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1.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-321955

ABSTRACT

Background: Evaluation of biomarkers in the context of ARDS is used to detect the presence of endothelial and/or alveolar epithelial injuries. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aim of this study was to evaluate whether the trends in plasma concentration of the biomarkers mentioned above were different in survivors and non-survivors of COVID-19-related ARDS. Furthermore, we compared the expression of biomarkers of vascular and endothelial injury in patients with COVID-19-related ARDS and classical ARDS. Methods: This prospective study was performed in two COVID-19 dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 10 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7±2 days (T2) and 14±2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. Results: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p=0.04 and p=0.03, respectively) whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS, than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19 related ARDS (all p<0.001). Conclusions: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration: NCT04343053 Date of registration: April 13, 2020

2.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310571

ABSTRACT

Background: Patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow could be more compromised in SARS-CoV-2 patients than in patients with “traditional” ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Materials: and Methods: Prospective, observational study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Results: : Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.71[0.67–0.78] vs 0.64[0.60–0.74], p=0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (p=0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r 2 =0.31;p=0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (p=0.46). Conclusions: : We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with “traditional” ARDS.

3.
ESC Heart Fail ; 9(1): 263-269, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1650198

ABSTRACT

Recent data support the existence of a distinctive 'vascular' phenotype with the involvement of both pulmonary parenchyma and its circulation in COVID-19 pneumonia. Its prompt identification is important for the accurate management of COVID-19 patients. The aim is to analyse the pro and contra of the different modalities to identify the 'vascular' phenotype. Chest computed tomography scan and angiogram may quantify both parenchyma and vascular damage, but the presence of thrombosis of pulmonary microcirculation may be missed. Increased d-dimer concentration confirms a thrombotic state, but it cannot localize the thrombus. An elevation of troponin concentration non-specifically reflects cardiac injury. Echocardiogram and electrocardiogram provide specific signs of right ventricular pressure overload. This is particularly relevant for the 'vascular' phenotype, which does not necessarily represent the result of thrombo-embolic venous complications, but more frequently, it is the result of pulmonary microcirculation thrombosis in situ and needs immediate therapeutic action. CONDENSED ABSTRACT: Despite diagnosis of the 'vascular' phenotype of COVID-19 pneumonia may be subtle, the evidence indicates a reasonable possibility of identifying it already in the initial stage of the infection. Chest computed tomography scan and angiogram, increased d-dimer concentration, and elevation of troponin concentration may be not sufficient to identify 'vascular' phenotype. Echocardiogram and electrocardiogram provide specific signs of right ventricular pressure overload. This is particularly relevant for the 'vascular' phenotype, which does not necessarily represent the result of thrombo-embolic venous complications, but more frequently, it is the result of pulmonary microcirculation thrombosis in situ and needs immediate therapeutic action.


Subject(s)
COVID-19 , Thrombosis , Humans , Lung , Phenotype , SARS-CoV-2
4.
Radiol Med ; 127(2): 162-173, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1626023

ABSTRACT

PURPOSE: COVID-19-related acute respiratory distress syndrome (ARDS) is characterized by the presence of signs of microvascular involvement at the CT scan, such as the vascular tree in bud (TIB) and the vascular enlargement pattern (VEP). Recent evidence suggests that TIB could be associated with an increased duration of invasive mechanical ventilation (IMV) and intensive care unit (ICU) stay. The primary objective of this study was to evaluate whether microvascular involvement signs could have a prognostic significance concerning liberation from IMV. MATERIAL AND METHODS: All the COVID-19 patients requiring IMV admitted to 16 Italian ICUs and having a lung CT scan recorded within 3 days from intubation were enrolled in this secondary analysis. Radiologic, clinical and biochemical data were collected. RESULTS: A total of 139 patients affected by COVID-19 related ARDS were enrolled. After grouping based on TIB or VEP detection, we found no differences in terms of duration of IMV and mortality. Extension of VEP and TIB was significantly correlated with ground-glass opacities (GGOs) and crazy paving pattern extension. A parenchymal extent over 50% of GGO and crazy paving pattern was more frequently observed among non-survivors, while a VEP and TIB extent involving 3 or more lobes was significantly more frequent in non-responders to prone positioning. CONCLUSIONS: The presence of early CT scan signs of microvascular involvement in COVID-19 patients does not appear to be associated with differences in duration of IMV and mortality. However, patients with a high extension of VEP and TIB may have a reduced oxygenation response to prone positioning. TRIAL REGISTRATION: NCT04411459.


