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Project Title
Unraveling the differences between mild and severe hantavirus infected patients: delineating mechanisms to propose novel therapies
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1201240
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Start Date
2020

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Assessing Pulmonary Epithelial Damage in Hantavirus Cardiopulmonary Syndrome: Challenging the Predominant Role of Vascular Endothelium through sRAGE as a Potential Biomarker

2023 , Gabriela Meza-Fuentes , LOPEZ HERNANDEZ, RENE RAMON , RETAMAL LUCERO, MAURICIO ANTONIO , CORTES SALINAS, LINA JIMENA , VIAL COX, MARIA CECILIA , DELGADO BECERRA, OROZIMBA IRIS , VIAL CLARO, PABLO AGUSTIN

Hantavirus cardiopulmonary syndrome (HCPS) is a severe respiratory illness primarily associated with microvascular endothelial changes, particularly in the lungs. However, the role of the pulmonary epithelium in HCPS pathogenesis remains unclear. This study explores the potential of soluble Receptors for Advanced Glycation End-products (sRAGE) as a biomarker for assessing pulmonary epithelial damage in severe HCPS, challenging the prevailing view that endothelial dysfunction is the sole driver of this syndrome. We conducted a cross-sectional study on critically ill HCPS patients, categorizing them into mild HCPS, severe HCPS, and negative control groups. Plasma sRAGE levels were measured, revealing significant differences between the severe HCPS group and controls. Our findings suggest that sRAGE holds promise as an indicator of pulmonary epithelial injury in HCPS and may aid in tracking disease progression and guiding therapeutic strategies. This study brings clarity on the importance of investigating the pulmonary epithelium’s role in HCPS pathogenesis, offering potential avenues for enhanced diagnostic precision and support in this critical public health concern.

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NPC1 as a Modulator of Disease Severity and Viral Entry of SARSCoV- 2

2021 , VIAL COX, MARIA CECILIA , CALDERON GIADROSIC, JUAN FRANCISCO , KLEIN POSTERNACK, ANDRES DAVID

The COVID-19 plague is hitting mankind. Several viruses, including SARS-CoV-1, MERS-CoV, EBOV, and SARS-CoV-2, use the endocytic machinery to enter the cell. Genomic variants in NPC1, which encodes for the endo-lysosomal Niemann-Pick type C1 protein, restricts the host-range of viruses in bats and susceptibility to infections in humans. Lack of NPC1 and its pharmacological suppression inhibits many viral infections including SARS-CoV-1 and Type I Feline Coronavirus Infection. Antiviral effects of NPC1-inhibiting drugs for COVID-19 treatment should be explored.

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Comparison of VSV Pseudovirus and Focus Reduction Neutralization Assays for Measurement of Anti-Andes orthohantavirus Neutralizing Antibodies in Patient Samples

2020 , VIAL COX, MARIA CECILIA , Annalis Whitaker , Jan Wilhelm , Jimena Ovalle , Ruth Perez , Francisca Valdivieso , Marcela Ferres , Constanza Martinez-Valdebenito , Philip Eisenhauer , Gregory J. Mertz , Jay W. Hooper , Jason W. Botten , VIAL CLARO, PABLO AGUSTIN

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Evaluation of the Immune Response Induced by CoronaVac 28-Day Schedule Vaccination in a Healthy Population Group

2022 , Alejandro Escobar , Felipe E. Reyes-López , Mónica L. Acevedo , Luis Alonso-Palomares , Fernando Valiente-Echeverría , Ricardo Soto-Rifo , Hugo Portillo , Jimena Gatica , Ivan Flores , Estefanía Nova-Lamperti , Carlos Barrera-Avalos , María Rosa Bono , Leonardo Vargas , Valeska Simon , Elias Leiva-Salcedo , VIAL COX, MARIA CECILIA , Daniel Valdés , Ana M. Sandino , CORTES SALINAS, LINA JIMENA , HORMAZABAL CASTILLO, JUAN PATRICIO , Mónica Imarai , Claudio Acuña-Castillo

CoronaVac vaccine from Sinovac Life Science is currently being used in several countries. In Chile, the effectiveness of preventing hospitalization is higher than 80% with a vaccination schedule. However, to date, there are no data about immune response induction or specific memory. For this reason, we recruited 15 volunteers without previous suspected/diagnosed COVID-19 and with negative PCR over time to evaluate the immune response to CoronaVac 28 and 90 days after the second immunization (dpi). The CoronaVac administration induces total and neutralizing anti-spike antibodies in all vaccinated volunteers at 28 and 90 dpi. Furthermore, using ELISpot analysis to assay cellular immune responses against SARS-CoV-2 spike protein, we found an increase in IFN-gamma- and Granzyme B-producing cells in vaccinated volunteers at 28 and 90 dpi. Together, our results indicate that CoronaVac induces a robust humoral immune response and cellular immune memory of at least 90 dpi.

