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EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320046


Background: The benefits of the use of extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) due to COVID-19 remain controversial.Methods: In this multicenter cohort study, we analyzed all the adult patients with ARDS due to COVID-19 who received extracorporeal respiratory support at 25 ECMO centers (23 in Spain and two in Portugal) during the first and second waves of the pandemic. Follow-up ended on December 1. Our primary aim was to describe this cohort taking into account its evolution during the pandemic. We also investigated hazard ratios for hospital mortality.Findings: A total of 334 patients were included. Patients supported during the second wave [176 (52.7%)] were older (54.6±9.7 vs 50.9±10.6,p=0.001), had more comorbidities, were more frequently coinfected at the start of ECMO [62 (35.2%) vs 37 (23.3%),p=0.028] and were less likely to be treated at a high-volume center [42 (23.9%) vs 54 (34.2%),p=0.008] than those supported during the first wave [158 (47.3%)]. At December 1, 134 (40.1%) patients had died and 49 (14.6%) were still on ECMO. Among patients supported during the first wave, 93 (58.8%) were discharged and all were alive at six months. Older age [HR 3.49 (1.94-6.28),p<0.001, for patients older than 65 years], low-volume center [HR 2.07 (1.19-3.59),p=0.009;for centers attending fewer than 15 cases] and coinfection at the start of ECMO [HR 1.49 (1.02-2.18),p=0.039] were associated with higher risk of hospital mortality, while a higher PEEP at day 3 of ECMO [HR 0.92 (0.86-0.98),p=0.019] was associated with a lower risk of death. Time on mechanical ventilation prior to ECMO was not associated with mortality [HR 1.01 (0.98-1.03),p=0.310].Interpretation: ECMO support provided at high volume centers should be considered in selected COVID-19 patients. Age and coinfection, but not mechanical ventilation days, should be taken into account at indication assessment.Funding Statement: No funding.Declaration of Interests: None.Ethics Approval Statement: The study protocol was approved by the local ethics committees at all the participating centers.

J Intern Med ; 291(2): 232-240, 2022 02.
Article in English | MEDLINE | ID: covidwho-1455598


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.

Antibodies, Viral/blood , Antigens, Viral/blood , COVID-19 , COVID-19/immunology , COVID-19/mortality , Critical Illness , Humans , RNA, Viral/blood , SARS-CoV-2
Crit Care ; 24(1): 691, 2020 12 14.
Article in English | MEDLINE | ID: covidwho-977684


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.

COVID-19/complications , RNA, Viral/analysis , Viral Load/immunology , Adult , Aged , Biomarkers/analysis , Biomarkers/blood , COVID-19/blood , Chi-Square Distribution , Critical Illness , Female , Humans , Male , Middle Aged , Multivariate Analysis , Polymerase Chain Reaction/methods , RNA, Viral/blood , Statistics, Nonparametric