RESUMO
BACKGROUND: Anti-SARS-CoV-2 S antibodies prevent viral replication. Critically ill COVID-19 patients show viral material in plasma, associated with a dysregulated host response. If these antibodies influence survival and viral dissemination in ICU-COVID patients is unknown. PATIENTS/METHODS: We studied the impact of anti-SARS-CoV-2 S antibodies levels on survival, viral RNA-load in plasma, and N-antigenaemia in 92 COVID-19 patients over ICU admission. RESULTS: Frequency of N-antigenaemia was >2.5-fold higher in absence of antibodies. Antibodies correlated inversely with viral RNA-load in plasma, representing a protective factor against mortality (adjusted HR [CI 95%], p): (S IgM [AUC ≥ 60]: 0.44 [0.22; 0.88], 0.020); (S IgG [AUC ≥ 237]: 0.31 [0.16; 0.61], <0.001). Viral RNA-load in plasma and N-antigenaemia predicted increased mortality: (N1-viral load [≥2.156 copies/ml]: 2.25 [1.16; 4.36], 0.016); (N-antigenaemia: 2.45 [1.27; 4.69], 0.007). CONCLUSIONS: Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. Our findings support that these antibodies contribute to prevent systemic dissemination of SARS-CoV-2.
Assuntos
Anticorpos Antivirais/sangue , Antígenos Virais/sangue , COVID-19 , COVID-19/imunologia , COVID-19/mortalidade , Estado Terminal , Humanos , RNA Viral/sangue , SARS-CoV-2RESUMO
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.
Assuntos
COVID-19/complicações , RNA Viral/análise , Carga Viral/imunologia , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , COVID-19/sangue , Distribuição de Qui-Quadrado , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Reação em Cadeia da Polimerase/métodos , RNA Viral/sangue , Estatísticas não ParamétricasRESUMO
BACKGROUND: Acute Respiratory Distress Syndrome (ARDS) necessitates personalized treatment strategies due to its heterogeneity, aiming to mitigate Ventilator-Induced Lung Injury (VILI). Advanced monitoring techniques, including imaging, driving pressure, transpulmonary pressure, and mechanical power, present potential avenues for tailored interventions. OBJECTIVE: To review some of the most important techniques for achieving greater personalization of mechanical ventilation in ARDS patients as evaluated in randomized clinical trials, by analyzing their effect on three clinically relevant aspects: mortality, ventilator-free days, and gas exchange. METHODS: Following PRISMA guidelines, we conducted a systematic review and meta-analysis of Randomized Clinical Trials (RCTs) involving adult ARDS patients undergoing personalized ventilation adjustments. Outcomes were mortality (primary end-point), ventilator-free days, and oxygenation improvement. RESULTS: Among 493 identified studies, 13 RCTs (n = 1255) met inclusion criteria. No personalized ventilation strategy demonstrated superior outcomes compared to traditional protocols. Meta-analysis revealed no significant reduction in mortality with image-guided (RR 0.88, 95 % CI 0.70-1.11), driving pressure-guided (RR 0.61, 95 % CI 0.29-1.30), or transpulmonary pressure-guided (RR 0.85, 95 % CI 0.58-1.24) strategies. Ventilator-free days and oxygenation outcomes showed no significant differences. CONCLUSION: Our study does not support the superiority of personalized ventilation techniques over traditional protocols in ARDS patients. Further research is needed to standardize ventilation strategies and determine their impact on mechanical ventilation outcomes.