Subject(s)
COVID-19/diagnostic imaging , COVID-19/therapy , Microvessels/diagnostic imaging , Respiration, Artificial/methods , Tomography, X-Ray Computed/methods , Aged , Female , Humans , Intensive Care Units , Italy , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Male , Middle Aged , Prospective Studies , SARS-CoV-2
5.
European heart journal supplements : journal of the European Society of Cardiology ; 23(Suppl G), 2021.
Article in English | EuropePMC | ID: covidwho-1601777

ABSTRACT

Recent data support the existence of a distinctive ‘vascular’ phenotype with the involvement of both pulmonary parenchyma and its circulation in COVID-19 pneumonia. Its prompt identification is important for the accurate management of COVID-19 patients. The aim is to analyse the pro and contra of the different modalities to identify the ‘vascular’ phenotype. Chest computed tomography scan and angiogram may quantify both parenchyma and vascular damage, but the presence of thrombosis of pulmonary micro-circulation may be missed. Increased d-dimer concentration confirms a thrombotic state, but it cannot localize the thrombus. An elevation of troponin concentration nonspecifically reflects cardiac injury. Echocardiogram and electrocardiogram provide specific signs of right ventricular pressure overload. This is particularly relevant for the ‘vascular’ phenotype which does not necessarily represent the result of thromboembolic venous complications but, more frequently, it is the result of pulmonary microcirculation thrombosis in situ and needs immediate therapeutic action.

6.
Respir Med ; 189: 106665, 2021.
Article in English | MEDLINE | ID: covidwho-1475040

ABSTRACT

BACKGROUND: Health-related quality of life (HRQoL) impairment is often reported among COVID-19 ICU survivors, and little is known about their long-term outcomes. We evaluated the HRQoL trajectories between 3 months and 1 year after ICU discharge, the factors influencing these trajectories and the presence of clusters of HRQoL profiles in a population of COVID-19 patients who underwent invasive mechanical ventilation (IMV). Moreover, pathophysiological correlations of residual dyspnea were tested. METHODS: We followed up 178 survivors from 16 Italian ICUs up to one year after ICU discharge. HRQoL was investigated through the 15D instrument. Available pulmonary function tests (PFTs) and chest CT scans at 1 year were also collected. A linear mixed-effects model was adopted to identify factors associated with different HRQoL trajectories and a two-step cluster analysis was performed to identify HRQoL clusters. RESULTS: We found that HRQoL increased during the study period, especially for the significant increase of the physical dimensions, while the mental dimensions and dyspnea remained substantially unchanged. Four main 15D profiles were identified: full recovery (47.2%), bad recovery (5.1%) and two partial recovery clusters with mostly physical (9.6%) or mental (38.2%) dimensions affected. Gender, duration of IMV and number of comorbidities significantly influenced HRQoL trajectories. Persistent dyspnea was reported in 58.4% of patients, and weakly, but significantly, correlated with both DLCO and length of IMV. CONCLUSIONS: HRQoL impairment is frequent 1 year after ICU discharge, and the lowest recovery is found in the mental dimensions. Persistent dyspnea is often reported and weakly correlated with PFTs alterations. TRIAL REGISTRATION: NCT04411459.


