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1.
Front Immunol ; 13: 989556, 2022.
Article in English | MEDLINE | ID: covidwho-2109766

ABSTRACT

COVID-19 manifests a spectrum of respiratory symptoms, with the more severe often requiring hospitalization. To identify markers for disease progression, we analyzed longitudinal gene expression data from patients with confirmed SARS-CoV-2 infection admitted to the intensive care unit (ICU) for acute hypoxic respiratory failure (AHRF) as well as other ICU patients with or without AHRF and correlated results of gene set enrichment analysis with clinical features. The results were then compared with a second dataset of COVID-19 patients separated by disease stage and severity. Transcriptomic analysis revealed that enrichment of plasma cells (PCs) was characteristic of all COVID-19 patients whereas enrichment of interferon (IFN) and neutrophil gene signatures was specific to patients requiring hospitalization. Furthermore, gene expression results were used to divide AHRF COVID-19 patients into 2 groups with differences in immune profiles and clinical features indicative of severe disease. Thus, transcriptomic analysis reveals gene signatures unique to COVID-19 patients and provides opportunities for identification of the most at-risk individuals.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/genetics , Humans , Intensive Care Units , Interferons , SARS-CoV-2 , Severity of Illness Index
2.
Eur J Med Res ; 27(1): 218, 2022 Oct 28.
Article in English | MEDLINE | ID: covidwho-2108966

ABSTRACT

PURPOSE: This study aimed to investigate air leakage during invasive mechanical ventilation (IMV) in a pediatric intensive care unit (PICU) and explore potential risk factors. METHODS: We conducted a retrospective cohort study of children who underwent IMV in a single-center PICU in a tertiary referral hospital. Air leakage risk factors and factors associated with an improved outcome were assessed. RESULTS: A total of 548 children who underwent IMV were enrolled in this study. Air leakage occurred in 7.5% (41/548) of the cases in the PICU. Air leakage increased the duration of IMV and hospitalization time. Multivariate logistic regression analysis showed a higher risk of air leakage during IMV for PICU patients with acute respiratory dyspnea syndrome (ARDS) (OR = 4.38), a higher pediatric critical illness score (PCIS) (OR = 1.08), or a higher peak inspiratory pressure (PIP) (OR = 1.08), whereas the risk was lower for patients with central respiratory failure (OR = 0.14). The logistic model had excellent predictive power for air leakage, with an area under the curve of 0.883 and tenfold cross-validation. Patients aged between 1 and 6 years who were diagnosed with measles or pneumonia and had a low positive end-expiratory pressure (PEEP) or high PaO2/FiO2 ratio were associated with improved outcomes. Patients diagnosed with central respiratory failure or congenital heart diseases were associated with less desirable outcomes. CONCLUSIONS: Patients with ARDS, a higher PCIS at admission or a higher PIP were at higher risk of air leakage.


Subject(s)
Respiratory Distress Syndrome , Respiratory Insufficiency , Child , Humans , Infant , Child, Preschool , Respiration, Artificial/adverse effects , Retrospective Studies , Intensive Care Units, Pediatric , Risk Factors , Respiratory Distress Syndrome/epidemiology , Respiratory Distress Syndrome/therapy , Intensive Care Units
3.
Crit Care ; 26(1): 338, 2022 11 04.
Article in English | MEDLINE | ID: covidwho-2108872

ABSTRACT

We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.


Subject(s)
COVID-19 , Pneumonia, Ventilator-Associated , Respiratory Distress Syndrome , Humans , Intensive Care Units , Pepsin A , Pronation , Equipment Design , Pneumonia, Ventilator-Associated/etiology , Intubation, Intratracheal/adverse effects , alpha-Amylases
4.
J Cardiothorac Surg ; 17(1): 282, 2022 Nov 06.
Article in English | MEDLINE | ID: covidwho-2108857

