Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 80
Filter
Add filters

Document Type
Year range
3.
Balkan Med J ; 38(5): 296-303, 2021 09.
Article in English | MEDLINE | ID: covidwho-1438838

ABSTRACT

BACKGROUND: There are limited data on the long-term outcomes of COVID-19 from different parts of the world. AIMS: To determine risk factors of 90-day mortality in critically ill patients in Turkish intensive care units (ICUs), with respiratory failure. STUDY DESIGN: Retrospective, observational cohort. METHODS: Patients with laboratory-confirmed COVID-19 and who had been followed up in the ICUs with respiratory failure for more than 24 hours were included in the study. Their demographics, clinical characteristics, laboratory variables, treatment protocols, and survival data were recorded. RESULTS: A total of 421 patients were included. The median age was 67 (IQR: 57-76) years, and 251 patients (59.6%) were men. The 90-day mortality rate was 55.1%. The factors independently associated with 90-day mortality were invasive mechanical ventilation (IMV) (HR 4.09 [95% CI: [2.20-7.63], P < .001), lactate level >2 mmol/L (2.78 [1.93-4.01], P < .001), age ≥60 years (2.45 [1.48-4.06)], P < .001), cardiac arrhythmia during ICU stay (2.01 [1.27-3.20], P = .003), vasopressor treatment (1.94 [1.32-2.84], P = .001), positive fluid balance of ≥600 mL/day (1.68 [1.21-2.34], P = .002), PaO2/FiO2 ratio of ≤150 mmHg (1.66 [1.18-2.32], P = .003), and ECOG score ≥1 (1.42 [1.00-2.02], P = .050). CONCLUSION: Long-term mortality was high in critically ill patients with COVID-19 hospitalized in intensive care units in Turkey. Invasive mechanical ventilation, lactate level, age, cardiac arrhythmia, vasopressor therapy, positive fluid balance, severe hypoxemia and ECOG score were the independent risk factors for 90-day mortality.


Subject(s)
COVID-19/complications , COVID-19/mortality , Respiratory Insufficiency/mortality , Respiratory Insufficiency/virology , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/therapy , Critical Care , Critical Illness , Female , Follow-Up Studies , Humans , Intensive Care Units , Male , Middle Aged , Prognosis , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , Retrospective Studies , Risk Factors , Survival Analysis , Turkey/epidemiology
4.
Lancet Respir Med ; 9(8): 933-936, 2021 08.
Article in English | MEDLINE | ID: covidwho-1413072

ABSTRACT

The 2012 Berlin definition of acute respiratory distress syndrome (ARDS) provided validated support for three levels of initial arterial hypoxaemia that correlated with mortality in patients receiving ventilatory support. Since 2015, high-flow nasal oxygen (HFNO) has become widely used as an effective therapeutic support for acute respiratory failure, most recently in patients with severe COVID-19. We propose that the Berlin definition of ARDS be broadened to include patients treated with HFNO of at least 30 L/min who fulfil the other criteria for the Berlin definition of ARDS. An expanded definition would make the diagnosis of ARDS more widely applicable, allowing patients at an earlier stage of the syndrome to be recognised, independent of the need for endotracheal intubation or positive-pressure ventilation, with benefits for the testing of early interventions and the study of factors associated with the course of ARDS. We identify key questions that could be addressed in refining an expanded definition of ARDS, the implementation of which could lead to improvements in clinical practice and clinical outcomes for patients.


Subject(s)
COVID-19 , Oxygen Inhalation Therapy/methods , Respiratory Insufficiency , COVID-19/blood , COVID-19/diagnosis , COVID-19/therapy , Early Diagnosis , Humans , Patient Selection , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2 , Severity of Illness Index , Time-to-Treatment/standards
5.
Lancet Respir Med ; 9(9): 989-998, 2021 09.
Article in English | MEDLINE | ID: covidwho-1392669

