Viral shedding and viraemia of Andes virus during acute hantavirus infection: a prospective study.

BACKGROUND: Andes virus (ANDV) is a zoonotic Orthohantavirus leading to hantavirus cardiopulmonary syndrome. Although most transmissions occur through environmental exposure to rodent faeces and urine, rare person-to-person transmission has been documented, mainly for close contacts. This study investigates the presence and infectivity of ANDV in body fluids from confirmed cases and the duration of viraemia. METHODS: In this prospective study, 131 participants with confirmed ANDV infection were enrolled in Chile in a prospective study between 2008 and 2022. Clinical samples (buffy coat, plasma, gingival crevicular fluid [GCF], saliva, nasopharyngeal swabs [NPS], and urine) were collected weekly for 3 weeks together with clinical and epidemiological data. Samples were categorised as acute or convalescent (up to and after 16 days following onset of symptoms). Infectivity of positive fluids was assessed after the culture of samples on Vero E6 cells and use of flow cytometry assays to determine the production of ANDV nucleoprotein. FINDINGS: ANDV RNA was detected in 100% of buffy coats during acute phase, declining to 95% by day 17, and to 93% between days 23-29. ANDV RNA in GCF and saliva decreased from 30% and 12%, respectively, during the acute phase, to 12% and 11% during the convalescent phase. Successful infectivity assays of RT-qPCR-positive fluids, including GCF, saliva, NPS, and urine, were observed in 18 (42%) of 43 samples obtained during the acute phase of infection. After re-culture, the capacity to infect Vero E6 cells was maintained in 16 (89%) of 18 samples. Severity was associated with the presence of ANDV RNA in one or more fluids besides blood (odds ratio 2·58 [95% CI 1·42-5·18]). INTERPRETATION: ANDV infection is a systemic and viraemic infection, that affects various organs. The presence of infectious particles in body fluids contributes to our understanding of potential mechanisms for person-to-person transmission, supporting the development of preventive strategies. Detection of ANDV RNA in additional fluids at hospital admission is a predictor of disease severity. FUNDING: None. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

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

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.

Factors influencing neutralizing antibody response to the original SARS-CoV-2 virus and the Omicron variant in a high vaccination coverage country, a population-based study.

The study compared immunity to the original SARS-CoV-2 virus (Wuhan) and the Omicron variant using neutralizing antibodies (NAbs), that provide a good approximation of protective immunity. The results might help determine immunization strategies. DESIGN AND METHODS: Unlike previous studies, we analyzed NAbs in a random sample of 110 IgG positive sera from individuals who participated in a population-based seroprevalence transversal study, carried out in May 2022 in two Chilean cities, a country with high vaccination coverage. RESULTS: Our findings indicate that 98.2% of individuals had NAbs against Wuhan, 65.5% against Omicron, and 32.7% tested positive for Wuhan but not Omicron. Factors influencing protective immunity included a prior natural infection and the number of vaccines received. NAbs titers against the original virus were high, demonstrating vaccine effectiveness in the population. However, the level of antibodies decreased when measuring NAbs against Omicron, particularly among older individuals, indicating a decline in vaccine protection. Previous COVID-19 episodes acted as a natural booster, increasing NAbs titers against both virus strains. CONCLUSIONS: Protective immunity against the original Wuhan SARS-CoV-2 virus is reduced when compared to Omicron variant. Updating vaccine to target emerging variants and continued monitoring of effectiveness at the population level are necessary.

Desarrollo e implementación de un programa de investigación durante la residencia de ortopedia y traumatología

