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2.
J Opioid Manag ; 16(4): 237-238, 2020.
Article in English | MEDLINE | ID: covidwho-745232

ABSTRACT

The COVID-19 ARDS appears to have worse outcomes than ARDS from other causes. It is a predictable serious complication and the key strategy is to maintain oxygenation. Adopting the prone position for conscious COVID-19 patients requiring basic respiratory support, is shown to benefit patients in terms of improving oxygenation, reducing the need for invasive ventilation and potentially even reducing mortality. Cough and myalgia are the common and most distressing symptoms seen in conscious COVID-19 patients which can impair tolerance to awake proning. Modified awake proning with application of transdermal fentanyl patch (TFP) can improve the compliance to conscious proning in COVID-19 patients.


Subject(s)
Analgesics, Opioid/administration & dosage , Consciousness , Coronavirus Infections/therapy , Fentanyl/administration & dosage , Pneumonia, Viral/therapy , Prone Position , Betacoronavirus , Humans , Pandemics , Respiratory Distress Syndrome, Adult/therapy , Respiratory Distress Syndrome, Adult/virology , Transdermal Patch
3.
In Vivo ; 34(5): 3027-3028, 2020.
Article in English | MEDLINE | ID: covidwho-740632

ABSTRACT

The FDA-approved drugs raloxifene and bazedoxifene could be among the best candidates to prevent mortality in severe COVID-19 patients. Raloxifene and bazedoxifene inhibit IL-6 signaling at therapeutic doses, suggesting they have the potential to prevent the cytokine storm, ARDS and mortality in severe COVID-19 patients, as is being shown with humanized antibodies blocking IL-6 signaling. In addition, raloxifene and bazedoxifene are selective estrogen receptor modulators with strong antiviral activity.


Subject(s)
Coronavirus Infections/drug therapy , Indoles/pharmacology , Pneumonia, Viral/drug therapy , Raloxifene Hydrochloride/pharmacology , Respiratory Distress Syndrome, Adult/drug therapy , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , Coronavirus Infections/genetics , Coronavirus Infections/mortality , Coronavirus Infections/virology , Cytokines/antagonists & inhibitors , Cytokines/genetics , Humans , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Pandemics , Pneumonia, Viral/genetics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Receptors, Estrogen/antagonists & inhibitors , Respiratory Distress Syndrome, Adult/prevention & control , Respiratory Distress Syndrome, Adult/virology , Selective Estrogen Receptor Modulators/pharmacology , Signal Transduction/drug effects
4.
Int J Mol Sci ; 21(17)2020 Aug 28.
Article in English | MEDLINE | ID: covidwho-740495

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.


Subject(s)
Apoptosis/drug effects , Betacoronavirus/physiology , Cannabinoid Receptor Agonists/therapeutic use , Coronavirus Infections/drug therapy , Cytokines/immunology , Dronabinol/therapeutic use , Pneumonia, Viral/drug therapy , Respiratory Distress Syndrome, Adult/drug therapy , Aged , Animals , Bronchoalveolar Lavage Fluid/immunology , Coronavirus Infections/mortality , Coronavirus Infections/virology , Enterotoxins/adverse effects , Female , Humans , Lung/immunology , Lung/virology , Male , Mice , Mice, Inbred C3H , MicroRNAs/genetics , Middle Aged , Pandemics , Pneumonia/drug therapy , Pneumonia/virology , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Respiratory Distress Syndrome, Adult/mortality , Respiratory Distress Syndrome, Adult/virology , Signal Transduction/drug effects
6.
PLoS One ; 15(8): e0238413, 2020.
Article in English | MEDLINE | ID: covidwho-732993

