SCIENTIFIC PROJECTS COVID-19

Brief description: Although the SARS-CoV-2 transmission pathway is by aerosols, recent visions suggest that the gold-fecal pathway would be a potential form of pandemic transmission. Our goal is to characterize the role of the oro-fecal pathway as a source of SARS-CoV-2 transmission in asymptomatic patients for COVID-19. To do this, we'll assess demographic background, clinical and immune response patients in asymptomatic patients for COVID-19. We will detect SARS-CoV-2 in nasal swabs and faecal samples (Bowel movements). In positive cases we will characterize phylogenetics and viral variants and evaluate viral viability in depositions as evidence of transmissibility. The study results will advance the characterization of the oro-fecal pathway as a new form of SARS-CoV-2 transmission.

Name of participating researchers and their affiliations:

*Alejandro Corvalán, Hematology and Oncology Department/ACCDiS, Medicine, PUC, Chile.
*Alberto Espino, Gastroenterology Department, Medicine, PUC, Chile.
*Robinson Gonzalez, Gastroenterology Department, Medicine, PUC, Chile.
*Pablo Valenzuela, Infectology Department, Medicine, PUC, Chile.
*Wilda Olivares, Hematology and Oncology Department/ACCDiS, Medicine, PUC, Chile.

Execution status: Running for ANID-Quick Assignment – COVID19

National or international collaboration: Elmer Fernandez, Cordoba, Argentina

Responsible researcher: Alejandro Corvalan, Hematology and Oncology Department/ACCDiS, Medicine, PUC, Chile. acorvalan@accdis.cl

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: We propose that T-cell dysfunction contributes to immunopathology associated with the most severe cases, and that therefore these cells and the proteins that generate this phenotype could be markers of severity. From blood samples from COVID19 patients, we will evaluate the frequency of dysfunctional T cells and immunomarkers to generate a classification model that can be validated as a COVID-19 risk test.

Name of participating researchers and their affiliations:

*Owen G, Hill C, Saavedra F, Córdova M.
*Researchers from the Faculty of Biological Sciences, UC

Execution status: Running

National or international collaboration: University of New South Wales, Australia,

Responsible researcher: Gareth Owen, UC, gowen@bio.puc.cl

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: The requirements for vaccines against biologically threatened agents are somewhat different from those of conventional vaccines, Including (i) reduced time to mount a protective immune response; (Ⅱ) speed and ease of manufacture; and (Ⅲ) the inherent stability of the final product formulated to allow long-term storage. None of the vaccines currently authorized against certain bioterrorism agents meet all of these performance requirements, including the currently-authorized anthrax vaccine. The current FDA-approved anthrax vaccine in the United States is produced from the filtered culture supernatant fraction of the V770-NP1-R strain of B. anthracis and consists mainly of the PA antigen adsorbed in aluminium hydroxide. The production process is complex. There is a batch-to-batch variation in vaccine preparation batches, and the precise composition of the vaccine is undetermined. In addition, the full vaccination cycle requires five doses administered over an 18-month period. These concerns, and the debate around the production and use of the current anthrax vaccine, efforts to develop an alternative anthrax vaccine, including AP-based recombinant subunit vaccines. In recent years, there has been a growing demand for single doses, easy-to-administer vaccines. This helps improve patient compliance and facilitates large-scale immunization. Oral immunization has become an interesting possibility for rapid mucosal immunization and this project will assess its feasibility by implementing inkjet printing film manufacturing technology for vaccine administration in the mucosa.

Name of participating researchers and their affiliations:

*Javier O. Morales, Faculty of Chemical and Pharmaceutical Cs, CENDHY, ACCDiS , Chile.
*Rikhav P. Gala, Fraunhofer USA Center for Molecular Biotechnology, Newark, USA.

