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1.
J Infect ; 2022 Jun 30.
Article in English | MEDLINE | ID: covidwho-1914623

ABSTRACT

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

2.
Intensive Care Med ; 48(7): 850-864, 2022 07.
Article in English | MEDLINE | ID: covidwho-1899125

ABSTRACT

PURPOSE: Although there is evidence supporting the benefits of corticosteroids in patients affected with severe coronavirus disease 2019 (COVID-19), there is little information related to their potential benefits or harm in some subgroups of patients admitted to the intensive care unit (ICU) with COVID-19. We aim to investigate to find candidate variables to guide personalized treatment with steroids in critically ill patients with COVID-19. METHODS: Multicentre, observational cohort study including consecutive COVID-19 patients admitted to 55 Spanish ICUs. The primary outcome was 90-day mortality. Subsequent analyses in clinically relevant subgroups by age, ICU baseline illness severity, organ damage, laboratory findings and mechanical ventilation were performed. High doses of corticosteroids (≥ 12 mg/day equivalent dexamethasone dose), early administration of corticosteroid treatment (< 7 days since symptom onset) and long term of corticosteroids (≥ 10 days) were also investigated. RESULTS: Between February 2020 and October 2021, 4226 patients were included. Of these, 3592 (85%) patients had received systemic corticosteroids during hospitalisation. In the propensity-adjusted multivariable analysis, the use of corticosteroids was protective for 90-day mortality in the overall population (HR 0.77 [0.65-0.92], p = 0.003) and in-hospital mortality (SHR 0.70 [0.58-0.84], p < 0.001). Significant effect modification was found after adjustment for covariates using propensity score for age (p = 0.001 interaction term), Sequential Organ Failure Assessment (SOFA) score (p = 0.014 interaction term), and mechanical ventilation (p = 0.001 interaction term). We observed a beneficial effect of corticosteroids on 90-day mortality in various patient subgroups, including those patients aged ≥ 60 years; those with higher baseline severity; and those receiving invasive mechanical ventilation at ICU admission. Early administration was associated with a higher risk of 90-day mortality in the overall population (HR 1.32 [1.14-1.53], p < 0.001). Long-term use was associated with a lower risk of 90-day mortality in the overall population (HR 0.71 [0.61-0.82], p < 0.001). No effect was found regarding the dosage of corticosteroids. Moreover, the use of corticosteroids was associated with an increased risk of nosocomial bacterial pneumonia and hyperglycaemia. CONCLUSION: Corticosteroid in ICU-admitted patients with COVID-19 may be administered based on age, severity, baseline inflammation, and invasive mechanical ventilation. Early administration since symptom onset may prove harmful.


Subject(s)
COVID-19 , Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Critical Illness/therapy , Humans , Intensive Care Units , Precision Medicine , Respiration, Artificial , Steroids/therapeutic use
3.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-337888

ABSTRACT

Background: Optimal time to intubate patients with SARS-CoV-2 pneumonia is controversial. Whereas some authors recommend trying noninvasive respiratory support before intubate, others argue that delaying intubation can cause patient-self-induced lung injury and worsen the prognosis. We hypothesized that delayed intubation would increase the risk mortality in COVID-19 patients. Methods: This preplanned retrospective observational study used prospectively collected data from adult patients with COVID-19 and respiratory failure admitted to 73 intensive care units between February 2020 and March 2021. Patients with limitations on life support and those with missing data were excluded. We collected demographic, laboratory, clinical variables and outcomes. Intubation was classified as 1) Very early: before or at ICU admission;2) Early: < 24 hours after ICU admission;or 3) Late: ≥24 hours after ICU admission. We compared the early group versus those intubated late, using chi-square tests for categorical variables and the Mann-Whitney U for continuous variables. To assess the relationship between early versus late intubation and mortality, we used multivariable binary logistic regression. Statistical significance was set at p<0.05. Results: We included 4198 patients [median age, 63 (54‒71) years;70.8% male;median SOFA score, 4 (3‒7);median APACHE score, 13 (10‒18)], and median PaO 2 /FiO 2 , 131 (100‒190)];intubation was very early in 2024 (48.2%) patients, early in 928 (22.1%), and late in 441 (10.5%). ICU mortality was 30.2% and median ICU stay was 14 (7‒28) days. Although patients in the late group were younger [62 vs. 64, respectively, p<0.05] and had less severe disease [APACHE II (13 vs. 14, respectively, p<0.05) and SOFA (3 vs. 4, respectively, p<0.05) scores], and higher PaO2/FiO 2 at admission (116 vs. 100, respectively, p<0.05), mortality was higher in the late group than in the early group (36.9% vs. 31.6%, p<0.05). Late intubation was independently associated with mortality (OR1.83;95%CI 1.35‒2.47). Conclusions: Delaying intubation beyond the first 24 hours of admission in patients with COVID-19 pneumonia increases the risk of mortality. Trial registration clinical-Trial.gov (NCT 04948242)

