Browsing by Author "Calvo, Mario"
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Publication A non-randomized multicentre trial of human immune plasma for treatment of hantavirus cardiopulmonary syndrome caused by Andes virus(International Medical Press, 2015) Vial, Pablo; Valdivieso, Francisca; Calvo, Mario; Rioseco, María; Riquelme, Raúl; Araneda, Andrés; Tomicic, Vinko; Graf, Jerónimo; Paredes, Laura; Fiorenzano, Matías; Bidart, Teresa; Cuiza, Analía; Marco, Claudia; Hjelle, Brian; Ye, Chunyan; Hanfelt-Goade, Daniel; Vial, Cecilia; Rivera, Juan; Mertz, Gregory; Hantavirus Study Group in Chile; Delgado, IrisBACKGROUND: In Chile, Andes virus (ANDV) is the sole aetiological agent of hantavirus cardiopulmonary syndrome (HCPS) with mean annual incidence of 55 cases, 32% case fatality rate (CFR) and no specific treatment. Neutralizing antibody (NAb) titres at hospital admission correlate inversely with HCPS severity. We designed an open trial to explore safety and efficacy and evaluate pharmacokinetics of immune plasma as a treatment strategy for this disease. METHODS: We performed plasmapheresis on donors at least 6 months after HCPS and measured NAb titres through a focus-reduction neutralization test. Subjects admitted to 10 study sites with suspected/confirmed HCPS were eligible for treatment with immune plasma by intravenous infusion at an ANDV NAb dose of 5,000 U/kg. HCPS was confirmed through immunoglobulin M serology or reverse transcriptase-PCR. The main outcome was mortality within 30 days. RESULTS: From 2008-2012, we enrolled and treated 32 cases and confirmed HCPS in 29. CFR of hantavirus plasma-treated cases was 4/29 (14%); CFR of non-treated cases in the same period in Chile was 63/199 (32%; P=0.049, OR=0.35, CI=0.12, 0.99); CFR of non-treated cases at the same study sites between 2005-2012 was 18/66 (27%; (P=0.15, OR=0.43, CI=0.14, 1.34) and CFR in a previous methylprednisolone treatment study was 20/60 (33%; P=0.052, OR=0.32, CI=0.10, 1.00). We detected no serious adverse events associated to plasma infusion. Plasma NAb titres reached in recipients were variable and viral load remained stable. CONCLUSIONS: Human ANDV immune plasma infusion appears safe for HCPS. We observed a decrease in CFR in treated cases with borderline significance that will require further studies for confirmation.Publication Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile(2023) Le Corre, Nicole; Abarca, Katia; Astudillo, Patricio; Potin, Marcela; López, Sofía; Goldsack, Macarena; Valenzuela, Vania; Schilling Redlich, Andrea; Gaete, Victoria; Rubio, Lilian; Calvo, Mario; Twele, Loreto; González, Marcela; Fuentes, Daniela; Gutiérrez, Valentina; Reyes, Felipe; Tapia, Lorena I.; Villena, Rodolfo; Retamal-Díaz, Angello; Cárdenas, Antonio; Alarcón-Bustamante, Eduardo; Meng, Xing; Xin, Qianqian; González-Aramundiz, José V.; Alvarez-Figueroa, María Javiera; González, Pablo A.; Bueno, Susan M.; Soto, Jorge A.; on behalf of the PedCoronaVac03CL Study Group; Perret, Cecilia; Kalergis, Alexis M.During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3–5 years old and headache in 6–17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.Item Factores de riesgo socio-demográficos del síndrome cardiopulmonar por hantavirus(2019) Vial, Cecilia; Valdivieso, Francisca; Cuiza, Analía; Delgado, Iris; Ribeiro, Grazielle; Llop, Elena; Ferrés, Marcela; Repetto, Gabriela; Riquelme, Raúl; Rioseco, María Luisa; Calvo, Mario; Mertz, Gregory; Vial, PabloBackground: Hantavirus cardiopulmonary syndrome (HCPS) is caused by new world hantaviruses, among which Andes hantavirus (ANDV) is endemic to Chile and Southern Argentina. The disease caused by ANDV produces plasma leakage leading to enhanced vascular permeability and has a high case fatality rate (35%), mainly due to respiratory failure, pulmonary edema and myocardial dysfunction, hypoperfusion and shock. Host sociodemographic and genetic factors might influence the course and outcome of the disease. Yet, they have not been thoroughly characterized. Aim: To evaluate sociodemographic factors as risk factors in severity of HCPS. Patients and Methods: Study period: 2004-20013, attending in eight collaborative centers, etiological diagnosis was performed