses.

The objective of the project is (1) to identify phenotypes predictive of the need for mechanical ventilation in the initial evaluation of patients and their evolution in the first days of admission, and (2) to evaluate the efficacy and safety of immunosuppressive treatments used in patients without mechanical ventilation with elevated markers of macrophage activation syndrome. They will be carried out through retrospective multicentre cohort studies, with advanced statistical analyzes for observational studies.

The project aims the validation of a reliable method for diagnosis of SARS-COV-2 infection. This novel method will allow the improved detection of the viral RNA molecule by means of a virus-specific linear probe that becomes circularized only in the presence of the viral RNA. Once the probe becomes circular, an engineered form of phi29 DNA polymerase (CSIC patent licensed to 4basebio) will start copying the circular template by generating an unlimited synthesis reaction defined as "rolling-circle replication" (RCR), which depends on the unique and robust strand-displacement synthesis capacity of this phi29 DNA polymerase variant. This peculiar mode of synthesis, a hallmark of the isothermal DNA amplification of full genomes used worldwide, could be easily detected as a readout of the presence of SARS-COV-2 genomic RNA.

Currently, there are no formal studies on the efficacy of BF in the transfer of protective factors against SARS_COV-2, and its safety, understood as the exclusion of it as a source of virus spread and cause of disease in the infant. The LM is fundamental for the correct development of the most vulnerable neonatal populations. This cohort study will evaluate if there is transmission of the virus through LM (using highly sensitive technology) and if it depends on the viral load. In addition, it will investigate the transfer of immune / inflammatory factors and microbiological markers potentially associated with Covid-19 severity.

The use of high-flow nasal cannulas (CNAFs) in SARS-CoV-2 disease (the causative agent of COVID-19) may be limited by the risk of aerosol generation that has been associated with increased risk of transmission of airborne pathogens. Our objective will be to determine the degree of contamination of the surfaces and personal protective equipment of patients with SARS-CoV-2 disease treated with CNAF or mechanical ventilation (MV) that require admission to the Intensive Medicine Service. Smears will be taken from surfaces and from personal protective equipment (PPE) and RT-qPCR will be performed to detect the presence of SARS-CoV-2. Furthermore, RT-qPCR positive samples were cultured in Vero E6 cells to determine the presence of infectious virus.

This project aims to build an own and realistic model of society to study the transmission dynamics of the SARS-CoV-2 virus in Spain. The model is based on the random movement to transmission dynamics of the SARS-CoV-2 virus in Spain. The model is based on the random movement through the Metropolis Monte Carlo method of a large number of individuals (from 100,000 to 1,000,000) who interact in certain interconnected scenarios whose parameterization tries to describe the different social collectivities of people (work , school, family, etc.). An expanded SIR model will be used, for the characteristics of the individuals and by means of an adequate calibration with the available data, the values ​​of the effective number of reproduction and generation time of the virus in each social layer will be obtained, assessing the validity of possible scenarios and measures to control the epidemic.

CoviNanoVax arose from our previous experience in the development of polymeric nanosystems loaded with genetic material selectively targeting dendritic cells (DCs). These nanosystems will be used here as vaccines for the prevention of CoVid19. A coding mRNA will be encapsulated for the SARS-CoV-2 nucleocapsid antigenic proteins, so that once the nanoparticles are injected into a healthy patient, they will selectively target and transfect DCs. As an mRNA encoding only the antigenic proteins, and taking into account that retrotranscriptase will not be present, the safety of the vaccine will be very high and, at the same time, since the mRNA is a highly antigenic macromolecule, it will develop a specific immune response to immunize healthy but susceptible people and protect them against future SARS-CoV-2 infections.

Randomized clinical trial to evaluate the efficacy of Tenofovir (TDF) (245 mg) / Emtricitabine (FTC) (200 mg) single tablet daily dose, Hydroxychloroquine (HC) single tablet daily dose (200 mg), and dose daily TDF (245 mg) / FTC (200 mg) plus HC (200 mg) or placebo, for 12 weeks in: (1) decreased incidence of symptomatic disease and (2) decreased clinical severity of infection by coronavirus (COVID-19) in hospital health personnel aged 18 to 65 years exposed to coronavirus infection (COVID-19) in Spain.

The project tries to generate a registry of all patients diagnosed with SARS-CoV2 infection and previously diagnosed rheumatic disease. For this, data from the ECHR of SARS-CoV2 + patients and rheumatological diseases will be collected in relation to their underlying disease, their previous treatment, the treatment that was being used when the symptoms of the infection began, the course of the disease until its resolution, including the appearance of complications, the therapies used as treatment and the presence of risk factors. The objective is to subsequently analyze the data obtained in order to determine what is the influence of rheumatic diseases in the course of infection and whether the therapies administered can be beneficial or harmful in terms of prophylaxis and / or less or greater severity of the infection.

The project consists of a prospective, observational, multicenter study that will evaluate changes in lung function (forced spirometry, measurement of static lung volumes using plethysmography and pulmonary carbon monoxide diffusion test) that patients admitted with pneumonia will present. by CoVid19 according to the level of severity at 4 and 26 weeks after discharge from hospital. Restrictive pulmonary abnormalities will be confirmed by imaging tests (high resolution chest CT). The presence of immune response phenomena that lead to pulmonary fibrosis will be related to demographic, clinical variables and a series of biological markers, some of them already described as co-participants in the pathogenesis of pulmonary interstitial diseases, specifically the idiopathic pulmonary fibrosis.

We will develop a series of mathematical models that describe the current epidemic of coronavirus COVID19, with different levels of sophistication: SIR, SEIR, SSEEIIR, with various delays and infectious structures adapted to the updated medical literature, according to medical studies that specify the parameters of the local situation. . The adjustment method of the various parameters will be performed using linear regression (normal equation) and machine learning (gradient descent). We will take into account the impact of the social distancing imposed in various states, as well as other control strategies, in order to measure its effectiveness and determine the best measures to prevent future COVID outbreaks in the future.

Highly pathogenic human respiratory coronaviruses of the SARS family (SARS-CoV, MERS and SARS-CoV-2) cause acute lethal disease characterized by responses exuberant inflammatory and lung damage. The fundamental step of virus replication and dissemination is its complete assembly in the intermediate region between the ER and the Golgi (ERGIC), which depends on protein-protein interactions between structural viral proteins, mainly intramembrane interactions. However, the complexity of this type of interactions and the lack of structural information has to date made it impossible to understand how CoV viruses are assembled and to design therapeutic tools that prevent this. With the achievement of this project we will provide structural information of these interactions to the scientific and pharmaceutical community as a first step to achieve their inhibition and the subsequent viral assembly.

The objective of the project is to carry out a dynamic structural analysis of the SARS-CoV-2 virus capsid in order to obtain its own frequencies and modes of vibration, and determine the characteristics of a radio frequency emission that may cause its collapse. These results will define the design parameters of an emitting device (probably microwave in the SHF and EHF bands of the electromagnetic spectrum) that allows destroying the virus capsid totally or partially by induced resonance. In your case, the construction of a prototype and its subsequent manufacture could be carried out in a short time and with low costs. The device could be used for prophylactic purposes immediately for disinfecting inert material and contaminated biological waste. In case the vibration frequencies and the energy necessary to cause the destruction of the capsid are innocuous, the same principle could also be applied for therapeutic treatment.

The immune response is crucial in patients from 5-7 days of symptom evolution. At that time, certain patients trigger an exaggerated immune response that exacerbates their clinical condition (cytokine storm), while others progress without known cause. Being able to analyze the Th1, Th2, Treg and Th17 response in these patients on admission could have predictive value for subsequent disease severity. An exacerbated activation of the Th1 response and low Th2 could produce this described cytokine storm. The Treg and Th17 response could also modulate that response. In parallel, the initial control of SARS-CoV-2 infection is also limited by the expression of Toll receptors as receptors (TLR) expressed on monocytes and dendritic (TLR-7 and TLR-8). Likewise, the KIR receptors of NK cells are important for the elimination of viral infections.

SARS-Cov-2 infection is mild or even asymptomatic in many patients, but can cause severe disease (COVID-19), primarily in patients older than 50 years, especially those with comorbidities. There are, however, young patients without risk factors with severe forms of the disease. Some of these patients may have congenital immunity errors (diseases often with incomplete penetrance). The main objective is the sequencing of the complete exome, using massive sequencing techniques, in patients under 50 years of age in Spain without comorbidities or risk factors. The project is part of an international consortium, of which we are one of the participating groups (https://www.cvidhge.com), in which the information will be shared to carry out population studies that allow progress towards precision medicine in patients with COVID-19.

SARS-Cov-2 infection is mild or even asymptomatic in many patients, but can cause severe disease (COVID-19), primarily in patients older than 50 years, especially those with comorbidities. There are, however, young patients without risk factors with severe forms of the disease. Some of these patients may have congenital immunity errors (diseases often with incomplete penetrance). The main objective is the sequencing of the complete exome, using massive sequencing techniques, in patients under 50 years of age in Spain without comorbidities or risk factors. The project is part of an international consortium, of which we are one of the participating groups (https://www.cvidhge.com), in which the information will be shared to carry out population studies that allow progress towards precision medicine in patients with COVID-19.

Combating 2019-nCoV: Advanced Nanobiosensing platforms for POC global diagnostics and surveillance

Multidisciplinary European network for research, prevention and control of the COVID-19 Pandemic

Rapid interaction profiling of 2019-nCoV for network-based deep drug- repurpose learning (DDRL

Exploration of safety, tolerability and clinical efficacy of Solnatide IMP in patients infected with the 2019 new coronavirus

The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are overwhelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.