ABSTRACT

BACKGROUND: Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is an effective, but highly resource intensive salvage treatment option in COVID patients with acute respiratory distress syndrome (ARDS). Right ventricular (RV) dysfunction is a known sequelae of COVID-19 induced ARDS, yet there is a paucity of data on the incidence and determinants of RV dysfunction on VV ECMO. We retrospectively examined the determining factors leading to RV failure and means of early identification of this phenomenon in patients on VV ECMO. METHODS: The data was extracted from March 2020 to March 2021 from the regional University of Washington Extracorporeal Life Support database. The inclusion criteria included patients > 18 years of age with diagnosis of COVID-19. All had already been intubated and mechanically ventilated prior to VV ECMO deployment. Univariate analysis was performed to identify risk factors and surrogate markers for RV dysfunction. In addition, we compared outcomes between those with and without RV dysfunction. RESULTS: Of the 33 patients that met inclusion criteria, 14 (42%) had echocardiographic evidence of RV dysfunction, 3 of whom were placed on right ventricular assist device support. Chronic lung disease was an independent risk factor for RV dysfunction (p = 0.0002). RV dysfunction was associated with a six-fold increase in troponin I (0.07 ng/ml vs. 0.44 ng/ml, p = 0.039) and four-fold increase in brain natriuretic peptide (BNP) (158 pg/ml vs. 662 pg/ml, p = 0.037). Deep vein thrombosis (DVT, 21% vs. 43%, p = 0.005) and pulmonary embolism (PE, 11% vs. 21%, p = 0.045) were found to be nearly twice as common in the RV dysfunction group. Total survival rate to hospital discharge was 39%. Data trended towards shorter duration of hospital stay (47 vs. 65.6 days, p = 0.15), shorter duration of ECMO support (21 days vs. 36 days, p = 0.06) and improved survival rate to hospital discharge (42.1% vs. 35.7%, p = 0.47) for those with intact RV function compared to the RV dysfunction group. CONCLUSIONS: RV dysfunction in critically ill patients with COVID-19 pneumonia in common. Trends of troponin I and BNP may be important surrogates for monitoring RV function in patients on VV ECMO. We recommend echocardiographic assessment of the RV on such patients.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Ventricular Dysfunction, Right , Humans , Extracorporeal Membrane Oxygenation/adverse effects , Ventricular Dysfunction, Right/etiology , Ventricular Dysfunction, Right/therapy , COVID-19/complications , COVID-19/therapy , Retrospective Studies , Troponin I
5.
Respir Res ; 23(1): 301, 2022 Nov 04.
Article in English | MEDLINE | ID: covidwho-2108780

ABSTRACT

PURPOSE: Acute respiratory distress syndrome (ARDS) is an acute and critical disease among children and adults, and previous studies have shown that the administration of corticosteroids remains controversial. Therefore, a meta-analysis of randomized controlled trials (RCTs) was performed to evaluate the safety and efficacy of corticosteroids. METHODS: The RCTs investigating the safety and efficacy of corticosteroids in ARDS were searched from electronic databases (Embase, Medline, and the Cochrane Central Register of Controlled Trials). The primary outcome was 28-day mortality. Heterogeneity was assessed using the Chi square test and I2 with the inspection level of 0.1 and 50%, respectively. RESULTS: Fourteen RCTs (n = 1607) were included for analysis. Corticosteroids were found to reduce the risk of death in patients with ARDS (relative risk (RR) = 0.78, 95% confidence interval (CI): 0.70-0.87; P < 0.01). Moreover, no significant adverse events were observed, compared to placebo or standard support therapy. Further subgroup analysis showed that variables, such as adults (RR = 0.78; 95% CI: 0.70-0.88; P < 0.01), non-COVID-19 (RR = 0.71; 95% CI: 0.62-0.83; P < 0.01), methylprednisolone (RR = 0.70; 95% CI: 0.56-0.88; P < 0.01), and hydrocortisone (RR = 0.79; 95% CI: 0.63-0.98; P = 0.03) were associated with 28-day mortality among patients who used corticosteroids. However, no association was found, regarding children (RR = 0.21; 95% CI: 0.01-4.10; P = 0.30). CONCLUSION: The use of corticosteroids is an effective approach to reduce the risk of death in ARDS patients. However, this effect is associated with age, non-COVID-19 diseases, and methylprednisolone and hydrocortisone use. Therefore, evidence suggests patients with age ≥ 18 years and non-COVID-19 should be encouraged during the corticosteroid treatment. However, due to substantial differences in the use of corticosteroids among these studies, questions still remain regarding the dosage, optimal corticosteroid agent, and treatment duration in patients with ARDS.