ABSTRACT

BACKGROUND: Although COVID-19 has greatly affected many low-income and middle-income countries, detailed information about patients admitted to the intensive care unit (ICU) is still scarce. Our aim was to examine ventilation characteristics and outcomes in invasively ventilated patients with COVID-19 in Argentina, an upper middle-income country. METHODS: In this prospective, multicentre cohort study (SATICOVID), we enrolled patients aged 18 years or older with RT-PCR-confirmed COVID-19 who were on invasive mechanical ventilation and admitted to one of 63 ICUs in Argentina. Patient demographics and clinical, laboratory, and general management variables were collected on day 1 (ICU admission); physiological respiratory and ventilation variables were collected on days 1, 3, and 7. The primary outcome was all-cause in-hospital mortality. All patients were followed until death in hospital or hospital discharge, whichever occurred first. Secondary outcomes were ICU mortality, identification of independent predictors of mortality, duration of invasive mechanical ventilation, and patterns of change in physiological respiratory and mechanical ventilation variables. The study is registered with ClinicalTrials.gov, NCT04611269, and is complete. FINDINGS: Between March 20, 2020, and Oct 31, 2020, we enrolled 1909 invasively ventilated patients with COVID-19, with a median age of 62 years [IQR 52-70]. 1294 (67·8%) were men, hypertension and obesity were the main comorbidities, and 939 (49·2%) patients required vasopressors. Lung-protective ventilation was widely used and median duration of ventilation was 13 days (IQR 7-22). Median tidal volume was 6·1 mL/kg predicted bodyweight (IQR 6·0-7·0) on day 1, and the value increased significantly up to day 7; positive end-expiratory pressure was 10 cm H2O (8-12) on day 1, with a slight but significant decrease to day 7. Ratio of partial pressure of arterial oxygen (PaO2) to fractional inspired oxygen (FiO2) was 160 (IQR 111-218), respiratory system compliance 36 mL/cm H2O (29-44), driving pressure 12 cm H2O (10-14), and FiO2 0·60 (0·45-0·80) on day 1. Acute respiratory distress syndrome developed in 1672 (87·6%) of patients; 1176 (61·6%) received prone positioning. In-hospital mortality was 57·7% (1101/1909 patients) and ICU mortality was 57·0% (1088/1909 patients); 462 (43·8%) patients died of refractory hypoxaemia, frequently overlapping with septic shock (n=174). Cox regression identified age (hazard ratio 1·02 [95% CI 1·01-1·03]), Charlson score (1·16 [1·11-1·23]), endotracheal intubation outside of the ICU (ie, before ICU admission; 1·37 [1·10-1·71]), vasopressor use on day 1 (1·29 [1·07-1·55]), D-dimer concentration (1·02 [1·01-1·03]), PaO2/FiO2 on day 1 (0·998 [0·997-0·999]), arterial pH on day 1 (1·01 [1·00-1·01]), driving pressure on day 1 (1·05 [1·03-1·08]), acute kidney injury (1·66 [1·36-2·03]), and month of admission (1·10 [1·03-1·18]) as independent predictors of mortality. INTERPRETATION: In patients with COVID-19 who required invasive mechanical ventilation, lung-protective ventilation was widely used but mortality was high. Predictors of mortality in our study broadly agreed with those identified in studies of invasively ventilated patients in high-income countries. The sustained burden of COVID-19 on scarce health-care personnel might have contributed to high mortality over the course of our study in Argentina. These data might help to identify points for improvement in the management of patients in middle-income countries and elsewhere. FUNDING: None. TRANSLATION: For the Spanish translation of the Summary see Supplementary Materials section.


Subject(s)
COVID-19/therapy , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/therapy , Adult , Aged , Argentina/epidemiology , COVID-19/complications , COVID-19/diagnosis , COVID-19/mortality , COVID-19 Nucleic Acid Testing , Female , Hospital Mortality , Humans , Intensive Care Units/statistics & numerical data , Intubation, Intratracheal/statistics & numerical data , Male , Middle Aged , Prospective Studies , Respiration, Artificial/methods , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/mortality , Respiratory Insufficiency/virology , Risk Factors , SARS-CoV-2/isolation & purification , Tidal Volume , Treatment Outcome , Young Adult
7.
J Med Virol ; 93(9): 5416-5424, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1363679

