Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 444
Filter
Add filters

Document Type
Year range
1.
Open Heart ; 8(2)2021 12.
Article in English | MEDLINE | ID: covidwho-1582998

ABSTRACT

OBJECTIVE: Soluble ST2 (sST2) reflects inflammation, endothelial dysfunction and myocardial fibrosis, is produced in the lungs and is an established biomarker in heart failure. We sought to determine the role of sST2 in COVID-19 by assessing pathophysiological correlates and its association to in-hospital outcomes. METHODS: We enrolled 123 consecutive, hospitalised patients with COVID-19 in the prospective, observational COVID-19 MECH study. Biobank samples were collected at baseline, day 3 and day 9. The key exposure variable was sST2, and the outcome was ICU treatment with mechanical ventilation or in-hospital death. RESULTS: Concentrations of sST2 at baseline was median 48 (IQR 37-67) ng/mL, and 74% had elevated concentrations (>37.9 ng/mL). Higher baseline sST2 concentrations were associated with older age, male sex, white race, smoking, diabetes, hypertension and chronic kidney disease. Baseline sST2 also associated with the presence of SARS-CoV-2 viraemia, lower oxygen saturation, higher respiratory rate and increasing concentrations of biomarkers reflecting inflammation, thrombosis and cardiovascular disease. During the hospitalisation, 8 (7%) patients died and 27 (22%) survivors received intensive care unit (ICU) treatment. Baseline sST2 concentrations demonstrated a graded association with disease severity (median, IQR): medical ward 43 (36-59) ng/mL; ICU 67 (39-104) ng/mL and non-survivors 107 (72-116) ng/mL (p<0.001 for all comparisons). These associations persisted at day 3 and day 9 . CONCLUSIONS: sST2 concentrations associate with SARS-CoV-2 viraemia, hypoxaemia and concentrations of inflammatory and cardiovascular biomarkers. There was a robust association between baseline sST2 and disease severity that was independent of, and superior to, established risk factors. sST2 reflects key pathophysiology and may be a promising biomarker in COVID-19. TRIAL REGISTRATION NUMBER: NCT04314232.


Subject(s)
COVID-19 , Hypoxia , Interleukin-1 Receptor-Like 1 Protein/analysis , SARS-CoV-2/isolation & purification , Viremia , Aged , Biomarkers/analysis , COVID-19/blood , COVID-19/mortality , COVID-19/physiopathology , Comorbidity , Correlation of Data , Female , Hospital Mortality , Humans , Hypoxia/diagnosis , Hypoxia/etiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Norway/epidemiology , Prognosis , Risk Factors , Severity of Illness Index , Smoking/epidemiology , Viremia/diagnosis , Viremia/etiology
2.
Crit Care ; 25(1): 431, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1582034

ABSTRACT

BACKGROUND: We hypothesized that as CARDS may present different pathophysiological features than classic ARDS, the application of high levels of end-expiratory pressure is questionable. Our first aim was to investigate the effects of 5-15 cmH2O of PEEP on partitioned respiratory mechanics, gas exchange and dead space; secondly, we investigated whether respiratory system compliance and severity of hypoxemia could affect the response to PEEP on partitioned respiratory mechanics, gas exchange and dead space, dividing the population according to the median value of respiratory system compliance and oxygenation. Thirdly, we explored the effects of an additional PEEP selected according to the Empirical PEEP-FiO2 table of the EPVent-2 study on partitioned respiratory mechanics and gas exchange in a subgroup of patients. METHODS: Sixty-one paralyzed mechanically ventilated patients with a confirmed diagnosis of SARS-CoV-2 were enrolled (age 60 [54-67] years, PaO2/FiO2 113 [79-158] mmHg and PEEP 10 [10-10] cmH2O). Keeping constant tidal volume, respiratory rate and oxygen fraction, two PEEP levels (5 and 15 cmH2O) were selected. In a subgroup of patients an additional PEEP level was applied according to an Empirical PEEP-FiO2 table (empirical PEEP). At each PEEP level gas exchange, partitioned lung mechanics and hemodynamic were collected. RESULTS: At 15 cmH2O of PEEP the lung elastance, lung stress and mechanical power were higher compared to 5 cmH2O. The PaO2/FiO2, arterial carbon dioxide and ventilatory ratio increased at 15 cmH2O of PEEP. The arterial-venous oxygen difference and central venous saturation were higher at 15 cmH2O of PEEP. Both the mechanics and gas exchange variables significantly increased although with high heterogeneity. By increasing the PEEP from 5 to 15 cmH2O, the changes in partitioned respiratory mechanics and mechanical power were not related to hypoxemia or respiratory compliance. The empirical PEEP was 18 ± 1 cmH2O. The empirical PEEP significantly increased the PaO2/FiO2 but also driving pressure, lung elastance, lung stress and mechanical power compared to 15 cmH2O of PEEP. CONCLUSIONS: In COVID-19 ARDS during the early phase the effects of raising PEEP are highly variable and cannot easily be predicted by respiratory system characteristics, because of the heterogeneity of the disease.


