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1.
J Transl Med ; 20(1): 526, 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2115628

ABSTRACT

BACKGROUND: COVID-19 infections could be complicated by acute respiratory distress syndrome (ARDS), increasing mortality risk. We sought to assess the methylome of peripheral blood mononuclear cells in COVID-19 with ARDS. METHODS: We recruited 100 COVID-19 patients with ARDS under mechanical ventilation and 33 non-COVID-19 controls between April and July 2020. COVID-19 patients were followed at four time points for 60 days. DNA methylation and immune cell populations were measured at each time point. A multivariate cox proportional risk regression analysis was conducted to identify predictive signatures according to survival. RESULTS: The comparison of COVID-19 to controls at inclusion revealed the presence of a 14.4% difference in promoter-associated CpGs in genes that control immune-related pathways such as interferon-gamma and interferon-alpha responses. On day 60, 24% of patients died. The inter-comparison of baseline DNA methylation to the last recorded time point in both COVID-19 groups or the intra-comparison between inclusion and the end of follow-up in every group showed that most changes occurred as the disease progressed, mainly in the AIM gene, which is associated with an intensified immune response in those who recovered. The multivariate Cox proportional risk regression analysis showed that higher methylation of the "Apoptotic execution Pathway" genes (ROC1, ZNF789, and H1F0) at inclusion increases mortality risk by over twofold. CONCLUSION: We observed an epigenetic signature of immune-related genes in COVID-19 patients with ARDS. Further, Hypermethylation of the apoptotic execution pathway genes predicts the outcome. TRIAL REGISTRATION: IMRPOVIE study, NCT04473131.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Humans , COVID-19/complications , COVID-19/genetics , DNA Methylation/genetics , Leukocytes, Mononuclear , Respiration, Artificial , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/genetics , SARS-CoV-2
2.
Kardiologiia ; 62(8): 27-32, 2022 Aug 30.
Article in Russian, English | MEDLINE | ID: covidwho-2025893

ABSTRACT

Aim      To study the effectiveness of nebulized surfactant therapy as a part of a multimodality treatment of severe and extremely severe COVID-19 viral pneumonia with concomitant cardiovascular diseases (CVDs).Material and methods  This retrospective controlled study analyzed a multimodality treatment of 38 patients with severe and extremely severe COVID-19 viral pneumonia and concomitant CVDs who were administered nebulized surfactant for correction of acute respiratory distress syndrome (ARDS). The control group consisted of 105 patients with severe and extremely severe novel coronavirus infection with concomitant CVDs who were not administered surfactant as a part of the multimodality therapy.Results Administration of nebulized surfactant as a part of the multimodality treatment in patients with COVID-19 allowed alleviating the severity of respiratory insufficiency (р<0.001), which decreased the death rate of patients with severe and extremely severe COVID-19 and undoubtedly demonstrated the effectiveness of this medicine. The timely multimodality therapy, including nebulized surfactant, improves the course of the disease. Thus, the absence of a possibility for administering nebulized surfactant for more than 4 days was associated with fatal outcomes (р=0.045).Conclusion      Administration of nebulized surfactant as a part of the multimodality treatment of severe and extremely severe COVID-19 and concomitant CVDs increases the survival (р<0.001) and reduces the mortality by 46 %. The risk factors of an unfavorable outcome of this disease include an age older than 65 (р=0.020), a positive polymerase chain reaction test (р=0.037), a ferritin concentration at baseline >600 mg /ml (р<0.001), and a surfactant treatment duration < 4 days (р=0.045). Further study of the efficacy of nebulized surfactants as a part of the multimodality therapy is required and should include randomized clinical trials with a large number of patients and the development of distinct criteria for the treatment of ARDS.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/complications , Humans , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/drug therapy , Retrospective Studies , SARS-CoV-2 , Surface-Active Agents
3.
Clin Lab ; 68(8)2022 Aug 01.
Article in English | MEDLINE | ID: covidwho-1994477