Subject(s)
COVID-19/epidemiology , Intensive Care Units , Quality of Life , Respiration, Artificial , Respiratory Function Tests , Aged , Dyspnea/epidemiology , Female , Follow-Up Studies , Humans , Italy/epidemiology , Male , Middle Aged , Patient Discharge , Prospective Studies , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/therapy , Survivors
7.
Life Sci Alliance ; 4(9)2021 09.
Article in English | MEDLINE | ID: covidwho-1298278

ABSTRACT

Here, we recorded serum proteome profiles of 33 severe COVID-19 patients admitted to respiratory and intensive care units because of respiratory failure. We received, for most patients, blood samples just after admission and at two more later time points. With the aim to predict treatment outcome, we focused on serum proteins different in abundance between the group of survivors and non-survivors. We observed that a small panel of about a dozen proteins were significantly different in abundance between these two groups. The four structurally and functionally related type-3 cystatins AHSG, FETUB, histidine-rich glycoprotein, and KNG1 were all more abundant in the survivors. The family of inter-α-trypsin inhibitors, ITIH1, ITIH2, ITIH3, and ITIH4, were all found to be differentially abundant in between survivors and non-survivors, whereby ITIH1 and ITIH2 were more abundant in the survivor group and ITIH3 and ITIH4 more abundant in the non-survivors. ITIH1/ITIH2 and ITIH3/ITIH4 also showed opposite trends in protein abundance during disease progression. We defined an optimal panel of nine proteins for mortality risk assessment. The prediction power of this mortality risk panel was evaluated against two recent COVID-19 serum proteomics studies on independent cohorts measured in other laboratories in different countries and observed to perform very well in predicting mortality also in these cohorts. This panel may not be unique for COVID-19 as some of the proteins in the panel have previously been annotated as mortality markers in aging and in other diseases caused by different pathogens, including bacteria.


Subject(s)
COVID-19/blood , COVID-19/mortality , Proteome/metabolism , Severity of Illness Index , Aged , COVID-19/virology , Cohort Studies , Female , Hospitalization , Humans , Immunoglobulins/blood , Male , SARS-CoV-2/physiology , Survivors
8.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1241490

ABSTRACT

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
9.
Qual Life Res ; 30(10): 2805-2817, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1225004

ABSTRACT

PURPOSE: The onset of the coronavirus disease 19 (COVID-19) pandemic in Italy induced a dramatic increase in the need for intensive care unit (ICU) beds for a large proportion of patients affected by COVID-19-related acute respiratory distress syndrome (ARDS). The aim of the present study was to describe the health-related quality of life (HRQoL) at 90 days after ICU discharge in a cohort of COVID-19 patients undergoing invasive mechanical ventilation and to compare it with an age and sex-matched sample from the general Italian and Finnish populations. Moreover, the possible associations between clinical, demographic, social factors, and HRQoL were investigated. METHODS: COVID-19 ARDS survivors from 16 participating ICUs were followed up until 90 days after ICU discharge and the HRQoL was evaluated with the 15D instrument. A parallel cohort of age and sex-matched Italian population from the same geographic areas was interviewed and a third group of matched Finnish population was extracted from the Finnish 2011 National Health survey. A linear regression analysis was performed to evaluate potential associations between the evaluated factors and HRQoL. RESULTS: 205 patients answered to the questionnaire. HRQoL of the COVID-19 ARDS patients was significantly lower than the matched populations in both physical and mental dimensions. Age, sex, number of comorbidities, ARDS class, duration of invasive mechanical ventilation, and occupational status were found to be significant determinants of the 90 days HRQoL. Clinical severity at ICU admission was poorly correlated to HRQoL. CONCLUSION: COVID-19-related ARDS survivors at 90 days after ICU discharge present a significant reduction both on physical and psychological dimensions of HRQoL measured with the 15D instrument. TRIAL REGISTRATION: NCT04411459.