Introducción: Dentro de las recomendaciones internacionales para la formación de médicos expertos, se encuentra el integrar la mejor evidencia disponible a la práctica clínica y contribuir a la creación del conocimiento científico. El objetivo de este trabajo es describir la implementación de un programa formal de investigación en residentes de ortopedia y traumatología. Metodología: Se desarrolló un programa de investigación para residentes de ortopedia y traumatología, coordinado por un equipo con formación en metodología y bioestadística. El objetivo principal fue que los residentes lograran adquirir herramientas en el desarrollo del método científico e integrar la medicina basada en la evidencia en la práctica profesional. Para ello, se enfocó en tres ejes: 1. formación general 2. análisis crítico de la literatura y 3. desarrollo de investigación científica. Resultados: El año 2015 se implementó el programa. Comenzó con el módulo de formación general a través de seminarios de investigación y una rotación mensual obligatoria. De forma semanal se implementaron reuniones de revisiones críticas de la literatura a partir de casos clínicos y cada dos o tres meses sesiones de journal club. Se han formulado 30 proyectos de investigación, 22 de ellos se han presentado en congresos y ha habido un total de 27 publicaciones con coautoría de residentes (6 de primer autor). Conclusión: A través del programa de investigación, los residentes han adquirido herramientas para poder integrar la medicina basada en la evidencia a su práctica profesional y desarrollar proyectos científicos.

Introduction: In the international recommendations for resident education, there is integrating the best available evidence into clinical practice and contributing to the creation of scientific knowledge. This research aims to describe implementing a formal research program for orthopedic residents. Methodology: We developed a research program for orthopedic residents coordinated by a team trained in methodology and biostatistics. The main objective for residents was to acquire tools to develop the scientific method and to integrate evidence-based medicine into professional practice. To do this, it focused on: 1. theoretical courses, 2. critical analysis of literature, and 3. creation of scientific research. Results: 2015, the program started with a theoretical course through research seminars and a mandatory monthly rotation. Critical analysis of articles meetings were weekly, and journal club sessions every 2 or 3 months. Residents formulated 30 research projects and presented 22 at national and international congresses. There were 27 scientific publications with resident participation (6 were lead authors). Conclusion: Through the research program, residents have acquired tools to integrate evidence-based medicine into their professional practice and develop scientific projects.

Hantavirus in humans: a review of clinical aspects and management.

Hantavirus infections are part of the broad group of viral haemorrhagic fevers. They are also recognised as a distinct model of an emergent zoonotic infection with a global distribution. Many factors influence their epidemiology and transmission, such as climate, environment, social development, ecology of rodent hosts, and human behaviour in endemic regions. Transmission to humans occurs by exposure to infected rodents in endemic areas; however, Andes hantavirus is unique in that it can be transmitted from person to person. As hantaviruses target endothelial cells, they can affect diverse organ systems; increased vascular permeability is central to pathogenesis. The main clinical syndromes associated with hantaviruses are haemorrhagic fever with renal syndrome (HFRS), which is endemic in Europe and Asia, and hantavirus cardiopulmonary syndrome (HCPS), which is endemic in the Americas. HCPS and HFRS are separate clinical entities, but they share several features and have many overlapping symptoms, signs, and pathogenic alterations. For HCPS in particular, clinical outcomes are highly associated with early clinical suspicion, access to rapid diagnostic testing or algorithms for presumptive diagnosis, and prompt transfer to a facility with critical care units. No specific effective antiviral treatment is available.

Perceived barriers and facilitators for adhering to COVID-19 preventive measures in Chile: a qualitative study in three large cities.

BACKGROUND: Globally, it has been reported that different social determinants of health -structural, sociodemographic, economic, living conditions and cultural factors- may affect opportunities to adhere to prevention measures against SARS-CoV-2. The objective of this study was to explore the perceptions around barriers and facilitators for adherence to COVID-19 prevention measures among the adult population residing in three large cities in Chile from a social determinants of health perspective. METHODS: Qualitative paradigm, multiple case-study design. Online semi-structured interviews were conducted with men and women aged 18 and over from different socioeconomic groups residing in three large cities. For participant recruitment and selection, purposive contacts were made based on community and social media networks, followed by snowball sampling. Saturation was reached at 61 participants, after which a thematic analysis was carried out with the support of AtlasTi software. The Ethics Committee of the Universidad del Desarrollo in Chile approved this study. RESULTS: The main perceived barriers to adherence to COVID-19 preventive measures are linked to structural social determinants of health such as income, occupation, gender, access to basic supplies, and housing. Perceived facilitators are the fear of contagion and the incorporation of measures into daily habits. The social communication of preventive measures by health authorities is perceived as punitive, affecting adherence once the fear of contagion decreased in the country. It is also perceived that the recommended preventive measures are disconnected from communities' cultural practices and people´s identity, as well as affected by gender inequities and socioeconomic conditions that stakeholders in the country do not sufficiently address. CONCLUSION: Study findings suggest that adherence to preventive measures, such as social distancing, mask use, and hand washing, could be promoted through their incorporation into the daily life habits of people and communities. These measures should consider the structural social determinants that generate multiple barriers to adherence, like poverty, occupational risks, and overcrowding. Socio-cultural dimensions of health and everyday risks need further understanding among the different communities in the country, allowing for differences in viewpoints and practices based on gender, age, place, and social identity.