The manifestations of COVID-19 in children are not yet well understood, and may be atypical when compared to adults. We propose to carry out a two-year global prospective study that will enroll and follow-up children with suspected COVID-19 from 50 participating emergency departments (ED) across 19 countries. Patient epidemiological and demographic information, clinical characteristics, and disease outcomes, will be collected at the time of ED admission, during the course of illness, and at three weeks and three months after enrollment, using WHO-compliant case report forms. Statistical analysis of the collected data will allow for the identification of risk factors associated with children having confirmed SARS-CoV-2 infection, and/or severe COVID-19 outcomes. In order to enable rapid implementation, this study will be built as a parallel study that borrows the infrastructure from an ongoing study - the called Pediatric Emergency Research Network (PERN)-Pneumonia study, which has ethics approval, a centralized database, data sharing agreements, and established study teams that are actively enrolling children in 70 sites worldwide. Our multidisciplinary team of investigators includes pediatric infectious disease and emergency medicine clinicians, epidemiologists, statisticians, and public health leaders (from PHAC and the CDC), all with extensive experience pertaining directly to the research topic. As data will be shared in real-time with appropriate national and international authorities, this study will enable policymakers to make rapid evidence-based adaptations to case screening and management procedures that will then allow for the earlier identification of children at high risk of SARS-CoV-2 infection and severe COVID-19 outcomes. Furthermore, the establishment of this global multi-site study will be the first trial of a rapid PERN response to a novel virus, which, applying lessons-learned, can be urgently reactivated for future public health emergencies.

Clinical Terapheutical Trial (TT): hidroxicloroquina, azitromicina y tocilizumab

Plasma with antibodies from already cured patients TT: plasma con anticuerpos de pacientes ya curados

TT: Comparing efficacy between hidroxicloroquina, lopinavir-ritonavir y combination of hidroxicloroquina y azitromicina

TT Comparing efficacy between remdesevir, ritonavir/lopinavir, hidroxicloroquina e interferón beta.

Preventive Trial (PT): quimiopreventivo weekly doses of oral mefloquina

PT Defibrotide ( anticoagulante) to prevent Lung SDS

TT: Sevoflurano as anesthesia for patient who need intubation.

PCR: Quick diagnostic test based on nanotecnología techniques

Preclinical Research (PR): SARS-COV2 proteins into microspheres to upgrade immune respond

TT and PT: Hidroxicloroquina for pregnant women infected by SARS-CoV-2. Hidroxicloroquina for healthy PW as COVID19 preventive treatment.Efficacy of hydroxychloroquine in preventing infection and reducing viral load and disease severity in SARS-CoV-2 infected pregnant women in Spain It is unclear how SARS-CoV-2 affects pregnant women and their offspring, as well as which factors may influence obstetrical disease and outcomes. This will be a randomized, double blinded, placebo-equivalent controlled multicentre trial aiming to assess the effect of hydroxychloroquine (HCQ) in reducing maternal viral load and the efficacy of HCQ to prevent incident SARS-CoV-2 infection. Pregnant women of any gestational age, parity and age, undergoing pre-natal follow up at four maternity hospitals with a positive PCR test, or who are contacts of a confirmed case, will be recruited and randomised 1:1 to receive HCQ orally (400 mg/day for 3 days, followed by 200 mg/day for 11 days) or ascorbic acid orally (500 mg for 3 days, then 250 mg/day for 11 days). Women will be followed up for the duration of the intervention when PCR tests for SARS-CoV-2 will be repeated, and up to delivery, when the pregnancy outcome will be registered, a cord blood sample and a neonatal throat swab will be collected after birth to be tested for SARS-CoV-2

PCR: modification by isothermal which allow to reduce meaningfully diagnostic time PCR: modificación de la PCR mediante isotermia, que permite reducir el tiempo del diagnóstico desde las 4 horas a los 45 minutos

REMAP-CAP for COVID 19REMAP-CAP is an existing multi-site international adaptive platform trial that was predesigned to adapt in the event of a pandemic.ObjectivesGenerate evidence that can be applied to clinical practice during the pandemic, regarding the impact of multiple candidate interventions to reduce mortality or reduce the length of intensive care unit admission or both in critically ill patients with COVID-19 infection

Proof of concept: Surface optical visualization system in order to identify virus residues

Identification of immunoglobulin antibodies (IgG) thanks to the use of nanosensors

Searching for new antiviral drugs repurposing by supercomputing techniques

Nonspecific immunity to SARS-CoV-2 by MTBVAC plus BCG tuberculosis vaccine

SARS-CoV2 Air Transmission: Innovative Technologies for Hospital virus detection No existen actualmente metodologías eficaces para detectar virus en el aire. Nuestro grupo ha optimizado recientemente métodos basados en filtros capaces de retener la comunidad completa de virus en el aire. SARS-CoV2 es estable en el aire durante al menos 3h y es muy eficaz en la transmisión, pero su diseminación aérea no se ha estudiado. Proponemos utilizar esta metodología para detectar SARS-CoV2 en hospitales y realizar un estudio longitudinal de la prevalencia del virus en espacios hospitalarios. En paralelo, desarrollaremos nanopartículas como métodos colorimétricos de detección sencillos, aplicables a hospitales, para monitorizar rápidamente la presencia de virus captados en el aire. Desarrollaremos sensores laser-induced fluorescence (LIF) como un método de detección directa de partículas de SARS-CoV2 y otros virus en el aire, sin necesidad de procesar las muestras

Early diagnosis of COVID19 through isolation of exomes in suspected cases

SARS-COV-2 diagnosis by phi29 polymerase amplification The project aims the validation of a reliable method for diagnosis of SARS-COV-2 infection. This novel method will allow the improved detection of the viral RNA molecule by means of a virus-specific linear probe that becomes circularized only in the presence of the viral RNA. Once the probe becomes circular, an engineered form of phi29 DNA polymerase (CSIC patent licensed to 4basebio) will start copying the circular template by generating an unlimited synthesis reaction defined as "rolling-circle replication" (RCR), which depends on the unique and robust strand-displacement synthesis capacity of this phi29 DNA polymerase variant. This peculiar mode of synthesis, a hallmark of the isothermal DNA amplification of full genomes used worldwide, could be easily detected as a readout of the presence of SARS-COV-2 genomic RNA

This research proposal builds on a recent project which solicited video tours of the homes of people during the COVID-19 pandemic. These videos give an insight into the ways that people in households around the world negotiated the radical restrictions of their activities during the initial lockdown period, and how they reconfigured their domestic spaces to accommodate functions that previously occurred outside the home. The current study aims to build on this project by shifting the focus to the ways that households are now adjusting to the relaxation of lockdown restrictions in the UK, Spain and the USA. We seek to explore the challenges of adjusting to ‘the new normal’; the ways that people are orienting to the novel set of social and spatial norms that characterise this crucial transitional period of the pandemic; and the ways that household activity spaces and boundaries are now being redrawn, renegotiated, and extended.

Existing work on policy responses to the COVID-19 pandemic has overwhelmingly concentrated on the national level, but more often than not responsibility for public health lies with the regional level of government. By wrongly attributing all authority to the national level, this “methodological nationalism” risks producing some misleading claims. In contrast to existing work, this project therefore analyses the divergence in regional policy responses across five OECD countries: Germany, Italy, Spain, the United Kingdom, and the United States. Divergence in responses can be the result of policies being tailored to specific regional contexts, but given the highly interdependent nature of the COVID-19 context, uncoordinated policy decisions taken might have severe negative externalities on other jurisdictions. This project seeks to find out whether divergence is the result of a lack of coordination or does whether it reflects a coordinated decision to allow divergence?

The United Kingdom was found wanting when the covid-19 pandemic struck. The military had to step in to provide support. Its personnel, for instance, planned and built temporary hospitals, took over the NHS logistics system and ran the vast majority of mobile testing facilities in the country (92 out of 96). The UK government was lucky in that, almost uniquely, a large number of military personnel were available in early 2020. It may not be so lucky next time. Other European countries, though, do not rely on luck. Virtually every one of them has a standing Civil Defence or Emergency Situations body whose sole function it is to deal with sudden national emergencies. This project examines, by comparing and contrasting with other European states badly affected by the pandemic (Italy, Russia and Spain), and which utilised their Civil Defence bodies, whether the UK needs such a body of its own.

The outbreak of the new coronavirus in Wuhan, China has infected over 75,000 people and has caused close to 2,000 deaths. One of the major problems with this outbreak is that emergency rooms, hospitals and ICU wards are overwhelmed with patients. In an effort to find a test for rapidly determining who should be admitted to the hospital and who should be placed in ICU, we have undertaken an international study to find a set of biomarkers that can be used to help Emergency Room doctors to make decisions on whether a patient will become severe. We have established an international team based in China, Vietnam, Spain, Italy, Mozambique, Sudan, Ethiopia, Egypt, Morocco, Cote D' Ivoire and Canada. This team will examine patients peripheral blood for biomarkers that predict the course of disease as mild or severe. The results of the study will be used to make a device that can be used in any situation and rapidly give results to predict the course of coronavirus infections.