ABSTRACT

The kinetics of IgG antibodies after coronavirus disease 2019 (COVID-19) remain poorly understood. We investigated factors influencing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody levels and time to seronegativation during the follow-up of severe and critically ill patients. We retrospectively reviewed serological evaluations drawn during the follow-up of severe or critical laboratory-proven COVID-19 patients hospitalized at a large academic hospital. Specific IgG titers were measured using a chemiluminescent assay targeting anti-spike and anti-nucleocapsid protein IgG. The influence of time, demographic factors, clinical and paraclinical characteristics, and COVID-19 therapeutics on IgG levels were assessed through linear regression using a mixed-effect model, and delay until IgG negativation through a Weibull regression model. The cohort included 116 patients with a total of 154 IgG measurements drawn at a median of 79 days after diagnosis. IgG antibodies were increased with age (p = 0.005) and decreased significantly over time (p = 0.0002). Using elapsed time and age as covariates, we demonstrated higher IgG levels in patients with a higher body mass index (BMI) (p = 0.0026) and lower IgG levels in immunocompromised patients (p = 0.032). A high BMI was further found to delay and immunodeficiency to hasten significantly seronegativation, whereas no significant effect was observed with corticosteroids. These data highlight the waning over time of IgG antibodies after severe or critical COVID-19. Age, BMI, and immunosuppression also appear to influence the IgG kinetics, while short-term corticotherapy does not. Those data improve the understanding of SARS-CoV-2 serology while further research should determine the determinants of long-term seroprotection.


Subject(s)
Antibodies, Viral/blood , COVID-19/immunology , Immunocompromised Host , Immunoglobulin G/blood , Respiratory Insufficiency/immunology , SARS-CoV-2/immunology , Adrenal Cortex Hormones/therapeutic use , Aged , Body Mass Index , COVID-19/blood , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Serological Testing , Convalescence , Female , Humans , Hydroxychloroquine/therapeutic use , Male , Middle Aged , Respiratory Insufficiency/blood , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/drug therapy , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time Factors
9.
Respir Med ; 187: 106571, 2021 10.
Article in English | MEDLINE | ID: covidwho-1347816

ABSTRACT

Since the beginning of COVID-19 pandemic, clinical, radiological and histopathological features consistent with viral-induced organizing pneumonia (OP) have been reported as hallmark characteristics of the disease. Here, we describe the case of ten patients with severe COVID-19 pneumonia treated with methylprednisolone 1mg/kg for showing clinical and radiological features suggestive of OP at least 20 days after symptom onset and despite standard treatment for COVID-19.


Subject(s)
COVID-19/complications , COVID-19/therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Methylprednisolone/administration & dosage , Respiratory Insufficiency/drug therapy , Aged , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology
10.
Respir Med ; 187: 106550, 2021 10.
Article in English | MEDLINE | ID: covidwho-1331211

ABSTRACT

INTRODUCTION: In COVID-19 associated hypoxemic acute respiratory failure (ARF) without mandatory indication for urgent endotracheal intubation, a trial of CPAP may be considered. We aimed to evaluate HACOR (heart rate, acidosis, consciousness, oxygenation, respiratory rate) score performance in these patients as predictor of CPAP failure. METHODS: Prospective observational multicentric study (three centers in different countries), including adult patients with SARS-CoV-2 pneumonia admitted to a respiratory intermediate care unit, presenting PaO2/FiO2 < 300 and PaCO2 < 45 mmHg, who received CPAP. One hour after starting CPAP, HACOR was calculated. RESULTS: We enrolled 128 patients, mean age 61,7 years. Mean HACOR at 1 h after starting CPAP was 3,27 ± 3,84 and mean PaO2/FiO2 was 203,30 ± 92,21 mmHg; 35 patients (27,3 %) presented CPAP failure: 29 underwent oro-tracheal intubation and 6 died due to COVID-19 (all having a do-not-intubate order). HACOR accuracy for predicting CPAP failure was 82,03 %, while PaO2/FiO2 accuracy was 81,25 %. CONCLUSION: Although HACOR score had a good diagnostic performance in predicting CPAP failure in COVID-19-related ARF, PaO2/FiO2 has also shown to be a good predictor of failure.


