Low anti-SARS-CoV-2 S antibody levels predict increased mortality and dissemination of viral components in the blood of critical COVID-19 patients.

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.

Clinical and biological markers for predicting ARDS and outcome in septic patients.

Sepsis is a common cause of acute respiratory distress syndrome (ARDS) associated with a high mortality. A panel of biomarkers (BMs) to identify septic patients at risk for developing ARDS, or at high risk of death, would be of interest for selecting patients for therapeutic trials, which could improve ARDS diagnosis and treatment, and survival chances in sepsis and ARDS. We measured nine protein BMs by ELISA in serum from 232 adult septic patients at diagnosis (152 required invasive mechanical ventilation and 72 had ARDS). A panel including the BMs RAGE, CXCL16 and Ang-2, plus PaO2/FiO2, was good in predicting ARDS (area under the curve = 0.88 in total septic patients). Best performing panels for ICU death are related to the presence of ARDS, need for invasive mechanical ventilation, and pulmonary/extrapulmonary origin of sepsis. In all cases, the use of BMs improved the prediction by clinical markers. Our study confirms the relevance of RAGE, Ang-2, IL-1RA and SP-D, and is novel supporting the inclusion of CXCL16, in BMs panels for predicting ARDS diagnosis and ARDS and sepsis outcome.

Epidemiology and Changes in Mortality of Sepsis After the Implementation of Surviving Sepsis Campaign Guidelines.

PURPOSE: To determine the epidemiology and outcome of severe sepsis and septic shock after 9 years of the implementation of the Surviving Sepsis Campaign (SSC) and to build a mortality prediction model. METHODS: This is a prospective, multicenter, observational study performed during a 5-month period in 2011 in a network of 11 intensive care units (ICUs). We compared our findings with those obtained in the same ICUs in a study conducted in 2002. RESULTS: The current cohort included 262 episodes of severe sepsis and/or septic shock, and the 2002 cohort included 324. The prevalence was 14% (95% confidence interval: 12.5-15.7) with no differences to 2002. The population-based incidence was 31 cases/100 000 inhabitants/year. Patients in 2011 had a significantly lower Acute Physiology and Chronic Health Evaluation II (APACHE II; 21.9 ± 6.6 vs 25.5 ± 7.07), Logistic Organ Dysfunction Score (5.6 ± 3.2 vs 6.3 ± 3.6), and Sequential Organ Failure Assessment (SOFA) scores on day 1 (8 ± 3.5 vs 9.6 ± 3.7; P < .01). The main source of infection was intraabdominal (32.5%) although microbiologic isolation was possible in 56.7% of cases. The 2011 cohort had a marked reduction in 48-hour (7% vs 14.8%), ICU (27.2% vs 48.2%), and in-hospital (36.7% vs 54.3%) mortalities. Most relevant factors associated with death were APACHE II score, age, previous immunosuppression and liver insufficiency, alcoholism, nosocomial infection, and Delta SOFA score. CONCLUSION: Although the incidence of sepsis/septic shock remained unchanged during a 10-year period, the implementation of the SSC guidelines resulted in a marked decrease in the overall mortality. The lower severity of patients on ICU admission and the reduced early mortality suggest an improvement in early diagnosis, better initial management, and earlier antibiotic treatment.

The protective association of endogenous immunoglobulins against sepsis mortality is restricted to patients with moderate organ failure.

BACKGROUND: Pre-evaluation of endogenous immunoglobulin levels is a potential strategy to improve the results of intravenous immunoglobulins in sepsis, but more work has to be done to identify those patients who could benefit the most from this treatment. The objective of this study was to evaluate the impact of endogenous immunoglobulins on the mortality risk in sepsis depending on disease severity. METHODS: This was a retrospective observational study including 278 patients admitted to the ICU with sepsis fulfilling the SEPSIS-3 criteria, coming from the Spanish GRECIA and ABISS-EDUSEPSIS cohorts. Patients were distributed into two groups depending on their Sequential Organ Failure Assessment score at ICU admission (SOFA < 8, n = 122 and SOFA ≥ 8, n = 156), and the association between immunoglobulin levels at ICU admission with mortality was studied in each group by Kaplan-Meier and multivariate logistic regression analysis. RESULTS: ICU/hospital mortality in the SOFA < 8 group was 14.8/23.0%, compared to 30.1/35.3% in the SOFA ≥ 8 group. In the group with SOFA < 8, the simultaneous presence of total IgG < 407 mg/dl, IgM < 43 mg/dl and IgA < 219 mg/dl was associated with a reduction in the survival mean time of 6.6 days in the first 28 days and was a robust predictor of mortality risk either during the acute or during the post-acute phase of the disease (OR for ICU mortality: 13.79; OR for hospital mortality: 7.98). This predictive ability remained in the absence of prior immunosuppression (OR for ICU mortality: 17.53; OR for hospital mortality: 5.63). Total IgG < 407 mg/dl or IgG1 < 332 mg/dl was also an independent predictor of ICU mortality in this group. In contrast, in the SOFA ≥ 8 group, we found no immunoglobulin thresholds associated with neither ICU nor hospital mortality. CONCLUSIONS: Endogenous immunoglobulin levels may have a different impact on the mortality risk of sepsis patients based on their severity. In patients with moderate organ failure, the simultaneous presence of low levels of IgG, IgA and IgM was a consistent predictor of both acute and post-acute mortalities.