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Geriatric patients with COVID-19 are more likely to progress to severe disease, and they are at increased risk of hospitalization and mortality. In this study we aimed to investigate the risk factors for predicting mortality in geriatric patients with COVID 19 by reviewing the clinical data of survivors and non-survivors. METHODS: This was a retrospective study of 189 geriatric patients with COVID- 19 pneumonia who were hospitalized in pulmonology clinic, in Duzce University, Medical Faculty Hospital between March 2020 and January 2021 in Turkey. RESULTS: In the study, 60.3% (n = 114) of the patients were male and the median age was 75. 80.4% (n = 152) of the patients were discharged. The presence of cardiovascular disease, chronic renal failure, malignancy, increased number of comorbidities, complaints of anorexia, no fever, decreased oxygen saturation value, increased pulse rate, high values of maximum (max) D-dimer, aspartate aminotransferase, urea, creatinine, troponin, lactate dehydrogenase (LDH), max LDH, ferritin and max ferritin, C-reactive protein (CRP), max CRP, procalcitonin, max procalcitonin, potassium values and low albumin values, complications as bacterial infection, cardiac disease, acute respiratory distress syndrome, liver function tests failure, arrhythmia and shock, the need for corticosteroid and pulse corticosteroid therapy increased the mortality. According to multiple logistic regression model, the de-velopment of cardiac disease, acute respiratory distress syndrome, bacterial infection, the need for pulse steroids, and the max ferritin value increased the risk of mortality by between 1.001 and 28.715 times. CONCLUSIONS: Both clinical and laboratory parameters predicting mortality in geriatric patients with COVID-19 pneumonia should be monitored very carefully. Complications that develop should be evaluated and multidisciplinary and necessary treatments should be initiated without delay.


Subject(s)
COVID-19 , Heart Diseases , Respiratory Distress Syndrome , Aged , C-Reactive Protein/analysis , COVID-19/diagnosis , COVID-19/mortality , Female , Ferritins , Heart Diseases/complications , Hospitalization , Humans , L-Lactate Dehydrogenase/metabolism , Male , Procalcitonin , Respiratory Distress Syndrome/complications , Retrospective Studies , SARS-CoV-2 , Turkey/epidemiology
4.
Nature ; 609(7928): 801-807, 2022 09.
Article in English | MEDLINE | ID: covidwho-1960390

ABSTRACT

Anorexia and fasting are host adaptations to acute infection, and induce a metabolic switch towards ketogenesis and the production of ketone bodies, including ß-hydroxybutyrate (BHB)1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we show that the production of BHB is impaired in individuals with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) but not in those with  influenza-induced ARDS. We found that BHB promotes both the survival of and the production of interferon-γ by CD4+ T cells. Applying a metabolic-tracing analysis, we established that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but could be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we show in mice that a ketogenic diet and the delivery of BHB as a ketone ester drink restores CD4+ T cell metabolism and function in severe respiratory infections, ultimately reducing the mortality of mice infected with SARS-CoV-2. Altogether, our data reveal that BHB is an alternative source of carbon that promotes T cell responses in pulmonary viral infections, and highlight impaired ketogenesis as a potential confounding factor in severe COVID-19.


Subject(s)
COVID-19 , Energy Metabolism , Ketones , Respiratory Distress Syndrome , SARS-CoV-2 , T-Lymphocytes , 3-Hydroxybutyric Acid/biosynthesis , 3-Hydroxybutyric Acid/metabolism , Amino Acids/biosynthesis , Amino Acids/metabolism , Animals , COVID-19/complications , COVID-19/immunology , COVID-19/pathology , Diet, Ketogenic , Esters/metabolism , Glutathione/biosynthesis , Glutathione/metabolism , Glycolysis , Interferon-gamma/biosynthesis , Ketone Bodies/metabolism , Ketones/metabolism , Mice , Orthomyxoviridae/pathogenicity , Oxidation-Reduction , Oxidative Phosphorylation , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/immunology , Respiratory Distress Syndrome/metabolism , Respiratory Distress Syndrome/virology , SARS-CoV-2/pathogenicity , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , T-Lymphocytes/pathology
6.
Intensive Crit Care Nurs ; 72: 103257, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-1783407