ABSTRACT

Hypercoagulability and endotheliopathy reported in patients with coronavirus disease 2019 (COVID-19) combined with strict and prolonged immobilization inherent to deep sedation and administration of neuromuscular blockers for Acute Respiratory Distress Syndrome (ARDS) may expose critically ill COVID-19 patients to an increased risk of venous thrombosis and pulmonary embolism (PE). We aimed to assess the rate and to describe the clinical features and the outcomes of ARDS COVID-19 patients diagnosed with PE during ICU stay. From March 13th to April 24th 2020, a total of 92 patients (median age: 61 years, 1st-3rd quartiles [55-70]; males: n = 73/92, 79%; baseline SOFA: 4 [3-7] and SAPS II: 31 [21-40]; invasive mechanical ventilation: n = 83/92, 90%; ICU mortality: n = 45/92, 49%) were admitted to our 41-bed COVID-19 ICU for ARDS due to COVID-19. Among them, 26 patients (n = 26/92, 28%) underwent a Computed Tomography Pulmonary Angiography which revealed PE in 16 (n = 16/26, 62%) of them, accounting for 17% (n = 16/92) of the whole cohort. PE was bilateral in 3 (19%) patients and unilateral in 13 (81%) patients. The most proximal thrombus was localized in main (n = 4, 25%), lobar (n = 2, 12%) or segmental (n = 10, 63%) pulmonary artery. Most of the thrombi (n = 13/16, 81%) were located in a parenchymatous condensation. Only three of the 16 patients (19%) had lower limb venous thrombosis on Doppler ultrasound. Three patients were treated with alteplase and anticoagulation (n = 3/16, 19%) while the 13 others (n = 13/16, 81%) were treated with anticoagulation alone. ICU mortality was higher in patients with PE compared to that of patients without PE (n = 11/16, 69% vs. n = 2/10, 20%; p = 0.04). The low rate of lower limb venous thrombosis together with the high rate of distal pulmonary thrombus argue for a local immuno-thrombotic process associated with the classic embolic process. Further larger studies are needed to assess the real prevalence and the risk factors of pulmonary embolism/thrombosis together with its prognostic impact on critically ill patients with COVID-19.


Subject(s)
Coronavirus Infections/complications , Pneumonia, Viral/complications , Pulmonary Embolism/virology , Respiratory Distress Syndrome, Adult/virology , Thrombosis/virology , Aged , Betacoronavirus , Computed Tomography Angiography , Female , France , Humans , Incidence , Male , Middle Aged , Pandemics , Retrospective Studies
8.
BMJ Case Rep ; 13(8)2020 Aug 18.
Article in English | MEDLINE | ID: covidwho-725540

ABSTRACT

This case describes the successful pulmonary rehabilitation of a premorbidly independent female in the early 80s who was admitted for acute respiratory distress syndrome secondary to COVID-19 requiring 14 days of intubation. Patient was admitted to the acute rehabilitation unit 1 month after hospitalisation. Patient initially had poor endurance and was only able to ambulate with a front wheel walker for 150 feet, and also had tachycardia and decreased oxygen saturation after ambulation. During patient's rehabilitation course, therapy was focused on improving activity tolerance. Ten days after admission, patient was able to ambulate without an assistive device for 250 feet and with a rollator for over 900 feet. Patient also showed improvement in gait speed, heart rate, oxygen saturation after ambulation and incentive spirometer volume. This case demonstrates that pulmonary rehabilitation is an important component of inpatient care for patients with COVID-19 to improve functional exercise capacity and aerobic capacity.


Subject(s)
Betacoronavirus , Coronavirus Infections/rehabilitation , Pneumonia, Viral/rehabilitation , Respiratory Distress Syndrome, Adult/rehabilitation , Respiratory Therapy/methods , Subacute Care/methods , Aged, 80 and over , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Female , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Recovery of Function , Respiratory Distress Syndrome, Adult/physiopathology , Respiratory Distress Syndrome, Adult/virology , Treatment Outcome , Walking
9.
mSphere ; 5(4)2020 08 12.
Article in English | MEDLINE | ID: covidwho-725309

ABSTRACT

Many coronavirus disease 2019 (COVID-19) patients demonstrate lethal respiratory complications caused by cytokine release syndrome (CRS). Multiple cytokines have been implicated in CRS, but levels of tumor necrosis factor superfamily 14 (TNFSF14) (LIGHT) have not been previously measured in this setting. In this study, we observed significantly elevated serum LIGHT levels in hospitalized COVID-19 patients compared to healthy age- and gender-matched control patients. The assay detected bioavailable LIGHT unbound to the inhibitor Decoy receptor-3 (DcR3). Bioavailable LIGHT levels were elevated in patients both on and off ventilatory support, with a trend toward higher levels in patients requiring mechanical ventilation. In hospitalized patients over the age of 60, who exhibited a mortality rate of 82%, LIGHT levels were significantly higher (P = 0.0209) in those who died than in survivors. As previously reported, interleukin 6 (IL-6) levels were also elevated in these patients, with significantly (P = 0.0076) higher levels observed in patients who died than in survivors, paralleling the LIGHT levels. Although attempts to block IL-6 binding to its receptor have shown limited success in COVID-19 CRS, neutralization of LIGHT may prove to be more effective owing to its more central role in regulating antiviral immune responses. The findings presented here demonstrate that LIGHT is a cytokine which may play an important role in COVID-19 patients presenting with acute respiratory distress syndrome (ARDS) and CRS and suggest that LIGHT neutralization may be beneficial to COVID-19 patients.