RAPID REPURPOSING OF MANUFACTURING FOR VITAL MEDICAL SUPPLIES & EQUIPMENT –

RAPID REPURPOSING OF MANUFACTURING FOR VITAL MEDICAL SUPPLIES & EQUIPMENT –

RAPID REPURPOSING OF MANUFACTURING FOR VITAL MEDICAL SUPPLIES & EQUIPMENT –

RAPID REPURPOSING OF MANUFACTURING FOR VITAL MEDICAL SUPPLIES & EQUIPMENT –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

MEDICAL TECHNOLOGIES, DIGITAL TOOLS AND ARTIFICIAL INTELLIGENCE –

BEHAVIOURAL, SOCIAL AND ECONOMIC IMPACTS OF THE OUTBREAK RESPONSES – Policymakers and public health experts unanimously recognise the disproportionate impacts of COVID-19 on vulnerable persons: even in countries with well-developed responses, the outbreak and its repercussions imperil the basic well-being of social groups whose livelihoods are already precarious, while the uneven distribution of suffering threatens to aggravate inequality and division. One complicating factor here is the intersectional nature of health and socioeconomic vulnerabilities. Another is the complexity of risk in contemporary socioecological systems. The COVINFORM project will draw upon intersectionality theory and complex systems analysis in an interdisciplinary critique of COVID-19 responses on the levels of government, public health, community, and information and communications. The project will conduct research on three levels: 1) on an EU27 MS plus UK level, quantitative secondary data will be analysed and models will be developed; 2) Within 15 target countries, documentary sources on the national level and in at least one local community per country will be analysed; 3) in 10 target communities, primary empirical research will be conducted, utilising both classical and innovative quantitative and qualitative methods (e.g. visual ethnography, participatory ethnography, and automated analysis of short video testimonials). Promising practices will be evaluated in target communities through case studies spanning diverse disciplines (social epidemiology, the economics of unpaid labour, the sociology of migration, etc.) and vulnerable populations (COVID-19 patients, precarious families, migrating health care workers, etc.). The project will culminate in the development of an online portal and visual toolkit for stakeholders in government, public health, and civil society integrating data streams, indices and indicators, maps, models, primary research and case study findings, empirically grounded policy guidance, and creative assessment tools.

BEHAVIOURAL, SOCIAL AND ECONOMIC IMPACTS OF THE OUTBREAK RESPONSES – The impact of the COVID-19 pandemic has been deep and wide. In spite of unprecedented efforts to understand the COVID-19 disease and its causative virus SARS-CoV-2, months after the emergence of the first local case in Europe (San Matteo hospital, Pavia, 21st February 2020) significant knowledge gaps persist. While social and natural scientists managed to develop new research and shed light on the dynamics of the outbreak and the most effective possible containment measures, governments have been increasingly faced with the need to adopt urgent decisions. Against this background, PERISCOPE plans to contribute to a dramatically deeper understanding of the dynamics of the outbreak, by means of an intense multi-disciplinary research, both theoretical and experimental, and the consideration of different viewpoints: clinic and epidemiologic; humanistic and psychologic; socio-economic and political; statistical and technological. The overarching objectives of PERISCOPE are to map and analyse the unintended impacts of the COVID-19 outbreak; develop solutions and guidance for policymakers and health authorities on how to mitigate the impact of the outbreak; enhance Europe’s preparedness for future similar events; and reflect on the future multi-level governance in the health as well as other domains affected by the outbreak. In pursuing this objective, PERISCOPE sheds new light on the unintended and indirect consequences of the outbreak and the related government responses, with the intention to preserve evidence-based policymaking by collecting an unprecedented amount of data and information on the social, economic and behavioural consequences of the current pandemic. At the same time, PERISCOPE will produce new information on the conditions that led to the impact of the pandemic, the differences in “policy mix” adopted at the national level in EU and associated countries, and the behavioural impacts of both the outbreak and the policies adopted.

BEHAVIOURAL, SOCIAL AND ECONOMIC IMPACTS OF THE OUTBREAK RESPONSES – The non-intended consequences of the epidemic control decisions to contain the COVID-19 pandemic are huge and affect the well-being of European citizens in terms of economics, social relationships and health: Europe is experiencing the largest recession since WWII; social contacts have been interrupted; people avoid seeking medical treatment in fear of infection. The overarching objective of this project is to understand these non-intended consequences and to devise improved health, economic and social policies. In our policy recommendations, we strive to make healthcare systems and societies in the EU more resilient to pandemics in terms of prevention, protection and treatment of the population 50+, a most vulnerable part of the population. The project aims to identify healthcare inequalities before, during and after the pandemic; to understand the lockdown effects on health and health behaviours; to analyse labour market implications of the lockdown; to assess the impacts of pandemic and lockdown on income and wealth inequality; to mitigate the effects of epidemic control decisions on social relationships; to optimise future epidemic control measures by taking the geographical patterns of the disease and their relationship with social patterns into account; and to better manage housing and living arrangements choices between independence, co-residence or institutionalisation. The project pursues a transdisciplinary and internationally comparative approach by exploiting the data sources of the SHARE research infrastructure. It covers all EU MS. The project’s team represents medicine, public health, economics and sociology and has worked together since the creation of SHARE. It is experienced in translating data analysis into concrete policy advice. The project’s policy recommendation are targeted at policy makers in the Commission and in national ministries as well as at national and international NGOs and social organisations.

BEHAVIOURAL, SOCIAL AND ECONOMIC IMPACTS OF THE OUTBREAK RESPONSES – The mission of RESPOND is 1) to identify critical resilience factors and specific vulnerable groups at risk of immediate and long-term adverse mental health impact of the COVID-19 pandemic; 2) To improve the resilience, wellbeing and mental health of frontline health and care workers and other vulnerable groups by implementing scalable World Health Organization (WHO) programmes, and 3) to steer future policy decisions by understanding and disentangling the effects of the COVID-19 pandemic and different public health containment and subsequently relaxation strategies on mental health and wellbeing in vulnerable groups across Europe’s different health systems. RESPOND is centred around core questions regarding the short and long-term impacts of the pandemic on mental health and health inequalities on vulnerable groups within the general population, including frontline workers. In the first immediate delivery phase, an impressive set of existing longitudinal datasets are examined for resilience factors and risk factors. Furthermore, the responsiveness of health systems and identification of best practice responses that protect resilience, mental health and wellbeing are assessed in eight EU countries. The long-terms effects are determined of the pandemic and the control measures on demand for (mental) health services in health registers in Sweden, Lombardy and Barcelona and the scalable WHO SH+/PM+ stepped care programmes adapted for COVID-19 will be implemented and evaluated both in frontline workers and vulnerable groups. RESPOND provides policy recommendations within 3 months on vulnerability factors for developing poor mental health resulting from current containment and mitigation measures. Further lessons learnt and evidence-based policy recommendations will be made available during the project’s lifetime through Policy Briefs in month 6, 12, 18, 24 and 36 for immediate consideration and use by all EU member states.

PAN-EUROPEAN COVID-19 COHORTS

COLLABORATION OF EXISTING EU AND INTERNATIONAL COHORTS

DIAGNOSTICS To develop a low-cost, miniaturised, disposable molecular diagnostic system that will make it possible to test patients with laboratory quality performance almost anywhere in 15 minutes or less.

To identify candidates among existing drugs that could be effective as treatments (drug repurposing), and develop new drugs specially designed to tackle the SARS-CoV2 virus, in order to deliver treatments for the current outbreak, as well as future coronavirus outbreaks.

To develop new COVID-19 treatments by engineering human tissue to test new antiviral treatments in the laboratory.

Application of novel phenotype prediction algorithm to DNA data from direct-to-consumer tests collected via online participation and to participants from the UK, Italian and Spanish Biobanks who have tested positive for coronavirus, with aim to identify genetic risk factors

Innovation: Project BEAMitup aims at providing a tool to evaluate hygiene in food-related environments, by validating if a rapid test used for bacteria can be adapted to the detection of viruses on surfaces. For this a platform will be developed to help food companies to quickly detect the presence of Coronavirus on food processing surfaces. Expected Results: A Consortium consisting of research, academia and the industry from five European countries, plans to develop a platform in the form of an automated testing device which will be installed directly at food processing facilities, providing results in less than one hour with no need for complex instrumentation or specialized personnel. The flexibility of this technology allows the incorporation of a varied group of tests within the food industry, including other emerging viruses. This simple, fast and inexpensive test kit could well be used in the industry as well as at e.g. artisanal level.

Innovation: A virtual control centre for patients who have tested positive for COVID-19 that will be under the supervision of an expert infectious disease specialist. Expert can independently assess, validate, or augment the patient treatment plan to support optimal outcomes and target most seriously ill patients to be prioritised for specialist supervision. Acquired learnings about different patient needs will inform an artificial intelligence algorithm to provide predictions for patients who are likely to experience the worst outcomes. Expected Results: The project has already demonstrated positive impact with a study published in Clinical Infectious Diseases demonstrating a 50% reduction in mortality rate

Innovation: Improving the delivery of COVID-19 interventions in the built environment, such as cycling or walking schemes. RAPID will use rapid prototyping in 3D to support city decision-making and citizen engagement around changes and interventions to the built environment in response to COVID-19 mobility restrictions, de-escalation phases and social distancing. Expected Results: Rapid will result in more informed decision-making and more engaged citizens leading to greater acceptance of new ways of moving around a city through participatory redesign of public spaces. Engaging citizens in these decisions is more likely to get their support than simply imposing new approaches. Whilst the focus of RAPID is the response to the current COVID-19 crisis, it will have value beyond as cities explore new urban designs in response to changing behaviours.