4.
Archivos de bronconeumologia ; 2022.
Article in English | EuropePMC | ID: covidwho-1801724

ABSTRACT

Introduction The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. Methods CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. Results This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. Conclusions We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.

5.
Arch Bronconeumol ; 58 Suppl 1: 22-31, 2022 Apr.
Article in English, Spanish | MEDLINE | ID: covidwho-1797167

ABSTRACT

INTRODUCTION: The COVID-19 pandemic created tremendous challenges for health-care systems. Intensive care units (ICU) were hit with a large volume of patients requiring ICU admission, mechanical ventilation, and other organ support with very high mortality. The Centro de Investigación Biomédica en Red-Enfermedades Respiratorias (CIBERES), a network of Spanish researchers to investigate in respiratory disease, commissioned the current proposal in response to the Instituto de Salud Carlos III (ISCIII) call. METHODS: CIBERESUCICOVID is a multicenter, observational, prospective/retrospective cohort study of patients with COVID-19 admitted to Spanish ICUs. Several work packages were created, including study population and ICU data collection, follow-up, biomarkers and miRNAs, data management and quality. RESULTS: This study included 6102 consecutive patients admitted to 55 ICUs homogeneously distributed throughout Spain and the collection of blood samples from more than 1000 patients. We enrolled a large population of COVID-19 ICU-admitted patients including baseline characteristics, ICU and MV data, treatments complications, and outcomes. The in-hospital mortality was 31%, and 76% of patients required invasive mechanical ventilation. A 3-6 month and 1 year follow-up was performed. Few deaths after 1 year discharge were registered. Low anti-SARS-CoV-2 S antibody levels predict mortality in critical COVID-19. These antibodies contribute to prevent systemic dissemination of SARS-CoV-2. The severity of COVID-19 impacts the circulating miRNA profile. Plasma miRNA profiling emerges as a useful tool for risk-based patient stratification in critically ill COVID-19 patients. CONCLUSIONS: We present the methodology used in a large multicenter study sponsored by ISCIII to determine the short- and long-term outcomes in patients with COVID-19 admitted to more than 50 Spanish ICUs.


Subject(s)
COVID-19 , MicroRNAs , COVID-19/epidemiology , Critical Illness/therapy , Humans , Intensive Care Units , Pandemics , Prospective Studies , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
6.
EuropePMC;
Preprint in English | EuropePMC | ID: ppcovidwho-328780