Subject(s)
COVID-19/complications , COVID-19/therapy , Continuous Positive Airway Pressure , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Acidosis , Aged , Blood Gas Analysis , COVID-19/physiopathology , Consciousness , Female , Heart Rate , Humans , Intubation, Intratracheal , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , ROC Curve , Respiratory Insufficiency/diagnosis , Respiratory Rate , Treatment Failure
11.
SLAS Discov ; 26(9): 1079-1090, 2021 10.
Article in English | MEDLINE | ID: covidwho-1314244

ABSTRACT

The recent renascence of phenotypic drug discovery (PDD) is catalyzed by its ability to identify first-in-class drugs and deliver results when the exact molecular mechanism is partially obscure. Acute respiratory distress syndrome (ARDS) is a severe, life-threatening condition with a high mortality rate that has increased in frequency due to the COVID-19 pandemic. Despite decades of laboratory and clinical study, no efficient pharmacological therapy for ARDS has been found. An increase in endothelial permeability is the primary event in ARDS onset, causing the development of pulmonary edema that leads to respiratory failure. Currently, the detailed molecular mechanisms regulating endothelial permeability are poorly understood. Therefore, the use of the PDD approach in the search for efficient ARDS treatment can be more productive than classic target-based drug discovery (TDD), but its use requires a new cell-based assay compatible with high-throughput (HTS) and high-content (HCS) screening. Here we report the development of a new plate-based image cytometry method to measure endothelial barrier function. The incorporation of image cytometry in combination with digital image analysis substantially decreases assay variability and increases the signal window. This new method simultaneously allows for rapid measurement of cell monolayer permeability and cytological analysis. The time-course of permeability increase in human pulmonary artery endothelial cells (HPAECs) in response to the thrombin and tumor necrosis factor α treatment correlates with previously published data obtained by transendothelial resistance (TER) measurements. Furthermore, the proposed image cytometry method can be easily adapted for HTS/HCS applications.


Subject(s)
COVID-19/diagnostic imaging , High-Throughput Screening Assays/methods , Image Cytometry/methods , Respiratory Distress Syndrome/diagnostic imaging , COVID-19/diagnosis , COVID-19/virology , Cell Membrane Permeability/genetics , Drug Discovery , Endothelial Cells/ultrastructure , Endothelial Cells/virology , Humans , Image Processing, Computer-Assisted , Pandemics/prevention & control , Phenotype , Pulmonary Artery/diagnostic imaging , Pulmonary Artery/pathology , Pulmonary Artery/virology , Pulmonary Edema/diagnosis , Pulmonary Edema/diagnostic imaging , Pulmonary Edema/virology , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/virology , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/diagnostic imaging , Respiratory Insufficiency/virology , SARS-CoV-2/pathogenicity , Thrombin/pharmacology , Tumor Necrosis Factor-alpha/pharmacology
12.
Molecules ; 25(19)2020 Sep 24.
Article in English | MEDLINE | ID: covidwho-1302391