Subject(s)
COVID-19/therapy , Positive-Pressure Respiration , Respiratory Distress Syndrome/therapy , Ventilator-Induced Lung Injury , COVID-19/diagnosis , Critical Care , Humans , Hypoxia , Middle Aged , Oxygen/therapeutic use , SARS-CoV-2 , Ventilator-Induced Lung Injury/diagnostic imaging
4.
PLoS Comput Biol ; 17(12): e1009712, 2021 12.
Article in English | MEDLINE | ID: covidwho-1581905

ABSTRACT

Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT predicts both occurrence and magnitude of potential hypoxemic events 30 minutes in the future, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond.


Subject(s)
COVID-19/physiopathology , Critical Illness , Deep Learning , Hypoxia/blood , COVID-19/epidemiology , COVID-19/virology , Humans , Intensive Care Units , Pandemics , SARS-CoV-2/isolation & purification
5.
Biol Res ; 54(1): 39, 2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1577124

ABSTRACT

BACKGROUND: The aim of the study was to investigate the effect of mild cerebral hypoxia on haemoglobin oxygenation (HbO2), cerebrospinal fluid dynamics and cardiovascular physiology. To achieve this goal, four signals were recorded simultaneously: blood pressure, heart rate / electrocardiogram, HbO2 from right hemisphere and changes of subarachnoid space (SAS) width from left hemisphere. Signals were registered from 30 healthy, young participants (2 females and 28 males, body mass index = 24.5 ± 2.3 kg/m2, age 30.8 ± 13.4 years). RESULTS: We analysed the recorded signals using wavelet transform and phase coherence. We demonstrated for the first time that in healthy subjects exposed to mild poikilokapnic hypoxia there were increases in very low frequency HbO2 oscillations (< 0.052 Hz) in prefrontal cortex. Additionally, SAS fluctuation diminished in the whole frequency range which could be explained by brain oedema. CONCLUSIONS: Consequently the study provides insight into mechanisms governing brain response to a mild hypoxic challenge. Our study supports the notion that HbO2 and SAS width monitoring might be beneficial for patients with acute lung disease.


Subject(s)
Cerebrovascular Circulation , Lung Diseases , Adolescent , Adult , Female , Hemoglobins , Humans , Hypoxia , Male , Prefrontal Cortex , Spectroscopy, Near-Infrared , Young Adult
6.
Medicina (Kaunas) ; 57(12)2021 Dec 14.
Article in English | MEDLINE | ID: covidwho-1572561

ABSTRACT

Background and Objectives: The aim of this study was to assess the association between prehospital peripheral oxygen saturation (SpO2) and intensive care unit (ICU) admission in confirmed or suspected coronavirus disease 19 (COVID-19) patients. Materials and Methods: We carried out a retrospective cohort study on patients requiring prehospital intervention between 11 March 2020 and 4 May 2020. All adult patients in whom a diagnosis of COVID-19 pneumonia was suspected by the prehospital physician were included. Patients who presented a prehospital confounding respiratory diagnosis and those who were not eligible for ICU admission were excluded. The main exposure was "Low SpO2" defined as a value < 90%. The primary outcome was 48-h ICU admission. Secondary outcomes were 48-h mortality and 30-day mortality. We analyzed the association between low SpO2 and ICU admission or mortality with univariable and multivariable regression models. Results: A total of 145 patients were included. A total of 41 (28.3%) patients had a low prehospital SpO2 and 21 (14.5%) patients were admitted to the ICU during the first 48 h. Low SpO2 was associated with an increase in ICU admission (OR = 3.4, 95% CI = 1.2-10.0), which remained significant after adjusting for sex and age (aOR = 5.2, 95% CI = 1.8-15.4). Mortality was higher in low SpO2 patients at 48 h (OR = 7.1 95% CI 1.3-38.3) and at 30 days (OR = 3.9, 95% CI 1.4-10.7). Conclusions: In our physician-staffed prehospital system, first low prehospital SpO2 values were associated with a higher risk of ICU admission during the COVID-19 pandemic.