ABSTRACT

OBJECTIVES: To examine the effectiveness of prone positioning on COVID-19 patients with acute respiratory distress syndrome with moderating factors in both traditional prone positioning (invasive mechanical ventilation) and awake self-prone positioning patients (non-invasive ventilation). RESEARCH METHODOLOGY: A comprehensive search was conducted in CINAHL, Cochrane library, Embase, Medline-OVID, NCBI SARS-CoV-2 Resources, ProQuest, Scopus, and Web of Science without language restrictions. All studies with prospective and experimental designs evaluating the effect of prone position patients with COVID-19 related to acute respiratory distress syndrome were included. Pooled standardised mean differences were calculated after prone position for primary (PaO2/FiO2) and secondary outcomes (SpO2 and PaO2) RESULTS: A total of 15 articles were eligible and included in the final analysis. Prone position had a statistically significant effect in improving PaO2/FiO2 with standardised mean difference of 1.10 (95%CI 0.60-1.59), SpO2 with standardised mean difference of 3.39 (95% CI 1.30-5.48), and PaO2 with standardised mean difference of 0.77 (95% CI 0.19-1.35). Patients with higher body mass index and longer duration/day are associated with larger standardised mean difference effect sizes for prone positioning. CONCLUSIONS: Our findings demonstrate that prone position significantly improved oxygen saturation in COVID-19 patients with acute respiratory distress syndrome in both traditional prone positioning and awake self-prone positioning patients. Prone position should be recommended for patients with higher body mass index and longer durations to obtain the maximum effect.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Duration of Therapy , Humans , Obesity , Prone Position , Prospective Studies , Respiration, Artificial , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/therapy , SARS-CoV-2
7.
J Cardiothorac Vasc Anesth ; 36(8 Pt B): 3197-3201, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1758416

ABSTRACT

Often labeled the forgotten ventricle, the right ventricle's (RV) importance has been magnified over the last 2 years as providers witnessed how severe acute respiratory syndrome coronavirus 2 infection has a predilection for exacerbating RV failure. Venovenous extracorporeal membranous oxygenation (VV-ECMO) has become a mainstay treatment modality for a select patient population suffering from severe COVID-19 acute respiratory distress syndrome. Concomitant early implementation of a right ventricular assist device with ECMO (RVAD-ECMO) may confer benefit in patient outcomes. The underlying mechanism of RV failure in COVID-19 has a multifactorial etiopathogenesis; nonetheless, clinical evaluation of a patient necessitating RV support remains unchanged. Herein, the authors report the case of a critically ill patient who was transitioned from a conventional VV-ECMO Medtronic Crescent cannula to RVAD-ECMO, with the insertion of the LivaNova ProtekDuo dual-lumen RVAD cannula.


Subject(s)
COVID-19 , Heart Failure , Respiratory Distress Syndrome , COVID-19/complications , COVID-19/therapy , Extracorporeal Membrane Oxygenation/methods , Heart Failure/therapy , Heart Failure/virology , Heart-Assist Devices , Humans , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/therapy , Respiratory Distress Syndrome/virology
8.
Rehabil Nurs ; 47(2): 72-81, 2022.
Article in English | MEDLINE | ID: covidwho-1741065

ABSTRACT

PURPOSE: The primary objective of this scoping review was to identify prominent cognitive impairment sequelae in adult survivors of an intensive care unit admission for acute respiratory distress syndrome (ARDS). DESIGN: A scoping review was performed. METHODS: Search terms were entered into multiple EBSCOhost databases. Articles pertaining to pediatric survivors, not in English, lacking cognitive impairment sequelae, or focused on a single sequela were excluded; 12 articles remained. RESULTS: Cognitive impairment developed in 83.5% of patients with ARDS prior to discharge and persisted in 51.3% (n = 300/585) of survivors at the 1 year mark after discharge (range: 16.7%-100% across studies). Prominent sequelae included impairments in executive function, mental processing speed, immediate memory, and attention/concentration. CONCLUSIONS: Survivors of an intensive care unit stay for ARDS often develop cognitive impairment persisting long after their admission. Clinicians in rehabilitation facilities should screen for these sequelae and connect survivors with treatment to improve cognitive outcomes. CLINICAL RELEVANCE: Early recognition of prominent cognitive impairment sequelae by rehabilitation clinicians and referrals to neuropsychologists by providers are critical to limiting the severity of impairment.