Innovation: The aim of #GoSAFE is to establish an interoperability model to enable cross border mobility during COVID-19 crisis, based on: (1) Solid national back offices providing information on people infected and (2) the GoSAFE BioSurveillance Kit BSK. The #GoSafe passport is a token or a tag (that can be physical or virtual). Once the user will log in to a generic system of a mobility operator, he/she will ask both for the ticket and at the same time for the virtual token for the assessment of his/her health status with respect to COVID-19. No other data of any other people will be requested from the application. Expected Results: GoSAFE’s main goal is to create the conditions and the standards for an EU free COVID-19 passport, in other words a, ‘#GoSafe passport’ that gives the holder the right to travel safely among different countries. The approach is totally privacy-preserving.

Innovation: INNOV-ventilator is a purely pneumatic (air-powered) ventilator. It is simple and safe to operate using existing equipment and is also much easier to manufacture than a traditional ventilator. The INNOV-Ventilator functionalities are easily upgraded into commonly used sensors and display technologies. Expected Results: The outbreak of COVID-19 has left many health-systems struggling, due to a shortage of key medical equipment, including ventilators. The global shortage of ventilators has even meant that many patients have been denied critical care. The accelerated the advancement of the air-powered INNOV-VENTILATOR, which is simple to use and manufacture, can help ensure broader access to life-saving ventilators around the world.

Innovation: Inclusiv-Ebike will develop and demonstrate a new concept of rickshaw e-bikes capable of promoting safety and comfort by extending inclusiveness to fragile and vulnerable who have experienced decreased mobility.Inclusiv-Ebike promotes a new era of personalised transport capable of promoting inclusion and assuring social distancing, transport sustainability and healthy aging. Expected Results: Inclusiv-Ebike will improve safety, comfort and accessibility. It will also contribute to the increase use of eBikes within cities, directly affecting the wellbeing of individuals and at the same time assuring social distancing measures.

This work aims to provide knowledge about the immunological, transcriptome and epigenome state of SARS-CoV-2 infection in patients with pre-existing immunological disorders. We will characterize the overall local (nasal swab) and systemic (peripheral blood) immune response to SARS-CoV-2 infection in a spectrum of patients with primary immunodeficiency and autoimmune disease. Knowledge generated from this study will be key to understand the underlying immunopathogenesis and host susceptibility to SARS-CoV-2 infection.

When the severely ill COVID-19 patients are admitted to the Intensive Care Unit (ICU) for respiratory support (breathing with the support of a mechanical ventilator), it is crucial that the upper airways of these patients are being suctioned many times daily to remove secretion and mucus, in order to prevent lung infections. If not removed efficiently, there is >50% likelihood of mortality. Unfortunately, the suctioning techniques today have 2 major limitations 1) it cant remove secretions efficiently and thereby preventing lung infections and 2) it induces a very high risk of COVID-19 spread amongst ICU patients and staff, as secretion is suctioned outside the patients body. AW Technologies aims to solve these problems with TrachFlush – a patented suctioning assist system. As an add-on to standard mechanical ventilation systems used in the ICU, TrachFlush automatically flushes ALL secretion out of the airways and has already shown to cut cost and to reduce contamination in a small feasibility study on general ICU patients. The aim of this project is to take TrachFlush to market and battle the COVID-19 outbreak. In collaboration with experts from 5 leading hospitals from Denmark, Italy, Holland and Spain, this COVID-19 ICU-CARE project concerns a large-scale clinical study to reach TRL 8 and aims to demonstrate: 1) a 90% efficient secretion removal and implicit reduction in lung infections, 2) a 90% reduction in ICU nurse workload and, 3) elimination of any contamination between patients and staff – on COVID-19 patients! When we reach these goals, we can help EU battle the COVID-19 outbreak. The business opportunity is huge. Our market is €3,6Bn and will reach €4,5Bn by 2025. Via a recently signed distribution agreement with an ICU ventilator manufacturer, we aim for rapid market penetration and a market share of 5,3%, a turnover of €100M, an EBITDA of €57M and additional employment of 22 people by 2025. We foresee a total budget of €1.7M for this project

A new project supported by the Health Research Board and the Irish Research Council will look at decisions made during the pandemic in several European countries and their impact on people with disabilities. The research will provide guidance for decision-making bodies to help them maintain their obligations under the United Nations Convention on the Rights of People with Disabilities. What is the issue? Strategic decisions made by countries and healthcare systems in the pandemic may not always support the rights of people with disabilities. What will the research project do? Using a framework developed by the United Nations Convention on the Rights of People with Disabilities, the project will analyse laws, policies and guidelines that emerged in response to the COVID-19 pandemic in Ireland, Spain, UK, Italy, Sweden and Germany. What will the impact be? This project will provide guidance to governments, medical councils and healthcare professionals in order to maintain obligations under the United Nations Convention on the Rights of People with Disabilities. Lead researcher Professor Eilionoir Flynn, Established Professor at the School of Law and Director of the Centre for Disability Law and Policy at NUI Galway, says: “Emerging research findings, including from the International Disability Alliance and other disability groups, demonstrate that disabled people globally are disproportionately impacted by the current pandemic. Not only are disabled people at greater risk of contracting the virus and experiencing adverse effects (especially those living in institutional settings) but they are also disproportionately affected by restrictions in access to community services and supports. This research will help us to understand in more depth how countries can respond to the challenge in ways that protect the human rights of disabled people."

La situation vécue parles individus pendant une pandémie, qui peut inclure le confinement, la distanciation sociale et les craintes liées à l'insécurité économique, peut avoir des effets négatifs sur la santé mentale susceptibles d’être particulièrement nocifs pourles femmes enceintes,les jeunes mères et leur progéniture. Comprendre cet impact surla santé mentale est crucial pour la gestion adéquate des mesures de confinement de ces populations vulnérables, pendant la crise actuelle et les épidémies futures. C'est l'objectif des études de la lauréate du prix du Fonds AXA pour la Recherche, le Dr Maria Foraster, dont la recherche évalue les effets de la pandémie de COVID-19 surla santé mentale et le bien-être des mères et des nouveau-nés. [Google Translate: The situation experienced by individuals during a pandemic, which may include containment, social distancing and fears related to economic insecurity, can have negative effects on mental health issues that may be particularly harmful to pregnant women, young mothers and their offspring. Understanding this impact on mental health is crucial for the proper management of containment measures for these vulnerable populations, during the current crisis and epidemics futures. This is the objective of the studies of the winner of the AXA Fund for Research Prize, Dr Maria Foraster, whose research assesses the effects of the COVID-19 pandemic on the mental health and well-being of mothers and newborns.]

L'épidémie de COVID-19 de 2020 a révélé des infections qui entraînent des résultats particulièrement variés : certains patients restent asymptomatiques pendant l'infection, d'autres présentent des symptômes modérés pendant quelques semaines, tandis que d'autres encore souffrent de complications aiguës voire critiques. Cet éventail de résultats pose un défi majeur pour le confinement lié au COVID-19, car les mesures de protection les plus efficaces lorsque des infections sont détectées varient significativement pour chaque type de patient. Pour relever ce défi, le Dr Santiago Mazuelas, prix du Fonds de recherche AXA au Centre basque de mathématiques appliquées (BCAM) en Espagne, développera des techniques d'apprentissage automatique pour le pronostic précoce des infections à COVID-19 qui prédisent la gravité future des infections en utilisant les données de santé obtenues au moment de la détection de l'infection. [Google Translate: The 2020 COVID-19 outbreak revealed infections that have particularly varied outcomes: some patients remain asymptomatic during infection, others have moderate symptoms for a few weeks, while still others suffer from acute complications even critical. This range of results poses a major challenge for COVID-19-related containment, as the most effective protective measures when infections are detected vary significantly for each type of patient. To meet this challenge, Dr Santiago Mazuelas, AXA Research Fund Prize winner at the Basque Center for Applied Mathematics (BCAM) in Spain, will develop machine learning techniques for the early prognosis of COVID-19 infections that predict future severity infections using health data obtained at the time of infection detection.]

La pandémie et le confinement de la Covid-19 pourraient augmenter l'anxiété et les symptômes dépressifs chez les individus. Bien que les experts en santé recommandent plusieurs comportements pour faire face à de tels symptômes, comme limiter trop l'exposition trop fréquente aux informations sur la pandémie, les preuves scientifiques de leur efficacité font encore défaut. Pour combler cette lacune, le Dr Joaquim Radua, boursier AXA de l'Institut espagnol d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), se concentre sur les associations entre les comportements d'adaptation et l'anxiété et les symptômes dépressifs qui en découlent. Ses conclusions aideront à produire des recommandations conçues pour améliorer le bien-être émotionnel lors de situations exceptionnelles telles que la crise de santé publique mondiale 2020. [Google Translate: The Covid-19 pandemic and containment could increase anxiety and depressive symptoms in individuals. Although health experts recommend several behaviors to deal with such symptoms, such as limiting too frequent exposure to information about the pandemic, scientific evidence for their effectiveness is still lacking. To fill this gap, Dr Joaquim Radua, AXA Fellow of the Spanish Institute for Biomedical Investigations August Pi i Sunyer (IDIBAPS), focuses on the associations between coping behaviors and anxiety and depressive symptoms that arise. His findings will help produce recommendations designed to improve emotional well-being in situations exceptional events such as the 2020 global public health crisis.]