Subject(s)
COVID-19 , Emergency Medical Services , Adult , Humans , Hypoxia/epidemiology , Intensive Care Units , Pandemics , Retrospective Studies , SARS-CoV-2
7.
Drug Discov Ther ; 15(5): 273-277, 2021 Nov 21.
Article in English | MEDLINE | ID: covidwho-1542926

ABSTRACT

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Hypoxia/prevention & control , Administration, Oral , Adrenal Cortex Hormones/administration & dosage , Adult , COVID-19/complications , Disease Progression , Female , Humans , Hypoxia/drug therapy , Hypoxia/etiology , Kaplan-Meier Estimate , Male , Middle Aged , Treatment Outcome
8.
PLoS One ; 16(10): e0258856, 2021.
Article in English | MEDLINE | ID: covidwho-1542176

ABSTRACT

Hypoxia is a common pathway to the progression of end-stage kidney disease. Retinoic acid-inducible gene I (RIG-I) encodes an RNA helicase that recognizes viruses including SARS-CoV2, which is responsible for the production of interferon (IFN)-α/ß to prevent the spread of viral infection. Recently, RIG-I activation was found under hypoxic conditions, and klotho deficiency was shown to intensify the activation of RIG-I in mouse brains. However, the roles of these functions in renal inflammation remain elusive. Here, for in vitro study, the expression of RIG-I and IFN-α/ß was examined in normal rat kidney (NRK)-52E cells incubated under hypoxic conditions (1% O2). Next, siRNA targeting RIG-I or scramble siRNA was transfected into NRK52E cells to examine the expression of RIG-I and IFN-α/ß under hypoxic conditions. We also investigated the expression levels of RIG-I and IFN-α/ß in 33 human kidney biopsy samples diagnosed with IgA nephropathy. For in vivo study, we induced renal hypoxia by clamping the renal artery for 10 min in wild-type mice (WT mice) and Klotho-knockout mice (Kl-/- mice). Incubation under hypoxic conditions increased the expression of RIG-I and IFN-α/ß in NRK52E cells. Their upregulation was inhibited in NRK52E cells transfected with siRNA targeting RIG-I. In patients with IgA nephropathy, immunohistochemical staining of renal biopsy samples revealed that the expression of RIG-I was correlated with that of IFN-α/ß (r = 0.57, P<0.001, and r = 0.81, P<0.001, respectively). The expression levels of RIG-I and IFN-α/ß were upregulated in kidneys of hypoxic WT mice and further upregulation was observed in hypoxic Kl-/- mice. These findings suggest that hypoxia induces the expression of IFN-α/ß through the upregulation of RIG-I, and that klotho deficiency intensifies this hypoxia-induced expression in kidneys.


Subject(s)
Glucuronidase/metabolism , Hypoxia/metabolism , Interferon-alpha/metabolism , Kidney/metabolism , RNA Helicases/metabolism , Up-Regulation , Animals , Glucuronidase/genetics , Hypoxia/genetics , Mice , Mice, Knockout , RNA, Small Interfering , Rats
9.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1527380

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
10.
JAMA Netw Open ; 4(11): e2134241, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1508587

ABSTRACT

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.