Subject(s)
Cognitive Dysfunction , Respiratory Distress Syndrome , Adult , Child , Cognitive Dysfunction/etiology , Humans , Intensive Care Units , Patient Discharge , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/therapy , Survivors/psychology
9.
Ultrasound Med Biol ; 48(5): 945-953, 2022 05.
Article in English | MEDLINE | ID: covidwho-1740249

ABSTRACT

Recent research has revealed that COVID-19 pneumonia is often accompanied by pulmonary edema. Pulmonary edema is a manifestation of acute lung injury (ALI), and may progress to hypoxemia and potentially acute respiratory distress syndrome (ARDS), which have higher mortality. Precise classification of the degree of pulmonary edema in patients is of great significance in choosing a treatment plan and improving the chance of survival. Here we propose a deep learning neural network named Non-local Channel Attention ResNet to analyze the lung ultrasound images and automatically score the degree of pulmonary edema of patients with COVID-19 pneumonia. The proposed method was designed by combining the ResNet with the non-local module and the channel attention mechanism. The non-local module was used to extract the information on characteristics of A-lines and B-lines, on the basis of which the degree of pulmonary edema could be defined. The channel attention mechanism was used to assign weights to decisive channels. The data set contains 2220 lung ultrasound images provided by Huoshenshan Hospital, Wuhan, China, of which 2062 effective images with accurate scores assigned by two experienced clinicians were used in the experiment. The experimental results indicated that our method achieved high accuracy in classifying the degree of pulmonary edema in patients with COVID-19 pneumonia by comparison with previous deep learning methods, indicating its potential to monitor patients with COVID-19 pneumonia.


Subject(s)
COVID-19 , Pulmonary Edema , Respiratory Distress Syndrome , COVID-19/complications , COVID-19/diagnostic imaging , Humans , Lung/diagnostic imaging , Pulmonary Edema/complications , Pulmonary Edema/diagnostic imaging , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnostic imaging , Ultrasonography
10.
Future Microbiol ; 17: 161-167, 2022 02.
Article in English | MEDLINE | ID: covidwho-1638319

ABSTRACT

The authors describe a case series of co-infection with COVID-19 and scrub typhus in two Indian patients. Clinical features like fever, cough, dyspnea and altered sensorium were common in both patients. Case 1 had lymphopenia, elevated IL-6 and history of hypertension, while case 2 had leukocytosis and an increased liver enzymes. Both patients had hypoalbuminemia and required admission to the intensive care unit; one of them succumbed to acute respiratory distress syndrome further complicated by multiple organ dysfunction syndrome. Seasonal tropical infections in COVID-19 patients in endemic settings may lead to significant morbidity and mortality. Therefore, high clinical suspicion and an early diagnosis for co-infections among COVID-19 patients are essential for better patient management.


Subject(s)
COVID-19/complications , COVID-19/diagnosis , Coinfection/diagnosis , Scrub Typhus/complications , Scrub Typhus/diagnosis , Adult , COVID-19/blood , Coinfection/microbiology , Coinfection/virology , Cough , Diagnosis, Differential , Dyspnea , Early Diagnosis , Fever , Humans , India , Male , Middle Aged , Multiple Organ Failure/complications , Respiratory Distress Syndrome/complications , Scrub Typhus/blood
12.
Front Endocrinol (Lausanne) ; 12: 747732, 2021.
Article in English | MEDLINE | ID: covidwho-1598924

