Papers by Rocío María Coelho
bioRxiv (Cold Spring Harbor Laboratory), Jan 7, 2022
Short title: Orthohantavirus infection in wetlands of central-east region of Argentina .

Los roedores silvestres son reservorios de Orthohantavirus, el agente etiológico del síndrome pul... more Los roedores silvestres son reservorios de Orthohantavirus, el agente etiológico del síndrome pulmonar por hantavirus (SPH). La región central de Argentina es endémica para SPH, con tasas de mortalidad de entre 24 y 31 %. En dicha región se han identificado tres Orthohantavirus patógenos para los humanos, aunque su asociación con especies de roedores hospedadores no es del todo clara. En los últimos años, además, se han incrementado los casos de SPH en el centro y norte de la provincia de Santa Fe. El objetivo de este trabajo fue determinar infecciones con Orthohantavirus en roedores de tres comunidades ribereñas cercanas a la ciudad de Santa Fe, pertenecientes al valle de inundación del río Paraná. Cada asentamiento fue dividido en tres sitios de estudio según el nivel de perturbación antrópica, colocándose en cada sitio una grilla de 25estaciones de trampeo consistentes en una trampa tipo Sherman y una trampa jaula. Los sitios se muestrearon entre 2014 y 2015, en dos primaveras y un otoño.Trabajo publicado en Cagliada, Maria del Pilar Lilia y Galosi, Cecilia Mónica (comps.). I Congreso de Microbiología Veterinaria. Libro de resúmenes. La Plata: Facultad de Ciencias Veterinarias, 2021.Facultad de Ciencias Veterinaria

STRUCTURED ABSTRACTWe performed whole-genome sequencing with bait-enrichment techniques to analyz... more STRUCTURED ABSTRACTWe performed whole-genome sequencing with bait-enrichment techniques to analyze Andes virus (ANDV), a cause of human hantavirus pulmonary syndrome. We used cryopreserved lung tissues from a naturally infected long-tailed colilargo; early, intermediate, and late cell-culture passages of an ANDV isolate from that animal; and lung tissues from golden hamsters experimentally exposed to that ANDV isolate. The resulting complete genome sequences were subjected to detailed comparative genomic analysis against American orthohantaviruses. We identified four amino-acid substitutions related to cell-culture adaptation that resulted in attenuation of ANDV in the typically lethal golden hamster animal model of hantavirus pulmonary syndrome. Mutations in the ANDV nucleocapsid protein, glycoprotein, and small nonstructural protein open reading frames correlated with mutations typical for ANDV strains associated with increased pathogenesis in the small animal model. Finally, we i...
Emerging Infectious Diseases, 2022
Her primary research interest is emerging infectious diseases. References 1. Tang X, Musa SS, Zha... more Her primary research interest is emerging infectious diseases. References 1. Tang X, Musa SS, Zhao S, He D. Reinfection or reactivation of severe acute respiratory syndrome coronavirus 2: a systematic review.
Revista Argentina de Microbiología, 2021
Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight nati... more Hantavirus Pulmonary Syndrome (HPS) is an emerging infectious disease of the Americas. Eight native rodent species have been identified as HPS virus reservoirs in Argentina. The aim of this work was to detect the orthohantavirus genotypes present in a rodent community that inhabits a zone where a fatal HPS case occurred within an endemic locality of Central Argentina. We captured 27 rodents with a trapping effort of 723 trap nights. We detected 14.3% of infected Akodon azarae with the Pergamino genotype. This result expands the known distribution of this orthohantavirus. Although the Pergamino genotype has not been associated with human cases, the information about its distribution is relevant for risk assessment against potential changes in the virus infectivity.