Execution status: Developing with discontinued face-to-face activities

National or international collaboration: International

Responsible researcher: Javier O. Morales, Faculty of Chemical and Pharmaceutical Cs, CENDHY, ACCDiS , Chile. jomorales@ciq.uchile.cl

Execution funds or to which it was applied: Fraunhofer USA inmates

Brief description: Proposal inserts in COhort MAUCO, Molina, chronic disease study, 9,400 participants aged 38-74, with regular health tests, Psychosocial, Cognitive, Environmental, genetic, microbiome, Agrochemicals, antibiotic resistance and a biobank. MAUCO COVID-19 Sentry Center: With MAUCO's research infrastructure, monitoring is expanded by incorporating pandemic surveillance. This first year we will implement the COVID-19 sentinel center model to detect early entry of the new infectious agent into the population and characterize the virus and clinical picture. Coordinated with the local health authority, we will seek the partnership with WHO, to join the international pandemic monitoring network. We will collect real-time information:

1. SARS-VOC2 activity in the population
2. Genetic characterization
3. Circulating virus changes, magnitude of outpatient illness, hospitalized and mortality.

We will continue regular survey of the psychosocial impact of the epidemic. Components:
1) COVID-19 clinical-epidemiological-social surveillance
2) COVID-19 Serological Surveillance
3) Biobank COVID-19
4) VIRological surveillance SARS-COV2
5) Impact of containment measures
6) Integration with local health system.

Name of participating researchers and their affiliations:

*Catterina Ferreccio (PUC), Chile.
*Andrea Huidobro (UCM), Chile.
*Marcela Ferres (PUC), Chile.
*Vanessa Van De Wyngard (PUC), Chile.
*Sandra Cortés (PUC), Chile.
*Claudio Vargas (USACH), Chile.
*José Patricio Miranda (PhD student, PUC), Chile.
*Juan Pablo Valenzuela (student magister, PUC), Chile.
*Vicente Cid (undergraduate, USACH), Chile.

Execution status: Running

National or international collaboration: Regional/national linkage: MAUCO works with Molina Municipality in community outreach and training to health professionals. Molina Hospital provides infrastructure for biobanking. The hospitals of Curicó and Talca, they also collaborate in the analysis of cohort samples and facilitate access to clinical records.

MAUCO conducts educational activities and develops research in collaboration with researchers from local universities: Universidad Catolica del Maule, University of Talca and other regions: Udd (Santiago), UFRO (Temuco), PUC (Santiago), UCH (Santiago), O'Higgins University (Rancagua), U of Aysén, Ucn (Antofagasta) and UTA (Arica).

International linkage: MAUCO is a member of: AGRICOH, consortium of agricultural cohorts led by IARC; NCD-RisC, chronic diseases consortium coordinated by Imperial College of London, UK; International 100K Cohorts Consortium (Ihcc), led by the NIH of the USA and the Wellcome Trust, UK and coordinated by Duke University, with 3 Latin American members (Chile, Mexico, Brazil). Collaborative research at MAUCO: National Cancer Institute/NIH (microbiome, digestive cancers), CDC/USA (microbial resistance), Lund University/Sweden (pesticides in agricultural workers), IARC/France (Helicobacter pylori), Heidelberg University (family cancer, HP and HP serology), NIH/Guanacaste Costa Rica cohort: common protocols for COVID-19 studies.