ABSTRACT

Objective: To evaluate the association between overweight and obesity on the clinical course and outcomes in patients hospitalized with COVID-19. Design: Retrospective, observational cohort study. Methods: We performed a multicenter, retrospective, observational cohort study of hospitalized COVID-19 patients to evaluate the associations between overweight and obesity on the clinical course and outcomes. Results: Out of 1634 hospitalized COVID-19 patients, 473 (28.9%) had normal weight, 669 (40.9%) were overweight, and 492 (30.1%) were obese. Patients who were overweight or had obesity were younger, and there were more women in the obese group. Normal-weight patients more often had pre-existing conditions such as malignancy, or were organ recipients. During admission, patients who were overweight or had obesity had an increased probability of acute respiratory distress syndrome [OR 1.70 (1.26-2.30) and 1.40 (1.01-1.96)], respectively and acute kidney failure [OR 2.29 (1.28-3.76) and 1.92 (1.06-3.48)], respectively. Length of hospital stay was similar between groups. The overall in-hospital mortality rate was 27.7%, and multivariate logistic regression analyses showed that overweight and obesity were not associated with increased mortality compared to normal-weight patients. Conclusion: In this study, overweight and obesity were associated with acute respiratory distress syndrome and acute kidney injury, but not with in-hospital mortality nor length of hospital stay.


Subject(s)
Acute Kidney Injury/complications , COVID-19/mortality , Hospital Mortality , Hospitalization , Obesity/complications , Respiratory Distress Syndrome/complications , Aged , Female , Humans , Intensive Care Units , Length of Stay , Male , Middle Aged , Patient Discharge , Respiration, Artificial , Retrospective Studies , Treatment Outcome
13.
Biomed Pharmacother ; 146: 112592, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1588215

ABSTRACT

INTRODUCTION: The most grievous complication of the COVID-19 is the acute respiratory distress syndrome. A specific, rescue treatment for rapidly deteriorating patients should emerge to improve respiratory function and help patients to survive the most challenging period. Drugs used in targeted therapy of pulmonary arterial hypertension (PAH) appears to be suitable for this task and this article describes their potential for treatment of severe cases of COVID-19. METHODS: The authors reviewed the following databases for randomized controlled trials, reviews and meta-analyses published up to July 2020: Pubmed, Scopus, Google Scholar, Cochrane Database and ClinicalKey. The authors included every study contributory to the assessment of the potential of drugs used in targeted PAH therapy in treatment of COVID-19. RESULTS: Endothelin receptor antagonists, phosphodiesterase 5 inhibitors, riociguat and prostacyclin have proven ani-inflammatory effect and reduce pulmonary artery blood pressure, lung oedema and remodelling. Bosentan shows antiviral properties and sildenafil, as well as epoprostenol, inhibits apoptosis of lung epithelial cells. Among patients with lung lesions the decrease of pulmonary blood pressure can lead to increase of ventilation/perfusion mismatch and decrease of blood oxygenation. CONCLUSIONS: Among all assessed drugs bosentan, sildenafil and epoprostenol appear to be most promising and a combination of these drugs should be considered due to synergism. The targeted PAH therapy in treatment of COVID-19 associated ARDS could be a useful tool saving lives of patients with severe SARS-CoV-2 infection, however, its introduction should be investigated and monitored very carefully as it can lead to transient deterioration of patient condition.


Subject(s)
COVID-19/drug therapy , Pulmonary Artery/metabolism , Respiratory Distress Syndrome/drug therapy , Animals , COVID-19/complications , Endothelin Receptor Antagonists/therapeutic use , Humans , Phosphodiesterase Inhibitors/therapeutic use , Prostaglandins/therapeutic use , Pulmonary Artery/drug effects , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Respiratory Distress Syndrome/complications
14.
Ren Fail ; 43(1): 1621-1633, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1562360