ABSTRACT

There is a vast practice of using antimalarial drugs, RAS inhibitors, serine protease inhibitors, inhibitors of the RNA-dependent RNA polymerase of the virus and immunosuppressants for the treatment of the severe form of COVID-19, which often occurs in patients with chronic diseases and older persons. Currently, the clinical efficacy of these drugs for COVID-19 has not been proven yet. Side effects of antimalarial drugs can worsen the condition of patients and increase the likelihood of death. Peptides, given their physiological mechanism of action, have virtually no side effects. Many of them are geroprotectors and can be used in patients with chronic diseases. Peptides may be able to prevent the development of the pathological process during COVID-19 by inhibiting SARS-CoV-2 virus proteins, thereby having immuno- and bronchoprotective effects on lung cells, and normalizing the state of the hemostasis system. Immunomodulators (RKDVY, EW, KE, AEDG), possessing a physiological mechanism of action at low concentrations, appear to be the most promising group among the peptides. They normalize the cytokines' synthesis and have an anti-inflammatory effect, thereby preventing the development of disseminated intravascular coagulation, acute respiratory distress syndrome and multiple organ failure.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Immunologic Factors/therapeutic use , Peptides/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory System Agents/therapeutic use , Acute Disease , Anti-Inflammatory Agents/chemical synthesis , Antiviral Agents/chemical synthesis , Betacoronavirus/drug effects , Betacoronavirus/growth & development , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/drug therapy , Cytokine Release Syndrome/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/virology , Host-Pathogen Interactions/drug effects , Humans , Immunologic Factors/chemical synthesis , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Pandemics , Peptides/chemical synthesis , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/prevention & control , Respiratory Insufficiency/virology , Respiratory System Agents/chemical synthesis , SARS-CoV-2 , Structure-Activity Relationship
13.
Am J Physiol Lung Cell Mol Physiol ; 321(2): L485-L489, 2021 08 01.
Article in English | MEDLINE | ID: covidwho-1299247

ABSTRACT

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.


Subject(s)
COVID-19/complications , Complement Activation/immunology , Complement C3b/immunology , Complement C4b/immunology , Erythrocytes/immunology , Peptide Fragments/immunology , Respiratory Insufficiency/diagnosis , Sepsis/diagnosis , COVID-19/immunology , COVID-19/virology , Complement C3b/metabolism , Complement C4b/metabolism , Erythrocytes/metabolism , Erythrocytes/virology , Female , Humans , Male , Middle Aged , Peptide Fragments/metabolism , Respiratory Insufficiency/immunology , Respiratory Insufficiency/metabolism , Respiratory Insufficiency/virology , SARS-CoV-2/isolation & purification , Sepsis/immunology , Sepsis/metabolism , Sepsis/virology
14.
Lancet Respir Med ; 9(9): 957-968, 2021 09.
Article in English | MEDLINE | ID: covidwho-1275790

ABSTRACT

BACKGROUND: The major complication of COVID-19 is hypoxaemic respiratory failure from capillary leak and alveolar oedema. Experimental and early clinical data suggest that the tyrosine-kinase inhibitor imatinib reverses pulmonary capillary leak. METHODS: This randomised, double-blind, placebo-controlled, clinical trial was done at 13 academic and non-academic teaching hospitals in the Netherlands. Hospitalised patients (aged ≥18 years) with COVID-19, as confirmed by an RT-PCR test for SARS-CoV-2, requiring supplemental oxygen to maintain a peripheral oxygen saturation of greater than 94% were eligible. Patients were excluded if they had severe pre-existing pulmonary disease, had pre-existing heart failure, had undergone active treatment of a haematological or non-haematological malignancy in the previous 12 months, had cytopenia, or were receiving concomitant treatment with medication known to strongly interact with imatinib. Patients were randomly assigned (1:1) to receive either oral imatinib, given as a loading dose of 800 mg on day 0 followed by 400 mg daily on days 1-9, or placebo. Randomisation was done with a computer-based clinical data management platform with variable block sizes (containing two, four, or six patients), stratified by study site. The primary outcome was time to discontinuation of mechanical ventilation and supplemental oxygen for more than 48 consecutive hours, while being alive during a 28-day period. Secondary outcomes included safety, mortality at 28 days, and the need for invasive mechanical ventilation. All efficacy and safety analyses were done in all randomised patients who had received at least one dose of study medication (modified intention-to-treat population). This study is registered with the EU Clinical Trials Register (EudraCT 2020-001236-10). FINDINGS: Between March 31, 2020, and Jan 4, 2021, 805 patients were screened, of whom 400 were eligible and randomly assigned to the imatinib group (n=204) or the placebo group (n=196). A total of 385 (96%) patients (median age 64 years [IQR 56-73]) received at least one dose of study medication and were included in the modified intention-to-treat population. Time to discontinuation of ventilation and supplemental oxygen for more than 48 h was not significantly different between the two groups (unadjusted hazard ratio [HR] 0·95 [95% CI 0·76-1·20]). At day 28, 15 (8%) of 197 patients had died in the imatinib group compared with 27 (14%) of 188 patients in the placebo group (unadjusted HR 0·51 [0·27-0·95]). After adjusting for baseline imbalances between the two groups (sex, obesity, diabetes, and cardiovascular disease) the HR for mortality was 0·52 (95% CI 0·26-1·05). The HR for mechanical ventilation in the imatinib group compared with the placebo group was 1·07 (0·63-1·80; p=0·81). The median duration of invasive mechanical ventilation was 7 days (IQR 3-13) in the imatinib group compared with 12 days (6-20) in the placebo group (p=0·0080). 91 (46%) of 197 patients in the imatinib group and 82 (44%) of 188 patients in the placebo group had at least one grade 3 or higher adverse event. The safety evaluation revealed no imatinib-associated adverse events. INTERPRETATION: The study failed to meet its primary outcome, as imatinib did not reduce the time to discontinuation of ventilation and supplemental oxygen for more than 48 consecutive hours in patients with COVID-19 requiring supplemental oxygen. The observed effects on survival (although attenuated after adjustment for baseline imbalances) and duration of mechanical ventilation suggest that imatinib might confer clinical benefit in hospitalised patients with COVID-19, but further studies are required to validate these findings. FUNDING: Amsterdam Medical Center Foundation, Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ZonMW, and the European Union Innovative Medicines Initiative 2.


