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1.
Braz J Cardiovasc Surg ; 37(1): 35-47, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-2311398

ABSTRACT

INTRODUCTION: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. METHODS: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. RESULTS: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. CONCLUSION: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/therapy , Heparin/therapeutic use , Humans , Intensive Care Units , Respiratory Distress Syndrome/therapy , SARS-CoV-2
2.
J Intensive Med ; 2(2): 103-109, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-2240988

ABSTRACT

Background: There are insufficient data regarding the impact of acute respiratory distress syndrome related to coronavirus disease 2019 (C-ARDS) - caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - on health-related quality of life (HRQoL) and the occurrence of stress-related disorders in coronavirus disease 2019 (COVID-19) intensive care unit (ICU) survivors. The aim of this study is to assess HRQoL and the occurrence of stress-related disorders (acute stress disorder [ASD] and post-traumatic stress disorder [PTSD]) in C-ARDS ICU survivors at 1 and 6 months following hospital discharge. Methods: This prospective observational study included 90 patients treated for C-ARDS between March and May 2020 in the ICU and discharged alive from the hospital. All patients included in the study were contacted by telephone 1 month and 6 months post-hospital discharge to assess the presence of symptoms of stress-related disorders and HRQoL using the 8-item Treatment Outcome Post-traumatic Stress Disorder scale (TOP-8) and 36-item Short Form survey (SF-36). We performed univariate analyses to evaluate differences between patients who developed stress and those who did not. We also compared SF-36 scores in our sample with data from the general Spanish population and from cohorts of non-C-ARDS and severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) survivors. Results: There are 24.1% of patients showed symptoms of ASD; in 13.5% of cases the symptoms persisted 6 months later. Risk factors for the development of symptoms of ASD and PTSD are younger age, female sex, obesity, a previously diagnosed psychiatric disease and disease severity at ICU admission (P < 0.05). HRQoL was greatly affected by C-ARDS; however, there was improvement on all scales of the SF-36 at the 6-month follow-up (P < 0.05). The mean SF-36 score of our sample was higher than those previously reported in non-C-ARDS survivors (P < 0.05) for physical functioning (78.0 vs. 52.0), role functioning/physical (51.0 vs. 31.0), bodily pain (76.1 vs. 57.0), vitality (58.6 vs. 48.0), social function (72.6 vs. 63.0) and role emotional (77.4 vs. 55.0), except on the general health scale. C-ARDS survivors also scored better than SARS-CoV-1 survivors on all scales except for body pain (P < 0.05). Conclusions: The impact of C-ARDS on HRQoL is substantial, with frequent occurrence of PTSD symptoms. Patients are heavily affected in all areas of health in the first month of post-hospital discharge but show a dramatic improvement within 6 months, especially in terms of physical health.

3.
Rev Med Inst Mex Seguro Soc ; 58(Supl 2): S323-328, 2020 09 21.
Article in Spanish | MEDLINE | ID: covidwho-1485718

ABSTRACT

BACKGROUND: The COVID-19 (from Coronavirus Disease 2019) is a disease that has generated a pandemic that has affected the world, Mexico included. The spectrum of the disease ranges from asymptomatic infection to severe acute respiratory distress syndrome (ARDS). The objective of the case is to demonstrate the usefulness of the prone position in non-intubated patients. CLINICAL CASE: We present the case of a woman without comorbidities with COVID-19 and moderate ARDS, in whom intubation was avoided after improvement with the prone position, as determined by arterial oxygen saturation by pulse oximetry and by the relationship of arterial oxygen pressure and the fraction of inspired oxygen (PaO2/FiO2). CONCLUSION: There is scarce evidence of this therapeutic maneuver in awake patients. However, it can help to improve oxygenation and to avoid intubation in these patients.


INTRODUCCIÓN: la COVID-19 (del inglés Coronavirus Disease 2019) es una enfermedad que ha generado una pandemia, la cual ha afectado a todo el mundo, incluido México. Esta enfermedad puede presentarse desde una infección asintomática hasta síndrome de distrés respiratorio agudo (SDRA) grave. El objetivo del reporte de caso es mostrar la utilidad de la posición prono en pacientes no intubados. CASO CLÍNICO: presentamos el caso de una mujer sin comorbilidades con COVID-19 y SDRA moderado, en quien se evitó la intubación tras la mejoría con la posición prono, evaluada por la saturación arterial de oxígeno por pulsioximetría y por la relación de la presión arterial de oxígeno y la fracción inspirada de oxígeno (PaO2/FiO2). CONCLUSIÓN: existe poca evidencia sobre esta maniobra terapéutica en pacientes despiertos. Sin embargo, puede ser de ayuda para mejorar la oxigenación y evitar la intubación en estos pacientes.