ABSTRACT

BACKGROUND: Acute kidney injury (AKI) is common among patients with COVID-19. However, AKI incidence may increase when COVID-19 patients develop acute respiratory distress syndrome (ARDS). Thus, this systematic review and meta-analysis aimed to assess the incidence and risk factors of AKI, need for kidney replacement therapy (KRT), and mortality rate among COVID-19 patients with and without ARDS from the first wave of COVID-19. METHODS: The databases MEDLINE and EMBASE were searched using relevant keywords. Only articles available in English published between December 1, 2019, and November 1, 2020, were included. Studies that included AKI in COVID-19 patients with or without ARDS were included. Meta-analyses were conducted using random-effects models. RESULTS: Out of 618 studies identified and screened, 31 studies met the inclusion criteria. A total of 27,500 patients with confirmed COVID-19 were included. The overall incidence of AKI in patients with COVID-19 was 26% (95% CI 19% to 33%). The incidence of AKI was significantly higher among COVID-19 patients with ARDS than COVID-19 patients without ARDS (59% vs. 6%, p < 0.001). Comparing ARDS with non-ARDS COVID-19 cohorts, the need for KRT was also higher in ARDS cohorts (20% vs. 1%). The mortality among COVID-19 patients with AKI was significantly higher (Risk ratio = 4.46; 95% CI 3.31-6; p < 0.00001) than patients without AKI. CONCLUSION: This study shows that ARDS development in COVID-19-patients leads to a higher incidence of AKI and increased mortality rate. Therefore, healthcare providers should be aware of kidney dysfunction, especially among elderly patients with multiple comorbidities. Early kidney function assessment and treatments are vital in COVID-19 patients with ARDS.


Subject(s)
Acute Kidney Injury/epidemiology , COVID-19/complications , Respiratory Distress Syndrome/complications , COVID-19/epidemiology , Humans , Incidence , Respiratory Distress Syndrome/epidemiology , Risk Factors
15.
J Med Virol ; 93(12): 6641-6652, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544314

ABSTRACT

Acute kidney injury (AKI) may develop in patients with coronavirus disease 2019 (COVID-19) and is associated with in-hospital death. We investigated the incidence of AKI in 223 hospitalized COVID-19 patients and analyzed the influence factors of AKI. The incidence of cytokine storm syndrome and its correlation with other clinicopathologic variables were also investigated. We retrospectively enrolled adult patients with virologically confirmed COVID-19 who were hospitalized at three hospitals in Wuhan and Guizhou, China between February 13, 2020, and April 8, 2020. We included 124 patients with moderate COVID-19 and 99 with severe COVID-19. AKI was present in 35 (15.7%) patients. The incidence of AKI was 30.3% for severe COVID-19 and 4.0% for moderate COVID-19 (p < 0.001). Furthermore, cytokine storm was found in 30 (13.5%) patients and only found in the severe group. Kidney injury at admission (odds ratio [OR]: 3.132, 95% confidence interval [CI]: 1.150-8.527; p = 0.025), cytokine storm (OR: 4.234, 95% CI: 1.361-13.171; p = 0.013), and acute respiratory distress syndrome (ARDS) (OR: 7.684, 95% CI: 2.622-22.523; p < 0.001) were influence factors of AKI. Seventeen (48.6%) patients who received invasive mechanical ventilation developed AKI, of whom 64.7% (11/17) died. Up to 86.7% of AKI patients with cytokine storms may develop a secondary bacterial infection. The leukocyte counts were significantly higher in AKI patients with cytokine storm than in those without (13.0 × 109/L, interquartile range [IQR] 11.3 vs. 8.3 × 109/L, IQR 7.5, p = 0.005). Approximately 1/6 patients with COVID-19 eventually develop AKI. Kidney injury at admission, cytokine storm and ARDS are influence factors of AKI. Cytokine storm and secondary bacterial infections may be responsible for AKI development in COVID-19 patients.


Subject(s)
Acute Kidney Injury/etiology , Bacterial Infections/etiology , COVID-19/complications , Cytokine Release Syndrome/complications , Adult , Aged , China , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Respiration, Artificial/adverse effects , Respiration, Artificial/statistics & numerical data , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/etiology , Retrospective Studies , Risk Factors
16.
Cells ; 10(12)2021 11 25.
Article in English | MEDLINE | ID: covidwho-1542428