Subject(s)
COVID-19 , Critical Illness , Patient Discharge , Quality of Life , Respiratory Distress Syndrome , Survivors , Aged , Female , Follow-Up Studies , Humans , Intensive Care Units , Male , Middle Aged , Quality of Life/psychology , SARS-CoV-2/pathogenicity , Severity of Illness Index
10.
Ann Intensive Care ; 11(1): 63, 2021 Apr 26.
Article in English | MEDLINE | ID: covidwho-1202278

ABSTRACT

BACKGROUND: Prone positioning (PP) has been used to improve oxygenation in patients affected by the SARS-CoV-2 disease (COVID-19). Several mechanisms, including lung recruitment and better lung ventilation/perfusion matching, make a relevant rational for using PP. However, not all patients maintain the oxygenation improvement after returning to supine position. Nevertheless, no evidence exists that a sustained oxygenation response after PP is associated to outcome in mechanically ventilated COVID-19 patients. We analyzed data from 191 patients affected by COVID-19-related acute respiratory distress syndrome undergoing PP for clinical reasons. Clinical history, severity scores and respiratory mechanics were analyzed. Patients were classified as responders (≥ median PaO2/FiO2 variation) or non-responders (< median PaO2/FiO2 variation) based on the PaO2/FiO2 percentage change between pre-proning and 1 to 3 h after re-supination in the first prone positioning session. Differences among the groups in physiological variables, complication rates and outcome were evaluated. A competing risk regression analysis was conducted to evaluate if PaO2/FiO2 response after the first pronation cycle was associated to liberation from mechanical ventilation. RESULTS: The median PaO2/FiO2 variation after the first PP cycle was 49 [19-100%] and no differences were found in demographics, comorbidities, ventilatory treatment and PaO2/FiO2 before PP between responders (96/191) and non-responders (95/191). Despite no differences in ICU length of stay, non-responders had a higher rate of tracheostomy (70.5% vs 47.9, P = 0.008) and mortality (53.7% vs 33.3%, P = 0.006), as compared to responders. Moreover, oxygenation response after the first PP was independently associated to liberation from mechanical ventilation at 28 days and was increasingly higher being higher the oxygenation response to PP. CONCLUSIONS: Sustained oxygenation improvement after first PP session is independently associated to improved survival and reduced duration of mechanical ventilation in critically ill COVID-19 patients.

11.
Int J Environ Res Public Health ; 18(8)2021 04 20.
Article in English | MEDLINE | ID: covidwho-1194651

ABSTRACT

Co-infections in critically ill patients hospitalized for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an important impact on the outcome of coronavirus disease 2019 (COVID-19). We compared the microbial isolations found in COVID-19 patients hospitalized in an intensive care unit (ICU) with those in a non-COVID-19 ICU from 22 February to 30 April 2020 and in the same period of 2019. We considered blood, urine or respiratory specimens obtained with bronchoalveolar lavage (BAL) or bronchial aspirate (BASP), collected from all patients admitted in ICUs with or without COVID-19 infection. We found a higher frequency of infections due to methicillin-resistant (MR) staphylococci, vancomycin-resistant Enterococcus faecium, carbapenem-resistant Acinetobacter baumannii and Candida parapsilosis in COVID-19-positive patients admitted in ICUs compared to those who were COVID-19 negative. Carbapenem-resistant Pseudomonas aeruginosa was more frequently isolated from patients admitted in non-COVID-19 ICUs. Several conditions favor the increased frequency of these infections by antibiotic-resistant microorganisms. Among all, the severity of the respiratory tracts was definitely decisive, which required assisted ventilation with invasive procedures. The turnover in the ICU of a large number of patients in a very short time requiring urgent invasive interventions has favored the not always suitable execution of assistance procedures. No less important is the increased exposure to infectious risk from bacteria and fungi in patients with severe impairment due to ventilation. The highest costs for antifungal drugs were shown in the ICU-COVID group.


Subject(s)
COVID-19 , Coinfection , Coinfection/epidemiology , Critical Illness , Humans , Intensive Care Units , SARS-CoV-2
12.
Front Immunol ; 12: 648004, 2021.
Article in English | MEDLINE | ID: covidwho-1175544

ABSTRACT

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile. Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay. Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-ß with IFN-ß levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels. Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053.


