Viral RNA load in plasma is associated with critical illness and a dysregulated host response in COVID-19.

BACKGROUND: COVID-19 can course with respiratory and extrapulmonary disease. SARS-CoV-2 RNA is detected in respiratory samples but also in blood, stool and urine. Severe COVID-19 is characterized by a dysregulated host response to this virus. We studied whether viral RNAemia or viral RNA load in plasma is associated with severe COVID-19 and also to this dysregulated response. METHODS: A total of 250 patients with COVID-19 were recruited (50 outpatients, 100 hospitalized ward patients and 100 critically ill). Viral RNA detection and quantification in plasma was performed using droplet digital PCR, targeting the N1 and N2 regions of the SARS-CoV-2 nucleoprotein gene. The association between SARS-CoV-2 RNAemia and viral RNA load in plasma with severity was evaluated by multivariate logistic regression. Correlations between viral RNA load and biomarkers evidencing dysregulation of host response were evaluated by calculating the Spearman correlation coefficients. RESULTS: The frequency of viral RNAemia was higher in the critically ill patients (78%) compared to ward patients (27%) and outpatients (2%) (p < 0.001). Critical patients had higher viral RNA loads in plasma than non-critically ill patients, with non-survivors showing the highest values. When outpatients and ward patients were compared, viral RNAemia did not show significant associations in the multivariate analysis. In contrast, when ward patients were compared with ICU patients, both viral RNAemia and viral RNA load in plasma were associated with critical illness (OR [CI 95%], p): RNAemia (3.92 [1.183-12.968], 0.025), viral RNA load (N1) (1.962 [1.244-3.096], 0.004); viral RNA load (N2) (2.229 [1.382-3.595], 0.001). Viral RNA load in plasma correlated with higher levels of chemokines (CXCL10, CCL2), biomarkers indicative of a systemic inflammatory response (IL-6, CRP, ferritin), activation of NK cells (IL-15), endothelial dysfunction (VCAM-1, angiopoietin-2, ICAM-1), coagulation activation (D-Dimer and INR), tissue damage (LDH, GPT), neutrophil response (neutrophils counts, myeloperoxidase, GM-CSF) and immunodepression (PD-L1, IL-10, lymphopenia and monocytopenia). CONCLUSIONS: SARS-CoV-2 RNAemia and viral RNA load in plasma are associated with critical illness in COVID-19. Viral RNA load in plasma correlates with key signatures of dysregulated host responses, suggesting a major role of uncontrolled viral replication in the pathogenesis of this disease.

Pacientes con indicación de traqueostomía en una cohorte de cuidados intensivos / Patients with tracheostomy indication in an intensive care cohort

Introduction: Tracheostomy is a procedure indicated for patients with extended mechanical ventilation. Objective: The objective of the study was to learn about the technical characteristics, the appropriate timing for the procedure and its evolution. Material and method: Observational, retrospective study of ICU admitted patients during 2012, with elective tracheostomy. The demographic variables, the Apache II, the pathologies, the number of days in MV, length of stay and mortality were analyzed, both globally and by groups, depending on the early or late use of the technique. The study was approved by the Ethics Committee for Clinical Research of the institution, in accordance with the institutional bioethical principles. Results: The mean age in the sample with 42 patients was 61.36, and the mean Apache II was 18. The most frequent pathology was neurological. The approach was percutaneous in 71.5%, with minor complications in 20% of the cases. In the early tracheostomy group, the number of days in MV and the length of stay were both considerably shorter. Conclusions:Elective tracheostomy is a commonly used technique in the ICU and the procedure is performed according to the protocol. The percutaneous approach is the most frequently used, with few complications. In neurological critical patients with extended weaning, an early approach reduces the number of days with ventilation and the length of stay, with no positive impact on mortality.

Introducción: La traqueostomía es un procedimiento indicado en los pacientes con ventilación mecánica prolongada. Objetivo: El objetivo del estudio fue conocer sus características, técnica, momento adecuado de realización y evolución. Material y método: Estudio observacional retrospectivo, de pacientes ingresados en UCI durante 2012, con traqueostomía electiva. Se analizaron variables demográficas, escala Apache II, patologías, días de VM, estancia y mortalidad; de forma global, y por grupos según técnica precoz o tardía. El estudio fue aprobado por el Comité Ético de Investigación Clínica del centro, cumpliendo con los principios bioéticos del mismo. Resultados: En la muestra de 42 pacientes la edad media fue 61.36, con mediana de Apache II de 18. La patología más frecuente fueron los pacientes neurológicos, se realizó la forma percutánea en el 71.5%, con complicaciones menores del 20%. En el grupo de traqueostomía precoz se observó menor número de días de VM y estancia de forma significativa. Conclusiones: La traqueostomía electiva es una técnica frecuente en UCI, realizado el procedimiento según protocolo; la modalidad percutánea es la más empleada, con escasas complicaciones. En los pacientes neurocríticos y con destete prolongado la técnica precoz reduce los días de ventilación y estancia, sin beneficio en la mortalidad.