ABSTRACT

Acute respiratory distress syndrome (ARDS) is a serious lung condition characterized by severe hypoxemia leading to limitations of oxygen needed for lung function. In this study, we investigated the effect of anandamide (AEA), an endogenous cannabinoid, on Staphylococcal enterotoxin B (SEB)-mediated ARDS in female mice. Single-cell RNA sequencing data showed that the lung epithelial cells from AEA-treated mice showed increased levels of antimicrobial peptides (AMPs) and tight junction proteins. MiSeq sequencing data on 16S RNA and LEfSe analysis demonstrated that SEB caused significant alterations in the microbiota, with increases in pathogenic bacteria in both the lungs and the gut, while treatment with AEA reversed this effect and induced beneficial bacteria. AEA treatment suppressed inflammation both in the lungs as well as gut-associated mesenteric lymph nodes (MLNs). AEA triggered several bacterial species that produced increased levels of short-chain fatty acids (SCFAs), including butyrate. Furthermore, administration of butyrate alone could attenuate SEB-mediated ARDS. Taken together, our data indicate that AEA treatment attenuates SEB-mediated ARDS by suppressing inflammation and preventing dysbiosis, both in the lungs and the gut, through the induction of AMPs, tight junction proteins, and SCFAs that stabilize the gut-lung microbial axis driving immune homeostasis.


Subject(s)
Arachidonic Acids/therapeutic use , Endocannabinoids/therapeutic use , Gastrointestinal Microbiome , Gastrointestinal Tract/pathology , Lung/pathology , Polyunsaturated Alkamides/therapeutic use , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/microbiology , Animals , Arachidonic Acids/pharmacology , Butyrates/metabolism , Cecum/pathology , Cell Separation , Colon/drug effects , Colon/pathology , Discriminant Analysis , Dysbiosis/complications , Dysbiosis/microbiology , Endocannabinoids/pharmacology , Enterotoxins , Female , Gastrointestinal Tract/drug effects , Lymph Nodes/drug effects , Lymph Nodes/pathology , Lymphocyte Activation/drug effects , Mice, Inbred C57BL , Pneumonia/drug therapy , Pneumonia/microbiology , Polyunsaturated Alkamides/pharmacology , Respiratory Distress Syndrome/complications , T-Lymphocytes/drug effects
17.
Biol Sex Differ ; 12(1): 63, 2021 11 22.
Article in English | MEDLINE | ID: covidwho-1528694

ABSTRACT

BACKGROUND: Several biomarkers have been identified to predict the outcome of COVID-19 severity, but few data are available regarding sex differences in their predictive role. Aim of this study was to identify sex-specific biomarkers of severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19. METHODS: Plasma levels of sex hormones (testosterone and 17ß-estradiol), sex-hormone dependent circulating molecules (ACE2 and Angiotensin1-7) and other known biomarkers for COVID-19 severity were measured in male and female COVID-19 patients at admission to hospital. The association of plasma biomarker levels with ARDS severity at admission and with the occurrence of respiratory deterioration during hospitalization was analysed in aggregated and sex disaggregated form. RESULTS: Our data show that some biomarkers could be predictive both for males and female patients and others only for one sex. Angiotensin1-7 plasma levels and neutrophil count predicted the outcome of ARDS only in females, whereas testosterone plasma levels and lymphocytes counts only in males. CONCLUSIONS: Sex is a biological variable affecting the choice of the correct biomarker that might predict worsening of COVID-19 to severe respiratory failure. The definition of sex specific biomarkers can be useful to alert patients to be safely discharged versus those who need respiratory monitoring.


Subject(s)
Biomarkers/blood , COVID-19/complications , Hospitalization , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/diagnosis , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Sex Characteristics , Adult , Angiotensin-Converting Enzyme 2/blood , Angiotensins/blood , COVID-19/blood , Estradiol/blood , Female , Humans , Male , Middle Aged , Respiratory Distress Syndrome/blood , Respiratory Insufficiency/blood , SARS-CoV-2 , Testosterone/blood
18.
CNS Neurol Disord Drug Targets ; 20(5): 473-477, 2021.
Article in English | MEDLINE | ID: covidwho-1526730