Subject(s)
COVID-19/therapy , Imatinib Mesylate/administration & dosage , Protein Kinase Inhibitors/administration & dosage , Respiration, Artificial/statistics & numerical data , Respiratory Insufficiency/therapy , Aged , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Capillary Permeability/drug effects , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Double-Blind Method , Female , Humans , Imatinib Mesylate/adverse effects , Male , Middle Aged , Netherlands , Oxygen/administration & dosage , Placebos/administration & dosage , Placebos/adverse effects , Protein Kinase Inhibitors/adverse effects , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology , SARS-CoV-2/isolation & purification , Severity of Illness Index , Time Factors , Treatment Outcome
15.
J Pediatr ; 237: 143-147, 2021 10.
Article in English | MEDLINE | ID: covidwho-1242546

ABSTRACT

OBJECTIVE: To assess whether use of an N95 mask by children is associated with episodes of desaturation or respiratory distress. STUDY DESIGN: Twenty-two healthy children were assigned at random to 1 of 2 groups: one group wearing N95 masks without an exhalation valve and the other group wearing N95 masks with an exhalation valve. We tracked changes in partial pressure of end-tidal carbon dioxide (PETCO2), oxygen saturation, pulse rate, and respiratory rate over 72 minutes of mask use. All subjects were monitored every 15 minutes, the first 30 minutes while not wearing a mask and the next 30 minutes while wearing a mask. They then performed a 12-minute walking test. RESULTS: The children did not experience a statistically significant change in oxygen saturation or pulse rate during the study. There were significant increases in respiratory rate and PETCO2 in the children wearing an N95 mask without an exhalation valve, whereas these increases were seen in the children wearing a mask with an exhalation valve only after the walking test. CONCLUSIONS: The use of an N95 mask could potentially cause breathing difficulties in children if the mask does not have an exhalation valve, particularly during a physical activity. We believe that wearing a surgical mask may be more appropriate for children.


Subject(s)
N95 Respirators/adverse effects , Respiratory Insufficiency/etiology , Biomarkers/metabolism , Carbon Dioxide/metabolism , Child , Child, Preschool , Exercise/physiology , Female , Heart Rate , Humans , Male , Oxygen/metabolism , Respiratory Function Tests , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/metabolism , Respiratory Rate , Risk Factors , Walk Test
16.
J Biomed Inform ; 119: 103802, 2021 07.
Article in English | MEDLINE | ID: covidwho-1219050