Subject(s)
Coronavirus Infections/immunology , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/virology , Pneumonia, Viral/immunology , Respiratory Distress Syndrome, Adult/immunology , Respiratory Distress Syndrome, Adult/virology , Tumor Necrosis Factor Ligand Superfamily Member 14/blood , Adult , Age Factors , Aged , Antibodies, Monoclonal/therapeutic use , Betacoronavirus , Clinical Trials as Topic , Coronavirus Infections/complications , Hospitalization/statistics & numerical data , Humans , Interleukin-6/immunology , Middle Aged , Pandemics , Pneumonia, Viral/complications , Respiration, Artificial/statistics & numerical data
10.
J Intensive Care Med ; 35(10): 963-970, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-722236

ABSTRACT

BACKGROUND: The first confirmed case of novel coronavirus (2019-nCoV) infection in the United States was reported from the state of Washington in January, 2020. By March, 2020, New York City had become the epicenter of the outbreak in the United States. METHODS: We tracked all patients with confirmed coronavirus-19 (COVID-19) infection admitted to intensive care units (ICU) at Montefiore Medical Center (Bronx, NY). Data were obtained through manual review of electronic medical records. Patients had at least 30 days of follow-up. RESULTS: Our first 300 ICU patients were admitted March 10 through April 11, 2020. The majority (60.7%) of patients were men. Acute respiratory distress syndrome (ARDS) was documented in 91.7% of patients; 91.3% required mechanical ventilation. Prone positioning was employed in 58% of patients and neuromuscular blockade in 47.8% of mechanically-ventilated patients. Neither intervention was associated with decreased mortality. Vasopressors were required in 77.7% of patients. Acute kidney injury (AKI) was present on admission in 40.7% of patients, and developed subsequently in 36.0%; 50.9% of patients with AKI received renal replacement therapy (RRT). Overall 30-day mortality rate was 52.3%, and 55.8% among patients receiving mechanical ventilation. In univariate analysis, higher mortality rate was associated with increasing age, male sex, hypertension, obesity, smoking, number of comorbidities, AKI on presentation, and need for vasopressor support. A representative multivariable model for 30-day mortality is also presented, containing patient age, gender, body mass index, and AKI at admission. As of May 11, 2020, 2 patients (0.7%) remained hospitalized. CONCLUSIONS: Mortality in critical illness associated with COVID-19 is high. The majority of patients develop ARDS requiring mechanical ventilation, vasopressor-dependent shock, and AKI. The variation in mortality rates reported to date likely reflects differences in the severity of illness of the evaluated populations.


Subject(s)
Betacoronavirus , Coronavirus Infections/mortality , Critical Care/statistics & numerical data , Critical Illness/mortality , Pneumonia, Viral/mortality , Acute Kidney Injury/mortality , Acute Kidney Injury/virology , Adult , Aged , Coronavirus Infections/complications , Critical Care/methods , Female , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , New York City/epidemiology , Pandemics , Pneumonia, Viral/complications , Respiration, Artificial/mortality , Respiratory Distress Syndrome, Adult/mortality , Respiratory Distress Syndrome, Adult/virology
16.
Lancet ; 395(10223): 497-506, 2020 02 15.
Article in English | MEDLINE | ID: covidwho-665705

ABSTRACT

BACKGROUND: A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. METHODS: All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. FINDINGS: By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. INTERPRETATION: The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. FUNDING: Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.