Subject(s)
COVID-19/blood , Inflammation Mediators/blood , Interferon-alpha/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Female , Hospitalization , Host-Pathogen Interactions , Humans , Male , Middle Aged , Prognosis , Prospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index
13.
Chest ; 159(4): 1426-1436, 2021 04.
Article in English | MEDLINE | ID: covidwho-921554

ABSTRACT

BACKGROUND: Sigh is a cyclic brief recruitment maneuver: previous physiologic studies showed that its use could be an interesting addition to pressure support ventilation to improve lung elastance, decrease regional heterogeneity, and increase release of surfactant. RESEARCH QUESTION: Is the clinical application of sigh during pressure support ventilation (PSV) feasible? STUDY DESIGN AND METHODS: We conducted a multicenter noninferiority randomized clinical trial on adult intubated patients with acute hypoxemic respiratory failure or ARDS undergoing PSV. Patients were randomized to the no-sigh group and treated by PSV alone, or to the sigh group, treated by PSV plus sigh (increase in airway pressure to 30 cm H2O for 3 s once per minute) until day 28 or death or successful spontaneous breathing trial. The primary end point of the study was feasibility, assessed as noninferiority (5% tolerance) in the proportion of patients failing assisted ventilation. Secondary outcomes included safety, physiologic parameters in the first week from randomization, 28-day mortality, and ventilator-free days. RESULTS: Two-hundred and fifty-eight patients (31% women; median age, 65 [54-75] years) were enrolled. In the sigh group, 23% of patients failed to remain on assisted ventilation vs 30% in the no-sigh group (absolute difference, -7%; 95% CI, -18% to 4%; P = .015 for noninferiority). Adverse events occurred in 12% vs 13% in the sigh vs no-sigh group (P = .852). Oxygenation was improved whereas tidal volume, respiratory rate, and corrected minute ventilation were lower over the first 7 days from randomization in the sigh vs no-sigh group. There was no significant difference in terms of mortality (16% vs 21%; P = .337) and ventilator-free days (22 [7-26] vs 22 [3-25] days; P = .300) for the sigh vs no-sigh group. INTERPRETATION: Among hypoxemic intubated ICU patients, application of sigh was feasible and without increased risk. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03201263; URL: www.clinicaltrials.gov.


Subject(s)
Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/therapy , Aged , Female , Humans , Intubation, Intratracheal , Male , Middle Aged , Pilot Projects , Respiratory Distress Syndrome/physiopathology , Respiratory Insufficiency/physiopathology , Respiratory Mechanics
14.
Front Immunol ; 12: 648004, 2021.
Article in English | MEDLINE | ID: covidwho-1154220

ABSTRACT

Background: Deficient interferon responses have been proposed as one of the relevant mechanisms prompting severe manifestations of COVID-19. Objective: To evaluate the interferon (IFN)-α levels in a cohort of COVID-19 patients in relation to severity, evolution of the clinical manifestations and immune/inflammatory profile. Methods: This is prospective study recruiting consecutive hospitalized patients with respiratory failure associated with SARS-COV-2 infection and matched controls. After enrollment, patients were assessed every 7 ± 2 days for additional 2 consecutive visits, for a total of 21 days. The severity of the clinical condition was ranked based on the level of respiratory support required. At each time-point blood samples were obtained to assess immune cells and mediators by multiplex immunoassay. Results: Fifty-four COVD-19 and 11 control patients matched for severity were enrolled. At recruitment, lower levels of blood IFN-α were found in COVID-19 patients compared to controls (3.8-fold difference, p < 0.01). Improvements in COVID-19 severity were paralleled by a significant increase of blood IFN-α levels. A significant increase in blood IFN-α was found over the study period in survivors (70% of the study population). A similar trend was found for blood IFN-ß with IFN-ß levels below the threshold of detectability in a substantial proportion of subjects. Significantly higher values of blood lymphocytes and lower levels of IL-10 were found at each time point in patients who survived compared to patients who died. In patients who clinically improved and survived during the study, we found an inverse association between IL-10 and IFN-α levels. Conclusion: The study identifies a blood immune profile defined by deficient IFN-α levels associated with increased IL-10 expression in patients progressing to severe/life threatening COVID-19 conditions, suggesting the involvement of immunological pathways that could be target of pharmacological intervention. Clinical Trial Registration: ClinicalTrials.gov identifier NCT04343053.