4.
Intensive Care Med Exp ; 8(1): 10, 2020 Feb 21.
Article in English | MEDLINE | ID: covidwho-1453066

ABSTRACT

BACKGROUND: Real-time bedside information on regional ventilation and perfusion during mechanical ventilation (MV) may help to elucidate the physiological and pathophysiological effects of MV settings in healthy and injured lungs. We aimed to study the effects of positive end-expiratory pressure (PEEP) and tidal volume (VT) on the distributions of regional ventilation and perfusion by electrical impedance tomography (EIT) in healthy and injured lungs. METHODS: One-hit acute lung injury model was established in 6 piglets by repeated lung lavages (injured group). Four ventilated piglets served as the control group. A randomized sequence of any possible combination of three VT (7, 10, and 15 ml/kg) and four levels of PEEP (5, 8, 10, and 12 cmH2O) was performed in all animals. Ventilation and perfusion distributions were computed by EIT within three regions-of-interest (ROIs): nondependent, middle, dependent. A mixed design with one between-subjects factor (group: intervention or control), and two within-subjects factors (PEEP and VT) was used, with a three-way mixed analysis of variance (ANOVA). RESULTS: Two-way interactions between PEEP and group, and VT and group, were observed for the dependent ROI (p = 0.035 and 0.012, respectively), indicating that the increase in the dependent ROI ventilation was greater at higher PEEP and VT in the injured group than in the control group. A two-way interaction between PEEP and VT was observed for perfusion distribution in each ROI: nondependent (p = 0.030), middle (p = 0.006), and dependent (p = 0.001); no interaction was observed between injured and control groups. CONCLUSIONS: Large PEEP and VT levels were associated with greater pulmonary ventilation of the dependent lung region in experimental lung injury, whereas they affected pulmonary perfusion of all lung regions both in the control and in the experimental lung injury groups.

5.
IDCases ; 26: e01274, 2021.
Article in English | MEDLINE | ID: covidwho-1377724

ABSTRACT

Severe coronavirus disease (COVID-19) associated pneumonia leads to acute respiratory distress syndrome and emerging data suggest fungal coinfections also contribute to mortality in this patient population. Aspergillus ventilator associated pneumonia is increasingly recognized. We describe a case of likely reactivation of community acquired Cryptococcus neoformans in a patient with severe COVID-19.

6.
BMC Anesthesiol ; 21(1): 145, 2021 05 12.
Article in English | MEDLINE | ID: covidwho-1225757

ABSTRACT

BACKGROUND: Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach. CASE PRESENTATION: A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg. CONCLUSIONS: An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient's oxygenation has to be ensured at the expense of lung protective ventilation concepts.


Subject(s)
COVID-19/therapy , Respiration, Artificial/methods , Air Pressure , COVID-19/complications , Compliance , Female , Humans , Intubation, Intratracheal , Middle Aged , Positive-Pressure Respiration , Precision Medicine , Respiratory Distress Syndrome/etiology , Respiratory Distress Syndrome/therapy , Respiratory Mechanics , Stress, Mechanical , Tomography, X-Ray Computed , Ventilators, Mechanical
7.
Crit Care ; 25(1): 106, 2021 03 16.
Article in English | MEDLINE | ID: covidwho-1136238