Subject(s)
Hydrocortisone , Respiratory Distress Syndrome , Child , Adult , Humans , Adolescent , Hydrocortisone/therapeutic use , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/drug therapy , Adrenal Cortex Hormones/adverse effects , Methylprednisolone/adverse effects , Randomized Controlled Trials as Topic
6.
Int J Environ Res Public Health ; 19(21)2022 Nov 07.
Article in English | MEDLINE | ID: covidwho-2099561

ABSTRACT

INTRODUCTION: COVID-19 is a public health emergency all around the world. Severe illness occurred in about 14% of patients and 5% of patients developed critical illness, but the prognosis for these patients remains unclear. OBJECTIVE: To describe the prognosis in hospitalized adults with COVID-19. METHODS: The MEDLINE, EMBASE, AMED, and COCHRANE databases were searched for studies published up to 28 June 2021 without language restrictions. Descriptors were related to "COVID-19" and "prognosis". Prospective inception cohort studies that assessed morbidity, mortality and recovery in hospitalized people over 18 years old with COVID-19 were included. Two independent reviewers selected eligible studies and extracted the available data. Acute respiratory distress syndrome (ARDS) and multiple organ failure (MOFS) were considered as outcomes for morbidity and discharge was considered for recovery. The Quality in Prognosis Studies (QUIPS) tool was used to assess risk of bias. Analyses were performed using Comprehensive Meta-Analysis (version 2.2.064). RESULTS: We included 30 inception cohort studies investigating 13,717 people hospitalized with COVID-19 from different countries. The mean (SD) age was 60.90 (21.87) years, and there was high proportion of males (76.19%) and people with comorbidities (e.g., 49.44% with hypertension and 29.75% with diabetes). Findings suggested a high occurrence of morbidity, mainly related to ARDS. Morbidity rates varied across studies from 19% to 36% in hospital wards, and from 13% to 90% in Intensive Care Units-ICU. Mortality rates ranged from 4% to 38% in hospital wards and from 8% to 51% in ICU. Recovery rates ranged up to 94% and 65% in hospital wards and ICU, respectively. The included studies had high risk of bias in the confounding domain. CONCLUSIONS: The prognosis of people hospitalized with COVID-19 is an issue for the public health system worldwide, with high morbidity and mortality rates, mainly in ICU and for patients with comorbidities. Its prognosis emphasizes the need for appropriate prevention and management strategies.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Male , Adult , Humans , Middle Aged , Adolescent , COVID-19/epidemiology , SARS-CoV-2 , Prospective Studies , Intensive Care Units
7.
Expert Rev Clin Immunol ; 17(9): 991-1001, 2021 09.
Article in English | MEDLINE | ID: covidwho-1820723

ABSTRACT

Introduction: Respiratory viruses can directly or indirectly damage the pulmonary defense barrier, potentially contributing to acute respiratory distress syndrome (ARDS). Despite developments in the understanding of the pathogenesis of ARDS, the underlying pathophysiology still needs to be elucidated.Areas covered: The PubMed database was reviewed for relevant papers published up to 2021. This review summarizes the currently immunological and clinical studies to provide a systemic overview of the epithelial-endothelial barrier, given the recently published immunological profiles upon viral pneumonia, and the potentially detrimental contribution to respiratory function caused by damage to this barrier.Expert opinion: The biophysical structure of host pulmonary defense is intrinsically linked with the ability of alveolar epithelial and capillary endothelial cells, known as the epithelial-endothelial barrier, to respond to, and instruct the delicate immune system to protect the lungs from infections and injuries. Recently published immunological profiles upon viral infection, and its contributions to the damage of respiratory function, suggest a central role for the pulmonary epithelial and endothelial barrier in the pathogenesis of ARDS. We suggest a central role and common pathways by which the epithelial-endothelial barrier contributes to the pathogenesis of ARDS.