Subject(s)
COVID-19/blood , Inflammation Mediators/blood , Interferon-alpha/blood , Aged , Biomarkers/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/virology , Case-Control Studies , Female , Hospitalization , Host-Pathogen Interactions , Humans , Male , Middle Aged , Prognosis , Prospective Studies , SARS-CoV-2/immunology , SARS-CoV-2/pathogenicity , Severity of Illness Index
15.
JAMA ; 325(17): 1731-1743, 2021 05 04.
Article in English | MEDLINE | ID: covidwho-1148761

ABSTRACT

Importance: High-flow nasal oxygen is recommended as initial treatment for acute hypoxemic respiratory failure and is widely applied in patients with COVID-19. Objective: To assess whether helmet noninvasive ventilation can increase the days free of respiratory support in patients with COVID-19 compared with high-flow nasal oxygen alone. Design, Setting, and Participants: Multicenter randomized clinical trial in 4 intensive care units (ICUs) in Italy between October and December 2020, end of follow-up February 11, 2021, including 109 patients with COVID-19 and moderate to severe hypoxemic respiratory failure (ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤200). Interventions: Participants were randomly assigned to receive continuous treatment with helmet noninvasive ventilation (positive end-expiratory pressure, 10-12 cm H2O; pressure support, 10-12 cm H2O) for at least 48 hours eventually followed by high-flow nasal oxygen (n = 54) or high-flow oxygen alone (60 L/min) (n = 55). Main Outcomes and Measures: The primary outcome was the number of days free of respiratory support within 28 days after enrollment. Secondary outcomes included the proportion of patients who required endotracheal intubation within 28 days from study enrollment, the number of days free of invasive mechanical ventilation at day 28, the number of days free of invasive mechanical ventilation at day 60, in-ICU mortality, in-hospital mortality, 28-day mortality, 60-day mortality, ICU length of stay, and hospital length of stay. Results: Among 110 patients who were randomized, 109 (99%) completed the trial (median age, 65 years [interquartile range {IQR}, 55-70]; 21 women [19%]). The median days free of respiratory support within 28 days after randomization were 20 (IQR, 0-25) in the helmet group and 18 (IQR, 0-22) in the high-flow nasal oxygen group, a difference that was not statistically significant (mean difference, 2 days [95% CI, -2 to 6]; P = .26). Of 9 prespecified secondary outcomes reported, 7 showed no significant difference. The rate of endotracheal intubation was significantly lower in the helmet group than in the high-flow nasal oxygen group (30% vs 51%; difference, -21% [95% CI, -38% to -3%]; P = .03). The median number of days free of invasive mechanical ventilation within 28 days was significantly higher in the helmet group than in the high-flow nasal oxygen group (28 [IQR, 13-28] vs 25 [IQR 4-28]; mean difference, 3 days [95% CI, 0-7]; P = .04). The rate of in-hospital mortality was 24% in the helmet group and 25% in the high-flow nasal oxygen group (absolute difference, -1% [95% CI, -17% to 15%]; P > .99). Conclusions and Relevance: Among patients with COVID-19 and moderate to severe hypoxemia, treatment with helmet noninvasive ventilation, compared with high-flow nasal oxygen, resulted in no significant difference in the number of days free of respiratory support within 28 days. Further research is warranted to determine effects on other outcomes, including the need for endotracheal intubation. Trial Registration: ClinicalTrials.gov Identifier: NCT04502576.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Noninvasive Ventilation/instrumentation , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency/therapy , Aged , COVID-19/mortality , COVID-19/therapy , Female , Hospital Mortality , Humans , Hypoxia/etiology , Male , Middle Aged , Noninvasive Ventilation/methods , Respiratory Insufficiency/etiology , Treatment Failure
17.
Crit Care ; 25(1): 74, 2021 02 19.
Article in English | MEDLINE | ID: covidwho-1090628