ABSTRACT

Background: The COVID-19 pandemic has challenged ICUs all over the world and their capacity was often exceeded. Our aim is to measure the impact of the pandemic at different levels in Spanish ICUs. Methods: : On-line survey, conducted in April 2021, among members of the Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias . Results: : We received 246 answers from 157 hospitals. 67.7% of the ICUs were expanded during the pandemic, with an overall increase in beds of 58.6%. The ICU medical staff increased by 6.1% and there has been a nursing shortage in 93.7% of units. In 88% of the hospitals the collaboration of other specialists was necessary to manage the patient overload, which exceeded 200% of the pre-pandemic ICU capacity. The predominant collaboration model consisted of the intensive care medicine specialist being responsible for triage and coordinating the care of critically ill patients with COVID-19. Despite that 53.2% centres offered training for critically ill patient care, a deterioration in the quality of care was perceived. 84.2% hospitals drew up a Contingency Plan and in 77.8% of the hospitals a multidisciplinary committee was set up to agree on decision-making. Self-evaluation of the work performed was outstanding and 91.9% felt proud of what they had achieved. 16.7%, however, regretted becoming intensivist and up to 15% considered leaving their job. 61.8%, 79.3% and 89.4% of the participants have the feeling that the opinion about the ICU has improved for hospital management, for other specialists and for the general population (respectively). In 75.3% of the hospitals, at least one member of the ICU medical team has been infected with COVID-19. Conclusions: : The Spanish ICUs assumed an unprecedented increase in the number of patients. They achieved it without hardly increasing their staff and, while intensive care medicine training was carried out for other specialists who collaborated. Despite the overload, the degree of job satisfaction was consistent with pre-pandemic levels.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-320148

ABSTRACT

Background: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. Methods: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 Intensive Care Units(ICU) in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient’s factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. Results: : The database included a total of 2,022 patients (mean age 64[IQR5-71] years, 1423(70.4%) male, median APACHE II score (13[IQR10-17]) and SOFA score (5[IQR3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A(mild) phenotype (537;26.7%) included older age (<65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623,30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C(severe) phenotype was the most common (857;42.5%) and was characterized by the interplay of older age (>65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. Conclusion: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a “one-size-fits-all” model in practice .

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-317390

ABSTRACT

Background: The steroids are currently used as standard treatment for severe COVID-19. However, the evidence is weak. Our aim is to determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. Methods: A secondary analysis derived from multicenter, observational study of adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). The primary outcome was ICU mortality. We performed a Multivariate analysis after propensity score full matching (PS), Cox proportional hazards (CPH), Cox covariate time interaction (TIR), Weighted Cox Regression (WCR) and Fine-Gray analysis(sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. Results: : A total of 2,017 patients were analyzed, 1171(58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR:1.0,95%CI:0.98-1.15). Corticosteroids were administered in 298/537(55.5%) patients of “A” phenotype and their use was not associated with ICU mortality (HR=0.85[0.55-1.33]). A total of 338/623(54.2%) patients in “B” phenotype received corticosteroids. The CPH (HR =0.65 [0.46-0.91]) and TIR regression (1- 25 day tHR=0.56[0.39-0.82] and >25 days tHR=1.53[1.03-7.12]) showed a biphasic effect of corticosteroids due to proportional assumption violation. No effect of corticosteroids on ICU mortality was observed when WCR was performed (wHR=0.72[0.49-1.05]). Finally, 535/857(62.4%) patients in “C” phenotype received corticosteroids. The CPH (HR=0.73[0.63-0.98]) and TIR regression (1- 25 day tHR=0.69[ 0.53-0.89] and >25 days tHR=1.30[ 1.14-3.25]) showed a biphasic effect of corticosteroids and proportional assumption violation. However, wHR (0.75[0.58-0.98]) and sHR (0.79[0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. Conclusion: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate-high dose. Only patients with the highest severity could benefit from steroid treatment although this effect on clinical outcome was minimized during ICU stay.

9.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-316534

ABSTRACT

Background: . Some patients who had previously presented with COVID-19 have been reported to develop persistent COVID-19 symptoms. Whilst this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the prevalence and risk factors and characteristics of persistent COVID_19 . On other hand these patients have very often intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence in the poor health post-Covid 19 syndrome in ICU discharged patients Methods: This prospective, multicentre and observational study was done across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. Results: A total of 1,255 ICU patients were scheduled to be followed up at 3 months;however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP) Patients requiring invasive mechanical ventilation had persistent, post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, and development of ICUAP were independent risk factors for persistent poor health post-COVID-19. Conclusions: : Persistent, post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay and the onset of ICUAP comprised all independent risk factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-Covid 19