Only genetic tests have sufficient sensitivity to reliably diagnose COVID-19 infection in early and asymptomatic (yet contagious) stages of the disease, but they constitute current bottleneck for massive testing due to the need for specialized equipment. This imposes a spatial and temporal separation of sample collection, testing and decision-making that limits our capacity for disease contention by rapid identification and isolation of infected individuals. COVI-PHI is a simple genetic test that, by operating at room temperature, is adaptable to point-of-care testing and individual portable devices without compromising sensitivity and reliability. By decentralizing COVID-19 diagnosis, COVI-PHI will boost the capacity of primary care centers and even private end users to take quick and effective decisions on individual confinement measures. This will radically improve our capacity to control future outbreaks and minimize economic impact. Furthermore, the versatility of the method should allow its adaptation to the diagnosis of additional emerging infectious diseases. COVI-PHI is a novel method based on the extraordinary DNA synthesis and strand displacement capacity of Qualiphi®, an engineered version of phi29 DNA polymerase invented and commercially developed by members of the team, which is applied here for the detection and amplification of SARS-CoV-2 genomic RNA. As proof of concept, we have already validated the capacity of COVI-PHI to specifically detect target RNAs of synthetic origin in an ideal and controlled laboratory setting. We have obtained spectacular levels of on-target amplification with a complete absence of background; encouraging results that strongly vouch for the specificity and sensitivity of the method. hanks to the support of CaixaImpulse, we will fully optimize COVI-PHI, and adapt it to the detection of SARS-CoV-2 in real clinical samples, with the goal of validating, certifying and distributing point-of-care testing kits and devices to Spanish and other Health Systems. Taking into account the emergency situation, we will also launch a spin-off company in parallel that should be able to converge with the development of the product, and thus ensure its fastest possible implementation. Non-financial support from CaixaImpulse will also prove instrumental for establishing solid links between R&D activities, clinical validation and business/regulatory development activities.

Preferences, attitudes, and well-being affect people’s economic decisions and their effective adherence to policies. Arguably, the COVID-19 pandemics changed these factors, but we do not know the direction of the changes nor how permanent they are. Today more than ever, decision makers need timely information on these factors to effectively introduce policies to exit from the crisis, promote economic recovery, and support social cohesion. This project addresses this urgent need by informing about how people’s preferences, attitudes, and well-being changed during the COVID-19 crisis, and whether such changes are permanent or transitory. We use sentiment analysis on data sourced from Twitter to provide real-time tracking of the social change triggered by the pandemics. In this way we aim to provide timely information and to avoid delays typical of conventional large scale surveys. We will track the changes of life satisfaction, mental stress, trust in others and in institutions, loneliness, uncertainty about the future, populism, and attitudes towards globalization. The project will produce a time-series database for each of these aspects in Luxembourg and 5 European countries severely affected by the crisis (Italy, France, Germany, Spain, and United Kingdom). The data will go from December 2019 to December 2020. We believe that timely data releases produced by our project will be a useful tool to inform economic and social policies, and an important contribution to public and scientific debate at European level.

Thus, from the Biocruces Health Research Institute of Bilbao, Dr. Cristina Eguizábal, will coordinate a multicenter team that includes the Transfusion Center of the Community of Madrid, the Hospital Universitario La Paz in Madrid and the Hospital Clínico de Valencia, to create a "National bank" of cell therapy (lymphocytes) of donor patients who have passed Covid-19, to study acquired immunity and the use of these lymphocytes, specifically the so-called natural killer (NK), as a treatment for patients infected with coronavirus with moderate-severe prognosis. In addition, the project will be "open", that is, the samples will be available to researchers who require it.

In another study, which will be carried out at the 12 de Octubre University Hospital in Madrid, under the coordination of Dr. José María Aguado, head of the Infectious Diseases Unit, the scope and duration of acquired immunity (neutralizing antibodies ) by Covid-19 patients hospitalized and who have recovered. This study will allow to define the protection conferred by these neutralizing antibodies developed by patients who have been infected by Covid-19 and how they interfere with the evolution of the disease. In addition, it will try to clarify whether eventual infections by other variants of coronavirus could be equally protective.

The third work that will be funded by the Fundación Mutua Madrileña will try to demonstrate whether statins, a common drug for cholesterol control taken by between 20 and 40% of the adult population, could have a protective effect on the evolution of Covid-19 infection. To this end, from the A Coruña Health Research Institute, where this trial will be carried out, the team of cardiologist Marisa Crespo-Leiro will analyze the influence of statin treatment on cardiovascular disease and the immune and inflammatory response of patients with Covid -19. It should be remembered that in patients with Covid-19, the cardiovascular system is particularly affected, which increases their risk of mortality.

The destruction of natural habitats suggests the appearance of more epidemic outbreaks caused by other emerging coronaviruses in the future. The objective of this project is to develop and validate at a preclinical level a synthetic immunology strategy to generate 'pan-coronavirus' immunity, that is, not only against SARS-CoV-2, but in general against coronavirus species that use the protein ACE2 as a gateway to the human cell. The researchers will follow a very novel synthetic immunotherapy strategy: they will produce in the laboratory a new generation of molecules called spikebodies , due to their ability to block the interaction of ACE2 with the S glycoprotein ( spike ) of different coronaviruses. They will test their activity with various coronaviruses.

The most severe cases of COVID-19 are associated with an exacerbated response of the immune system, which has been dubbed a 'cytokine storm', and the appearance of fibrosis in the lungs. This symptomatology is largely due to the action of a type of defensive cell, macrophages. This project aims to understand the molecular mechanisms that lead to cytokine storm and pulmonary fibrosis, and to test the hypothesis that it is possible to 're-educate' macrophages so that these same cells act in a positive sense, avoiding further injury. severe COVID-19. The authors of the project have identified, in previous work, molecules that intervene in the inflammatory and fibrotic effects of macrophages - the transcription factors MAFB and MAF - and will use them to question their hypothesis. The collaboration in the project between a research group from the CSIC and the departments of Immunology and Internal Medicine of the Hospital Clínico San Carlos will allow the analysis of possible new therapeutic approaches based on the activation of macrophages, using plasma from COVID-19 patients. In these samples, the researchers will also look for new markers based on macrophages that predict the evolution of the disease.

By observing tissue samples from different organs, obtained postmortem from a score of patients shortly after their death in the intensive care unit, the authors of this project observed an exacerbated presence of macrophages. Macrophages are a key cell type in the body, for their role in trapping and destroying pathogens and eliminating dead cells. They are also essential in regulating the inflammatory response, and researchers consider them the main culprits of respiratory failure in COVID-19. Using advanced microscopy and gene expression techniques, the researchers will try to identify in this unique collection of micro-autopsy samples the mechanisms that explain the high presence and activation of macrophages.

To combat COVID-19 it is important to prevent the virus from entering cells, but also to understand what happens when it is already inside: what mechanisms of the cell the pathogen hijacks to replicate and continue infecting. This highly multidisciplinary project is led by researchers from three centers in different countries, who in the past months have already made key contributions to face the pandemic. The principal investigator Nuria Monserrat, an expert in developmental biology at the Institute of Bioengineering of Catalonia, demonstrated that SARS-CoV-2 also infects other organs, in addition to the lungs; Josef Penninger, from the Austrian Institute for Molecular Biotechnology, confirmed in vivo that the ACE2 protein is the main gateway to the new coronavirus cell; Ali Mirazimi, from the Karolinska Institute, in Sweden, he is an expert virologist in emerging viruses. In this project, they will study how SARS-CoV-2 infects mini-kidney cells, made by bioengineering from human stem cells. In these organs, it will be possible to open or close at will, using the CRISPR gene editing technique, the proteins that the virus uses as a gateway to cells -ACE2 and others-, and to study the consequences in each case. They will also be able to study the molecular pathways that are activated once the virus infects the cell. The use of mini-kidneys to model the SARS-CoV-2 infection thus allows accelerating a type of research that would otherwise take years - with genetically modified animal models. In this project, they will study how SARS-CoV-2 infects mini-kidney cells, made by bioengineering from human stem cells. In these organs, it will be possible to open or close at will, using the CRISPR gene editing technique, the proteins that the virus uses as a gateway to cells -ACE2 and others-, and to study the consequences in each case. They will also be able to study the molecular pathways that are activated once the virus infects the cell. The use of mini-kidneys to model the SARS-CoV-2 infection thus allows accelerating a type of research that would otherwise take years - with genetically modified animal models. In this project, they will study how SARS-CoV-2 infects mini-kidney cells, made by bioengineering from human stem cells. In these organs, it will be possible to open or close at will, using the CRISPR gene editing technique, the proteins that the virus uses as a gateway to cells -ACE2 and others-, and to study the consequences in each case. They will also be able to study the molecular pathways that are activated once the virus infects the cell. The use of mini-kidneys to model the SARS-CoV-2 infection thus accelerates a type of research that would otherwise take years - with genetically modified animal models. the proteins that the virus uses as a gateway to cells -ACE2 and others-, and to study the consequences in each case. They will also be able to study the molecular pathways that are activated once the virus infects the cell. The use of mini-kidneys to model the SARS-CoV-2 infection thus accelerates a type of research that would otherwise take years - with genetically modified animal models. the proteins that the virus uses as a gateway to cells -ACE2 and others-, and to study the consequences in each case. They will also be able to study the molecular pathways that are activated once the virus infects the cell. The use of mini-kidneys to model the SARS-CoV-2 infection thus accelerates a type of research that would otherwise take years - with genetically modified animal models.

Based on data from more than 9,000 patients treated for the SARS-CoV-2 coronavirus in the Madrid hospitals of Ramón y Cajal, Fundación Jiménez Díaz and La Zarzuela, this work will develop machine learning models to predict the risk of death or of being intubated that a person has by analyzing the factors that will determine the prognosis. In addition, it will evaluate the efficiency of a treatment from comparisons of patients who have been treated with one drug or another and the relationship with the death rate. As the last objective, a Bayesian network model will be built that captures all the relationships between various variables -both clinical, as well as treatments and results- to make probabilistic reasoning about the risk of mortality, the success or not of a treatment and the why. This model will also be left open on a web platform for the entire scientific community.