Subject(s)
COVID-19 , Cause of Death , Hospitalization , Severity of Illness Index , Sleep Apnea Syndromes/complications , Aged , COVID-19/complications , COVID-19/mortality , COVID-19/therapy , Case-Control Studies , Continuous Positive Airway Pressure , Delivery of Health Care, Integrated , Extracorporeal Membrane Oxygenation , Female , Florida , Hospital Mortality , Humans , Hypoxia , Logistic Models , Male , Middle Aged , Odds Ratio , Ohio , Respiration, Artificial , Risk Factors , SARS-CoV-2 , Sleep , Sleep Apnea Syndromes/pathology , Sleep Apnea Syndromes/therapy
11.
BMJ Open Respir Res ; 8(1)2021 11.
Article in English | MEDLINE | ID: covidwho-1504009

ABSTRACT

Delayed presentation of COVID-19 pneumonia increases the risk of mortality and need for high-intensity healthcare. Conversely, early identification of COVID-19 pneumonia grants an opportunity to intervene early and thus prevent more complicated, protracted and less successful hospital admissions. To improve the earlier detection of COVID-19 pneumonia in the community we provide a narrative review of current evidence examining the clinical parameters associated with early disease progression. Through an evolving literature review, we examined: the symptoms that may suggest COVID-19 progression; the timing of deterioration; the utility of basic observations, clinical examination and chest X-ray; the value of postexertion oxygen saturations; and the use of CRP to monitor disease progression. We go on to discuss the challenges in monitoring the COVID-19 patient in the community and discuss thresholds for further assessment. Confusion, persistent fever and shortness of breath were identified as worrying symptoms suggestive of COVID-19 disease progression necessitating urgent clinical contact. Importantly, a significant proportion of COVID-19 pneumonia patients appear not to suffer dyspnoea despite severe disease. Patients with this asymptomatic hypoxia seem to have a poorer prognosis. Such patients may present with other signs of hypoxia: severe fatigue, exertional fatigue and/or altered mental status. We found duration of symptoms to be largely unhelpful in determining risk, with evidence of deterioration at any point in the disease. Basic clinical parameters (pulse, respiratory rate, blood pressure, temperature and oxygen saturations (SpO2)) are likely of high value in detecting the deteriorating community COVID-19 patient and/or COVID-19 mimickers/complications (eg, sepsis, bacterial pneumonia and pulmonary embolism). Of these, SpO2 carried the greatest utility in detecting COVID-19 progression. CRP is an early biochemical parameter predictive of disease progression and used appropriately is likely to contribute to the early identification of COVID-19 pneumonia. Identifying progressive COVID-19 in the community is feasible using basic clinical questions and measurements. As such, if we are to limit the mortality, morbidity and the need for complicated, protracted admissions, monitoring community COVID-19 cases for signs of deterioration to facilitate early intervention is a viable strategy.


Subject(s)
COVID-19 , Humans , Hypoxia , Risk Assessment , SARS-CoV-2 , Treatment Outcome
13.
Am J Case Rep ; 22: e933975, 2021 Oct 26.
Article in English | MEDLINE | ID: covidwho-1485493

ABSTRACT

BACKGROUND Platypnea orthodeoxia syndrome (POS) presents with positional dyspnea and hypoxemia defined as arterial desaturation of at least 5% or a drop in PaO2 of at least 4 mmHg. Causes of POS include a variety of cardiopulmonary etiologies and has been reported in patients recovering from severe COVID-19 pneumonia. However, clinical presentation and outcomes in a patient with multiple interrelated mechanisms of shunting has not been documented. CASE REPORT An 85-year-old man hospitalized for hypertensive emergency and severe COVID-19 pneumonia was diagnosed with platypnea orthodeoxia on day 28 of illness. During his disease course, the patient required supplemental oxygen by high-flow nasal cannula but never required invasive mechanical ventilation. Chest imaging revealed evolving mixed consolidation and ground-glass opacities with a patchy and diffuse distribution, involving most of the left lung. Echocardiography was ordered to evaluate for intracardiac shunt, which revealed a patent foramen ovale. Closure of the patent foramen ovale was not pursued. Management included graded progression to standing and supplemental oxygen increases when upright. The patient was discharged to a skilled nursing facility and his positional oxygen requirement resolved on approximately day 78. CONCLUSIONS The present case highlights the multiple interrelated mechanisms of shunting in patients with COVID-related lung disease and a patent foramen ovale. Eight prior cases of POS after COVID-19 pneumonia have been reported to date but none with a known patent foramen ovale. In patients with persistent positional oxygen requirements at follow-up, quantifying shunt fraction over time through multiple modalities can guide treatment decisions.