10.
Crit Care ; 26(1): 11, 2022 01 04.
Article in English | MEDLINE | ID: covidwho-1607559

ABSTRACT

BACKGROUND: Recent multicenter studies identified COVID-19 as a risk factor for invasive pulmonary aspergillosis (IPA). However, no large multicenter study has compared the incidence of IPA between COVID-19 and influenza patients. OBJECTIVES: To determine the incidence of putative IPA in critically ill SARS-CoV-2 patients, compared with influenza patients. METHODS: This study was a planned ancillary analysis of the coVAPid multicenter retrospective European cohort. Consecutive adult patients requiring invasive mechanical ventilation for > 48 h for SARS-CoV-2 pneumonia or influenza pneumonia were included. The 28-day cumulative incidence of putative IPA, based on Blot definition, was the primary outcome. IPA incidence was estimated using the Kalbfleisch and Prentice method, considering extubation (dead or alive) within 28 days as competing event. RESULTS: A total of 1047 patients were included (566 in the SARS-CoV-2 group and 481 in the influenza group). The incidence of putative IPA was lower in SARS-CoV-2 pneumonia group (14, 2.5%) than in influenza pneumonia group (29, 6%), adjusted cause-specific hazard ratio (cHR) 3.29 (95% CI 1.53-7.02, p = 0.0006). When putative IPA and Aspergillus respiratory tract colonization were combined, the incidence was also significantly lower in the SARS-CoV-2 group, as compared to influenza group (4.1% vs. 10.2%), adjusted cHR 3.21 (95% CI 1.88-5.46, p < 0.0001). In the whole study population, putative IPA was associated with significant increase in 28-day mortality rate, and length of ICU stay, compared with colonized patients, or those with no IPA or Aspergillus colonization. CONCLUSIONS: Overall, the incidence of putative IPA was low. Its incidence was significantly lower in patients with SARS-CoV-2 pneumonia than in those with influenza pneumonia. Clinical trial registration The study was registered at ClinicalTrials.gov, number NCT04359693 .


Subject(s)
COVID-19 , Influenza, Human , Intubation , Invasive Pulmonary Aspergillosis , Adult , COVID-19/epidemiology , COVID-19/therapy , Europe/epidemiology , Humans , Incidence , Influenza, Human/epidemiology , Influenza, Human/therapy , Invasive Pulmonary Aspergillosis/epidemiology , Retrospective Studies , SARS-CoV-2
11.
J Clin Med ; 11(1)2021 12 31.
Article in English | MEDLINE | ID: covidwho-1580629

ABSTRACT

BACKGROUND: Some patients previously presenting with COVID-19 have been reported to develop persistent COVID-19 symptoms. While this information has been adequately recognised and extensively published with respect to non-critically ill patients, less is known about the incidence and factors associated with the characteristics of persistent COVID-19. On the other hand, these patients very often have intensive care unit-acquired pneumonia (ICUAP). A second infectious hit after COVID increases the length of ICU stay and mechanical ventilation and could have an influence on poor health post-COVID 19 syndrome in ICU-discharged patients. METHODS: This prospective, multicentre, and observational study was carrid out across 40 selected ICUs in Spain. Consecutive patients with COVID-19 requiring ICU admission were recruited and evaluated three months after hospital discharge. RESULTS: A total of 1255 ICU patients were scheduled to be followed up at 3 months; however, the final cohort comprised 991 (78.9%) patients. A total of 315 patients developed ICUAP (97% of them had ventilated ICUAP). Patients requiring invasive mechanical ventilation had more persistent post-COVID-19 symptoms than those who did not require mechanical ventilation. Female sex, duration of ICU stay, development of ICUAP, and ARDS were independent factors for persistent poor health post-COVID-19. CONCLUSIONS: Persistent post-COVID-19 symptoms occurred in more than two-thirds of patients. Female sex, duration of ICU stay, development of ICUAP, and ARDS all comprised independent factors for persistent poor health post-COVID-19. Prevention of ICUAP could have beneficial effects in poor health post-COVID-19.