ABSTRACT

BACKGROUND: Biomarkers can be used to detect the presence of endothelial and/or alveolar epithelial injuries in case of ARDS. Angiopoietin-2 (Ang-2), soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), P-selectin and E-selectin are biomarkers of endothelial injury, whereas the receptor for advanced glycation end-products (RAGE) reflects alveolar epithelial injury. The aims of this study were to evaluate whether the plasma concentration of the above-mentioned biomarkers was different 1) in survivors and non-survivors of COVID-19-related ARDS and 2) in COVID-19-related and classical ARDS. METHODS: This prospective study was performed in two COVID-19-dedicated Intensive Care Units (ICU) and one non-COVID-19 ICU at Ferrara University Hospital. A cohort of 31 mechanically ventilated patients with COVID-19 ARDS and a cohort of 11 patients with classical ARDS were enrolled. Ang-2, ICAM-1, VCAM-1, P-selectin, E-selectin and RAGE were determined with a bead-based multiplex immunoassay at three time points: inclusion in the study (T1), after 7 ± 2 days (T2) and 14 ± 2 days (T3). The primary outcome was to evaluate the plasma trend of the biomarker levels in survivors and non-survivors. The secondary outcome was to evaluate the differences in respiratory mechanics variables and gas exchanges between survivors and non-survivors. Furthermore, we compared the plasma levels of the biomarkers at T1 in patients with COVID-19-related ARDS and classical ARDS. RESULTS: In COVID-19-related ARDS, the plasma levels of Ang-2 and ICAM-1 at T1 were statistically higher in non-survivors than survivors, (p = 0.04 and p = 0.03, respectively), whereas those of P-selectin, E-selectin and RAGE did not differ. Ang-2 and ICAM-1 at T1 were predictors of mortality (AUROC 0.650 and 0.717, respectively). At T1, RAGE and P-selectin levels were higher in classical ARDS than in COVID-19-related ARDS. Ang-2, ICAM-1 and E-selectin were lower in classical ARDS than in COVID-19-related ARDS (all p < 0.001). CONCLUSIONS: COVID-19 ARDS is characterized by an early pulmonary endothelial injury, as detected by Ang-2 and ICAM-1. COVID-19 ARDS and classical ARDS exhibited a different expression of biomarkers, suggesting different pathological pathways. Trial registration NCT04343053 , Date of registration: April 13, 2020.


Subject(s)
Biomarkers/analysis , Lung Injury/diagnosis , Respiration, Artificial/adverse effects , Aged , Antigens, Neoplasm/analysis , Antigens, Neoplasm/blood , Area Under Curve , COVID-19/blood , COVID-19/prevention & control , Cohort Studies , E-Selectin/analysis , E-Selectin/blood , Female , Humans , Intensive Care Units/organization & administration , Intensive Care Units/statistics & numerical data , Intercellular Adhesion Molecule-1/analysis , Intercellular Adhesion Molecule-1/blood , Lung Injury/blood , Lung Injury/physiopathology , Male , Middle Aged , Mitogen-Activated Protein Kinases/analysis , Mitogen-Activated Protein Kinases/blood , P-Selectin/analysis , P-Selectin/blood , Prospective Studies , ROC Curve , Respiration, Artificial/standards , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/physiopathology , Versicans/analysis , Versicans/blood , Vesicular Transport Proteins/analysis , Vesicular Transport Proteins/blood
18.
Europace ; 22(12): 1848-1854, 2020 12 23.
Article in English | MEDLINE | ID: covidwho-1059441

