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.

[Lemierre syndrome: several clinical features of "a forgotten disease"]. / Síndrome de Lemierre: distintas presentaciones clínicas de «una enfermedad olvidada¼

INTRODUCTION: Lemierre syndrome (LS) is considered as a forgotten disease since the beginning of Penicillin. The lack of use of beta-lactamase inhibitors antibiotics together with the increase in the use of macrolids or second-generation and third-generation cephalosporins for oropharyngeal processes has led to an increasing incidence. We propose to review all LS cases seen in an Emergency Department over the last 5 years. METHODS: Retrospective study of patients diagnosed as LS in the Emergency Department of Hospital general universitario Gregorio Marañón from 2004 to the present. Descriptive analysis of age, gender, clinical features, laboratory and radiological results, management and outcome. RESULTS: We had 6 patients with LS. 5 males. Median age: 25 years old. All with sore throat and pulmonary embolisms. 2 patients with negative blood cultures. 1 patient was admitted into ICU because of severe sepsis. One of the 6 developed acute renal failure, another one hemoptysis, and another a hydropneumothorax which was drained. All the patients were managed with antibiotics against anaerobes, carbapenems in 3 cases. Two patients did not receive anticoagulants, with no complications recorded. There were no deaths. CONCLUSION: LS still has a high morbidity, therefore it must be on mind in young people with febrile pharyngeal symptoms in order to start specific treatment as soon as possible to decrease complications. Carbapenems appears to be a good therapeutic choice.

Síndrome de Lemierre: distintas presentaciones clínicas de «una enfermedad olvidada» / Lemierre syndrome: Several clinical features of “A forgotten disease”

Introducción El síndrome de Lemierre (SL) se considera una enfermedad olvidada tras el inicio de la penicilina. El menor uso de antibióticos inhibidores de beta-lactamasas junto con el incremento en el uso de macrólidos o cefalosporinas de segunda y tercera generación en los procesos orofaringeos ha condicionado un aumento en su incidencia. Nos propusimos revisar los casos de SL ingresados desde el servicio de urgencias en los últimos 5 años. Métodos Estudio retrospectivo de pacientes con SL ingresados desde el servicio de urgencias del hospital general universitario Gregorio Marañón, desde 2004 hasta el momento actual. Análisis descriptivo de edad, sexo, manifestaciones clínicas, resultados de laboratorio y de imagen, tratamiento y complicaciones. Resultados Se incluyen 6 pacientes con diagnóstico de SL. Cinco varones. Mediana de edad: 25 años. Todos ellos con foco orofaríngeo y embolismos pulmonares. En 2 pacientes los hemocultivos fueron estériles. Un paciente fue ingresado en UCI por sepsis grave. Uno de los 6 desarrolló insuficiencia renal aguda, otro hemoptisis y otro hidropioneumotórax que obligó a su drenaje. Todos fueron tratados con antibióticos frente a anaerobios, siendo carbapenemes en 3 de ellos. 2 pacientes no fueron anticoagulados, sin evidencia de complicaciones por este motivo. No se registraron fallecimientos. Conclusión El SL sigue presentado una elevada morbilidad por lo que debemos considerarlo en pacientes jóvenes con cuadros febriles orofaríngeos, para iniciar su tratamiento específico precozmente y disminuir sus complicaciones. Los carbapenemes representan una buena opción terapéutica (AU)

Introduction Lemierre syndrome (LS) is considered as a forgotten disease since the beginning of Penicillin. The lack of use of beta-lactamase inhibitors antibiotics together with the increase in the use of macrolids or second-generation and third-generation cephalosporins for oropharyngeal processes has led to an increasing incidence. We propose to review all LS cases seen in an Emergency Department over the last 5 years. Methods Retrospective study of patients diagnosed as LS in the Emergency Department of Hospital general universitario Gregorio Marañón from 2004 to the present. Descriptive analysis of age, gender, clinical features, laboratory and radiological results, management and outcome. Results We had 6 patients with LS. 5 males. Median age: 25 years old. All with sore throat and pulmonary embolisms. 2 patients with negative blood cultures. 1 patient was admitted into ICU because of severe sepsis. One of the 6 developed acute renal failure, another one hemoptysis, and another a hydropneumothorax which was drained. All the patients were managed with antibiotics against anaerobes, carbapenems in 3 cases. Two patients did not receive anticoagulants, with no complications recorded. There were no deaths.ConclusionLS still has a high morbidity, therefore it must be on mind in young people with febrile pharyngeal symptoms in order to start specific treatment as soon as possible to decrease complications. Carbapenems appears to be a good therapeutic choice (AU)