13.
Ann Intensive Care ; 11(1): 159, 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1538089

ABSTRACT

BACKGROUND: Some unanswered questions persist regarding the effectiveness of corticosteroids for severe coronavirus disease 2019 (COVID-19) patients. We aimed to assess the clinical effect of corticosteroids on intensive care unit (ICU) mortality among mechanically ventilated COVID-19-associated acute respiratory distress syndrome (ARDS) patients. METHODS: This was a retrospective study of prospectively collected data conducted in 70 ICUs (68 Spanish, one Andorran, one Irish), including mechanically ventilated COVID-19-associated ARDS patients admitted between February 6 and September 20, 2020. Individuals who received corticosteroids for refractory shock were excluded. Patients exposed to corticosteroids at admission were matched with patients without corticosteroids through propensity score matching. Primary outcome was all-cause ICU mortality. Secondary outcomes were to compare in-hospital mortality, ventilator-free days at 28 days, respiratory superinfection and length of stay between patients with corticosteroids and those without corticosteroids. We performed survival analysis accounting for competing risks and subgroup sensitivity analysis. RESULTS: We included 1835 mechanically ventilated COVID-19-associated ARDS, of whom 1117 (60.9%) received corticosteroids. After propensity score matching, ICU mortality did not differ between patients treated with corticosteroids and untreated patients (33.8% vs. 30.9%; p = 0.28). In survival analysis, corticosteroid treatment at ICU admission was associated with short-term survival benefit (HR 0.53; 95% CI 0.39-0.72), although beyond the 17th day of admission, this effect switched and there was an increased ICU mortality (long-term HR 1.68; 95% CI 1.16-2.45). The sensitivity analysis reinforced the results. Subgroups of age < 60 years, severe ARDS and corticosteroids plus tocilizumab could have greatest benefit from corticosteroids as short-term decreased ICU mortality without long-term negative effects were observed. Larger length of stay was observed with corticosteroids among non-survivors both in the ICU and in hospital. There were no significant differences for the remaining secondary outcomes. CONCLUSIONS: Our results suggest that corticosteroid treatment for mechanically ventilated COVID-19-associated ARDS had a biphasic time-dependent effect on ICU mortality. Specific subgroups showed clear effect on improving survival with corticosteroid use. Therefore, further research is required to identify treatment-responsive subgroups among the mechanically ventilated COVID-19-associated ARDS patients.

14.
Lancet Reg Health Eur ; 11: 100243, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1500123

ABSTRACT

BACKGROUND: It is unclear whether the changes in critical care throughout the pandemic have improved the outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the intensive care units (ICUs). METHODS: We conducted a retrospective cohort study in adults with COVID-19 pneumonia admitted to 73 ICUs from Spain, Andorra and Ireland between February 2020 and March 2021. The first wave corresponded with the period from February 2020 to June 2020, whereas the second/third waves occurred from July 2020 to March 2021. The primary outcome was ICU mortality between study periods. Mortality predictors and differences in mortality between COVID-19 waves were identified using logistic regression. FINDINGS: As of March 2021, the participating ICUs had included 3795 COVID-19 pneumonia patients, 2479 (65·3%) and 1316 (34·7%) belonging to the first and second/third waves, respectively. Illness severity scores predicting mortality were lower in the second/third waves compared with the first wave according with the Acute Physiology and Chronic Health Evaluation system (median APACHE II score 12 [IQR 9-16] vs 14 [IQR 10-19]) and the organ failure assessment score (median SOFA 4 [3-6] vs 5 [3-7], p<0·001). The need of invasive mechanical ventilation was high (76·1%) during the whole study period. However, a significant increase in the use of high flow nasal cannula (48·7% vs 18·2%, p<0·001) was found in the second/third waves compared with the first surge. Significant changes on treatments prescribed were also observed, highlighting the remarkable increase on the use of corticosteroids to up to 95.9% in the second/third waves. A significant reduction on the use of tocilizumab was found during the study (first wave 28·9% vs second/third waves 6·2%, p<0·001), and a negligible administration of lopinavir/ritonavir, hydroxychloroquine, and interferon during the second/third waves compared with the first wave. Overall ICU mortality was 30·7% (n = 1166), without significant differences between study periods (first wave 31·7% vs second/third waves 28·8%, p = 0·06). No significant differences were found in ICU mortality between waves according to age subsets except for the subgroup of 61-75 years of age, in whom a reduced unadjusted ICU mortality was observed in the second/third waves (first 38·7% vs second/third 34·0%, p = 0·048). Non-survivors were older, with higher severity of the disease, had more comorbidities, and developed more complications. After adjusting for confounding factors through a multivariable analysis, no significant association was found between the COVID-19 waves and mortality (OR 0·81, 95% CI 0·64-1·03; p = 0·09). Ventilator-associated pneumonia rate increased significantly during the second/third waves and it was independently associated with ICU mortality (OR 1·48, 95% CI 1·19-1·85, p<0·001). Nevertheless, a significant reduction both in the ICU and hospital length of stay in survivors was observed during the second/third waves. INTERPRETATION: Despite substantial changes on supportive care and management, we did not find significant improvement on case-fatality rates among critical COVID-19 pneumonia patients. FUNDING: Ricardo Barri Casanovas Foundation (RBCF2020) and SEMICYUC.