Age-related injury patterns in Spanish trauma ICU patients. Results from the RETRAUCI.

BACKGROUND: Injury patterns may differ in trauma patients when age is considered. This information is relevant in the management of trauma patients and for planning preventive measures. METHODS: We included in the study all patients admitted for traumatic disease in the participating ICUs from November 23rd, 2012 to July 31st, 2015 with complete records. Data on epidemiology, injury patterns, severity scores, acute management, resources utilisation and outcome were recorded and compared in the following groups of age: ≤55years (young adults), 56-65 years (adults), 66-75 years (elderly), >75years (very elderly). Quantitative data were reported as median (Interquartile Range (IQR) 25-75) and categorical data as number and percentage. Comparison between groups of age with quantitative variables was performed using the analysis of variance (ANOVA) test. Differences between groups with categorical variables were compared using the chi-square test. A value of p<0.05 was considered significant. RESULTS: We included 2700 patients (78.9% male). Median age was 46 (31-62) years. Blunt trauma was present in 93.7% of the patients. Median RTS was 7.55 (5.97-7.84). Median ISS was 20 (13-26). High-energy trauma secondary to motor-vehicle accident with rhabdomyolysis and drugs abuse showed an inverse linear association with ageing, whilst pedestrian falls with isolated brain injury, being run-over and pre-injury antiplatelets or anticoagulant treatment increased with age (in all cases p<0.001). Multiple injuries were more common in young adults (p<0.001). Acute kidney injury prevalence was higher in elderly and very elderly patients (p<0.001). ICU Mortality increased with age in spite of similar severity scores in all groups (p<0.001). The main cause of death in all groups was intracranial hypertension. CONCLUSIONS: Different injury patterns exist in relation with ageing in trauma ICU patients. Adult patients were more likely to present high-energy trauma with significant injuries in different areas whilst elderly patients were prone to low-energy falls, complicated by antiplatelets or anticoagulants use, resulting in severe brain injury and increased mortality.

Mortality Reduction and Long-Term Compliance with Surviving Sepsis Campaign: A Nationwide Multicenter Study.

PURPOSE: To determine the long-term degree of compliance with the Surviving Sepsis Campaign (SSC) bundles and related outcomes after an educational program in septic patients admitted to a network of intensive care units (ICU). METHODS: Prospective, observational, multicenter study in several ICUs during a 5-month period for evaluating the degree of compliance with the SSC bundles of resuscitation in the first 6 h (B6H) and management in the following 24 h (B24H). We compared the findings with those from a historical cohort at the same ICUs after an educational program (EDUSEPSIS) 5 years earlier. RESULTS: The study cohort comprised 231 episodes of severe sepsis and the historical cohort included 217. In the current cohort, we found a better compliance with B6H compared with the historical cohort (27.7% vs. 9.7%, P < 0.001), and lower compliance with B24H (4.3% vs. 12.9%, P < 0.001). ICU and in-hospital mortalities were reduced from 37.3% to 27.1% (P = 0.02) and from 45.3% to 36.7% (P = 0.06), respectively. This reduction occurred linearly with the number of B6H items completed (P for trend <0.001). All B6H measures were individually associated with lower ICU mortality. Measurement of plasma lactate, blood cultures, and administration of broad-spectrum antibiotics were associated with lower in-hospital mortality. No benefit was observed regarding B24H. CONCLUSIONS: Our study confirmed that an educational campaign aimed at early recognition and management of patients with severe sepsis improves compliance with management recommendations and hospital survival in the long term.

A randomized trial of intravenous glutamine supplementation in trauma ICU patients.

PURPOSE: To evaluate the effect of the intravenous (i.v.) L-alanyl-L-glutamine dipeptide supplementation during 5 days on clinical outcome in trauma patients admitted to the intensive care unit (ICU). METHODS: This was a prospective, randomized, double-blind, multicenter trial. Glutamine was not given as a component of nutrition but as an extra infusion. The primary outcome variable was the number of new infections within the first 14 days. RESULTS: We included 142 patients. There were no differences between groups in baseline characteristics. Up to 62 % of the patients in the placebo group and 63 % in the treatment group presented confirmed infections (p = 0.86). ICU length of stay was 14 days in both groups (p = 0.54). Hospital length of stay was 27 days in the placebo group and 29 in the treatment group (p = 0.88). ICU mortality was 4.2 % in both groups (p = 1). Sixty percent of the patients presented low glutamine levels before randomization. At the end of the treatment (6th day), 48 % of the patients maintained low glutamine levels (39 % of treated patients vs. 57 % in the placebo group). Patients with low glutamine levels at day 6 had more number of infections (58.8 vs. 80.9 %; p = 0.032) and longer ICU (9 vs. 20 days; p < 0.01) and hospital length of stay (24 vs. 41 days; p = 0.01). CONCLUSIONS: There was no benefit with i.v. L-alanyl-L-glutamine dipeptide supplementation (0.5 g/kg body weight/day of the dipeptide) during 5 days in trauma patients admitted to the ICU. The i.v. glutamine supplementation was not enough to normalize the plasma glutamine levels in all patients. Low plasma glutamine levels at day 6 were associated with a worse outcome.