Subject(s)
Respiratory Distress Syndrome , Viruses , Endothelial Cells/pathology , Humans , Immune System , Lung
8.
J Int Med Res ; 50(11): 3000605221135446, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-2098199

ABSTRACT

OBJECTIVE: To determine the incidence and significance of ventilator avoidance in patients with critical coronavirus disease 2019 (COVID-19). METHODS: This prospective observational cohort study evaluated hospital mortality and 1-year functional outcome among critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-associated acute respiratory distress syndrome (ARDS). The explanatory variable was ventilator avoidance, modeled as 'initial refusal' of intubation (yes/no). Modified Rankin Scale (mRS) scores were obtained from surviving patients (or their surrogates) via phone or email questionnaire. RESULTS: Among patients for whom intubation was recommended (n = 102), 40 (39%) initially refused (95% confidence interval [CI] 30%, 49%). The risk of death was 79.3% (49/62) in those who did not initially refuse intubation compared with 77.5% (31/40) in those who initially refused, with an adjusted odds ratio for death of 1.27 (95% CI 0.47, 3.48). The distribution of 1-year mRS scores was not significantly different between groups. CONCLUSION: Among critically ill patients with COVID-19-associated ARDS, ventilator avoidance was common, but was not associated with increased in-hospital mortality or 1-year functional outcome.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , SARS-CoV-2 , Critical Illness , Prospective Studies , Respiratory Distress Syndrome/therapy , Ventilators, Mechanical
10.
Sci Rep ; 12(1): 18418, 2022 Nov 01.
Article in English | MEDLINE | ID: covidwho-2096793

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS) is common in COVID-19 patients and is associated with high mortality. The aim of this observational study was to describe patients' characteristics and outcome, identifying potential risk factors for in-hospital mortality and for developing Long-COVID symptoms. This retrospective study included all patients with COVID-19 associated ARDS (cARDS) in the period from March 2020 to March 2021 who were invasively ventilated at the intensive care unit (ICU) of the University Hospital Dresden, Germany. Between October 2021 and December 2021 patients discharged alive (at minimum 6 months after hospital discharge-midterm survival) were contacted and interviewed about persistent symptoms possibly associated with COVID-19 as well as the quality of their lives using the EQ-5D-5L-questionnaire. Long-COVID was defined as the occurrence of one of the symptoms at least 6 months after discharge. Risk factors for mortality were assessed with Cox regression models and risk factors for developing Long-COVID symptoms by using relative risk (RR) regression. 184 Patients were included in this study (male: n = 134 (73%), median age 67 (range 25-92). All patients were diagnosed with ARDS according to the Berlin Definition. 89% of patients (n = 164) had severe ARDS (Horovitz-index < 100 mmHg). In 27% (n = 49) extracorporeal membrane oxygenation was necessary to maintain gas exchange. The median length of in-hospital stay was 19 days (range 1-60). ICU mortality was 51%, hospital mortality 59%. Midterm survival (median 11 months) was 83% (n = 55) and 78% (n = 43) of these patients presented Long-COVID symptoms with fatigue as the most common symptom (70%). Extreme obesity (BMI > 40 kg/m2) was the strongest predictor for in-hospital mortality (hazard ratio: 3.147, confidence interval 1.000-9.897) and for developing Long-COVID symptoms (RR 1.61, confidence interval 1.26-2.06). In-hospital mortality in severe cARDS patients was high, but > 80% of patients discharged alive survived the midterm observation period. Nonetheless, most patients developed Long-COVID symptoms. Extreme obesity with BMI > 40 kg/m2 was identified as independent risk factor for in-hospital mortality and for developing Long-COVID symptoms.Trial registration DRKS-ID DRKS00027856.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Aged , Humans , Male , Hospital Mortality , Intensive Care Units , Obesity , Prevalence , Respiration, Artificial , Retrospective Studies , Female , Adult , Middle Aged , Aged, 80 and over
11.
J Allergy Clin Immunol ; 147(1): 81-91, 2021 01.
Article in English | MEDLINE | ID: covidwho-2095538