ABSTRACT

BACKGROUND: Unlike well-established diseases that base clinical care on randomized trials, past experiences, and training, prognosis in COVID19 relies on a weaker foundation. Knowledge from other respiratory failure diseases may inform clinical decisions in this novel disease. The objective was to predict 48-hour invasive mechanical ventilation (IMV) within 48 h in patients hospitalized with COVID-19 using COVID-like diseases (CLD). METHODS: This retrospective multicenter study trained machine learning (ML) models on patients hospitalized with CLD to predict IMV within 48 h in COVID-19 patients. CLD patients were identified using diagnosis codes for bacterial pneumonia, viral pneumonia, influenza, unspecified pneumonia and acute respiratory distress syndrome (ARDS), 2008-2019. A total of 16 cohorts were constructed, including any combinations of the four diseases plus an exploratory ARDS cohort, to determine the most appropriate cohort to use. Candidate predictors included demographic and clinical parameters that were previously associated with poor COVID-19 outcomes. Model development included the implementation of logistic regression and three ensemble tree-based algorithms: decision tree, AdaBoost, and XGBoost. Models were validated in hospitalized COVID-19 patients at two healthcare systems, March 2020-July 2020. ML models were trained on CLD patients at Stanford Hospital Alliance (SHA). Models were validated on hospitalized COVID-19 patients at both SHA and Intermountain Healthcare. RESULTS: CLD training data were obtained from SHA (n = 14,030), and validation data included 444 adult COVID-19 hospitalized patients from SHA (n = 185) and Intermountain (n = 259). XGBoost was the top-performing ML model, and among the 16 CLD training cohorts, the best model achieved an area under curve (AUC) of 0.883 in the validation set. In COVID-19 patients, the prediction models exhibited moderate discrimination performance, with the best models achieving an AUC of 0.77 at SHA and 0.65 at Intermountain. The model trained on all pneumonia and influenza cohorts had the best overall performance (SHA: positive predictive value (PPV) 0.29, negative predictive value (NPV) 0.97, positive likelihood ratio (PLR) 10.7; Intermountain: PPV, 0.23, NPV 0.97, PLR 10.3). We identified important factors associated with IMV that are not traditionally considered for respiratory diseases. CONCLUSIONS: The performance of prediction models derived from CLD for 48-hour IMV in patients hospitalized with COVID-19 demonstrate high specificity and can be used as a triage tool at point of care. Novel predictors of IMV identified in COVID-19 are often overlooked in clinical practice. Lessons learned from our approach may assist other research institutes seeking to build artificial intelligence technologies for novel or rare diseases with limited data for training and validation.


Subject(s)
COVID-19 , Respiratory Insufficiency , Adult , Artificial Intelligence , Hospitalization , Humans , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2 , Triage , Ventilators, Mechanical
17.
Carbohydr Res ; 505: 108326, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1213065

ABSTRACT

The viral infection caused by SARS-CoV-2 has increased the mortality rate and engaged several adverse effects on the affected individuals. Currently available antiviral drugs have found to be unsuccessful in the treatment of COVID-19 patients. The demand for efficient antiviral drugs has created a huge burden on physicians and health workers. Plasma therapy seems to be less accomplishable due to insufficient donors to donate plasma and low recovery rate from viral infection. Repurposing of antivirals has been evolved as a suitable strategy in the current treatment and preventive measures. The concept of drug repurposing represents new experimental approaches for effective therapeutic benefits. Besides, SARS-CoV-2 exhibits several complications such as lung damage, blood clot formation, respiratory illness and organ failures in most of the patients. Based on the accumulation of data, sulfated marine polysaccharides have exerted successful inhibition of virus entry, attachment and replication with known or unknown possible mechanisms against deadly animal and human viruses so far. Since the virus entry into the host cells is the key process, the prevention of such entry mechanism makes any antiviral strategy effective. Enveloped viruses are more sensitive to polyanions than non-enveloped viruses. Besides, the viral infection caused by RNA virus types embarks severe oxidative stress in the human body that leads to malfunction of tissues and organs. In this context, polysaccharides play a very significant role in providing shielding effect against the virus due to their polyanionic rich features and a molecular weight that hinders their reactive surface glycoproteins. Significantly the functional groups especially sulfate, sulfate pattern and addition, uronic acids, monosaccharides, glycosidic linkage and high molecular weight have greater influence in the antiviral activity. Moreover, they are very good antioxidants that can reduce the free radical generation and provokes intracellular antioxidant enzymes. Additionally, polysaccharides enable a host-virus immune response, activate phagocytosis and stimulate interferon systems. Therefore, polysaccharides can be used as candidate drugs, adjuvants in vaccines or combination with other antivirals, antioxidants and immune-activating nutritional supplements and antiviral materials in healthcare products to prevent SARS-CoV-2 infection.