ABSTRACT

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare system globally. Lack of high-quality evidence on the respiratory management of COVID-19-related acute respiratory failure (C-ARF) has resulted in wide variation in clinical practice. METHODS: Using a Delphi process, an international panel of 39 experts developed clinical practice statements on the respiratory management of C-ARF in areas where evidence is absent or limited. Agreement was defined as achieved when > 70% experts voted for a given option on the Likert scale statement or > 80% voted for a particular option in multiple-choice questions. Stability was assessed between the two concluding rounds for each statement, using the non-parametric Chi-square (χ2) test (p < 0·05 was considered as unstable). RESULTS: Agreement was achieved for 27 (73%) management strategies which were then used to develop expert clinical practice statements. Experts agreed that COVID-19-related acute respiratory distress syndrome (ARDS) is clinically similar to other forms of ARDS. The Delphi process yielded strong suggestions for use of systemic corticosteroids for critical COVID-19; awake self-proning to improve oxygenation and high flow nasal oxygen to potentially reduce tracheal intubation; non-invasive ventilation for patients with mixed hypoxemic-hypercapnic respiratory failure; tracheal intubation for poor mentation, hemodynamic instability or severe hypoxemia; closed suction systems; lung protective ventilation; prone ventilation (for 16-24 h per day) to improve oxygenation; neuromuscular blocking agents for patient-ventilator dyssynchrony; avoiding delay in extubation for the risk of reintubation; and similar timing of tracheostomy as in non-COVID-19 patients. There was no agreement on positive end expiratory pressure titration or the choice of personal protective equipment. CONCLUSION: Using a Delphi method, an agreement among experts was reached for 27 statements from which 20 expert clinical practice statements were derived on the respiratory management of C-ARF, addressing important decisions for patient management in areas where evidence is either absent or limited. TRIAL REGISTRATION: The study was registered with Clinical trials.gov Identifier: NCT04534569.


Subject(s)
COVID-19/complications , Consensus , Delphi Technique , Respiratory Insufficiency/therapy , Respiratory Insufficiency/virology , Humans
8.
J Anesth ; 35(2): 213-221, 2021 04.
Article in English | MEDLINE | ID: covidwho-1042487

ABSTRACT

PURPOSE: Coronavirus disease 2019 (COVID-19) has placed a great burden on critical care services worldwide. Data regarding critically ill COVID-19 patients and their demand of critical care services outside of initial COVID-19 epicenters are lacking. This study described clinical characteristics and outcomes of critically ill COVID-19 patients and the capacity of a COVID-19-dedicated intensive care unit (ICU) in Kobe, Japan. METHODS: This retrospective observational study included critically ill COVID-19 patients admitted to a 14-bed COVID-19-dedicated ICU in Kobe between March 3, 2020 and June 21, 2020. Clinical and daily ICU occupancy data were obtained from electrical medical records. The last follow-up day was June 28, 2020. RESULTS: Of 32 patients included, the median hospital follow-up period was 27 (interquartile range 19-50) days. The median age was 68 (57-76) years; 23 (72%) were men and 25 (78%) had at least one comorbidity. Nineteen (59%) patients received invasive mechanical ventilation for a median duration of 14 (8-27) days. Until all patients were discharged from the ICU on June 5, 2020, the median daily ICU occupancy was 50% (36-71%). As of June 28, 2020, six (19%) died during hospitalization. Of 26 (81%) survivors, 23 (72%) were discharged from the hospital and three (9%) remained in the hospital. CONCLUSION: During the first months of the outbreak in Kobe, most critically ill patients were men aged ≥ 60 years with at least one comorbidity and on mechanical ventilation; the ICU capacity was not strained, and the case-fatality rate was 19%.


Subject(s)
COVID-19 , Critical Illness , Aged , Humans , Intensive Care Units , Japan , Male , Respiration, Artificial , Retrospective Studies , SARS-CoV-2
10.
Lasers Med Sci ; 36(5): 935-938, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-947037

ABSTRACT

COVID-19 is now a worldwide concern, causing an unprecedented pandemic. The infected cases show different symptoms based on the severity of the disease. In asymptomatic and non-severe symptomatic cases, the host immune system can successfully eliminate the virus and its effects. In severe cases, however, immune system impairment causes cytokine release syndrome which eventually leads to acute respiratory distress syndrome (ARDS). In recent years, photobiomodulation (PBM) has shown promising results in reducing acute pulmonary inflammation. Considering the high potential impact of PBM on immune responses, we hypothesized that using PBM could be an effective treatment modality for ARDS management in COVID-19 patients.