ABSTRACT

BACKGROUND: Severe immunopathology may drive the deleterious manifestations that are observed in the advanced stages of coronavirus disease 2019 (COVID-19) but are poorly understood. OBJECTIVE: Our aim was to phenotype leukocyte subpopulations and the cytokine milieu in the lungs and blood of critically ill patients with COVID-19 acute respiratory distress syndrome (ARDS). METHODS: We consecutively included patients less than 72 hours after intubation following informed consent from their next of kin. Bronchoalveolar lavage fluid was evaluated by microscopy; bronchoalveolar lavage fluid and blood were assessed by 10-color flow cytometry and a multiplex cytokine panel. RESULTS: Four mechanically ventilated patients (aged 40-75 years) with moderate-to-severe COVID-19 ARDS were included. Immature neutrophils dominated in both blood and lungs, whereas CD4 and CD8 T-cell lymphopenia was observed in the 2 compartments. However, regulatory T cells and TH17 cells were found in higher fractions in the lung. Lung CD4 and CD8 T cells and macrophages expressed an even higher upregulation of activation markers than in blood. A wide range of cytokines were expressed at high levels both in the blood and in the lungs, most notably, IL-1RA, IL-6, IL-8, IP-10, and monocyte chemoattactant protein-1, consistent with hyperinflammation. CONCLUSION: COVID-19 ARDS exhibits a distinct immunologic profile in the lungs, with a depleted and exhausted CD4 and CD8 T-cell population that resides within a heavily hyperinflammatory milieu.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Lung/immunology , Lymphopenia/immunology , Respiratory Distress Syndrome/immunology , SARS-CoV-2/immunology , Th17 Cells/immunology , Adult , Aged , CD8-Positive T-Lymphocytes/pathology , COVID-19/pathology , Cross-Sectional Studies , Cytokines/immunology , Female , Humans , Immunophenotyping , Lung/pathology , Lymphopenia/pathology , Male , Middle Aged , Respiratory Distress Syndrome/pathology , Th17 Cells/pathology
12.
Med Trop Sante Int ; 2(3)2022 09 30.
Article in French | MEDLINE | ID: covidwho-2091752

ABSTRACT

Introduction: Since December 2019, a novel coronavirus (SARS-CoV-2) has triggered a global pandemic with a heavy medical and societal-economic toll. The health consequences were not similar during the successive waves that affected several countries. The aim of our study was to compare the sociodemographic, clinical and evolutionary features of COVID-19 patients hospitalized at the Military Hospital of Tunis (HMPIT) during the 2nd and 3rd waves that affected the country. Patients and methods: Observational prospective study involving 1,527 COVID-19 patients hospitalized at HMPIT over 11 months, divided into two periods: from July 2020 to December 2020 called the second wave (V2) and from January 2021 to May 2021 called the third wave (V3). We compared the epidemiological data, the clinical form and the evolution of the patients for each period. Results: The number of hospitalized patients was 636 during V2 compared to 891 during V3. Average age was 63.5 ± 15.3 years during V2 versus 65.8 ± 17.8 years during V3 (P = not significant [NS]). The percentage of young adults [18-40 years] was 6.5% during V2 compared to 6.7% during V3 (P = NS). The gender ratio (M/F) was 1.59 for V2 and 1.42 for V3 (P = NS). Comorbidities were present in 65% of V2 patients and 66.3% of V3 patients (P = NS), with hypertension being the most prevalent one in both groups (47.2% for V2 versus 44.9% for V3; P = NS), followed by overweight, dyslipidemia and diabetes (33% for V2 versus 39.3% for V3; P = 0.012). The median duration between symptoms onset and hospitalization was 7 days [5-10] during V2 versus 8.5 days during V3 [5-12] (P = 0.0004). The severe clinical form was present in 49% of patients admitted during V2 compared to 34.8% during V3 (P < 10-3). The critical form represented 18.6% of cases during V2 against 16.8% during V3 (P = NS). The average hospital length of stay in COVID units (outside of intensive care unit) was 8.4 ± 5.4 days during V2 and 9.8 ± 5.7 days during V3. The average length of stay was significantly longer for the intensive care unit (11.3 ± 3.4 days for V2 versus 13.8 ± 3.9 days for V3; P = 0.01). The case fatality rate was 24.5% during V2 and 20.7% during V3 (P = NS). Median age of death was 70.2 years [42-88] during V2 and 70.4 years [22-96] during V3 with 2 patients less than 40 years of age (1%) for the latter period. The gender ratio (M/F) of deceased patients was 3.21 for V2 and 1.5 for V3 (P = 0.001). The case fatality rate was higher in the intensive care unit (65.4% for V2 versus 69.7% for V3; P = NS). Causes of death were dominated by ARDS (acute respiratory distress syndrome) for both periods (55.1% for V2 versus 70.8% for V3; P = 0.002), followed by septic shock (12.8% for V2 versus 10.8% for V3; P = NS) and multi-organ failure (9.6% for V2 versus 7.0% for V3; P = NS). Conclusion: This study revealed a decrease in severe and critical clinical forms during the 3rd wave, as well as a decrease in the case fatality rate compared to the previous wave, due to improved management and vaccination. On the other hand, the percentage of ARDS was significantly higher during this wave probably related to the beginning of circulation in our country of the Delta variant causing more severe clinical cases.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Young Adult , Humans , Middle Aged , Aged , COVID-19/epidemiology , SARS-CoV-2 , Tunisia/epidemiology , Prospective Studies , Hospitalization
13.
Am J Case Rep ; 23: e937147, 2022 Oct 25.
Article in English | MEDLINE | ID: covidwho-2090898