ABSTRACT

INTRODUCTION: Catatonia is a psychomotor syndrome that presents with severe symptoms which can lead to dangerous and lethal conditions if not diagnosed and treated properly. SARS-- CoV-2 is a positive-sense single-stranded RNA virus that can occur in severe cases with acute pneumonia, ARDS, sepsis and septic shock. In these cases, ICU admission is necessary. CASE SUMMARY: A 59-year-old Caucasian man with septic shock and bilateral interstitial pneumonia from SARS-CoV-2 and schizotypal personality disorder presented with catatonic behaviour manifested by soporous state, response to intense painful stimuli with the opening of the eyes, execution of simple verbal commands, maintenance of the same position, catalepsy, immobility, rigidity and mutism. At the same time, there were symptoms of septic shock and catatonic symptoms, causing greater difficulty in the correct formulation of the diagnosis. During the course of his hospitalization, he was treated with asenapine 20 mg/day. The catatonia responded rapidly and significantly to the asenapine. DISCUSSION: To date, the pathophysiology of catatonia is unclear, and few guidelines are available for the treatment of catatonia. In the literature, studies have reported the efficacy of benzodiazepines such as lorazepam and diazepam, GABAA agonists such as zolpidem, NMDA receptor antagonists such as memantine, antidepressant SSRIs such as fluoxetine and paroxetine, and antipsychotics such as olanzapine, clozapine and aripiprazole. We demonstrate that the antipsychotic asenapine is also effective in treating catatonic symptoms in psychiatric disorders. CONCLUSION: Asenapine produced a rapid and significant reduction in catatonic symptoms in our patient with schizotypal personality disorder.


Subject(s)
Antipsychotic Agents/therapeutic use , COVID-19/complications , Catatonia/drug therapy , Catatonia/etiology , Depressive Disorder, Major/complications , Dibenzocycloheptenes/therapeutic use , Schizotypal Personality Disorder/complications , Shock, Septic/complications , Shock, Septic/etiology , Catatonia/psychology , Humans , Male , Middle Aged , Pain/etiology , Respiratory Distress Syndrome/complications
20.
Dis Markers ; 2021: 4361844, 2021.
Article in English | MEDLINE | ID: covidwho-1523091

ABSTRACT

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA virus first identified in December 2019 in Wuhan, China, and responsible for coronavirus disease 2019 (COVID-19). The ongoing COVID-19 pandemic is impacting healthcare worldwide. Patients who develop coagulopathy have worse outcomes. The pathophysiology of COVID-19 suggests a strong interplay between hemostasis and immune cells, especially neutrophils. Our purpose was to assess neutrophil fluorescence as a potential biomarker of deep vein thrombosis (DVT) in patients with COVID-acute respiratory distress syndrome (COVID-ARDS). Sixty-one patients with COVID-ARDS admitted to the four intensive care units (ICUs) of a French general hospital were included in this prospective study. Neutrophil activation was assessed by measuring neutrophil fluorescence (NEUT-Side Fluorescence Light, NEUT-SFL) with a specific fluorescent dye staining analyzed by a routine automated flow cytometer Sysmex XN-3000™ (Sysmex, Kobe, Japan). DVT was diagnosed by complete duplex ultrasound (CDU). We found that NEUT-SFL was elevated on admission in patients with COVID-ARDS (49.76 AU, reference value 46.40 AU, p < 0.001), but did not differ between patients with DVT (49.99 AU) and those without (49.52 AU, p = 0.555). NEUT-SFL is elevated in patients with COVID-ARDS, reflecting neutrophil activation, but cannot be used as a marker of thrombosis. Because neutrophils are at interface between immune response and hemostasis through release of neutrophil extracellular traps, monitoring their activation could be an interesting approach to improve our management of coagulopathy during COVID-ARDS. Further research is needed to better understand the pathophysiology of COVID-19 and identify high-performance biomarkers.


Subject(s)
Biomarkers/blood , COVID-19/complications , Neutrophils/chemistry , Respiratory Distress Syndrome/complications , Venous Thrombosis/blood , Aged , COVID-19/blood , Female , Flow Cytometry/methods , Fluorescence , Humans , Intensive Care Units , Leukocyte Count , Male , Middle Aged , Respiratory Distress Syndrome/virology , Ultrasonography, Doppler, Duplex , Venous Thrombosis/diagnostic imaging , Venous Thrombosis/drug therapy , Venous Thrombosis/virology
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