Subject(s)
COVID-19/radiotherapy , Low-Level Light Therapy , Anti-Inflammatory Agents/therapeutic use , COVID-19/virology , Humans , Pneumonia/radiotherapy , SARS-CoV-2/physiology
11.
Autops Case Rep ; 10(3): e2020194, 2020 Aug 14.
Article in English | MEDLINE | ID: covidwho-940307

ABSTRACT

We report on a 3-month old infant male who had a seven-days history of fever and rhinorrhea associated with wheezing prior to his death, during the Covid-19 pandemic. Viral testing for Covid-19 (SARS-CoV-2) was negative but was positive for Coronavirus 229E and RP Human Rhinovirus. The pulmonary histological examination showed diffuse alveolar damage along with thrombotic microangiopathy affecting alveolar capillaries. Also, thrombotic microangiopathy was evident in the heart, lungs, brain, kidneys and liver. Thrombotic microangiopathy is a major pathologic finding in Acute Respiratory Distress Syndrome and in the multiorgan failure. This is the first report that illustrates thrombotic microangiopathy occurring in lung, heart, liver, kidney and brain in Acute Respiratory Distress Syndrome with Coronavirus 229E with Rhinovirus co-infection. The clinical presentation and pathological findings in our case share common features with Covid-19.

12.
Crit Care Explor ; 2(10): e0232, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-873086

ABSTRACT

Effective treatments for the critically ill patient with novel coronavirus disease 2019 are desperately needed. Given the role of cytokine release syndrome in the pathogenesis of coronavirus disease 2019-associated respiratory distress, therapies aimed at mitigating cytokine release, such as the interleukin-6 receptor-inhibiting monoclonal antibody tocilizumab, represent potential treatment strategies. Therefore, we examined the outcomes of critically ill coronavirus disease 2019 patients treated with tocilizumab and factors associated with clinical improvement. DESIGN: A retrospective cohort analysis of 21-day outcomes for consecutive mechanically ventilated patients treated with tocilizumab from March 24, 2020, to May 4, 2020. SETTING: Nine ICUs at six hospitals within a hospital system in Houston, Texas, United States. PATIENTS: The first 62 coronavirus disease 2019 patients on invasive mechanical ventilation who were treated with tocilizumab, which was considered for all patients with severe disease. INTERVENTIONS: Tocilizumab was administered either at a weight-based dose of 4-8 mg/kg or at a flat dose of 400 mg, with repeat administration in some patients at the physician's discretion. MEASUREMENTS AND MAIN RESULTS: The primary outcomes were mortality and clinical improvement, defined as extubation. By day 21 post-tocilizumab, clinical improvement occurred in 36 patients (58%) and 13 patients (21%) died. In both univariable and multivariable analyses, age less than 60 years was associated with clinical improvement. Transient transaminitis was the most common adverse reaction, occurring in 25 patients (40%). CONCLUSIONS: Based on clinical outcomes and mortality rates seen in previous reports of mechanically ventilated patients, tocilizumab, as part of the management strategy for severe coronavirus disease 2019, represents a promising option. These findings support the need for evaluation of tocilizumab in a randomized controlled trial.

14.
Ultrasound J ; 12(1): 39, 2020 Aug 17.
Article in English | MEDLINE | ID: covidwho-709902

ABSTRACT

Coronavirus disease of 2019 (COVID-19) is a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has rapidly spread to a global pandemic in March 2020. This emergency condition has been putting a severe strain on healthcare systems worldwide, and a prompt, dynamic response is instrumental in its management. While a definite diagnosis is based on microbiological evidence, the relationship between lung ultrasound (LU) and high-resolution computed tomography (HRCT) in the diagnosis and management of COVID-19 is less clear. Lung ultrasound is a point-of-care imaging tool that proved to be useful in the identification and severity assessment of different pulmonary conditions, particularly in the setting of emergency and critical care patients in intensive care units; HRCT of the thorax is regarded as the mainstay of imaging evaluation of lung disorders, enabling characterization and quantification of pulmonary involvement. Aims of this review are to describe LU and chest HRCT main imaging features of COVID-19 pneumonia, and to provide state-of-the-art insights regarding the integrated role of these techniques in the clinical decision-making process of patients affected by this infectious disease.