15.
Med Intensiva ; 2021 Oct 26.
Article in Spanish | MEDLINE | ID: covidwho-1482804

ABSTRACT

OBJECTIVE: To determine if the use of corticosteroids was associated with Intensive Care Unit (ICU) mortality among whole population and pre-specified clinical phenotypes. DESIGN: A secondary analysis derived from multicenter, observational studySetting: Critical Care UnitsPatients: Adult critically ill patients with confirmed COVID-19 disease admitted to 63 ICUs in Spain. INTERVENTIONS: corticosteroids vs no corticosteroidsMain variables of interest: Three phenotypes were derived by non-supervised clustering analysis from whole population and classified as (A: severe, B: critical and C: life-threatening). We performed a Multivariate analysis after propensity optimal full matching (PS) for whole population and weighted Cox regression (HR) and Fine-Gray analysis(sHR) to assess the impact of corticosteroids on ICU mortality according to the whole population and distinctive patient clinical phenotypes. RESULTS: A total of 2,017 patients were analyzed, 1171(58%) with corticosteroids. After PS, corticosteroids were shown not to be associated with ICU mortality (OR:1.0,95%CI:0.98-1.15). Corticosteroids were administered in 298/537(55.5%) patients of "A" phenotype and their use was not associated with ICU mortality (HR=0.85[0.55-1.33]). A total of 338/623(54.2%) patients in "B" phenotype received corticosteroids. No effect of corticosteroids on ICU mortality was observed when HR was performed (0.72[0.49-1.05]). Finally, 535/857(62.4%) patients in "C" phenotype received corticosteroids. In this phenotype HR (0.75[0.58-0.98]) and sHR (0.79[0.63-0.98]) suggest a protective effect of corticosteroids on ICU mortality. CONCLUSION: Our finding warns against the widespread use of corticosteroids in all critically ill patients with COVID-19 at moderate dose. Only patients with the highest inflammatory levels could benefit from steroid treatment.