Day after day the number of scientific articles published on the new SARS-CoV-2 coronavirus and references to new knowledge in this area increases. With the idea of ​​getting the most out of this documentation, Óscar Corcho García's project was born, focused on improving a database that already has more than 100,000 identified scientific articles. Through the use of natural language processing techniques and large-scale text mining, this database is able to establish relationships between drugs, symptoms, associated diseases and a large number of variables more applied to the coronavirus. "The initial idea arose as a result of requests from the Madrid health system that announced the end of some medications and wanted to know what others could be used," he explains. The system can now be consulted, But it needs improvements, as well as adding new publications and validating the results with experts so that it can be a very useful resource for researchers, medical personnel and managers of the health system. Members of the Madrid Health Service (SERMAS) of the Ministry of Health of the Community of Madrid will also participate in the development of the work.

The objective of this project is to develop an artificial intelligence tool based on deep learning algorithms that allows identifying, by means of chest radiography, the presence of lung involvement, even in incipient stages, caused by COVID-19. This would allow an automated detection system for COVID-19 in suspected patients. It will be carried out using a database of 740 radiographs of patients from the San Cecilio de Granada University Hospital, half healthy and the other half with COVID, and will be expanded with data from other national and international hospitals. In addition, the tool will be able to distinguish between COVID and other lung diseases, such as bacterial pneumonias, other viral pneumonias, tumors, etc. In this way, Any health center that has X-rays will be able to have a COVID probability alert and start the protocols in advance. 56 members of four Andalusian and Galician hospital centers will participate in the work, and three other hospitals in the national territory and a university center will participate as collaborating entities.

This project will analyze human mobility on a large scale from mobile phone data. This seeks to measure the impact of confinement measures and to what extent it reduces mobility, as well as to identify mobility between different geographic areas of a population and within it. This will serve, for example, to determine the maximum mobility that each health department can absorb before reaching its maximum contagion rate that causes a health collapse. In addition, it will develop computational epidemiological models to determine how the pandemic would spread based on different situations and predictive models on the number of hospitalizations to prepare the necessary resources. The data used for the analysis of mobility will come from the inhabitants of the Valencian Community through a collaboration with the National Institute of Statistics. Finally, it has alarge international citizen survey that already gathers more than 300,000 responses and that seeks to understand the public perception during the health crisis. Five university centers of the Valencian Community and the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (FISABIO) will participate as collaborating entities, together with the public administration of the autonomous community.

Between the incubation of the SARS-CoV-2 virus and the appearance of symptoms, there is a period in which those infected are highly infectious and breathe out viral particles that could contribute to a detectable increase in said particles in the atmosphere prior to the appearance of symptoms . These viral particles have been detected in air filters collected in Italy. The objective of this project is to explore and exploit this gap between peak infectivity associated with expiration of viral particles and the presence of symptoms, to propose an alert network and facilitate the design of emergency plans and action measures that allow reducing the impact of future COVID-19 episodes in the well-being of the population and the economy. The objective of this project is to explore and exploit the lag between peak infectivity associated with expiration of viral particles and the presence of symptoms, in order to propose an alert network and facilitate the design of emergency plans.

In the first place, it tries to know to what extent the levels of the main atmospheric pollutants have changed at the regional and national level as a consequence of the drastic reduction in traffic and a partial decrease in industrial activity, caused by the restrictions derived from the implementation. of the state of alarm in Spain. Second, it tries to find associations between exposure to certain atmospheric pollutants, especially those that affect respiratory and cardiovascular function such as particulate matter (PM) and nitrogen oxides (NOx), and the spread of the virus, as well as with its severity (ICU admissions and mortality rates). Finally, it tries to investigate the possible role that the PM present in ambient air can play as a vector of transmission of SARS-CoV-2.

The objective of this project is to generate the first transgenic mouse models that reproduce human infection and models of possible species that transmit SARS-Cov-2, such as companion animals (cats and dogs) and production animals (horses, pigs and cows). , all of them selected for having an ACE-2 protein, which acts as a gateway for the virus, very similar to the human one. Mice have a version of the ACE-2 protein that differs from human, so the virus cannot enter the mouse and therefore cannot be infected by SARS-Cov-2. Therefore, to model and study COVID-19 in mice, it is necessary that they express the human ACE-2 receptor, or of the species to be studied. These transgenic mice will be used to analyze infectivity, susceptible species, and the species that transmit SARS-Cov-2 and / or the new coronaviruses that could produce future pandemics. They would also be unique models to test new drugs against COVID-19 and against possible new outbreaks of this or other coronaviruses. The research team is made up of two research groups from the National Institute for Agricultural and Food Research and Technology (INIA), in which experts in the production of transgenic animals as well as in zoonoses and antivirals participate.

SARS-CoV-2 is considered a zoonotic pathogen that is basically transmitted between humans. However, there are different descriptions that indicate that pets can be exposed to the virus. Furthermore, experimental infections with cats, hamsters, and ferrets have shown that the virus can also be transmitted between animals. In all cases, the frequency of SARS-CoV-2 infection of pets is virtually unknown and the existing data are based on a few descriptions worldwide. Therefore, it is important to establish whether SARS-CoV-2 can be established in domestic species and to see if they pose a potential risk that could lead to outbreaks in people. The project aims to establish the frequency of SARS-CoV-2 infection in pets and determine their potential role in the epidemiology of COVID-19 as potential reservoirs.

The objective of this project, in which researchers from various institutions in the United Kingdom and the United States, in addition to Spanish, participate, is to quantitatively assess whether the measures in socio-economic policy that have been adopted in our country in the context of the pandemic (ERTE , the Minimum Vital Income, tax deductions and exemptions, etc.) are effective and manage to correct inequalities or, on the contrary, aggravate these imbalances. The team starts from the premise that the crisis is affecting the different sectors and agents in a very unequal way, in a situation that is enormously damaging for many, but in which there are also sectors and agents that are benefiting. They will use stochastic dynamic general equilibrium models for this. The objective of this project is to quantitatively evaluate whether the socio-economic policy measures that have been adopted in our country in the context of the pandemic are effective and manage to correct inequalities or, on the contrary, aggravate those imbalances.

This project already monitors in real time banking data, anonymized and aggregated, of millions of clients (individuals and companies) of financial entities, with the aim of analyzing the evolution of their income and consumption patterns. In this way, and through massive data processing techniques, they will be able to know, for example, what percentage of people have seen their income drop during the pandemic and by what amount; or to calculate how much social inequalities would have increased if public compensations such as ERTEs or subsidies had not been implemented (subtracting those public revenues from the total, since these techniques allow filtering the data in maximum detail). The ultimate goal is to create tools or indexes that monitor these variables month by month to allow public decision-makers to take action at the moment, without having to wait for longer periods, such as those now necessary for official statistics. For this, they will have the collaboration of the Einaudi Institute for Economics and Finance in Rome.

This research team assumes that it is much easier to take fake news, hoaxes and false news as true (or even enhance their dissemination, forwarding or sharing them) than to question them, collect the information, send it for verification and wait for the answer. To achieve the highest possible accuracy and reliability in the shortest time and with the least effort, for the general public opinion, they will collect a large amount of information about COVID-19, from various verification sources around the world, and will label it as true or false to, through deep machine learning techniques (Deep Learning) and natural language processing, create an engine that is easily integrated into Internet browsers and social networks and provides, immediately, evidence about whether that statement, news or content is true or a possible hoax. The international dimension of the project is one of the keys, according to Alejandro Martín García, its principal investigator, who has incorporated research centers from China, Finland, the Netherlands and Singapore into the team, and anticipates that institutions from all over the world will do so in the next steps. The balloon.

The pandemic has placed a huge burden on health professionals, who have seen their work centers and specialized units related to the disease, especially ICUs, completely overwhelmed. This has caused that a high number of them have experienced symptoms, both physical and cognitive and emotional, compatible with Post-Traumatic Stress Disorder; This research group estimates, according to preliminary studies, that up to 14.5% could have suffered severe symptoms. The objective of the project is to collect data from professionals who have had a relationship with COVID-19 patients to find out to what extent this experience has impacted their mental health. The data collection and processing will be carried out by a score of researchers who are in general hospitals, primary care and social health centers and universities in the Community of Madrid; Community of Valencia; Catalonia; Basque Country; Andalusia; Castilla La Mancha, Castilla y León; The Rioja; and the Balearic Islands. A follow-up and support service will also be offered, through face-to-face groups and online media, to those who need it.

The main objective of this project is to analyze the impact of the 1918 flu and the links between collective public policies against it and the discourses and processes developed from the beginning of the epidemic to the 1930s. It is about locating this pandemic in the historical development of the first half of the 20th century and, more specifically, in the context of the crisis of liberalism after the Great War. From a multidisciplinary perspective and rooted in cultural and political history, it will articulate a comparative study that includes scenarios from southern Europe (Spain, Italy and Portugal) and Latin America (Argentina, Brazil and Mexico). The project will also address the potential comparisons between what happened in the period 1918-1930 and the current responses to COVID-19, particularly those raised by populist movements and regimes in America and Europe; that is to say, it will look for possible links between the crisis of liberalism of the last century and the current one, focusing on the impact of pandemics.