ABSTRACT

BACKGROUND Inhaled nitric oxide (iNO) is used as a treatment for pulmonary arterial hypertension (PAH). Severe hypoxia with hypoxic vasoconstriction caused by severe acute respiratory distress syndrome (ARDS) can induce pulmonary hypertension with hemodynamic implications, mainly secondary to right ventricle (RV) systolic function impairment. We report the case of the use of iNO in a critically ill patient with bilateral SARS-CoV-2 pneumonia and severe ARDS and hypoxemia leading to acute severe PAH, causing a ventilation/perfusion mismatch, RV pressure overload, and RV systolic dysfunction. CASE REPORT A 36-year-old woman was admitted to the Intensive Care Unit with a severe ARDS associated with SARS-CoV-2 pneumonia requiring invasive mechanical ventilation. Severe hypoxia and hypoxic vasoconstriction developed, leading to an acute increase in pulmonary vascular resistance, severe to moderate tricuspid regurgitation, RV pressure overload, RV systolic function impairment, and RV dilatation. Following 24 h of treatment with iNO at 15 ppm, significant oxygenation and hemodynamic improvement were noted, allowing vasopressors to be stopped. After 24 h of iNO treatment, echocardiography showed very mild tricuspid regurgitation, a non-dilated RV, no impairment of transverse free wall contractility, and no paradoxical septal motion. iNO was maintained for 7 days. The dose of iNO was progressively decreased with no adverse effects and maintaining an improvement of oxygenation and hemodynamic status, allowing respiratory weaning. CONCLUSIONS Sustained acute hypoxia in ARDS secondary to SARS-CoV-2 pneumonia can lead to PAH, causing a ventilation/perfusion mismatch and RV systolic impairment. iNO can be considered in patients with significant PAH causing hypoxemia and RV dysfunction.


Subject(s)
COVID-19 , Hypertension, Pulmonary , Respiratory Distress Syndrome , Tricuspid Valve Insufficiency , Female , Humans , Adult , Nitric Oxide/therapeutic use , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/etiology , COVID-19/complications , Administration, Inhalation , SARS-CoV-2 , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Hypoxia/etiology
16.
Crit Care ; 26(1): 272, 2022 09 12.
Article in English | MEDLINE | ID: covidwho-2089223

