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: National Institutes of Health and Agencia de Investigación y Desarrollo. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Sustained Antibody-Dependent NK Cell Functions in Mild COVID-19 Outpatients During Convalescence.

The coronavirus disease 2019 (COVID19) pandemic has left researchers scrambling to identify the humoral immune correlates of protection from COVID-19. To date, the antibody mediated correlates of virus neutralization have been extensively studied. However, the extent that non-neutralizing functions contribute to anti-viral responses are ill defined. In this study, we profiled the anti-spike antibody subtype/subclass responses, along with neutralization and antibody-dependent natural killer cell functions in 83 blood samples collected between 4 and 201 days post-symptoms onset from a cohort of COVID-19 outpatients. We observed heterogeneous humoral responses against the acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Overall, anti-spike profiles were characterized by a rapid rise of IgA and sustained IgG titers. In addition, strong antibody-mediated natural killer effector responses correlated with milder disease and being female. While higher neutralization profiles were observed in males along with increased severity. These results give an insight into the underlying function of antibodies beyond neutralization and suggest that antibody-mediated natural killer cell activity is a key function of the humoral response against the SARS-CoV-2 spike protein.

Extracorporeal Membrane Oxygenation for COVID-19-associated Severe Acute Respiratory Distress Syndrome in Chile: A Nationwide Incidence and Cohort Study.

Rationale: The role of and needs for extracorporeal membrane oxygenation (ECMO) at a population level during the coronavirus disease (COVID-19) pandemic have not been completely established. Objectives: To identify the cumulative incidence of ECMO use in the first pandemic wave and to describe the Nationwide Chilean cohort of ECMO-supported patients with COVID-19. Methods: We conducted a population-based study from March 3 to August 31, 2020, using linked data from national agencies. The cumulative incidence of ECMO use and mortality risk of ECMO-supported patients were calculated and age standardized. In addition, a retrospective cohort analysis was performed. Outcomes were 90-day mortality after ECMO initiation, ECMO-associated complications, and hospital length of stay. Cox regression models were used to explore risk factors for mortality in a time-to-event analysis. Measurements and Main Results: Ninety-four patients with COVID-19 were supported with ECMO (0.42 per population of 100,000, 14.89 per 100,000 positive cases, and 1.2% of intubated patients with COVID-19); 85 were included in the cohort analysis, and the median age was 48 (interquartile range [IQR], 41-55) years, 83.5% were men, and 42.4% had obesity. The median number of pre-ECMO intubation days was 4 (IQR, 2-7), the median PaO2/FiO2 ratio was 86.8 (IQR, 64-99) mm Hg, 91.8% of patients were prone positioned, and 14 patients had refractory respiratory acidosis. Main complications were infections (70.6%), bleeding (38.8%), and thromboembolism (22.4%); 52 patients were discharged home, and 33 died. The hospital length of stay was a median of 50 (IQR, 24-69) days. Lower respiratory system compliance and higher driving pressure before ECMO initiation were associated with increased mortality. A duration of pre-ECMO intubation ≥10 days was not associated with mortality. Conclusions: Documenting nationwide ECMO needs may help in planning ECMO provision for future COVID-19 pandemic waves. The 90-day mortality of the Chilean cohort of ECMO-supported patients with COVID-19 (38.8%) is comparable to that of previous reports.

Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein.

Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection.

Protocolo de weaning rápido en pacientes obesos mórbidos, con ventilación mecánica no invasiva posextubación / Rapid weaning protocol in morbid obese patients using noninvasive ventilation immediately after extubation

Introducción: La dificultad de completar un protocolo de weaning convencional, en el paciente obeso mórbido, establece una estadía prolongada en ventilación mecánica (VMI) y en UCI. Se propone el protocolo de weaning “Fast-Fat”, en pacientes obesos mórbidos, con insuficiencia respiratoria aguda (IRA), utilizando VMNI posextubación inmediata. Metodología: A fin de evaluar el protocolo de weaning en relación a: mortalidad a los 28 días, días de VMI, días UCI, necesidad de reintubación, número de traqueotomías (TQ) realizadas, y días de VMNI; y a la vez, comparar los días de VMI y días UCI en relación a protocolo de weaning convencional; se realizó un estudio de corte transversal con reclutamiento prospectivo, entre mayo de 2010 y julio de 2011, incluyendo en el protocolo, al total de pacientes que estaban en condiciones de iniciar un proceso de weaning con antecedentes de obesidad (IMC >35) e IRA. Si completan de manera exitosa la PVE de 1 hora en VMI, y cumplen criterios de extubación, pasan directamente VMNI. Se incluyeron 30 pacientes adultos, con edades de 59,1 +/- 12,7; 50 por ciento varones, con APACHE II 16,3 (rango 7 a 33), que fueron comparados con una cohorte retrospectiva de 18 pacientes similares características. Resultados: Nuestro estudio no presentó mortalidad a los 28 días, ningún paciente requirió reintubación, ni TQ; con 2,1 +/- 1,1 días en VMNI. Con estadía en VMI 5,7 +/- 2,4 días, versus el grupo comparativo sin aplicación de protocolo de 14,4 +/- 6 días (p<0,05). Con estadía en UCI de 21,4 +/- 5,6 días sin protocolo versus 7,6 +/- 2,48 días (p <0,05) con protocolo de weaning. Conclusión: Es posible disminuir de manera significativa, la estadía en VMI, en UCI, con la aplicación de este protocolo de weaning rápido utilizando VMNI posextubación en pacientes obesos mórbidos; de manera eficaz y segura.