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

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.

Deep immunophenotyping reveals biomarkers of multisystemic inflammatory syndrome in children in a Latin American cohort.

BACKGROUND: Multisystemic inflammatory syndrome in children (MIS-C) is a life-threatening disease that occurs 2-5 weeks after severe acute respiratory syndrome coronavirus 2 exposure and is characterized by severe multisystemic inflammation. Early recognition of MIS-C is key to prognosis; therefore, establishing clinical and laboratory biomarkers that predict complications is urgently needed. OBJECTIVE: We characterized the immune response and clinical features of patients with acute MIS-C and determined biomarkers of disease in a cohort of 42 Latin American patients. METHODS: Immune characterization was performed using flow cytometry from peripheral mononuclear cells and severe acute respiratory syndrome coronavirus 2-specific humoral and cellular response was performed using flow cytometry, enzyme-linked immunospot, enzyme-linked immunosorbent assay, and neutralizing antibody assays. RESULTS: MIS-C is characterized by robust T-cell activation and cytokine storm. We uncovered that while C-X-C motif chemokine ligand (CXCL) 9, IL-10, CXCL8, CXCL10, IL-6, and IL-18 are significantly elevated in patients with shock, while CCL5 was increased in milder disease. Monocyte dysregulation was specifically associated with KD-like MIS-C. Interestingly, MIS-C patients show a natural killer cell degranulation defect that is persistent after 6 months of disease presentation, suggesting it could underlie disease susceptibility. Most MIS-C had gastrointestinal involvement, and higher levels of neopterin were identified in their stools, potentially representing a biomarker of intestinal inflammation in MIS-C. Severe acute respiratory syndrome coronavirus 2-specific cellular response and neutralizing antibodies were identifiable in convalescent MIS-C patients, suggesting sustained immunity. CONCLUSION: Clinical characterization and comprehensive immunophenotyping of Chilean MIS-C cohort provide valuable insights in understanding immune dysregulation in MIS-C and identify relevant biomarkers of disease that could be used to predict severity and organ involvement.

Immunization and SARS-CoV-2 Antibody Seroprevalence in a Country with High Vaccination Coverage: Lessons from Chile.

Chile is among the most successful nations worldwide in terms of its COVID-19 vaccine rollout. By 31 December 2021, 84.1% of the population was fully vaccinated, and 56.1% received booster doses using different COVID-19 vaccines. In this context, we aimed to estimate the prevalence of anti-SARS-CoV-2 antibodies following the infection and vaccination campaign. Using a three-stage stratified sampling, we performed a population-based cross-sectional serosurvey based on a representative sample of three Chilean cities. Selected participants were blood-sampled on-site and answered a short COVID-19 and vaccination history questionnaire using Wantai SARS-CoV-2 Ab ELISA to determine seroprevalence. We recruited 2198 individuals aged 7-93 between 5 October and 25 November 2021; 2132 individuals received COVID-19 vaccinations (97%), 67 (3.1%) received one dose, 2065 (93.9%) received two doses, and 936 received the booster jab (42.6%). Antibody seroprevalence reached 97.3%, ranging from 40.9% among those not vaccinated to 99.8% in those with booster doses (OR = 674.6, 154.8-2938.5). SARS-CoV-2 antibodies were associated with vaccination, previous COVID-19 diagnosis, age group, and city of residence. In contrast, we found no significant differences in the type of vaccine used, education, nationality, or type of health insurance. We found a seroprevalence close to 100%, primarily due to the successful vaccination program, which strongly emphasizes universal access.

SARS-CoV-2 Neutralizing Antibodies in Chile after a Vaccination Campaign with Five Different Schemes.