ABSTRACT

RATIONALE: It is unknown how to titrate positive end-expiratory pressure (PEEP) in patients with COVID-19-related acute respiratory distress syndrome (ARDS). Guidelines recommend the one-size-fits-all PEEP-FiO2 table. In this retrospective cohort study, an electrical impedance tomography (EIT)-guided PEEP trial was used to titrate PEEP. OBJECTIVES: To compare baseline PEEP according to the high PEEP-FiO2 table and personalized PEEP following an EIT-guided PEEP trial. METHODS: We performed an EIT-guided decremental PEEP trial in patients with moderate-to-severe COVID-19-related ARDS upon intensive care unit admission. PEEP was set at the lowest PEEP above the intersection of curves representing relative alveolar overdistention and collapse. Baseline PEEP was compared with PEEP set according to EIT. We identified patients in whom the EIT-guided PEEP trial resulted in a decrease or increase in PEEP of ≥ 2 cmH2O. MEASUREMENTS AND MAIN RESULTS: We performed a PEEP trial in 75 patients. In 23 (31%) patients, PEEP was decreased ≥ 2 cmH2O, and in 24 (32%) patients, PEEP was increased ≥ 2 cmH2O. Patients in whom PEEP was decreased had improved respiratory mechanics and more overdistention in the non-dependent lung region at higher PEEP levels. These patients also had a lower BMI, longer time between onset of symptoms and intubation, and higher incidence of pulmonary embolism. Oxygenation improved in patients in whom PEEP was increased. CONCLUSIONS: An EIT-guided PEEP trial resulted in a relevant change in PEEP in 63% of patients. These results support the hypothesis that PEEP should be personalized in patients with ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/complications , COVID-19/therapy , Electric Impedance , Humans , Respiration, Artificial , Respiratory Distress Syndrome/therapy , Retrospective Studies
17.
Cells ; 11(20)2022 Oct 21.
Article in English | MEDLINE | ID: covidwho-2082133

ABSTRACT

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a devastating disease that can be caused by a variety of conditions including pneumonia, sepsis, trauma, and most recently, COVID-19. Although our understanding of the mechanisms of ALI/ARDS pathogenesis and resolution has considerably increased in recent years, the mortality rate remains unacceptably high (~40%), primarily due to the lack of effective therapies for ALI/ARDS. Dysregulated inflammation, as characterized by massive infiltration of polymorphonuclear leukocytes (PMNs) into the airspace and the associated damage of the capillary-alveolar barrier leading to pulmonary edema and hypoxemia, is a major hallmark of ALI/ARDS. Endothelial cells (ECs), the inner lining of blood vessels, are important cellular orchestrators of PMN infiltration in the lung. Nuclear factor-kappa B (NF-κB) plays an essential role in rendering the endothelium permissive for PMN adhesion and transmigration to reach the inflammatory site. Thus, targeting NF-κB in the endothelium provides an attractive approach to mitigate PMN-mediated vascular injury, not only in ALI/ARDS, but in other inflammatory diseases as well in which EC dysfunction is a major pathogenic mechanism. This review discusses the role and regulation of NF-κB in the context of EC inflammation and evaluates the potential and problems of targeting it as a therapy for ALI/ARDS.


Subject(s)
Acute Lung Injury , COVID-19 , Respiratory Distress Syndrome , Humans , NF-kappa B , Endothelial Cells/pathology , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Inflammation
18.
Inflamm Res ; 71(12): 1417-1432, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2074066

ABSTRACT

Acute respiratory distress syndrome (ARDS) is an acute and diffuse inflammatory lung injury in a short time, one of the common severe manifestations of the respiratory system that endangers human life and health. As an innate immune cell, macrophages play a key role in the inflammatory response. For a long time, the role of pulmonary macrophages in ARDS has tended to revolve around the polarization of M1/M2. However, with the development of single-cell RNA sequencing, fate mapping, metabolomics, and other new technologies, a deeper understanding of the development process, classification, and function of macrophages in the lung are acquired. Here, we discuss the function of pulmonary macrophages in ARDS from the two dimensions of anatomical location and cell origin and describe the effects of cell metabolism and intercellular interaction on the function of macrophages. Besides, we explore the treatments for targeting macrophages, such as enhancing macrophage phagocytosis, regulating macrophage recruitment, and macrophage death. Considering the differences in responsiveness of different research groups to these treatments and the tremendous dynamic changes in the gene expression of monocyte/macrophage, we discussed the possibility of characterizing the gene expression of monocyte/macrophage as the biomarkers. We hope that this review will provide new insight into pulmonary macrophage function and therapeutic targets of ARDS.


