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.