Using levels of neutralizing antibodies (nAbs), we evaluate the successful Chilean SARS-CoV-2 vaccine campaign, which combines different vaccine technologies and heterologous boosters. From a population-based study performed in November 2021, we randomly selected 120 seropositive individuals, organized into six groups of positive samples (20 subjects each) according to natural infection history and the five most frequent vaccination schemes. We conclude that the booster dose, regardless of vaccine technology or natural infection, and mRNA vaccines significantly improve nAbs response.

First wave of SARS-CoV-2 in Santiago Chile: Seroprevalence, asymptomatic infection and infection fatality rate.

BACKGROUND: The first wave of SARS-CoV-2 infection in Chile occurred during the cold season reaching a peak by the end of June 2020, with 80 % of the cases concentrated in its capital, Santiago. The main objective of this study was to estimate the attack rate during this first wave of SARS-CoV-2 in a large, densely populated city with more than seven million inhabitants. Since the number of confirmed cases provides biased information due to individuals' potential self-selection, mostly related to asymptomatic patients and testing access, we measured antibodies against SARS-CoV-2 to assess infection prevalence during the first wave in the city, as well as estimate asymptomatic cases, and infection fatality ratio. To our knowledge this is one of the few population-based cross-sectional serosurvey during the first wave in a highly affected emerging country. The challenges of pandemic response in urban settings in a capital city like Santiago, with heterogeneous subpopulations and high mobility through public transportation, highlight the necessity of more accurate information regarding the first waves of new emerging diseases. METHODS: From April 24 to June 21, 2020, 1326 individuals were sampled from a long-standing panel of household representatives of Santiago. Immunochromatographic assays were used to detect IgM and IgG antibody isotypes. RESULTS: Seroprevalence reached 6.79 % (95 %CI 5.58 %-8.26 %) in the first 107 days of the pandemic, without significant differences among sex and age groups; this figure indicates an attack rate 2.8 times higher than the one calculated with registered cases. It also changes the fatality rate estimates, from a 2.33 % case fatality rate reported by MOH to an estimated crude 1.00 % (CI95 % 0.97-1.03) infection fatality rate (adjusted for test performance 1.66 % [CI95 % 1.61-1.71]). Most seropositive were symptomatic (81,1 %). CONCLUSIONS: Despite the high number of cases registered, mortality rates, and the stress produced over the health system, the vast majority of the people remained susceptible to potential new epidemic waves. We contribute to the understanding of the initial spread of emerging epidemic threats. Consequently, our results provide better information to design early strategies that counterattack new health challenges in urban contexts.

Seroprevalence and estimation of the impact of SARS-CoV-2 infection in older adults residing in Long-term Care Facilities in Chile. / Seroprevalencia y estimación del impacto de la infección por SARS-CoV-2 en personas mayores residentes en centros de larga estadía en Chile.

Introduction: Older adults are at a higher risk of severe illness and death from COVID-19. This vulnerability increases in those who live in long-term care facilities due to overcrowding, greater physical dependence, and contact with health workers. Evidence on the impact of the pandemic on these establishments in lowand middle-income countries has been scant. This study aims to determine the seroprevalence of SARS-CoV-2 in older people residing in long-term care facilities and estimate the impact of infection after the first wave of the pandemic. Methods: A cross-sectional design with 2099 residents in three regions of Chile was carried out between September and November 2020. Measurement of antibodies was performed with a rapid test. The impact of SARS-CoV-2 infection was estimated with seropositive residents, those who had a history of positive polymerase chain reaction tests, and those who died from COVID-19. Bivariate analysis with the region, sex, age, history of COVID-19, physical dependence, and serological results were performed. In addition, we performed a correlation analysis between the seroprevalence of the centers by the municipality and the rate of confirmed cases. Results: The seroprevalence of SARS-CoV-2 antibodies in the three regions was 14.7% (95% confidence interval: 13.2 to 16.3%), the infection impact was 46.4%, and the fatality rate was 19.6%. A significant correlation was found between the seroprevalence of older adults residing in long-term care facilities and the cumulative incidence by municipalities. Conclusions: The seroprevalence of older adults residing in long-term care facilities was higher than the general population. The high impact of infection among this population at the end of the first wave of the COVID-19 pandemic is similar to other countries. The centers' environment is directly related to COVID-19 infection. Morbidity and mortality monitoring systems should be implemented promptly to establish prevention and control measures.