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Hantavirus in humans: a review of clinical aspects and management

2023 , Pablo A Vial , Marcela Ferrés , VIAL COX, MARIA CECILIA , Jonas Klingström , Clas Ahlm , LOPEZ HERNANDEZ, RENE RAMON , Nicole Le Corre , Gregory J Mertz

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Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality

2021 , LOPEZ HERNANDEZ, RENE RAMON , Gregory Mertz , GRAF SANTOS, JERÓNIMO , Mauricio Espinoza , Marcela Ferrés , Mario Calvo , VIAL CLARO, PABLO AGUSTIN , VIAL COX, MARIA CECILIA

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Immunopathological signatures in multisystem inflammatory syndrome in children and pediatric COVID-19

2022 , Keith Sacco , Riccardo Castagnoli , Svetlana Vakkilainen , Can Liu , Ottavia M. Delmonte , Cihan Oguz , Ian M. Kaplan , Sara Alehashemi , Peter D. Burbelo , Farzana Bhuyan , Adriana A. de Jesus , Kerry Dobbs , Lindsey B. Rosen , Aristine Cheng , Elana Shaw , Mikko S. Vakkilainen , Francesca Pala , Justin Lack , Yu Zhang , Danielle L. Fink , Vasileios Oikonomou , Andrew L. Snow , Clifton L. Dalgard , Jinguo Chen , Brian A. Sellers , Gina A. Montealegre Sanchez , Karyl Barron , REY JURADO, EMMA , VIAL COX, MARIA CECILIA , POLI HARLOWE, MARIA CECILIA BERTA , Amelia Licari , Daniela Montagna , Gian Luigi Marseglia , Francesco Licciardi , Ugo Ramenghi , Valentina Discepolo , Andrea Lo Vecchio , Alfredo Guarino , Eli M. Eisenstein , Luisa Imberti , Alessandra Sottini , Andrea Biondi , Sayonara Mató , Dana Gerstbacher , Meng Truong , Michael A. Stack , Mary Magliocco , Marita Bosticardo , Tomoki Kawai , Jeffrey J. Danielson , Tyler Hulett , Manor Askenazi , Shaohui Hu , Jason Barnett , Xi Cheng , Krishnaveni Kaladi , Vasudev Kuram , Joseph Mackey , Neha M. Bansal , Andrew J. Martins , Boaz Palterer , Helen Matthews , Uma Mudunuri , Marshall Nambiar , Andrew J. Oler , Andre Rastegar , Smilee Samuel , Conrad Shyu , Varsha Waingankar , Sarah Weber , Sandhya Xirasagar , Yazmin Espinosa , Camila Astudillo , Cecilia Piñera , Ricardo González , Maria De Filippo , Martina Votto , Lorenza Montagna , Jeffrey I. Cohen , Helen C. Su , Douglas B. Kuhns , Michail S. Lionakis , Thomas M. Snyder , Steven M. Holland , Raphaela Goldbach-Mansky , John S. Tsang , Luigi D. Notarangelo

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An international, interlaboratory ring trial confirms the feasibility of an extraction-less “direct” RT-qPCR method for reliable detection of SARS-CoV-2 RNA in clinical samples