Responsible researcher: Catterina Ferreccio

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: In recent months, we are experiencing an epic and historic threat to public health around the world due to the spread of the new coronavirus (SARS-CoV-2) that caused the disease called coronavirus 2019 (COVID-19). There is still no solid information on the natural history of COVID-19, nor about the most appropriate clinical management of the disease, and there are a lot of details to be clarified. However, SARS-CoV-2 is known to have high transmissibility and causes acute respiratory syndrome ranging from mild to very severe cases with respiratory failure, requiring specialized treatment in intensive care units. Its lethality varies, but it seems to have a higher incidence in males, elderly and associated morbidities. The identification of individuals affected by SARS-CoV-2 is carried out using a methodology based on RNA techniques, reverse transcriptase reaction followed by polymerase chain reaction (RT-PCR), which showed a positive correlation with CT images. chest of those affected. However, RT-PCR has the disadvantage of having low sensitivity if the biological sample is collected too early or after 15 days after symptoms begin, the type of collection is very uncomfortable as it requires a swab of the nasal cavity and oropharyns, aspiration of secretion of the nasopharynge or even the lower airways, the test result can take up to three days and still does not predict the prognosis or risk of death. In this sense, the need to look for a biomarker or biomarker firm that is able to determine this lung condition, as well as gravity, treatment and disease progression, is an essential tool in the clinical follow-up of patients affected by COVID- 19. These become more relevant under conditions where resource availability is limited, causing the collapse of the health system, this is the largest mortality factor in the countries affected by this pandemic. Therefore, identification of biomarkers sensitive to the prognosis of infection, as well as identifying the molecular mechanisms that lead to death, would have a considerable clinical impact, as well as in the public health system, Their (Unique Health System). Identifying biomarkers will help us deepen our understanding of biology that guides sarS-CoV-2 interaction or communication with human cells, and how this dialogue can compromise the host's defense. Advances in understanding COVID-19 pathophysiology will open up new therapeutic horizons that will impact on the survival of those affected and the reduction of the costs of public health systems. The work will also feature the participation of the Rancagua Regional Hospital, the University of Chile, The National University of Cordoba (Argentina) Republic (Uruguay) and Baia Sul Hospital (Sc).

Name of participating researchers and their affiliations:

*Alexandra Latini, Bioenergy and Oxidative Stress Laboratório (LABOX), Federal University of Santa Catarina (Ufsc), Brazil.
*Anne Lucia De Paul, Center for Electronic Microscopy, Universidad Nacional de Córdoba, Argentina.
*Ramiro Zepeda, Coordinator of the Pain Center, University of Chile, Chile.
*Valentina Parra, Facultad de Ciencias Químicas y Farmacéuticas, University of Chile, Chile.
*Mauricio Latorre, Institute of Engineering Sciences, University of O'Higgins, Chile.
*Andrés Trostchansky, Department of Biochemistry, Faculty of medicine, University of the Republic, Uruguay.
*Israel Maia, Hospital Baia Sul, Santa Catarina, Brazil.

Execution status: Sent

National or international collaboration: National Council for Scientific and Technological Development, Brazil.

Responsible researcher: Alexandra Latini, Bioenergy and Oxidative Stress Laboratório (LABOX), Federal University of Santa Catarina (Ufsc), Brazil. alatinilabox@gmail.com

Execution funds or to which it was applied: Chamada MCTIC/CNPq/FNDCT/MS/SCTIE/Decit No. 07/2020. Research to tackle COVID-19, its consequences and other severe acute respiratory syndromes.

Brief description: Although COVID-19 infection is primarily asymptomatic at first; 10% of patients can develop to severe coronavirus pneumonia accompanied by acute respiratory failure with a lethality of close to 2%. These patients require invasive mechanical ventilation and critical beds which is the main cause of the collapse of health systems. Currently, there is no global consensus on the conditions that lead to the worsening of certain patients, However, individuals are known to have clinical alterations in ventilation/perfusion parameters, systemic hypoxia, but in many cases silent and without increased CO2; in addition to hemodynamic changes. Physiologically, all of the above processes are mediated by the renin-angiotensin-aldosterone system (Raas) which is involved in the ACE2 protein that has been described as the entry point of the SARS-CoV2 virus to the cells. Recently, RAAS has been described as being able to control the functioning of the mitochondria and thus cellular metabolism which depends on the body's constant oxygen consumption. If the entry of SARS-CoV2 into the cell prevents the correct functioning of the mitochondria, this could then be one of the causes of systemic hypoxia observed in coVID-19 status, which tests the multiorgan failure of oxygen-high-demand tissues (cardiovascular, Nervous, renal and musculoskeletal), which have been described, have a metabolic reflex in blood mononuclear cells. With this background, in this project, we seek to define new biomarkers prognostic disease which will allow individuals of negative prognosis to be determined, gravity, the treatment and evolution of patients, as well as starting an early ventilatory support; reducing the use of critical beds and invasive mechanical ventilation. These markers will be obtained from the analysis using molecular biology techniques of mononuclear cells obtained from the blood of COVID-19 patients.