15.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(8): 659-664, 2020 Aug 12.
Article in Chinese | MEDLINE | ID: covidwho-691351

ABSTRACT

Objective: To investigate the causes of death in patients with severe COVID-19. Methods: A retrospective analysis was performed on 64 patients with severe COVID-19 admitted to Wuhan Pulmonary Hospital from January 12, 2020 to February 28, 2020. There were 36 males and 28 females, aging from 44 to 85 years[median 68 (62, 72)]. Fifty-two patients (81%) had underlying comorbidities. The patients were divided into the death group (n=40) and the survival group (n=24) according to the treatment outcomes. In the death group, 24 were male, and 16 were female, aging from 49 to 85 years [median 69 (62, 72)], with 31 cases (78%) complicated with underlying diseases. In the survival group, there were 12 males and 12 females, aging from 44 to 82 years[median 66 (61,73)], with 21 cases (88%) with comorbidities. Clinical data of the two groups were collected and compared, including general information, laboratory examinations, imaging features and treatments. For normally distributed data, independent group t test was used; otherwise, Mann Whitney test was used to compare the variables. χ(2) test and Fisher exact test was used when analyzing categorical variables. Results: The median of creatine kinase isozyme (CK-MB) in the death group was 19.0 (17.0,23.0) U/L, which was higher than that in the survival group 16.5 (13.5,19.6) U/L. The median level of cTnI in the death group was 0.03 (0.03, 0.07) µg/L, which was significantly higher than that in the survival group (0.02, 0.03) µg/L, with a statistically significant difference between the two groups (P=0.007). The concentration of myoglobin in the death group was 79.5 (28.7, 189.0) µg/L, which was higher than 33.1 (25.7, 54.5) µg/L in the survival group. The level of D-dimer in the death group was 2.0 (0.6, 5.2) mg/L, which was higher than 0.7 (0.4, 2.0) mg/L in the survival group. The LDH level of the death group was 465.0 (337.5,606.5) U/L, which was higher than that of the survibal group, 341.0 (284.0,430.0) U/L, the difference being statistically significant (P=0.006). The concentration of alanine aminotransferase in the death group was 40.0 (30.0, 48.0) U/L, which was higher than 32.5 (24.0, 40.8) U/L in the survival group, and the difference was statistically significant (P=0.047).Abnormal ECG was found in 16 cases (62%) in the death group, which was significantly higher than that in the survival group (29%), the difference being statistically significant (P=0.024) .The main causes of death were severe pneumonia with acute respiratory distress syndrome (ARDS, n=20), acute heart failure(n=9), atrial fibrillation(n=3) and multiple organ dysfunction syndrome (MODS, n=3). Conclusions: ARDS caused by severe pneumonia and acute heart failure and atrial fibrillation caused by acute viral myocarditis were the main causes of death in severe COVID-19 patients. Early prevention of myocardial injury and treatment of acute viral myocarditis complicated with disease progression may provide insights into treatment and reduction of mortality in patients with severe COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Aged , Aged, 80 and over , COVID-19 , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , SARS-CoV-2
16.
Ochsner J ; 20(2): 134-138, 2020.
Article in English | MEDLINE | ID: covidwho-626294

ABSTRACT

Background: Cases of COVID-19 family clusters have been reported across the globe. While disease severity can vary widely, reports of severe infection leading to multiple fatalities within a family are limited. Case Report: Four family members each presented to the emergency department with fever and upper respiratory symptoms. Each individual tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection via nasopharyngeal swab. All individuals developed acute respiratory distress syndrome refractory to conventional medical therapy and subsequently died from their disease. Conclusion: This report describes a familial cluster of fatal COVID-19 infections and suggests a potential genetic predisposition for severe disease, emphasizing the importance of investigating family clusters of severe COVID-19 infection to determine host and viral factors that may predispose to a severe disease course. Such investigations could improve our understanding of the disease and guide preventive measures for at-risk populations.

17.
Zhonghua Jie He He Hu Xi Za Zhi ; 43(4): 273-277, 2020 Apr 12.
Article in Chinese | MEDLINE | ID: covidwho-590278

ABSTRACT

COVID-19 has been prevalent in Wuhan and spread rapidly to all of our country. Some cases can develop into ARDS, or even death. We will share the treatment experience of severe COVID-19 with the first-line treatment experience. The best respiratory support mode should be selected, but the timing of intubation and protection during intubation are two difficulties; patients with high level peep and poor effect in prone position can be given ECMO support. For COVID-19 patients with mechanical ventilation, reasonable sedation and analgesia strategies should be formulated; delirium should not be ignored. In addition, there is up regulation of inflammatory factors in patients with severe COVID-19, but the effect of renal replacement therapy needs to be further confirmed by clinical research.