Introducción: Las personas mayores tienen más riesgo de enfermar gravemente y fallecer por COVID-19. Esta vulnerabilidad aumenta en quienes viven en establecimientos de larga estadía, debido a hacinamiento, mayor dependencia física y contacto con los trabajadores. La evidencia sobre el impacto de la pandemia de estos establecimientos en países de medianos y bajos ingresos ha sido escasa. El objetivo es determinar la seroprevalencia de la infección por SARS-CoV-2 en personas mayores que residen en establecimientos de larga estadía. Así como estimar el impacto global de la infección después de la primera ola de la pandemia. Métodos: Diseño transversal con 2099 residentes en tres regiones de Chile, realizado entre septiembre y noviembre 2020. Anticuerpos fueron medidos con test rápido contra SARS-CoV-2. Se estimó el impacto de la infección con los residentes seropositivos, los residentes con antecedentes de reacción en cadena de la polimerasa de transcripción inversa positiva, y residentes que murieron por COVID-19. Análisis bivariado entre el resultado serológico y región, sexo, edad, antecedentes de COVID-19 y dependencia física fueron realizados. Además, realizamos un análisis de correlación entre la seroprevalencia de los centros por municipio y la tasa acumulada de casos confirmados. Resultados: La seroprevalencia de anticuerpos en las tres regiones fue 14,7% (intervalo de confianza del 95%: 13,2 a 16,3%). El impacto real de la infección se estimó en 46,4% y la tasa de letalidad en 19,6%. La seroprevalencia de los residentes de los centros por comuna se correlacionó positiva y significativamente con la frecuencia de la enfermedad a nivel comunal. Conclusiones: Seroprevalencia superior a la de la población general, observándose un alto impacto de la infección por COVID-19 al final de la primera ola de la pandemia. El lugar en el que se encuentran los establecimientos está directamente relacionado con la tasa de seroprevalencia en ellos. Sistemas de vigilancia epidemiológica deben aplicarse con prontitud para establecer medidas de prevención y control.

Seroprevalencia y estimación del impacto de la infección por SARS-CoV-2 en personas mayores residentes en centros de larga estadía en Chile / Seroprevalence and estimation of the impact of SARS-CoV-2 infection in older adults residing in Long-term Care Facilities in Chile

INTRODUCTION: Older adults are at a higher risk of severe illness and death from COVID-19. This vulnerability increases in those who live in long-term care facilities due to overcrowding, greater physical dependence, and contact with health workers. Evidence on the impact of the pandemic on these establishments in lowand middle-income countries has been scant. This study aims to determine the seroprevalence of SARS-CoV-2 in older people residing in long-term care facilities and estimate the impact of infection after the first wave of the pandemic. METHODS: A cross-sectional design with 2099 residents in three regions of Chile was carried out between September and November 2020. Measurement of antibodies was performed with a rapid test. The impact of SARS-CoV-2 infection was estimated with seropositive residents, those who had a history of positive polymerase chain reaction tests, and those who died from COVID-19. Bivariate analysis with the region, sex, age, history of COVID-19, physical dependence, and serological results were performed. In addition, we performed a correlation analysis between the seroprevalence of the centers by the municipality and the rate of confirmed cases. RESULTS: The seroprevalence of SARS-CoV-2 antibodies in the three regions was 14.7% (95% confidence interval: 13.2 to 16.3%), the infection impact was 46.4%, and the fatality rate was 19.6%. A significant correlation was found between the seroprevalence of older adults residing in long-term care facilities and the cumulative incidence by municipalities. CONCLUSIONS: The seroprevalence of older adults residing in long-term care facilities was higher than the general population. The high impact of infection among this population at the end of the first wave of the COVID-19 pandemic is similar to other countries. The centers' environment is directly related to COVID-19 infection. Morbidity and mortality monitoring systems should be implemented promptly to establish prevention and control measures.