Subject(s)
Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Adult , Age Distribution , Aged , China/epidemiology , Comorbidity , Coronavirus Infections/complications , Coronavirus Infections/transmission , Cough/epidemiology , Cough/virology , Female , Fever/epidemiology , Fever/virology , Hospitalization/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Myalgia/epidemiology , Myalgia/virology , Pneumonia, Viral/complications , Pneumonia, Viral/transmission , Prognosis , Radiography, Thoracic , Respiratory Distress Syndrome, Adult/epidemiology , Respiratory Distress Syndrome, Adult/virology , Time Factors , Tomography, X-Ray Computed , Young Adult
18.
PLoS One ; 15(7): e0236312, 2020.
Article in English | MEDLINE | ID: covidwho-658804

ABSTRACT

COVID-19 pneumonia typically begins with subpleural ground glass opacities with progressive extension on computerized tomography studies. Lung ultrasound is well suited to this interstitial, subpleural involvement, and it is now broadly used in intensive care units (ICUs). The extension and severity of lung infiltrates can be described numerically with a reproducible and validated lung ultrasound score (LUSS). We hypothesized that LUSS might be useful as a tool to non-invasively monitor the evolution of COVID-19 pneumonia at the bedside. LUSS monitoring was rapidly implemented in the management of our COVID-19 patients with RT-PCR-documented COVID-19. The LUSS was evaluated repeatedly at the bedside. We present a graphic description of the course of LUSS during COVID-19 in 10 consecutive patients admitted in our intensive care unit with moderate to severe ARDS between March 15 and 30th. LUSS appeared to be closely related to the disease progression. In successfully extubated patients, LUSS decreased and was lower than at the time of intubation. LUSS increased inexorably in a patient who died from refractory hypoxemia. LUSS helped with the diagnosis of ventilator-associated pneumonia (VAP), showing an increased score and the presence of new lung consolidations in all 5 patients with VAPs. There was also a good agreement between CT-scans and LUSS as for the presence of lung consolidations. In conclusion, our early experience suggests that LUSS monitoring accurately reflect disease progression and indicates potential usefulness for the management of COVID-19 patients with ARDS. It might help with early VAP diagnosis, mechanical ventilation weaning management, and potentially reduce the need for X-ray and CT exams. LUSS evaluation is easy to use and readily available in ICUs throughout the world, and might be a safe, cheap and simple tool to optimize critically ill COVID-19 patients care during the pandemic.


Subject(s)
Coronavirus Infections/diagnostic imaging , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Respiratory Distress Syndrome, Adult/virology , Ultrasonography , Betacoronavirus , Coronavirus Infections/complications , Disease Progression , Female , France , Humans , Intensive Care Units , Male , Middle Aged , Pandemics , Pneumonia, Ventilator-Associated/diagnostic imaging , Pneumonia, Ventilator-Associated/virology , Pneumonia, Viral/complications , Tomography, X-Ray Computed
20.
BMC Anesthesiol ; 20(1): 177, 2020 07 20.
Article in English | MEDLINE | ID: covidwho-656789

ABSTRACT

The management of Acute Respiratory Distress Syndrome (ARDS) secondary to the novel Coronavirus Disease 2019 (COVID-19) proves to be challenging and controversial. Multiple studies have suggested the likelihood of an atypical pathophysiology to explain the spectrum of pulmonary and systemic manifestations caused by the virus. The principal paradox of COVID-19 pneumonia is the presence of severe hypoxemia with preserved pulmonary mechanics. Data derived from the experience of multiple centers around the world have demonstrated that initial clinical efforts should be focused into avoid intubation and mechanical ventilation in hypoxemic COVID-19 patients. On the other hand, COVID-19 patients progressing or presenting into frank ARDS with typical decreased pulmonary compliance, represents another clinical enigma to many clinicians, since routine therapeutic interventions for ARDS are still a subject of debate.


Subject(s)
Betacoronavirus , Coronavirus Infections/therapy , Critical Care/methods , Pneumonia, Viral/therapy , Respiratory Distress Syndrome, Adult/therapy , Adrenal Cortex Hormones/therapeutic use , Biomarkers/metabolism , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/transmission , Cross Infection/transmission , Cytokines/metabolism , Diagnostic Imaging , Extracorporeal Membrane Oxygenation/methods , Humans , Hypoxia/virology , Immune System Diseases/virology , Intubation, Intratracheal , Neuromuscular Blockade/methods , Pandemics , Patient Positioning/methods , Pneumonia, Viral/diagnosis , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prone Position/physiology , Respiration, Artificial/methods , Respiratory Distress Syndrome, Adult/virology , Thrombophilia/virology , Vasodilator Agents/therapeutic use
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