Subject(s)
Anticoagulants/therapeutic use , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Immunologic Factors/therapeutic use , Polysaccharides/therapeutic use , Pulmonary Embolism/drug therapy , Respiratory Insufficiency/drug therapy , Anticoagulants/chemistry , Anticoagulants/isolation & purification , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/diagnosis , COVID-19/virology , Humans , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Phaeophyta/chemistry , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Pulmonary Embolism/virology , Respiratory Insufficiency/complications , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/virology , Rhodophyta/chemistry , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Sulfuric Acid Esters/chemistry , Virus Attachment/drug effects , Virus Internalization/drug effects
18.
Expert Rev Respir Med ; 15(8): 1013-1023, 2021 08.
Article in English | MEDLINE | ID: covidwho-1180435

ABSTRACT

INTRODUCTION: It is uncertain whether ventilation in patients with acute respiratory failure related to coronavirus disease 2019 (COVID-19) differs from that in patients with acute respiratory distress syndrome (ARDS) from another origin. AREAS COVERED: We undertook two literature searches in PubMed to identify observational studies reporting on ventilation management--one in patients with acute respiratory failure related to COVID-19, and one in patients with ARDS from another origin. The searches identified 14 studies in patients with acute respiratory failure related to COVID-19, and 8 studies in patients with ARDS from another origin. EXPERT OPINION: In patients with acute respiratory failure related to COVID-19, ventilation management seems to be similar to that of patients with ARDS from another origin. The future lies in studies focused on personalized treatment of ARDS of all origins, including COVID-19.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Respiratory Insufficiency , Humans , Lung , Respiration, Artificial , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/therapy , SARS-CoV-2
19.
Interact Cardiovasc Thorac Surg ; 33(3): 489-493, 2021 08 18.
Article in English | MEDLINE | ID: covidwho-1171685

ABSTRACT

OBJECTIVES: Treatment of severe acute respiratory distress syndrome (ARDS) induced by severe acute respiratory syndrome coronavirus 2 has been heavily debated. Our goal was to describe our findings in patients with severe ARDS due to severe coronavirus disease 2019 (sCOVID-19) treated with venovenous extracorporeal membrane oxygenation (vv-ECMO). METHODS: We retrospectively examined all patients treated with vv-ECMO for severe ARDS due to acute respiratory syndrome coronavirus 2. RESULTS: In total, 13 patients were treated with vv-ECMO in our medical centre. The mean patient age was 48.1 years. Most patients were obese (69%) and male (85%). All patients were mechanically ventilated before ECMO. The mean time from intubation to proning was 16.6 h; the time from start of prone therapy to vv-ECMO implantation was 155.1 h. The mean total ECMO run time was 358 h. Significant reduction of positive end-expiratory pressure (P = 0.02), peak pressure (P = 0.001) and minute volume (P = 0.03) could be achieved after implantation of vv-ECMO. All patients showed an inflammatory response. Overall mortality was 30.7%: 1 patient died of mesenteric ischaemia; 3 patients died of multiple organ failure. A worse prognosis was seen in patients with highly elevated concentrations of interleukin-6. CONCLUSIONS: The use of vv-ECMO in patients with sCOVID-19-induced ARDS is safe and associated with improved respiratory ventilation settings. The rate of immune system involvement plays a pivotal role in the development and outcome of sCOVID-19.


Subject(s)
COVID-19 , Extracorporeal Membrane Oxygenation , Respiratory Distress Syndrome , Respiratory Insufficiency , COVID-19/complications , Humans , Male , Middle Aged , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/etiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
SELECTION OF CITATIONS
SEARCH DETAIL
...