The economic crisis derived from social distancing measures and the confinements decreed in many countries has increased racial, gender and economic inequalities and has had a strong impact on chronic diseases, domestic abuse and gender violence. This is the starting point of a project that will analyze the appearance, in Spain and Latin America, of new forms of community solidarity to face these problems, highlighting the role that grassroots activism and emotional communities have played in the formation of those mutual aid networks. Special attention will be paid to initiatives aimed at vulnerable groups (the elderly, children, the homeless, residents of favelas) and the knowledge acquired will be transferred to various media (research articles, books,open access , exhibitions, documents) in order to provide useful information to political-health authorities and other social agents.

This project will generate a protocol that allows an ethical audit of the algorithms used in COVID-19 to prioritize admission to intensive care units (ICU) and to establish -through geolocation by mobile phone- the degree of infiltration of the virus in a specific area. The authors reason that algorithms facilitate decision-making, but their results may be unfair due to two types of biases: a) they lack complete information (for example, there is more data on men than women or certain minorities or situations are not sufficiently represented socioeconomic); and b) the decisions on which the machine learning system is built were not fair out (for example, the responsible health team decided not to admit the elderly, considering that they were less likely to survive). In the case of ICUs, it is about improving decisions when instead of prioritizing it is necessary to ration; and, in geolocation, to avoid discrimination, lack of privacy and abuse of power.

Social pressure to obtain solutions to the COVID-19 crisis has generated an urgent demand on researchers for certainties to guide decision-making. But generating robust evidence takes precisely time, and accelerating study timelines undermines their reliability for a number of factors - from using smaller samples to relaxing peer review or premature release of results to the media. communication - which act as biases and induce the publication of results that are, in fact, false positives. This project aims to evaluate, using recently created rigorous analytical techniques, the reliability of the studies published during the crisis to see if the explosion of scientific production that has characterized this period has led to a higher rate of weak results precisely when a solid knowledge.

The aim of RESISTIRE is to: 1) understand the impact of COVID-19 policy responses on behavioural, social and economic inequalities in the EU27, Serbia, Turkey and the UK on the basis of a conceptual gender+ framework, and 2) design, devise and pilot policy solutions and social innovations to be deployed by policymakers, stakeholders and actors in different policy domains. RESISTIRE proposes a three-cycle approach, combining quantitative and qualitative research with co-creation. The process is repeated every 6 months, each cycle producing operational results and integrating insights from the previous one. Each cycle involves: • Extensive mapping of policy and societal responses to COVID-19, secondary survey data, workshops with civil society, interviews with public authorities, and individual narratives collected from precarious and vulnerable groups, and translated into operational insights • Development of adequate responses and operational tools from a holistic perspective, with a co-design approach involving multiple stakeholders, with recommendations for actions for policymakers, stakeholders and actors in the field. • Launch of pilot actions to demonstrate the potential impact of a range of proposed solutions. • Dissemination of knowledge, development of policy recommendations and empowerment of stakeholders to exploit project results. RESISTIRE relies on a strong multi-disciplinary consortium of ten European research, innovation, and design partners, with a well-established network of healthcare stakeholders. It is designed to achieve its results through multi-disciplinary research insights, cross-sectoral co-creation, solution development and a wide dissemination strategy. The project will provide in-depth knowledge and understanding of existing problems, as well as current and future priorities and solutions. As a result, it will contribute to the reduction of inequalities arising from COVID-19 policy and how to redress them.

The outbreak of COVID-19 in 2020 inhibited face-to-face education and constrained exam taking. In many countries worldwide, high-stakes exams happening at the end of the school year determine college admissions. This paper investigates the impact of using historical data of school and high-stakes exams results to train a model to predict high-stakes exams given the available data in the Spring. The most transparent and accurate model turns out to be a linear regression model with high school GPA as the main predictor. Further analysis of the predictions reflect how high-stakes exams relate to GPA in high school for different subgroups in the population. Predicted scores slightly advantage females and low SES individuals, who perform relatively worse in high-stakes exams than in high school. Our preferred model accounts for about 50% of the out-of- sample variation in the high-stakes exam. On average, the student rank using predicted scores differs from the actual rank by almost 17 percentiles. This suggests that either high-stakes exams capture individual skills that are not measured by high school grades or that high-stakes exams are a noisy measure of the same skill.

The covid-19 pandemic led many countries to close schools and declare lockdowns during the Spring of 2020, with important impacts on the labor market. We document the effects of the covid-19 lockdown in Spain, which was hit early and hard by the pandemic and suffered one of the strictest lockdowns in Europe. We collected rich household survey data in early May of 2020. We document large employment losses during the lockdown, especially in “quarantined” sectors and non-essential sectors that do not allow for remote work. Employment losses were mostly temporary, and hit lower-educated workers particularly hard. Women were slightly more likely to lose their job than men, and those who remained employed were more likely to work from home. The lockdown led to a large increase in childcare and housework, given the closing of schools and the inability to outsource. We find that men increased their participation in housework and childcare slightly, but most of the burden fell on women, who were already doing most of the housework before the lockdown. Overall, we find that the covid-19 crisis appears to have increased gender inequalities in both paid and unpaid work in the short-term.

EPIORGABOLISM is studying how SARS-Co-V2, the coronavirus responsible for the 2019 novel coronavirus disease (COVID-19), interacts with and infects kidney cells. Together with the lung, the kidney is one of the main organs affected by the COVID-19 disease. Dr Carmen Hurtado, researcher of EPIORGABOLISM, is currently generating human kidney organoids from human pluripotent stem cells. The use of human organoids allows to test treatments against coronavirus in an agile way, dramatically reducing the time human drug trials take. Hurtado is part of international research team has identified a drug capable of blocking the effects of the SARS-CoV-2 virus.

The NeEDS consortium is currently focusing on the emerging data challenges that come with the COVID-19 pandemic. In Spain, the first cases of the COVID-19 pandemic were confirmed late February 2020 and data started to be collected daily by the different regions. Data and Data Science tools turned out to be crucial to assist decision makers in this highly uncertain context. NeEDS and the scientific collaborations they enjoy were fundamental to create a working group of data scientists from different European universities, which has developed an Artificial Intelligence tool to provide short-term predictions of the pandemic’s evolution. With this novel methodology, NeEDS as contributed to the cooperative efforts coordinated by the Spanish Commission of Mathematics to support data-driven decision making related to the COVID19 pandemic. In a recent interview, Project Coordinator Dolores Romero Morales has reflected on the potential of the NeEDS expertise and the efforts of tackling these data challenges within the team. The consortium is tackling other important Data Science questions, e.g., using spatial data to support COVID19 information apps or addressing the pressing data privacy needs.

Since the emergence of COVID-19, several fellows involved in the Martí i Franquès COFUND project have been working on solutions to the current crisis. Researchers are developing an epidemiological mathematical model that infers the status of the epidemic, thereby monitoring and estimating the impact of interventions on the spread of COVID-19. In parallel, another group of researchers is implementing an original virtual screening protocol to reposition approved drugs. This would allow predicting which of them could inhibit the main protease of the virus (M-pro), a key target for antiviral drugs given its essential role in the virus replication.

Polypharmacology-based anti-viral design led by Dr Daniel Soler from Nostrum Biodiscovery in Spain, and his team. They devised an approach for addressing compounds with activity among several strains of SARS-CoV-2, SARS, and MERS. These strains will be targets of a promising hit molecule that the team expects to obtain with virtual screening and experimental assays. The scientists need high computational power and algorithms to sample a considerable number of compounds by performing virtual screens of hundreds of millions of molecules. A hierarchical approach that integrates virtual screening of vast libraries together with state-of-the-art induced-fit techniques will allow to filter the most promising compounds within a reasonable amount of time. To perform these complicated calculations and simulations, PRACE awarded the project of Nostrum Biodiscovery with 4 000 000 core hours on SuperMUC-NG, hosted by GCS at LRZ, Germany.

CardioVascular-COVID is a project led by Dr Jazmin Aguado-Sierra from Barcelona Supercomputing Center that will shed light on the effect of anti-malarial drugs on cardiovascular systems – people with various heart diseases with different comorbidities are among the most affected by COVID-19. Researchers of Barcelona Supercomputing Center (BSC) will also study anti-malarial and antibiotic cardiotoxicity – two main problems that require quick generation of evidence and information towards their use by clinicians. The purpose of the project is to help to improve treatment of cardiac patients, affected most severely by the disease and ultimately reducing mortality. The above is the first goal of the project, the second is to explore Venous-Arterial Extracorporeal membrane oxygenation therapy and the North-South Syndrome on patients with profound respiratory failure. For many of them, infection with COVID-19 results in dangerous respiratory failure, requiring ventilatory support in the intensive care unit. All this requires a multidisciplinary team and for the project BSC will collaborate with the Visible Heart Laboratory, and the University of Minnesota Medical Centre. PRACE awarded 7 800 000 core hours on Joliot-Curie Rome, hosted by GENCI at CEA, France.

Targeting conformational changes implicated in early events of viral entry is a project devising another trap to catch the virus. The project is that of Prof. Francisco Javier Luque from the University of Barcelona in Spain. It has two ambitious goals. First, to disrupt viral entry by finding small molecules able to interfere with the conformational changes in the spike protein, prior to binding to the host cell. Second to characterise the structural and energetic changes, implicated in transition in both free and ligand-bound spike proteins. The team of Prof. Luque has a precise model of this collaboration between a spike and human cell receptor and found a specific inactive state. The scientists would like to find a small compound that might stabilise it. They will attempt this through binding to a pocket located at the hinge region, which defines a putative druggable cavity. This was estimated from two independent druggability predictors. These stabilisers are hiding the determinants of ACE2 binding and the disclosure of a moderate stabiliser could be a promising finding. PRACE awarded the project 15 300 000 core hours on Hawk, hosted by GCS at HLRS, Germany.

