scholarly journals Biomarkers of acute respiratory distress syndrome in adults hospitalised for severe SARS-CoV-2 infection in Tenerife Island, Spain

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Juan Marco Figueira Gonçalves ◽  
José María Hernández Pérez ◽  
Marco Acosta Sorensen ◽  
Aurelio Luis Wangüemert Pérez ◽  
Elena Martín Ruiz de la Rosa ◽  
...  

Abstract Objective The dramatic spread of SARS-CoV-2 infections calls for reliable, inexpensive tools to quickly identify patients with a poor prognosis. In this study, acute respiratory distress syndrome (ARDS) was assessed within 72 h after admission of each of 153 consecutive, SARS-CoV-2 infected, adult patients to either of two hospitals in Tenerife, Spain, using suitable routine laboratory tests for lymphocyte counts, as well as ferritin, lactate dehydrogenase (LDH), and C-reactive protein levels. Results were correlated with the patients’ respiratory function, defined through their pulse oximetric saturation/fraction of inspired oxygen (SpO2/FiO2) ratio. Results Within 72 h from admission, criteria matched ARDS (SpO2/FiO2 < 235) in 13.1% of cases. We found a significant, negative correlation between SpO2/FiO2 ratios and d-dimer, ferritin, and LDH levels (− 0.31, − 0.32, and − 0.41; p = 0.004, 0.004, and < 0.0001, respectively). In patients with ARDS, the mean LDH was 373 U/L (CI95%: 300.6–445.3), but only 298 U/L (CI95%: 274.7–323.1) when they did not develop the syndrome (p = 0.015). None of the additionally evaluated biomarkers correlated with the SpO2/FiO2 ratios. Serum LDH levels in patients hospitalised for COVID-19 correlate with ARDS, as defined by their SpO2/FiO2 ratio, and might help to predict said complication.

Blood ◽  
2020 ◽  
Vol 136 (10) ◽  
pp. 1169-1179 ◽  
Author(s):  
Elizabeth A. Middleton ◽  
Xue-Yan He ◽  
Frederik Denorme ◽  
Robert A. Campbell ◽  
David Ng ◽  
...  

Abstract COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P &lt; .0001) and death (P &lt; .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.


2020 ◽  
Vol 319 (5) ◽  
pp. L825-L832
Author(s):  
Eric D. Morrell ◽  
Serge Grazioli ◽  
Chi Hung ◽  
Osamu Kajikawa ◽  
Susanna Kosamo ◽  
...  

The cellular communication network factor 1 (CCN1) is a matricellular protein that can modulate multiple tissue responses, including inflammation and repair. We have previously shown that adenoviral overexpression of Ccn1 is sufficient to cause acute lung injury in mice. We hypothesized that CCN1 is present in the airspaces of lungs during the acute phase of lung injury, and higher concentrations are associated with acute respiratory distress syndrome (ARDS) severity. We tested this hypothesis by measuring 1) CCN1 in bronchoalveolar lavage fluid (BALF) and lung homogenates from mice subjected to ventilation-induced lung injury (VILI), 2) Ccn1 gene expression and protein levels in MLE-12 cells (alveolar epithelial cell line) subjected to mechanical stretch, and 3) CCN1 in BALF from mechanically ventilated humans with and without ARDS. BALF CCN1 concentrations and whole lung CCN1 protein levels were significantly increased in mice with VILI ( n = 6) versus noninjured controls ( n = 6). Ccn1 gene expression and CCN1 protein levels were increased in MLE-12 cells cultured under stretch conditions. Subjects with ARDS ( n = 77) had higher BALF CCN1 levels compared with mechanically ventilated subjects without ARDS ( n = 45) ( P < 0.05). In subjects with ARDS, BALF CCN1 concentrations were associated with higher total protein, sRAGE, and worse [Formula: see text]/[Formula: see text] ratios (all P < 0.05). CCN1 is present in the lungs of mice and humans during the acute inflammatory phase of lung injury, and concentrations are higher in patients with increased markers of severity. Alveolar epithelial cells may be an important source of CCN1 under mechanical stretch conditions.


2013 ◽  
Vol 305 (7) ◽  
pp. L467-L477 ◽  
Author(s):  
Xiaoguang Sun ◽  
Shwu-Fan Ma ◽  
Michael S. Wade ◽  
Marialbert Acosta-Herrera ◽  
Jesús Villar ◽  
...  

The genetic mechanisms underlying the susceptibility to acute respiratory distress syndrome (ARDS) are poorly understood. We previously demonstrated that sphingosine 1-phosphate (S1P) and the S1P receptor S1PR3 are intimately involved in lung inflammatory responses and vascular barrier regulation. Furthermore, plasma S1PR3 protein levels were shown to serve as a biomarker of severity in critically ill ARDS patients. This study explores the contribution of single nucleotide polymorphisms (SNPs) of the S1PR3 gene to sepsis-associated ARDS. S1PR3 SNPs were identified by sequencing the entire gene and tagging SNPs selected for case-control association analysis in African- and ED samples from Chicago, with independent replication in a European case-control study of Spanish individuals. Electrophoretic mobility shift assays, luciferase activity assays, and protein immunoassays were utilized to assess the functionality of associated SNPs. A total of 80 variants, including 29 novel SNPs, were identified. Because of limited sample size, conclusive findings could not be drawn in African-descent ARDS subjects; however, significant associations were found for two promoter SNPs (rs7022797 −1899T/G; rs11137480 −1785G/C), across two ED samples supporting the association of alleles −1899G and −1785C with decreased risk for sepsis-associated ARDS. In addition, these alleles significantly reduced transcription factor binding to the S1PR3 promoter; reduced S1PR3 promoter activity, a response particularly striking after TNF-α challenge; and were associated with lower plasma S1PR3 protein levels in ARDS patients. These highly functional studies support S1PR3 as a novel ARDS candidate gene and a potential target for individualized therapy.


PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249346
Author(s):  
Ahmed S. Doghish ◽  
Walid F. Elkhatib ◽  
Essam A. Hassan ◽  
Ahmed F. Elkhateeb ◽  
Eman E. Mahmoud ◽  
...  

Background Coronavirus disease 2019 (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and in severe cases associated with acute respiratory distress syndrome (ARDS). Objective To describe the clinical characteristics of patients with ARDS-COVID-19. Materials and methods This study involved 197 male Egyptian participants, among them111 COVID-19 patients presented with ARDS, 60 COVID-19 patients presented with non-ARDS, and 26 Non-COVID-19 patients. We reported the analysis results of clinical and laboratory information, including blood routine tests, blood biochemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine and C‐reactive protein (CRP)], thrombotic activity (D‐dimer) and serum ferritin and lactate dehydrogenase (LDH). Results The levels of hemoglobin, AST, creatinine, monocyte count, monocyte %, RBC count, TLC, and platelet count were not significantly different among the groups. The lymphopenia and increased CRP, ALT, D-dimer, ferritin, and LDH were observed in patients with ARDS-COVID-19. Conclusion COVID-19 patients with ARDS presented with lymphopenia, increased thrombotic activity, increased CRP, LDH, and ferritin levels. The results revealed that CRP, D-dimer, LDH levels, and lymphopenia have a significant association with the COVID-19 severity and can be used as biomarkers to predict the disease severity.


2019 ◽  
Vol 130 (2) ◽  
pp. 263-283 ◽  
Author(s):  
Tài Pham ◽  
Ary Serpa Neto ◽  
Paolo Pelosi ◽  
John Gerard Laffey ◽  
Candelaria De Haro ◽  
...  

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population. Methods This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: “worsening” if moderate or severe acute respiratory distress syndrome criteria were met, “persisting” if mild acute respiratory distress syndrome criteria were the most severe category, and “improving” if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2. Results Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening. Conclusions Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dan Li ◽  
Tian Sun ◽  
Laiting Chi ◽  
Dengming Zhao ◽  
Wenzhi Li

Background. This study investigated the potential therapeutic effects of acupoint catgut embedding (ACE) at ST36 and BL13 on lipopolysaccharide- (LPS-) induced acute respiratory distress syndrome (ARDS) in rats. Materials and Methods. Male Sprague-Dawley rats were randomized into the normal saline (NS group with a sham procedure), lipopolysaccharide (LPS group with a sham procedure), and LPS plus ACE (LPS+ACE with ACE at bilateral BL13 and ST36 acupoints one day before LPS injection) groups. After intratracheal instillation of normal saline or LPS (0.5 mg/kg), all rats were subjected to mechanical ventilation for 4 h. Their blood gas was analyzed before and after lung injury, and their lung pressure-volumes were measured longitudinally. The levels of TNF-α, IL-6, IL-10, and phosphatidylcholine (PC) and total proteins (TP) in bronchial alveolar lavage fluid (BALF) were assessed. Their wet to dry lung weight ratios, histology, myeloperoxidase (MPO), superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were measured. Their lung aquaporin 1 (AQP1) and Occludin protein levels were analyzed. Results. LPS administration significantly decreased the ratios of PaO2/FiO2 and pressure-volumes and induced lung inflammation and injury by increased concentrations of TNF-α, IL-6, IL-10, and TP in BALF and MPO and MDA in the lung but decreased PC in BALF and SOD activity in the lungs. LPS also reduced AQP1 and Occludin protein levels in the lung of rats. In contrast, ACE significantly mitigated the LPS-induced lung injury, inflammation, and oxidative stress and preserved the AQP1 and Occludin contents in the lung of rats. Conclusions. ACE significantly improved respiratory function by mitigating inflammation and oxidative stress and preserving AQP1 and Occludin expression in the lung in a rat model of LPS-induced ARDS.


2021 ◽  
Author(s):  
Seyedreza Mirsoleymani ◽  
Erfan Taherifard ◽  
Ehsan Taherifard ◽  
Mohammad Hossein Taghrir ◽  
Milad Ahmadi Marzaleh ◽  
...  

Late in 2019, the first case of COVID-19 was detected in China, and the disease caused a pandemic state worldwide. Up to now, many studies have investigated the impact of comorbid diseases, especially diabetes mellitus, on COVID-19 outcomes. In this study, we aimed to assess the para-clinic characteristics of COVID-19 patients with or without diabetes mellitus to identify factors indicative of poor prognoses. In this prospective study, 153 in-patients with COVID-19 were followed up from 1 March to 19 April. Paraclinical information of these patients was gathered from their medical records. Afterward, the association between these factors among both diabetic and non-diabetic patients was assessed in the correlation analyses. Discharge and expiration of 77.1% and 22.9% of the study participants resulted in a 1063 person-day follow-up for patients who were discharged healthily and 384 person-day follow-ups for expired patients. 41.8% of the participants had diabetes mellitus. Lymphocytopenia and Neutrolhilia prevalences increased during hospitalization; comparing with their initial prevalences. Thirty-seven patients got acute respiratory distress syndrome; of those, 35 died. The mean of the initial C reactive protein level was 42.49, and serum creatinine of 1.39. The study showed that higher initial neutrophil count, increasing neutrophil count more than 15000 and decreasing lymphocyte count below 1000 during hospitalization; development of acute respiratory distress syndrome and being intubated; initial C reactive protein and serum creatinine level were associated with higher mortality rates in COVID-19 victims.


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