INTRODUCCIÓN: Las personas mayores tienen más riesgo de enfermar gravemente y fallecer por COVID-19. Esta vulnerabilidad aumenta en quienes viven en establecimientos de larga estadía, debido a hacinamiento, mayor dependencia física y contacto con los trabajadores. La evidencia sobre el impacto de la pandemia de estos establecimientos en países de medianos y bajos ingresos ha sido escasa. El objetivo es determinar la seroprevalencia de la infección por SARS-CoV-2 en personas mayores que residen en establecimientos de larga estadía. Así como estimar el impacto global de la infección después de la primera ola de la pandemia. MÉTODOS: Diseño transversal con 2099 residentes en tres regiones de Chile, realizado entre septiembre y noviembre 2020. Anticuerpos fueron medidos con test rápido contra SARS-CoV-2. Se estimó el impacto de la infección con los residentes seropositivos, los residentes con antecedentes de reacción en cadena de la polimerasa de transcripción inversa positiva, y residentes que murieron por COVID-19. Análisis bivariado entre el resultado serológico y región, sexo, edad, antecedentes de COVID-19 y dependencia física fueron realizados. Además, realizamos un análisis de correlación entre la seroprevalencia de los centros por municipio y la tasa acumulada de casos confirmados. RESULTADOS: La seroprevalencia de anticuerpos en las tres regiones fue 14,7% (intervalo de confianza del 95%: 13,2 a 16,3%). El impacto real de la infección se estimó en 46,4% y la tasa de letalidad en 19,6%. La seroprevalencia de los residentes de los centros por comuna se correlacionó positiva y significativamente con la frecuencia de la enfermedad a nivel comunal. CONCLUSIONES: Seroprevalencia superior a la de la población general, observándose un alto impacto de la infección por COVID-19 al final de la primera ola de la pandemia. El lugar en el que se encuentran los establecimientos está directamente relacionado con la tasa de seroprevalencia en ellos. Sistemas de vigilancia epidemiológica deben aplicarse con prontitud para establecer medidas de prevención y control.

Seroprevalence, spatial distribution, and social determinants of SARS-CoV-2 in three urban centers of Chile.

BACKGROUND: Seroprevalence studies provide an accurate measure of SARS-CoV-2 spread and the presence of asymptomatic cases. They also provide information on the uneven impact of the pandemic, pointing out vulnerable groups to prioritize which is particularly relevant in unequal societies. However, due to their high cost, they provide limited evidence of spatial spread of the pandemic specially in unequal societies. Our objective was to estimate the prevalence of SARS-CoV-2 antibodies in Chile and model its spatial risk distribution. METHODS: During Oct-Nov 2020, we conducted a population-based serosurvey in Santiago, Talca, and Coquimbo-La Serena (2493 individuals). We explored the individual association between positive results and socio-economic and health-related variables by logistic regression for complex surveys. Then, using an Empirical Bayesian Kriging model, we estimated the infection risk spatial distribution using individual and census information, and compared these results with official records. RESULTS: Seroprevalence was 10.4% (95% CI 7.8-13.7%), ranging from 2% (Talca) to 11% (Santiago), almost three times the number officially reported. Approximately 36% of these were asymptomatic, reaching 82% below 15 years old. Seroprevalence was associated with the city of residence, previous COVID-19 diagnosis, contact with confirmed cases (especially at household), and foreign nationality. The spatial model accurately interpolated the distribution of disease risk within the cities finding significant differences in the predicted probabilities of SARS-CoV-2 infection by census zone (IQR 2.5-15.0%), related to population density and education. CONCLUSIONS: Our results underscore the transmission heterogeneity of SARS-CoV-2 within and across three urban centers of Chile. Socio-economic factors and the outcomes of this seroprevalence study enable us to identify priority areas for intervention. Our methodological approach and results can help guide the design of interdisciplinary strategies for urban contexts, not only for SARS-CoV-2 but also for other communicable diseases.

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.

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.

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

OBJECTIVES: 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.

Longitudinal assessment of SARS-CoV-2 IgG seroconversionamong front-line healthcare workers during the first wave of the Covid-19 pandemic at a tertiary-care hospital in Chile.