16.
Am J Respir Crit Care Med ; 2021 May 26.
Article in English | MEDLINE | ID: covidwho-1416749

ABSTRACT

RATIONALE: Early empirical antimicrobial treatment is frequently prescribed to critically ill patients with COVID-19, based on Surviving Sepsis Campaign guidelines. OBJECTIVE: We aimed to determine the prevalence of early bacterial identification in intubated patients with SARS-CoV-2 pneumonia, as compared to influenza pneumonia, and to characterize its microbiology and impact on outcomes. METHODS: Multicenter retrospective European cohort performed in 36 ICUs. All adult patients receiving invasive mechanical ventilation >48h were eligible if they had SARS-CoV-2 or influenza pneumonia at ICU admission. Bacterial identification was defined by a positive bacterial culture, within 48h after intubation, in endotracheal aspirates, bronchoalveolar lavage, blood cultures, or a positive pneumococcal or legionella urinary antigen test. MEASUREMENTS AND MAIN RESULTS: 1,050 patients were included (568 in SARS-CoV-2 and 482 in influenza groups). The prevalence of bacterial identification was significantly lower in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia (9.7 vs 33.6%, unadjusted odds ratio (OR) 0.21 (95% confidence interval (CI) 0.15 to 0.30), adjusted OR 0.23 (95% CI 0.16 to 0.33), p<0.0001). Gram-positive cocci were responsible for 58% and 72% of co-infection in patients with SARS-CoV-2 and influenza pneumonia, respectively. Bacterial identification was associated with increased adjusted hazard ratio for 28-day mortality in patients with SARS-CoV-2 pneumonia (1.57 (95% CI 1.01 to 2.44), p=0.043). However, no significant difference was found in heterogeneity of outcomes related to bacterial identification between the two study groups, suggesting that the impact of co-infection on mortality was not different between SARS-CoV-2 and influenza patients. CONCLUSIONS: Bacterial identification within 48h after intubation is significantly less frequent in patients with SARS-CoV-2 pneumonia as compared to patients with influenza pneumonia. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

17.
Crit Care ; 25(1): 331, 2021 09 13.
Article in English | MEDLINE | ID: covidwho-1413915

ABSTRACT

BACKGROUND: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. METHODS: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. RESULTS: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). CONCLUSIONS: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation.


Subject(s)
COVID-19/therapy , Respiration, Artificial/methods , Respiratory Distress Syndrome/therapy , Ventilation-Perfusion Ratio/physiology , Aged , Aged, 80 and over , COVID-19/epidemiology , COVID-19/physiopathology , Cohort Studies , Critical Care/methods , Critical Care/trends , Female , Hospital Mortality/trends , Humans , Intensive Care Units/trends , Male , Middle Aged , Prognosis , Prospective Studies , Pulmonary Ventilation/physiology , Respiration, Artificial/trends , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/physiopathology , Retrospective Studies , Spain/epidemiology
18.
Crit Care ; 25(1): 63, 2021 02 15.
Article in English | MEDLINE | ID: covidwho-1085162

ABSTRACT

BACKGROUND: The identification of factors associated with Intensive Care Unit (ICU) mortality and derived clinical phenotypes in COVID-19 patients could help for a more tailored approach to clinical decision-making that improves prognostic outcomes. METHODS: Prospective, multicenter, observational study of critically ill patients with confirmed COVID-19 disease and acute respiratory failure admitted from 63 ICUs in Spain. The objective was to utilize an unsupervised clustering analysis to derive clinical COVID-19 phenotypes and to analyze patient's factors associated with mortality risk. Patient features including demographics and clinical data at ICU admission were analyzed. Generalized linear models were used to determine ICU morality risk factors. The prognostic models were validated and their performance was measured using accuracy test, sensitivity, specificity and ROC curves. RESULTS: The database included a total of 2022 patients (mean age 64 [IQR 5-71] years, 1423 (70.4%) male, median APACHE II score (13 [IQR 10-17]) and SOFA score (5 [IQR 3-7]) points. The ICU mortality rate was 32.6%. Of the 3 derived phenotypes, the A (mild) phenotype (537; 26.7%) included older age (< 65 years), fewer abnormal laboratory values and less development of complications, B (moderate) phenotype (623, 30.8%) had similar characteristics of A phenotype but were more likely to present shock. The C (severe) phenotype was the most common (857; 42.5%) and was characterized by the interplay of older age (> 65 years), high severity of illness and a higher likelihood of development shock. Crude ICU mortality was 20.3%, 25% and 45.4% for A, B and C phenotype respectively. The ICU mortality risk factors and model performance differed between whole population and phenotype classifications. CONCLUSION: The presented machine learning model identified three clinical phenotypes that significantly correlated with host-response patterns and ICU mortality. Different risk factors across the whole population and clinical phenotypes were observed which may limit the application of a "one-size-fits-all" model in practice.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Aged , Cluster Analysis , Critical Illness , Female , Humans , Male , Middle Aged , Phenotype , Risk Assessment , Risk Factors , Spain/epidemiology
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