Name of participating researchers and their affiliations:

*Valentina Parra, Facultad de Ciencias Químicas y Farmacéuticas, University of Chile, Chile.
*Ramiro Zepeda, Coordinator of the Pain Center, University of Chile, Chile
*Andrea del Campo, Faculty of Chemistry and Pharmacy, Pontificia Universidad Católica de Chile, Chile
*Mauricio Latorre, Institute of Engineering Sciences, University of O'Higgins, Chile
*Andrés Cornejo, Head of Infectology Department, Bernardo O'Higgins Regional Liberation Hospital, Rancagua, Chile
*Veronica Change, Food Institute and Technology, University of Chile & Diagnofast Spa, Chile

State nomination: Sent

National or international collaboration: National. SOFOFA Hub, Cpc (Confederation of Production and Trade (Cpc), Chile.

Responsible researcher: Valentina Parra, Facultad de Ciencias Químicas y Farmacéuticas, University of Chile, Chile vparra@ciq.uchile.cl

Execution funds or to which it was applied: SiEMPRE Technology Adoption Fund (solidarity and business innovation), SOFOFA Hub, Cpc, Chile.

Brief description: Understanding that, until you get a vaccine or effective treatment for COVID-19, Chile faces population control strategies at the local and total level at least until the end of next year. In this respect, success in COVID-19 mitigation measures lie mainly in early and efficient detection. In this context, questions like: Where, how many and when to test? have become critical in quarantine decision-making. Currently, in our country the tests are carried out mainly in care centers, people with obvious symptoms or in contact with the disease, added to certain risk groups, like nursing homes. This strategy revives itself, while, to date has largely allowed the disease to progress to be controlled, given the increase in the number of cases in recent weeks, a critical situation in terms of hospital capacity is predicted in the short term, availability of inputs, facilities and staff trained to carry out the tests, coupled with a total closure of more localities with their respective economic impacts, scenario that multiplies at the regional level. In this context, several countries have now put in place random testing measures to establish preventive, models for early control of the progression of the disease. Known is the case of South Korea, where its strategic plan based on random testing positions it within the countries that best controlled the health and economic impact of COVID-19 (see annexes section I). Random testing information feeds mathematical models of two types: (1) of the statistical type that allow to estimate a spatial distribution of cases (both symptomatic and non-symptomatic) more accurately (2) of the type of temporal dynamics that simulate the evolution of contagion clusters and their spatial distribution. In this proposal, first we propose to carry out a massive random test within the city of Rancagua. This information will allow to build mathematical models with the aim of generating as a product a Strategic Plan for the Detection of COVID19 sustainable over time. Effective implementation will enable efficient planning to be designed, early and optimized place, number and temporality of COVID-19 tests in the population of the sixth region, vital information for decision-making local and sustainable totals over time.

Name of participating researchers and their affiliations:

*Mauricio Latorre, Institute of Engineering Sciences, University of O'Higgins, Chile. *Cristóbal Quiñinao, Institute of Engineering Sciences, University of O'Higgins, Chile.
*Maria Soledad Burrone, Institute of Health Sciences, University of O'Higgins, Chile.
*Valentina Parra, Facultad de Ciencias Químicas y Farmacéuticas, University of Chile, Chile.
*Raul Mera, Faculty of Chemistry and Biology, University of Santiago, Chile, Rancagua, Chile.

National or international collaboration: National. SOFOFA Hub, Cpc (Confederation of Production and Trade (Cpc), Chile.

Responsible researcher: Mauricio Latorre, Institute of Engineering Sciences, University of O'Higgins, Chile. mauricio.latorre@uoh.cl

Execution funds or to which it was applied: SiEMPRE Technology Adoption Fund (solidarity and business innovation), SOFOFA Hub, Cpc, Chile.