Zoonoses and Public Health, 2020
Hantavirus pulmonary syndrome is an emerging infectious disease caused by viruses of the genus Or... more Hantavirus pulmonary syndrome is an emerging infectious disease caused by viruses of the genus Orthohantavirus. The rodent Oligoryzomys flavescens is distributed along four countries of South America. In Argentina, O. flavescens acts as a reservoir of three genotypes of ANDV orthohantavirus. The aims of this work were to estimate home range size and movements—with spool‐and‐line and radiotelemetry—of infected and non‐infected O. flavescens in order to understand the spread and transmission of the virus. O. flavescens use a wide area to satisfice its requirements, reaching a home range of 1.82 ha during spring. Orthohantavirus infection did not change the behaviour of individuals. We observed a great overlapping in the home range of infected and non‐infected individuals resulting in a high probability of virus dispersion on rodent population. These results show that human health risks could be high on island environments and knowledge about the movement ecology of O. flavescens provi...
Emerging Infectious Diseases, 2020
P athogenic hantaviruses are members of the family Hantaviridae and genus Orthohantavirus. These ... more P athogenic hantaviruses are members of the family Hantaviridae and genus Orthohantavirus. These viruses are responsible for hantavirus pulmonary syndrome (HPS) in the Americas. In Argentina, HPS was first described in 1995 during an outbreak in the Andean region of Patagonia, leading to the characterization of Andes virus (ANDV) (1). Since then, >1,200 cases have been confirmed in Argentina (2,3). Hantaviruses are enveloped, single-stranded, RNA viruses with tripartite negative sense genomes. The small (S, 1.8-2.1 kb) segment encodes a nucleocapsid protein, the medium (M, 3.6-3.8 kb) a glycoprotein precursor, and the large (L, 6.5-6.7 kb) an RNA-dependent RNA polymerase (4). Humans usually become infected with hantaviruses through inhalation of aerosolized excreta produced by infected rodents.

EBioMedicine, 2022
BACKGROUND The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction... more BACKGROUND The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8+ T cells are believed to be the central players involved in pathogenesis. METHODS Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. FINDINGS High numbers of activated CD4+ and CD8+ T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. INTERPRETATION The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response. FUNDING This work was supported mainly by the Administración Nacional de Laboratorios e Institutos de Salud (ANLIS) "Dr. Carlos Malbrán". Further details of fundings sources is included in the appendix.

Orthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in... more Orthohantaviruses are emerging rodent-borne pathogens that cause Hantavirus Pulmonary Syndrome in humans. They have a wide range of rodent reservoir hosts and are transmitted to humans through aerosolized viral particles generated by the excretions of infected individuals. Since the first description of HPS in Argentina, new hantaviruses have been reported throughout the country, most of which are pathogenic to humans.We present here the first HPS case infected with Alto Paraguay virus reported in Argentina. Until now, Alto Paraguay virus was considered a non-pathogenic orthohantavirus since it was identified in a rodent, Hollochilus chacarius. In addition to this, with the goal of identifying potential hantavirus host species in the province of Santa Fe, we finally describe a novel orthohantavirus found in the native rodent Scapteromys aquaticus, which differed from other hantaviruses described in the country so far.Our findings implicate an epidemiological warning regarding these ...
Clinical Microbiology and Infection, 2019
bioRxiv (Cold Spring Harbor Laboratory), Jun 14, 2021

PLOS Neglected Tropical Diseases, 2020
Background Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two... more Background Rodent-borne hantaviruses (genus Orthohantavirus) are the etiologic agents causing two human diseases: hemorrhagic fever with renal syndrome (HFRS) in Euroasia; and hantavirus pulmonary syndrome (HPS) in North and South America. In South America fatality rates of HPS can reach up to 35%–50%. The transmission of pathogenic hantaviruses to humans occurs mainly via inhalation of aerosolized excreta from infected rodents. Thus, the epidemiology of HPS is necessarily linked to the ecology of their rodent hosts and the contact with a human, which in turn may be influenced by climatic variability. Here we examined the relationship between climatic variables and hantavirus transmission aim to develop an early warning system of potential hantavirus outbreaks based on ecologically relevant climatic factors. Methodology and main findings We compiled reported HPS cases in northwestern Argentina during the 1997–2017 period and divided our data into biannual, quarterly, and bimestrial ...