2022 , Margaret G. Mills , Emily Bruce , Meei-Li Huang , Jessica W. Crothers , Ollivier Hyrien , Christopher A. L. Oura , Lemar Blake , Arianne Brown Jordan , Susan Hester , Leah Wehmas , Bernard Mari , Pascal Barby , Caroline Lacoux , Julien Fassy , VIAL CLARO, PABLO AGUSTIN , VIAL COX, MARIA CECILIA , Jose R. W. Martinez , Olusola Olalekan Oladipo , Bitrus Inuwa , Ismaila Shittu , Clement A. Meseko , Roger Chammas , Carlos Ferreira Santos , Thiago José Dionísio , Thais Francini Garbieri , Viviane Aparecida Parisi , Maria Cassia Mendes-Correa , Anderson V. de Paula , Camila M. Romano , Luiz Gustavo Bentim Góes , Paola Minoprio , Angelica C. Campos , Marielton P. Cunha , Ana Paula P. Vilela , Tonney Nyirenda , Rajhab Sawasawa Mkakosya , Adamson S. Muula , Rebekah E. Dumm , Rebecca M. Harris , Constance A. Mitchell , Syril Pettit , Jason Botten , Keith R. Jerome , Massimo Caputi

Reverse transcription–quantitative polymerase chain reaction (RT-qPCR) is used worldwide to test and trace the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). “Extraction-less” or “direct” real time–reverse transcription polymerase chain reaction (RT-PCR) is a transparent and accessible qualitative method for SARS-CoV-2 detection from nasopharyngeal or oral pharyngeal samples with the potential to generate actionable data more quickly, at a lower cost, and with fewer experimental resources than full RT-qPCR. This study engaged 10 global testing sites, including laboratories currently experiencing testing limitations due to reagent or equipment shortages, in an international interlaboratory ring trial. Participating laboratories were provided a common protocol, common reagents, aliquots of identical pooled clinical samples, and purified nucleic acids and used their existing in-house equipment. We observed 100% concordance across laboratories in the correct identification of all positive and negative samples, with highly similar cycle threshold values. The test also performed well when applied to locally collected patient nasopharyngeal samples, provided the viral transport media did not contain charcoal or guanidine, both of which appeared to potently inhibit the RT-PCR reaction. Our results suggest that direct RT-PCR assay methods can be clearly translated across sites utilizing readily available equipment and expertise and are thus a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

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Targeted high volume hemofiltration could avoid extracorporeal membrane oxygenation in some patients with severe Hantavirus cardiopulmonary syndrome

2021 , LOPEZ HERNANDEZ, RENE RAMON , Rodrigo Pérez‐Araos , Álvaro Salazar , Mauricio Espinoza , Analia Cuiza , VIAL COX, MARIA CECILIA , VIAL CLARO, PABLO AGUSTIN , GRAF SANTOS, JERÓNIMO

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Seroprevalence of Natural and Acquired Immunity against the SARS-CoV-2 Virus in a Population Cohort from Two Chilean Cities, 2020–2022

2023 , Loreto Núñez-Franz , Muriel Ramírez-Santana , RUBILAR RAMIREZ, PAOLA , Macarena Said , VIAL COX, MARIA CECILIA , Luis Canales , GONZALEZ WIEDMAIER, CLAUDIA MARTA , APABLAZA SALINAS, MAURICIO IVÁN , Gloria Icaza , HORMAZABAL CASTILLO, JUAN PATRICIO , Rubén Quezada-Gaete , VIAL CLARO, PABLO AGUSTIN , Kathya Olivares , CORTES SALINAS, LINA JIMENA , AGUILERA SANHUEZA, XIMENA PAZ

Background: Chile has achieved the highest coverage for vaccines against the SARS-CoV-2 virus worldwide. Objective: To assess the progression of immunity (natural and acquired by vaccine) in a cohort from two Chilean cities. Methods: Individuals (n = 386) who participated in three phases of population-based serial prevalence studies were included (2020–2021 and 2022). Presence of SARS-CoV-2 antibodies was measured in serum. Data including time of vaccination and type of vaccine received were analysed with descriptive statistics. Results: Seroprevalence was 3.6% in the first round and increased to 96.9% in the second and 98.7% in the third. In the third round, 75% of individuals who had received the basal full scheme were seropositive at 180 days or more since their last dose; 98% of individuals who received one booster dose were seropositive at 180 days or more, and 100% participants who received two boosters were seropositive, regardless of time since their last dose. Participants receiving mRNA vaccines had higher seroprevalence rates over time. Conclusions: The high vaccination coverage in Chile enabled the population to maintain high levels of antibodies. Vaccination boosters are essential to maintain immunity over time, which also depends on the type of vaccine administered.

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