A computational study of the reactivity in the main protease of SARS-CoV-2 to guide the design of inhibitors is led by Prof. Iñaki Tuñón from the University of Valencia, Spain. Over two and a half months, the team will analyse the binding of the substrate and the reaction mechanisms of the main protease of SARS-CoV-2 (the virus strain causing disease COVID-19). The main protease (3CLpro) is an enzyme with essential role during the replication of the virus and is therefore an attractive drug target. That is why one of the strategies for the development of potential treatments against the SARS-CoV-2 is based on the disruption of the activity of those enzymes that are vital in the replication cycle of the virus, using adequate compounds. The project led by Prof. Iñaki Tuñón is structured in three work packages and there are five expected outcomes. One of those is the definition of the binding mode of different inhibitors and to propose a chemical modification of the inhibitors to improve their binding to the 3CLpro enzyme. All this supports the overall goal of the team to use the knowledge obtained from the simulation of the catalytic process to guide the design of more potent inhibitors to block the main protease of SARS-CoV-2. These complex studies require high computational power and PRACE awarded the group with 23 000 000 core hours on the main partition of MareNostrum4, hosted by BSC, Spain, as well as 288 000 core hours on its P9/V100 partition.

Identification of inhibitors of SARS-CoV-2 S protein is a PRACE-awarded project led by Dr Sonsoles Martin-Santamaria from the Spanish Research Council (CIB-CSIC), Spain. SARS-CoV-2 is the virus strain that causes the disease COVID-19 and the goal of the team is to block the binding of virus spike S to the human cell receptor ACE2, effectively stopping the virus from infecting the cell. The scientists plan to use virtual screening and computational design of peptides to find possible small molecules able to inhibit or block the S protein-mediated fusion mechanism through two processes. Firstly, targeting the protein-protein interface among the monomers (specific molecules), forming the S protein trimer. And secondly, stopping the S protein and ACE2 protein-protein interaction. The scientists will use the generic drug library (drug repurposing). If they find a promising inhibitory activity to block the coronavirus, these compounds could follow a faster and more direct way through clinical trials. The researchers will also screen antiviral libraries, databases such as ZINC, Molport, SPECS. All these processes require enormous computational power and PRACE awarded the project with 25 000 000 core hours on Marconi100, hosted by CINECA, Italy.

A Computational study to guide the development of new SARS-CoV-2 detection hyper-spectral platforms is led by Dr Juan Torras from the Polytechnic University of Catalonia, Spain. This project focusses on the earliest and fastest detection of the coronavirus causing COVID-19 in patients as well as the understanding of its infection mechanisms. The team is convinced that the knowledge developed in this project will help to obtain novel and better SARS-CoV-2 therapeutics and diagnostics based on antibodies. At the moment PCR tests allow the detection of viral RNA and are the most widely used to diagnose COVID-19. However, according to the group, this type of tests fail in different situations. Simultaneously, antibody tests have a great advantage and they could complement PCR tests. The team proposes to study silica and gold substrates with different antibodies with classical molecular dynamics. The group will use a nanoparticle (NP) detector for comparative study among different antibodies, their orientation, and their interaction with silica and gold surfaces. In parallel, the group is working on interactions between antibodies virus spike of the HIV-1 to create novel immunosensor devices. The team is ready to use this experience, all tools, and algorithms in the new COVID-19 project to study the antibody interactions with SARS-CoV-2 spike glycoprotein. Of course, they will use molecular dynamics, quantum mechanics, and molecular mechanics. According to the scientists, combining the new knowledge and results will help to obtain novel and better SARS-CoV-2 therapeutics and diagnostics based on antibodies. PRACE awarded the project with 40 000 000 core hours on Joliot-Curie KNL, hosted by GENCI at CEA, France.

Exploring COVID-19 Infectious Mechanisms and Host Selection Process is led by Prof. Modesto Orozco from the Institute for Research in Biomedicine (IRB Barcelona), Spain. The main goal of Orozco’s team is to understand the evolutionary path driving the virus from a bat to humans, to forecast human sensitivity to infection, and the impact of the virus mutations on the infectivity. Also, they aim to predict new variants of the virus emerging in a second wave and their potential for infectivity. With 93% identity, the COVID-19 RNA sequence is similar to a virus found in horseshoe bats (Rhinolophus Anis), but how this virus jumped to humans is unclear. Deciphering the pathways it took is key to avoid the emergence of new infections, which are in a cryptic state in other exotic animals. The scientists aim to anticipate the virus’ next move and clarify the pathway. They want to know its mutational space, understand varying susceptibility to infection, and predict genomic changes, impacting infectiveness. The group plans molecular dynamics (MD) simulations to provide information on potential cavities in the variants of viral proteins which can be tackled by drugs. To achieve this, the team involves four computational groups (N. López-Bigas and M. Orozco at IRB, and R. Badia and J.L. Gelpí at Barcelona Supercomputing Center) and experimental groups in Marseille and Milan. They will focus on the entrance of the virus into the human cell by binding the Spike protein to human cell receptor ACE2 and perhaps to protein CD147. The group estimated that ± 80% of the mutations impacting infection are located in the receptor-binding region of the Spike. It is unclear how the virus will mutate when specific drugs or antibodies attack it. Or if the virus’ proofreading protein will be fully inactivated. Through HPC study an in-depth analysis was made of mutations and potential future mutations, ranking those that are more likely to happen. PRACE awarded the project with 6 000 000 core hours on Joliot-Curie Rome, hosted by GENCI at CEA, France.

Epi-EWS is led by Dr Alejandro Marti from Mitiga Solutions, Spain. The idea of the project is to define, adapt and refine models that help to timely detect and contain the spread of epidemics, especially for populations on the move. Of course, the model will be adjusted to COVID-19 cases. The goal is to develop an early warning system (EWS) that will be able to provide fast detection of epidemic outbreaks, accurate predictions of the disease spread, and assessment of the outbreak’s economic impact. To achieve this general objective, it will be necessary to model the evolution of a large number of individuals related to the development (or absence thereof) of an epidemic outbreak. The scientists think that this model must take into account the habits of the individuals, their relationship with the environment, the spread of the disease, the performance of specific controls, and eventual treatment. The experts consider such a highly complex system will be complicated to build using analytical models. For this reason, they plan to use Agent-Based Modelling and Simulation (ABMS) for simulating citizens’ behaviour. The goal is to build a comparative platform – Epi-EWS (Model Aggregator Platform for Epidemics) aimed at evaluating different ABM platforms to exercise models from the Epi-EWS project and determine which alternative is better suited to COVID-19 modelling. Mitiga Solutions is a spin-off of the National Supercomputing Center in Spain. The company focuses on predicting and mitigating the impact of natural and social hazards. It is in collaboration with a large number of organisations around the world. The CEO of Mitiga is also a member of the Industrial Advisory Committee of PRACE. PRACE awarded the team of Mitiga 5 000 000 core hours on Beskow, hosted by KTH-PDC in Sweden.

Introduction: The high risk exposure of workers who perform delivery in the face of new contexts of precarious work and high unemployment rates in Brazil and other countries increases the chances of accidents and other illnesses in the face of the pandemic situation. coronavirus. On the other hand, this flexibilization of work and its consequent insecurity has a direct influence on the working and living conditions of these workers and their subjection to low wages without almost any social protection or labor rights. The negative effects produced by the dominant development model in the current world, where the interest of capital overrides the well-being of the majorities, predominate in the workers' health process. In the current context of the coronavirus pandemic and the quarantine practice adopted in the various affected cities, delivery workers are increasingly involved in the transportation of food, medicines and other inputs considered essential. Goals In this context, the proposed study aims to systematize the rights and generate evidence to support recommendations to the health of delivery workers in the context of the coronavirus pandemic in Brazil in a comparative analysis with the countries most affected: China, Italy, Spain, France and the United States. The contributions of this research will be able to subsidize the set of social actors involved in the worker's health such as government, organized civil society, private initiative and workers in the formulation of recommendations that incorporate the worker's health right in the responses to the coronavirus for this segment of workers. The numbers of the confinement change daily like the number of infections. Data released by the situation panel at John Hopkins University on March 30, 2020 report the existence of 723,740 confirmed cases worldwide; 34,018 deaths and 202 countries affected. The countries with the highest number of cases are China (82,156); Italy (97,689); Spain (80,110); France (40,723); United States (143,055); and in Brazil 4,256 cases have been registered. Methodology Methodologically, the study's proposal is a scope review that allows for a comparative perspective in the six chosen countries and whose contexts in terms of labor rights and worker protection policies are very diverse and may help to identify counterpoints, approaches and differences. Expected Results To build evidence on delivery workers from the perspective of the right to health considering that it is a relatively new phenomenon in contemporary societies and with gaps in knowledge about rights, health and the possible effects of exercising this activity in the context of an emergency situation public health issues of international importance.

Taking the advanced democracies as its starting point, this project aims to identify the nature of the dilemmas posed by the pandemic and to undertake an empirical analysis of people's preferences with respect to these dilemmas. Starting with four dilemmas (governance of the pandemic, individual freedom, the economy, and the pandemic as a global problem) the project proposes identifying a series of survey questions to identify citizens' priorities in this regard.