Subject(s)
Acute Lung Injury , Respiratory Distress Syndrome , Humans , Macrophages, Alveolar/metabolism , Macrophages , Lung/metabolism
19.
PLoS One ; 17(10): e0275181, 2022.
Article in English | MEDLINE | ID: covidwho-2079742

ABSTRACT

BACKGROUND: Glycyrrhizin, an active component of liquorice root extract, exhibits antiviral and immunomodulatory properties by direct inhibition of the pro-inflammatory alarmin HMGB1 (High-mobility group box 1). OBJECTIVE: The aim of this study was to explore the role of liquorice intake on the viral entry receptor ACE2 (angiotensin-converting enzyme 2) and the immunoregulatory HMGB1 in healthy individuals and to explore HMGB1 expression in coronavirus disease 2019 (COVID-19) or non-COVID-19 in ARDS (acute respiratory distress syndrome patients). MATERIAL AND METHODS: This study enrolled 43 individuals, including hospitalised patients with i) acute respiratory distress syndrome (ARDS) due to COVID-19 (n = 7) or other underlying causes (n = 12), ii) mild COVID-19 (n = 4) and iii) healthy volunteers (n = 20). Healthy individuals took 50 g of liquorice (containing 3% liquorice root extract) daily for 7 days, while blood samples were collected at baseline and on day 3 and 7. Changes in ACE2 and HMGB1 levels were determined by Western blot analysis and enzyme-linked immunosorbent assay, respectively. Additionally, HMGB1 levels were measured in hospitalised COVID-19 patients with mild disease or COVID-19 associated acute respiratory distress syndrome (ARDS) and compared with a non-COVID-19-ARDS group. RESULTS: Liquorice intake significantly reduced after 7 days both cellular membranous ACE2 expression (-51% compared to baseline levels, p = 0.008) and plasma HMGB1 levels (-17% compared to baseline levels, p<0.001) in healthy individuals. Half of the individuals had a reduction in ACE2 levels of at least 30%. HMGB1 levels in patients with mild COVID-19 and ARDS patients with and without COVID-19 were significantly higher compared with those of healthy individuals (+317%, p = 0.002), but they were not different between COVID-19 and non-COVID-19 ARDS. CONCLUSIONS: Liquorice intake modulates ACE2 and HMGB1 levels in healthy individuals. HMGB1 is enhanced in mild COVID-19 and in ARDS with and without COVID-19, warranting evaluation of HMGB1 as a potential treatment target and glycyrrhizin, which is an active component of liquorice root extract, as a potential treatment in COVID-19 and non-COVID-19 respiratory disease.


Subject(s)
COVID-19 , Glycyrrhiza , HMGB1 Protein , Respiratory Distress Syndrome , Alarmins , Angiotensin-Converting Enzyme 2 , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Glycyrrhiza/metabolism , Glycyrrhizic Acid/pharmacology , Glycyrrhizic Acid/therapeutic use , HMGB1 Protein/metabolism , Humans , Pilot Projects , Receptors, Virus/metabolism , Respiratory Distress Syndrome/drug therapy
20.
Eur Respir Rev ; 31(166)2022 Dec 31.
Article in English | MEDLINE | ID: covidwho-2079386

ABSTRACT

Respiratory virus infection can cause severe illnesses capable of inducing acute respiratory failure that can progress rapidly to acute respiratory distress syndrome (ARDS). ARDS is related to poor outcomes, especially in individuals with a higher risk of infection, such as the elderly and those with comorbidities, i.e. obesity, asthma, diabetes mellitus and chronic respiratory or cardiovascular disease. Despite this, effective antiviral treatments available for severe viral lung infections are scarce. The coronavirus disease 2019 (COVID-19) pandemic demonstrated that there is also a need to understand the role of airborne transmission of respiratory viruses. Robust evidence supporting this exists, but better comprehension could help implement adequate measures to mitigate respiratory viral infections. In severe viral lung infections, early diagnosis, risk stratification and prognosis are essential in managing patients. Biomarkers can provide reliable, timely and accessible information possibly helpful for clinicians in managing severe lung viral infections. Although respiratory viruses highly impact global health, more research is needed to improve care and prognosis of severe lung viral infections. In this review, we discuss the epidemiology, diagnosis, clinical characteristics, management and prognosis of patients with severe infections due to respiratory viruses.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Viruses , Humans , Aged , SARS-CoV-2 , Antiviral Agents/therapeutic use , Biomarkers
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