Introduction: The difficulty of completing a standard weaning protocol in morbid obese patient, provides an extended stay on invasive mechanical ventilation (MV) and in ICU. Intends a protocol of weaning “Fat-Fast”, in morbidly obese patients and acute respiratory failure (ARF) using noninvasive ventilation (NIV) immediately after extubation. Methodology: to assess the weaning protocol in relation to: mortality at 28 days, days in IMV, ICU days, need for reintubation, n° of tracheotomies performed; and also, compare IMV days, and ICU days in relation to conventional weaning protocol. We conducted a cross sectional study with prospective recruitment between May 2010and July 2011, including all patients who were able to initiate a process of weaning, with clinical history obesity (BMI > 35) and ARF. If completed successfully the designed spontaneous ventilatory trial for 1 hour in the IMV, and meet extubation criteria, pass directly to the NIV. We included 30 adult patients, aged 59.1 +/- 12.7, 50 percent male, and with APACHE II 16.3 (range 7 to 33), were compared with a retrospective cohort of 18 patients with similar characteristics. Results: no mortality at 28 days, no patient requires reintubation or TQ; with an average of 2.1 +/- 1.1 days in the NIV. IMV stay was 5.7 +/- 2.4 days with Fast-Fat, versus conventional weaning protocol was 14.4 +/- 6 days (p < 0, 05). ICU stay with the conventional protocol was 21.4 +/- 5.6 versus 7.6 +/- 2.48 days (p<0, 05) with “Fast Fat”. Conclusion: With the application of this rapid weaning protocol, using postextubation NIV in morbidly obese patients, it is possible to decrease effectively and safely the IMV and ICU stay, significantly.

Ventilación mecánica no invasiva y falla respiratoria aguda, variables de éxito y fracaso / Noninvasive ventilation and acute respiratory failure: variables in the success or failure

Introducción: La VMNI se utiliza en una gran variedad de condiciones clínicas, siendo necesario, determinar las variables que condicionan el éxito o fracaso de la VMNI en insuficiencia respiratoria aguda (IRA) tipo I y II, y en falla postextubación (FPEXT). Material y método: A fin de analizar las variables responsables del éxito o fracaso de la VMNI en IRA, y desarrollar un modelo predictivo precoz, del éxito de la VMNI; se analizaron 102 pacientes (edad 56,5 +/- 17,2 años, 64 por ciento hombres, con APACHE II: 14,7 +/-6,5); que utilizaron VMNI, en modalidad Bilevel. Se registraron parámetros demográficos, clínicos y gasométricos, basales y a la hora de inicio de la VMNI. Los datos fueron analizados con regresión lineal, tablas de contigencia, pruebas de normalidad Shapiro Wilks, Cramer Von Mises, Durbin-Watson; razón de verosimilitud, Chi cuadrado y árbol de clasificación. Resultados: La aplicación de la VMNI fue exitosa en 82,4 por ciento de los casos. El éxito no está supeditado al tipo de IRA; puesto que tanto en IRA I y II es >80 por ciento de los casos, con una leve tendencia hacia mejores resultados con VMNI en IRA tipo II (p= 0,93). En FPEXT,y en IRA, se logra evitar la intubación, en el 78 por ciento y 87 por ciento respectivamente. Se observan 6 variables, que mediante un flujograma propuesto, permiten predecir con el 96 por ciento de exactitud, el éxito o fracaso de la VMNI, en ambos tipos de IRA y en FPEXT. Además se aporta con un modelo que permite calcular la FiO2 administrada en equipos de VMNI sin blender de O2 (p = 0.09). Conclusiones: La VMNI es una herramienta eficaz en el manejo precoz de ambos tipos de IRA y FPEXT, evitando la conexión a VMI.No se encontraron variables individuales, que logren predecir el éxito o fracaso de la VMNI de manera significativa en ambos tipos de IRA, como tampoco en FPEXT. Sin embargo, la combinación de 6 variables permite, a través del flujograma propuesto...

Noninvasive ventilation (NIV) is used in a variety of clinical conditions, it is important to determine the variables that decide the success or failure of NIV in Acute Respiratory Failure (ARF) type I and II, and also in failure after extubation (FAE). Material and Methods: The aims of this study were asses with the variables in the success or failure of NIV in ARF, and develop an early prediction model of success or failure in the NIV. We analyzed 102 patients (age 56, 5 +/- 17,2 years; 64 percent men; APACHE II 14,7 +/- 6,5) who used NIV in bilevel mode. We recorded demographic, clinical and blood gas prior and an hour later, to the initiation of the NIV. Data were analyzed whit linear regression, contingency tables, Shapiro Wilks normality tests, Cramer Von Mises, Durbin-Watson, like hood ratio, chi square and classification tree. Results: the application of NIV was successful in 82, 4 percent of cases. The success does not depend of the type of ARF, since both of ARF have a success in >80 percent of cases, with a slight trend towards better outcome whit NIV to treat ARF type II(p=0,93). In FAE and in both ARF, intubations were avoided in 78 percent and 87 percent respectively. Six variables are obtained, through a proposed flow chart, whit 96 percent of accuracy, allows predicting success of NIV, in both types of ARF and in FAE. In addition, we delivered a new model that calculates the FiO2administrated in ventilators without an O2 blender (p =0.09). Conclusion: The noninvasive ventilator assistant is an effective tool in early management of both types of ARF, avoiding the connection to invasive ventilation, or reintubation. There were no isolated variables that are able to predict the success or failure of NIV significantly in both types of ARF, nor in FAE. However, the combination of 6 variables can, through the proposed flow chart, anticipates the evolution of the patients in the NIV.