State nomination: Sent

Brief description: While the COVID-19 condition is primarily asymptomatic; 10% of patients evolve to a severe case of pneumonia with a lethality of close to 2%. Currently, there is no consensus on the causes of worsening of certain patients, However, these are known to have alterations in ventilation/perfusion parameters, systemic hypoxia, in many cases silent and without increased CO2; in addition to hemodynamic changes. Physiologically, these processes are mediated by the renin system- angiotensin-aldosterone (Raas), in which the ECA2 protein that corresponds to the entry point of the SARS-CoV-2 virus participates to the cells. Recently, RAAS has been described as being able to control the functioning of the mitochondria and thus cellular metabolism. Considering the latter, and the metabolic and biochemical changes experienced by COVID-19 patients; this project postulates the development and validation of a profile of simple biochemical and clinical markers, based on the metabolism and bioenergy of COVID-19 patients, in order to obtain a quantifiable prognostic parameter associated with disease progression. This will reduce the specific mortality rate for COVID-19 and an optimization of resources in the country's public health.

Name of participating researchers and their affiliations:

*Ramiro Zepeda, Coordinator of the Pain Center, University of Chile, Chile.
*Valentina Parra, Facultad de Ciencias Químicas y Farmacéuticas, University of Chile, Chile.
*Andrea del Campo, Faculty of Chemistry and Pharmacy, Pontificia Universidad Católica de Chile, Chile
*Andrés Cornejo, Head of Infectology Department, Bernardo O'Higgins Regional Liberation Hospital, Rancagua, Chile.

State nomination: Sent

National or international collaboration: National Research and Development Agency (ANID), Chile.

Responsible researcher: Prof. Dr. Ramiro Zepeda, Coordinator of the Pain Center, University of Chile, Chile rzepeda@ciq.uchile.cl

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: The SARS-CoV-2 virus, COVID-19 cause, led to the largest pandemic outbreak of the last 100 years, pose a global threat to public health. While its detection in humans as a diagnosis is vitally important, so is its ongoing monitoring in other environments to control and/or prevent the spread of the disease and ensure a safe mass return of the population to socio-economic activities in the country.
This project will develop portable devices to detect the virus on high-persistence and mass-contact surfaces, those that have not been addressed to date. For this you will work with sandwich-type biosensors, obtained by integrating micro/nanostructured carbon materials with the specific antibody to the S protein (Sars-CoV-2-S1-AC) as an element of recognition of high affinity, integrated into electrochemical and x-ray fluorescence transducers, both portable.
The advantage of these biosensors will be their portability that will allow for quick and easy-to-use screening, in areas of mass turnout. At last, as the replication of the genetic material of the virus is not required, you'll get low-cost devices, opening up the possibility of bulking for large-scale field measurements.

Name of participating researchers and their affiliations: Soledad Bollo, Claudia Yáñez of the University of Chile, Chile

Execution status: Postulated

National or international collaboration: Paulina Sierra (UTEM), Gustavo Rivas (Universidad Nacional de Córdoba, Argentina)

Responsible researcher: Soledad Bollo. sbolllo@ciq.uchile.cl

Funds to which he applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: SARS-CoV2 enters cells through the ACE2 receptor present in the lung and heart. ACE2 is destroyed by virus action, affecting pulmonary homeostasis. ACE2 generates angiotensin (Angs)-(1-9) and (1-7) that counterbalance actions the classic ACE/Ang II axis. It is not known why 5% of COVID-19 patients progress to severe lung damage. Hypothesis: lung damage progression in COVID19 patients is associated with imbalance in ACE2 and ACE and their angiotensin bioactive peptides (Ang)-(1-9), Ang-(1-7) and Ang II. Overall goal: investigate whether the progression of lung damage in patients with COVID-19 is related to decreased ACE2 activity and levels of Ang-(1-9) and Ang-(1-7). Experimental design: PCR+ patients for SARS-CoV2 will be enrolled between 18-75 years, admitted to the Hospital Sotero del Río from COVID-19 pneumonia requiring mechanical ventilation. Peered patients with non-serious COVID-19 infection will also enter, who don't require hospitalization, from anCORA primary care centres and the MAUCO cohort (Molina). Expected results: ACE2 Activity and Ang-(1-9) and Ang-(1-7) predict prognosis of severe lung damage in COVID-19 patients.