Subject(s)
Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Analgesia , Betacoronavirus , COVID-19 , Conscious Sedation , Delirium , Humans , Inflammation , Intubation , Pandemics , Renal Replacement Therapy , Respiration, Artificial , SARS-CoV-2
18.
J Thromb Haemost ; 18(7): 1548-1555, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-116254

ABSTRACT

The global pandemic of coronavirus disease 2019 (COVID-19) is associated with the development of acute respiratory distress syndrome (ARDS), which requires ventilation in critically ill patients. The pathophysiology of ARDS results from acute inflammation within the alveolar space and prevention of normal gas exchange. The increase in proinflammatory cytokines within the lung leads to recruitment of leukocytes, further propagating the local inflammatory response. A consistent finding in ARDS is the deposition of fibrin in the air spaces and lung parenchyma. COVID-19 patients show elevated D-dimers and fibrinogen. Fibrin deposits are found in the lungs of patients due to the dysregulation of the coagulation and fibrinolytic systems. Tissue factor (TF) is exposed on damaged alveolar endothelial cells and on the surface of leukocytes promoting fibrin deposition, while significantly elevated levels of plasminogen activator inhibitor 1 (PAI-1) from lung epithelium and endothelial cells create a hypofibrinolytic state. Prophylaxis treatment of COVID-19 patients with low molecular weight heparin (LMWH) is important to limit coagulopathy. However, to degrade pre-existing fibrin in the lung it is essential to promote local fibrinolysis. In this review, we discuss the repurposing of fibrinolytic drugs, namely tissue-type plasminogen activator (tPA), to treat COVID-19 associated ARDS. tPA is an approved intravenous thrombolytic treatment, and the nebulizer form has been shown to be effective in plastic bronchitis and is currently in Phase II clinical trial. Nebulizer plasminogen activators may provide a targeted approach in COVID-19 patients to degrade fibrin and improving oxygenation in critically ill patients.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Fibrinolysis/drug effects , Fibrinolytic Agents/administration & dosage , Pneumonia, Viral/drug therapy , Thrombolytic Therapy , Tissue Plasminogen Activator/administration & dosage , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Drug Repositioning , Fibrinolytic Agents/adverse effects , Host-Pathogen Interactions , Humans , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , SARS-CoV-2 , Thrombolytic Therapy/adverse effects , Tissue Plasminogen Activator/adverse effects , Treatment Outcome , COVID-19 Drug Treatment
19.
Braz J Cardiovasc Surg ; 37(1): 35-47, 2022 03 10.
Article in English | MEDLINE | ID: covidwho-895827

ABSTRACT

INTRODUCTION: Severe coronavirus disease 2019 (COVID-19) is characterised by hyperinflammatory state, systemic coagulopathies, and multiorgan involvement, especially acute respiratory distress syndrome (ARDS). We here describe our preliminary clinical experience with COVID-19 patients treated via an early initiation of extracorporeal blood purification combined with systemic heparinisation and respiratory support. METHODS: Fifteen patients were included; several biomarkers associated with COVID-19 severity were monitored. Personalised treatment was tailored according to the levels of interleukin (IL)-6, IL-8, tumour necrosis factor alpha, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio, thrombocyte counts, D-dimers, and fibrinogen. Treatment consisted of respiratory support, extracorporeal blood purification using the AN69ST (oXiris®) hemofilter, and 300 U/kg heparin to maintain activation clotting time ≥ 180 seconds. RESULTS: Ten patients presented with severe to critical disease (dyspnoea, hypoxia, respiratory rate > 30/min, peripheral oxygen saturation < 90%, or > 50% lung involvement on X-ray imaging). The median intensive care unit length of stay was 9.3 days (interquartile range 5.3-10.1); two patients developed ARDS and died after 5 and 26 days. Clinical improvement was associated with normalisation (increase) of thrombocytes and white blood cells, stable levels of IL-6 (< 50 ng/mL), and a decrease of CRP and fibrinogen. CONCLUSION: Continuous monitoring of COVID-19 severity biomarkers and radiological imaging is crucial to assess disease progression, uncontrolled inflammation, and to avert irreversible multiorgan failure. The combination of systemic heparin anticoagulation regimens and extracorporeal blood purification using cytokine-adsorbing hemofilters may reduce hyperinflammation, prevent coagulopathy, and support clinical recovery.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , COVID-19/therapy , Heparin/therapeutic use , Humans , Intensive Care Units , Respiratory Distress Syndrome/therapy , SARS-CoV-2
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