by serology or molecular biology, mild and severe HCPS were compared.139 Chilean patients were analyzed, 64 (46%) with severe disease among which 12 (19 %) died. Results: European ethnicity had 5,1 times higher risk than Amerindian ethnic group to develop a severe HCPS, greater seriousness that was also associated with an urban residence. Conclusion: It was observed that ethnicity and type of residence were significant risk factors for HCPS severity. Hypotheses explaining these findings are discussed.Item High-dose intravenous methylprednisolone for hantavirus cardiopulmonary syndrome in Chile: a double-blind, randomized controlled clinical trial(Oxford University Press, 2013) Vial, Pablo; Valdivieso, Francisca; Ferres, Marcela; Riquelme, Raul; Rioseco, Maria; Calvo, Mario; Castillo, Constanza; Diaz, Ricardo; Scholz, Luis; Cuiza, Analía; Belmar, Edith; Hernandez, Carla; Martinez, Jessica; Lee, Sang-Joon; Mertz, GregoryBACKGROUND: Andes virus (ANDV)-related hantavirus cardiopulmonary syndrome (HCPS) has a 35% case fatality rate in Chile and no specific treatment. In an immunomodulatory approach, we evaluated the efficacy of intravenous methylprednisolone for HCPS treatment, through a parallel-group, placebo-controlled clinical trial. METHODS: Patients aged >2 years, with confirmed or suspected HCPS in cardiopulmonary stage, admitted to any of 13 study sites in Chile, were randomized by study center in blocks of 4 with a 1:1 allocation and assigned through sequentially numbered envelopes to receive placebo or methylprednisolone 16 mg/kg/day (≤1000 mg) for 3 days. All personnel remained blinded except the local pharmacist. Infection was confirmed by immunoglobulin M antibodies or ANDV RNA in blood. The composite primary endpoint was death, partial pressure of arterial oxygen/fraction of inspired oxygen ratio ≤55, cardiac index ≤2.2, or ventricular tachycardia or fibrillation within 28 days. Safety endpoints included the number of serious adverse events (SAEs) and quantification of viral RNA in blood. Analysis was by intention to treat. RESULTS: Infection was confirmed in 60 of 66 (91%) enrollees. Fifteen of 30 placebo-treated patients and 11 of 30 methylprednisolone-treated patients progressed to the primary endpoint (P = .43). We observed no significant difference in mortality between treatment groups (P = .41). There was a trend toward more severe disease in placebo recipients at entry. More subjects in the placebo group experienced SAEs (P = .02). There were no SAEs clearly related to methylprednisolone administration, and methylprednisolone did not increase viral load. CONCLUSIONS: Although methylprednisolone appears to be safe, it did not provide significant clinical benefit to patients. Our results do not support the use of methylprednisolone for HCPS. CLINICAL TRIALS REGISTRATION: NCT00128180.Publication Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children(2022) Soto, Jorge; Melo, Felipe; Gutierrez, Cristián; Schultz, Bárbara; Berríos, Roslye; Rivera, Daniela; Piña, Alejandro; Hoppe, Guillermo; Duarte, Luisa; Vázquez, Yaneisi; Moreno, Daniela; Ríos, Mariana; Palacios, Pablo; Garcia, Richard; Santibañez, Álvaro; Pacheco, Gaspar; Mendez, Constanza; Andrade, Catalina; Silva, Pedro; Diethelm, Benjamín; Astudillo, Patricio; Calvo, Mario; Cárdenas, Antonio; González, Marcela; Goldsack, Macarena; Gutiérrez, Valentina; Potin, Marcela; Schilling, Andrea; Tapia, Lorena; Twele, Loreto; Villena, Rodolfo; Grifoni, Alba; Sette, Alessandro; Weiskopf, Daniela; Fasce, Rodrigo; Fernández, Jorge; Mora, Judith; Ramírez, Eugenio; Gaete, Aracelly; Acevedo, Mónica; Valiente, Fernando; Soto, Ricardo; Retamal, Angello; Muñoz, Nathalia; PedCoronaVac03CL Study Group; Meng, Xing; Xin, Qianqian; Alarcón, Eduardo; González, José; Le Corre, Nicole; Álvarez, María; González, Pablo; Abarca, Katia; Perret, Cecilia; Carreño, Leandro; Bueno, Susan; Kalergisa, AlexisMultiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.Item Person-to-Person Household and Nosocomial Transmission of Andes Hantavirus, Southern Chile, 2011(Centers for Desease Control and Prevention, 2014) Martinez-Valdebenito, Constanza; Calvo, Mario; Vial, Cecilia; Mansilla, Rita; Marco, Claudia; Palma, Eduardo; Vial, Pablo; Valdivieso, Francisca; Mertz, Gregory; Ferrés, MarcelaAndes