Name of participating researchers and their affiliations:

*Maria Paz Ocaranza, Ph.D. Head Molecular Cardiology Laboratory, Div. Cardiovascular Diseases, PUC, Chile.
*Cecilia Ruiz, MD, Intensivista. Chief Critical Patient Unit, Care Complex, Sótero del Río (CASR), Chile.
*Andrés Aquevedo, MD, Intensivista. Head of the Intensive Care Unit (Icu) CASR, Chile.
*Claudio Montegro, MD, Chief Radiologist, CASR Imaging Unit, Chile.
*Jorge Jalil, MD, Cardiologist. Head of the Non-Invasive Cardiology Laboratory, Christus-UC Health Network, Chile.
*Claudia Bambs, MD, Epidemiologist. Head of Department of Public Health, Medical School, PUC, Chile.
*Sergio Lavandero, Ph.D. Director ACCDiS. University of Chile, Chile.
*Mario Chiong, Ph.D. Research associate ACCDiS, Director PAR Explora, Chile.
*Monica Chalhub, MD, Clinical Cardiologist. Hospital San Juan de Dios, Curicó, Chile.
*Claudia Muñoz, Ph.D. Postdoctoral researcher, Chile.
*Andrés Ramirez, MSc. Researcher Master's Program in Clinical Biochemistry, Chile.

Execution status: Postulated

National or international collaboration: Andrea Huidobro MAUCO population cohort, Marko Poglistch, Vienna, Austria.

Responsible researcher: María Paz Ocaranza, mocaran@med.puc.cl

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID.

Brief description: The MAUCO cohort, who belongs to the Advanced Center for Chronic Diseases, is the first cohort in Chile to study the factors that influence or prevent the development of chronic diseases and to date, has 9,400 participants aged 38 to 74. The COVID-19 "Social and Psychological Survey: Perceived threat questionnaires, government response, impacts and experience on coronavirus" of the University of Montana in the United States was adapted to The Chilean reality and was applied to April and May at 1,130 and 1,242, respectively. The objectives are to evaluate the physical and mental health of the MAUCO cohort, assess its difficulties in the face of the current situation and help resolve questions about the COVID-19 epidemic.

Name of participating researchers and their affiliations:

*Andrea Huidobro (UCM)
*Pius Venegas (UC)
*Christian Pinto (UC)
*Catterina Ferreccio (UC)

Execution status: Developing

National or international collaboration: Universidad Catolica del Maule (Talca), Hospital de Molina (Molina), Chile.

Responsible Researcher: Catterina Ferreccio, UC, catferre@gmail.com

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID

Brief description: The best-performing countries in the management of the SARS-CoV2 pandemic have opted for mass monitoring of the population to contain the disease. The standard diagnostic technique is RT-PCR, the result of which takes hours delaying the delivery of the reports. On the other hand, the rapid serological test does not detect the presence of the virus so it does not indicate the infecting condition of the individual. These systems are costly, require qualified personnel and/or do not occur in the national territory making it difficult to implement them massively to monitor the carrying of the virus. In our research group we have experience using gold nanoparticles (AuNp) to generate rapid detection systems using UV-Vis colorimetry and/or spectrophotometry. The AuNp interact with light, and modifications to its surface or aggregation phenomena generate changes in its coloration observable to the naked eye, or in its detectable absorption spectrum with a portable spectrophotometer. So, modifying the surface of AuNp with molecules that recognize viral macromolecules, the presence of the virus would be detected quickly and cost-effectively, with the naked eye or, failing, with a spectrophotometer, even omitting RNA extraction.

Name of participating researchers and their affiliations:

*Marcelo Kogan, University of Chile
*Francisco Morales Zavala
*Daniela Seelenfreund
*Vivian Luchsinger Farthias
* Sandra Ampuero Llanos
*Mónica Saldarriaga-Córdoba
*Pedro Jara Guajardo
*Aldo Adrián Rojas Morales
*Adrián Rodrigo Fuentes Miranda

Execution status: We are developing the kit.

National or international collaboration: Ricardo Soto, Fernando Valiente Faculty of Medicine. UCH

Responsible Researcher: Marcelo Kogan

Execution funds or to which it was applied: Application for Competition for rapid allocation of resources for Coronavirus Research Projects (COVID-19) year 2020 of ANID