ABSTRACT

AIMS: Our aim was to describe the electrocardiographic features of critical COVID-19 patients. METHODS AND RESULTS: We carried out a multicentric, cross-sectional, retrospective analysis of 431 consecutive COVID-19 patients hospitalized between 10 March and 14 April 2020 who died or were treated with invasive mechanical ventilation. This project is registered on ClinicalTrials.gov (identifier: NCT04367129). Standard ECG was recorded at hospital admission. ECG was abnormal in 93% of the patients. Atrial fibrillation/flutter was detected in 22% of the patients. ECG signs suggesting acute right ventricular pressure overload (RVPO) were detected in 30% of the patients. In particular, 43 (10%) patients had the S1Q3T3 pattern, 38 (9%) had incomplete right bundle branch block (RBBB), and 49 (11%) had complete RBBB. ECG signs of acute RVPO were not statistically different between patients with (n = 104) or without (n=327) invasive mechanical ventilation during ECG recording (36% vs. 28%, P = 0.10). Non-specific repolarization abnormalities and low QRS voltage in peripheral leads were present in 176 (41%) and 23 (5%), respectively. In four patients showing ST-segment elevation, acute myocardial infarction was confirmed with coronary angiography. No ST-T abnormalities suggestive of acute myocarditis were detected. In the subgroup of 110 patients where high-sensitivity troponin I was available, ECG features were not statistically different when stratified for above or below the 5 times upper reference limit value. CONCLUSIONS: The ECG is abnormal in almost all critically ill COVID-19 patients and shows a large spectrum of abnormalities, with signs of acute RVPO in 30% of the patients. Rapid and simple identification of these cases with ECG at hospital admission can facilitate classification of the patients and provide pathophysiological insights.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/virology , COVID-19/complications , Critical Illness , Electrocardiography , Aged , Aged, 80 and over , Biomarkers/blood , COVID-19/epidemiology , Cross-Sectional Studies , Female , Hospitalization/statistics & numerical data , Humans , Italy/epidemiology , Male , Middle Aged , Pandemics , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
20.
J Clin Monit Comput ; 36(1): 161-167, 2022 02.
Article in English | MEDLINE | ID: covidwho-1002124

ABSTRACT

Mechanically ventilated patients with ARDS due to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seem particularly susceptible to AKI. Our hypothesis was that the renal blood flow could be more compromised in SARS-CoV-2 patients than in patients with "classical" ARDS. We compared the renal resistivity index (RRI) and the renal venous flow (RVF) in ARDS patients with SARS-CoV-2 and in ARDS patients due to other etiologies. Prospective, observational pilot study performed on 30 mechanically ventilated patients (15 with SARS-COV-2 ARDS and 15 with ARDS). Mechanical ventilation settings included constant-flow controlled ventilation, a tidal volume of 6 ml/kg of ideal body weight and the PEEP level titrated to the lowest driving pressure. Ultrasound Doppler measurements of RRI and RVF pattern were performed in each patient. Patients with SARS-COV-2 ARDS had higher RRI than patients with ARDS (0.71[0.67-0.78] vs 0.64[0.60-0.74], p = 0.04). RVF was not-continuous in 9/15 patients (71%) in the SARS-COV-2 ARDS group and in and 5/15 (33%) in the ARDS group (p = 0.27). A linear correlation was found between PEEP and RRI in patients with SARS-COV-2 ARDS (r2 = 0.31; p = 0.03) but not in patients with ARDS. Occurrence of AKI was 53% in patients with SARS-COV-2 ARDS and 33% in patients with ARDS (p = 0.46). We found a more pronounced impairment in renal blood flow in mechanically ventilated patients with SARS-COV-2 ARDS, compared with patients with "classical" ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , Pilot Projects , Prospective Studies , Renal Circulation , Respiration, Artificial , Respiratory Distress Syndrome/therapy , SARS-CoV-2
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