hantavirus (ANDV) causes hantavirus cardiopulmonary syndrome in Chile and is the only hantavirus for which person-to-person transmission has been proven. We describe an outbreak of 5 human cases of ANDV infection in which symptoms developed in 2 household contacts and 2 health care workers after exposure to the index case-patient. Results of an epidemiologic investigation and sequence analysis of the virus isolates support person-to-person transmission of ANDV for the 4 secondary case-patients, including nosocomial transmission for the 2 health care workers. Health care personnel who have direct contact with ANDV case-patients or their body fluids should take precautions to prevent transmission of the virus. In addition, because the incubation period of ANDV after environmental exposure is longer than that for person-to-person exposure, all persons exposed to a confirmed ANDV case-patient or with possible environmental exposure to the virus should be monitored for 42 days for clinical symptoms.Item Platelet Count in Patients with Mild Disease at Admission is Associated with Progression to Severe Hantavirus Cardiopulmonary Syndrome(2019) López, René; Vial, Cecilia; Graf, Jerónimo; Calvo, Mario; Ferrés, Marcela; Mertz, Gregory; Cuiza, Analía; Agüero, Begonia; Aguilera, Dante; Araya, Diego; Pailamilla, Ignacia; Paratori, Flavia; Torres-Torres, Víctor; Vial, Pablo; HantavirusStudy Group in ChileBACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a mortality up to 35-40% and its treatment is mainly supportive. A variable to predict progression from mild to severe disease is unavailable. This study was performed in patients with documented infection by Andes orthohantavirus, and the aim was to find a simple variable to predict progression to moderate/severe HCPS in patients with mild disease at admission. METHODS: We performed a retrospective analysis of 175 patients between 2001 and 2018. Patients were categorized into mild, moderate, and severe disease according to organ failure and advanced support need at hospital admission (e.g., mechanical ventilation, vasopressors). Progression to moderate/severe disease was defined accordingly. Clinical and laboratory variables associated with progression were explored. RESULTS: Forty patients with mild disease were identified; 14 of them progressed to moderate/severe disease. Only platelet count was different between those who progressed versus those that did not (37 (34-58) vs. 83 (64-177) K/mm3, p < 0.001). A ROC curve analysis showed an AUC = 0.889 (0.78-1.0) p < 0.001, with a platelet count greater than 115K /mm3 ruling out progression to moderate/severe disease. CONCLUSIONS: In patients with mild disease at presentation, platelet count could help to define priority of evacuation to tertiary care centers.Item Proteinuria in Hantavirus Cardiopulmonary Syndrome: A Frequent Finding Linked To Mortality(2021) López, René; Espinoza, Mauricio; Graf, Jerónimo; Mertz, Gregory; Ferrés, Marcela; Calvo, Mario; Vial, Cecilia; Vial, Pablo; Hantavirus Study Group in ChileObjectives: To determine the relative frequency and prognosis value of proteinuria in hantavirus cardiopulmonary syndrome (HCPS) due to Andes virus. Methods: This observational analytical study prospectively obtained data from patients admitted to 12 health centers in nine Chilean cities between 2001 and 2018. Only patients with confirmed Andes virus HCPS and laboratory characterization that included qualitative proteinuria determination at admission were considered. Results: The database involved 175 patients, 95 of them had a measurement of urine protein at the time of hospital admission. They were mainly male (71%) and the median age was 35 [22-47] years. Median duration of the febrile prodromal time was 5 [4-7] days. Hospital length of stay and hospital mortality rate were 10 [7-14] days and 21.1%, respectively. Seventy-three patients (77%) were identified with proteinuria at admission, which was associated with increased mortality rate (26% versus 5%, p=0.036) and the relative risk was 1.3 [1.1-1.6], p=0.002. Conclusions: Proteinuria is a frequent finding in patients with HCPS, which is associated with a higher mortality rate.