eBioMedicine, 2022
Background The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction... more Background The hallmarks of HPS are increase of vascular permeability and endothelial dysfunction. Although an exacerbated immune response is thought to be implicated in pathogenesis, clear evidence is still elusive. As orthohantaviruses are not cytopathic CD8 + T cells are believed to be the central players involved in pathogenesis. Methods Serum and blood samples from Argentinean HPS patients were collected from 2014 to 2019. Routine white blood cell analyses, quantification and characterization of T-cell phenotypic profile, viral load, neutralizing antibody response and quantification of inflammatory mediators were performed. Findings High numbers of activated CD4 + and CD8 + T cells were found in all HPS cases independently of disease severity. We found increased levels of some proinflammatory mediators during the acute phase of illness. Nonetheless, viral RNA remained high, showing a delay in clearance from blood up to late convalescence, when titers of neutralizing antibodies reached a high level. Interpretation The high activated phenotypic profile of T cells seems to be unable to resolve infection during the acute and early convalescent phases, and it was not associated with the severity of the disease. Thus, at least part of the activated T cells could be induced by the dysregulated inflammatory response in an unspecific manner. Viral clearance seems to have been more related to high titers of neutralizing antibodies than to the T-cell response.

New England Journal of Medicine, 2020
, person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in C... more , person-to-person transmission of Andes virus (ANDV) hantavirus pulmonary syndrome occurred in Chubut Province, Argentina, and resulted in 34 confirmed infections and 11 deaths. Understanding the genomic, epidemiologic, and clinical characteristics of person-to-person transmission of ANDV is crucial to designing effective interventions. METHODS Clinical and epidemiologic information was obtained by means of patient report and from public health centers. Serologic testing, contact-tracing, and next-generation sequencing were used to identify ANDV infection as the cause of this outbreak of hantavirus pulmonary syndrome and to reconstruct person-to-person transmission events. RESULTS After a single introduction of ANDV from a rodent reservoir into the human population, transmission was driven by 3 symptomatic persons who attended crowded social events. After 18 cases were confirmed, public health officials enforced isolation of persons with confirmed cases and self-quarantine of possible contacts; these measures most likely curtailed further spread. The median reproductive number (the number of secondary cases caused by an infected person during the infectious period) was 2.12 before the control measures were enforced and decreased to 0.96 after the measures were implemented. Full genome sequencing of the ANDV strain involved in this outbreak was performed with specimens from 27 patients and showed that the strain that was present (Epuyén/18-19) was similar to the causative strain (Epilink/96) in the first known person-to-person transmission of hantavirus pulmonary syndrome caused by ANDV, which occurred in El Bolsón, Argentina, in 1996. Clinical investigations involving patients with ANDV hantavirus pulmonary syndrome in this outbreak revealed that patients with a high viral load and liver injury were more likely than other patients to spread infection. Disease severity, genomic diversity, age, and time spent in the hospital had no clear association with secondary transmission. CONCLUSIONS Among patients with ANDV hantavirus pulmonary syndrome, high viral titers in combination with attendance at massive social gatherings or extensive contact among persons were associated with a higher likelihood of transmission.

Journal of Medical Virology, 2019
Hantavirus pulmonary syndrome (HPS) is an endemic disease in Argentina, one of the most affected ... more Hantavirus pulmonary syndrome (HPS) is an endemic disease in Argentina, one of the most affected countries in the Americas. Andes virus (ANDV) is the main Orthohantavirus species causing HPS in Argentina. In this work, the geographical distribution, clinical presentation, and epidemiological features of HPS from all endemic regions of Argentina were analysed. We focused on the clinical and epidemiological data from 533 HPS cases confirmed during the period 2009 to 2017 by the National Reference Laboratory for Hantavirus (NRLH). A case-fatality rate of 21.4% was registered, and most of the cases presented a severe clinical picture requiring intensive care treatment (84%). In order to analyse HPS case-fatality rate trends in Argentina since its first detection in 1995 all laboratory-confirmed casepatients were considered, showing a general trend towards a decrease. After more than 22 years of experience in HPS diagnosis and surveillance, we discuss some possible factors implicated in this tendency. This clinical and epidemiological analysis gives a global perspective, being useful to detect trends and patterns, in order to update preventive actions at a national level and evaluate their impact on public health.
Uploads
Papers by Rocío María Coelho