BACKGROUND: Healthcare workers (HCWs) are at high risk of exposure to SARS-CoV-2. Cross-sectional studies have provided variable rates of seroprevalence in HCWs. Longitudinal assessments of the serological response to Covid-19 among HCWs are crucial to understanding the risk of infection and changes in antibody titers over time. We aimed to investigate seroprevalence and risk factors associated with seroconversion in a prospective cohort of HCWs during the peak of the first wave of the Covid-19 pandemic. METHODS: We conducted a longitudinal study among 446 front-line HCWsin a tertiary-care hospital in Chile from April to July 2020. IgG was determined monthly using two different ELISAs in serum samples of HCWs, during the three-month period. In each visit, demographic data, symptoms, risk factors, and exposure risks were also assessed. RESULTS: The overall seroprevalence at the end of the study period was 24% (95% CI20.2-28.3), with 43% of seropositive HCWs reporting no prior symptoms. Seroconversion rates significantly differed over the study period, from 2.1% to as high as 8.8% at the peak of the epidemic. There were no statistically significant differences observed between HCWs in direct clinical care of patients with Covid-19 and those working in low risk areas. Antibody titers appeared to wane over time. CONCLUSIONS: HCWs were severely affected with a high rate of seroconversion that appeared to mirror the local epidemiological situation. A significant amount of participants underwent an asymptomatic infection, highlighting the need for improved surveillance policies. Antibody titers appear to wane over time; further studies to understand this finding's impact on the risk of reinfection are warranted.

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

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 an open-access 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 open-access, direct RT-PCR assays are a feasible option for more efficient COVID-19 coronavirus disease testing as demanded by the continuing pandemic.

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

BACKGROUND: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. Severe cases may be rescued by venoarterial extracorporeal membrane oxygenation (VA ECMO), alongside substantial complications. High volume hemofiltration (HVHF) is a depurative technique that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. METHODS: We implemented HVHF before VA ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if VA ECMO was avoided and HVHF-nonresponders if VA ECMO support was needed despite HVHF. A targeted-HVHF strategy compounded by aggressive hyperoncotic albumin, sodium bicarbonate, and calcium supplementation plus ultrafiltration to avoid fluid overload was implemented on three patients. RESULTS: Patients had maximum serum lactate of 8.8 (8.7-12.8) mmol/L and a lowest cardiac index of 1.8 (1.8-1.9) L/min/m2 . The first two required VA ECMO. They were connected later to HVHF, displayed progressive tachycardia and declining stroke volume. The opposite was true for HVHF-responders who received targeted-HVHF. All patients survived, but one of the VA ECMO patients suffered a vascular complication. CONCLUSION: HVHF may contribute to support severe HCPS patients avoiding the need for VA ECMO in some. Early connection and targeted-HVHF may increase the chance of success.

Covid-19 in South America: clinical and epidemiological characteristics among 381 patients during the early phase of the pandemic in Santiago, Chile.

BACKGROUND: Understanding the characteristics of the Covid-19 pandemic in different geographical regions, ethnic and socioeconomic settings are of emerging importance. This study presents the demographic and clinical features of SARS-CoV-2 infected patients in a large private healthcare center in Santiago, Chile, during the first month of the pandemic. METHODS: We analyzed the demographics, laboratory and clinical characteristics including severity and outcome of all patients diagnosed with Covid-19 during the first month of the pandemic. SARS-2-CoV infection was confirmed by RT-PCR in nosopharyngeal samples. The primary outcome was a composite of ICU admission or all-cause, in-hospital mortality. Clinical and laboratory parameters of hospitalized patients were analyzed regarding their association with the primary outcome. RESULTS: From March 3 to April 4, 2020, 3679 individuals were tested for SARS-CoV-2 in our hospital. Of those, 381 had Covid-19 and were included into this analysis. Most patients (99.2%) were Chileans, 12% returning from recent travel. The median age was 39 years (IQR 31-49) and 52% were female. A total of 88 patients (23.1%) were hospitalized; 18 (3.7%) required ICU and/or died. The overall mortality was 0.7%. Increased body mass index (BMI) and elevated C-reactive protein (CRP) were independently associated with ICU care or death. CONCLUSION: During the first weeks of the pandemic in Chile, most Covid-19 patients were young, with low rates of hospitalization, ICU requirement, and fatality. BMI and CRP on admission were predictors for severity. Our data provide important information on the clinical course and outcome of Covid-19 in a Latin American setting.