Subject(s)
COVID-19 , Foramen Ovale, Patent , Aged, 80 and over , Dyspnea/etiology , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/diagnostic imaging , Humans , Hypoxia/etiology , Male , SARS-CoV-2
14.
JAMA ; 326(18): 1807-1817, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1482066

ABSTRACT

Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.


Subject(s)
COVID-19/drug therapy , Dexamethasone/administration & dosage , Glucocorticoids/administration & dosage , Life Support Care , Aged , COVID-19/complications , COVID-19/mortality , Dexamethasone/adverse effects , Dose-Response Relationship, Drug , Female , Glucocorticoids/adverse effects , Humans , Hypoxia/etiology , Hypoxia/therapy , Male , Middle Aged , Mycoses/etiology , Respiration, Artificial , Shock, Septic/etiology , Single-Blind Method
15.
Biomark Med ; 15(16): 1509-1517, 2021 11.
Article in English | MEDLINE | ID: covidwho-1477715

ABSTRACT

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml. Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.


Subject(s)
COVID-19 , Endostatins/blood , Hypoxia , Respiratory Distress Syndrome , SARS-CoV-2/metabolism , Adult , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/mortality , Disease-Free Survival , Female , Humans , Hypoxia/blood , Hypoxia/mortality , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Respiratory Distress Syndrome/blood , Respiratory Distress Syndrome/mortality , Survival Rate
16.
Prim Health Care Res Dev ; 22: e56, 2021 10 18.
Article in English | MEDLINE | ID: covidwho-1475228

ABSTRACT

AIM: To validate the Roth score as a triage tool for detecting hypoxaemia. BACKGROUNDS: The virtual assessment of patients has become increasingly important during the corona virus disease (COVID-19) pandemic, but has limitations as to the evaluation of deteriorating respiratory function. This study presents data on the validity of the Roth score as a triage tool for detecting hypoxaemia remotely in potential COVID-19 patients in general practice. METHODS: This cross-sectional validation study was conducted in Dutch general practice. Patients aged ≥18 with suspected or confirmed COVID-19 were asked to rapidly count from 1 to 30 in a single breath. The Roth score involves the highest number counted during exhalation (counting number) and the time taken to reach the maximal count (counting time).Outcome measures were (1) the correlation between both Roth score measurements and simultaneous pulse oximetry (SpO2) on room air and (2) discrimination (c-statistic), sensitivity, specificity and predictive values of the Roth score for detecting hypoxaemia (SpO2 < 95%). FINDINGS: A total of 33 physicians enrolled 105 patients (52.4% female, mean age of 52.6 ± 20.4 years). A positive correlation was found between counting number and SpO2 (rs = 0.44, P < 0.001), whereas only a weak correlation was found between counting time and SpO2 (rs = 0.15, P = 0.14). Discrimination for hypoxaemia was higher for counting number [c-statistic 0.91 (95% CI: 0.85-0.96)] than for counting time [c-statistic 0.77 (95% CI: 0.62-0.93)]. Optimal diagnostic performance was found at a counting number of 20, with a sensitivity of 93.3% (95% CI: 68.1-99.8) and a specificity of 77.8% (95% CI: 67.8-85.9). A counting time of 7 s showed the best sensitivity of 85.7% (95% CI: 57.2-98.2) and specificity of 81.1% (95% CI: 71.5-88.6). CONCLUSIONS: A Roth score, with an optimal counting number cut-off value of 20, maybe of added value for signalling hypoxaemia in general practice. Further external validation is warranted before recommending integration in telephone triage.


Subject(s)
COVID-19 , Triage , Adult , Aged , Cross-Sectional Studies , Family Practice , Female , Humans , Hypoxia/diagnosis , Male , Middle Aged , SARS-CoV-2
18.
Lit Med ; 38(2): 233-238, 2020.
Article in English | MEDLINE | ID: covidwho-1450720
20.
Lipids Health Dis ; 20(1): 126, 2021 Oct 03.
Article in English | MEDLINE | ID: covidwho-1448237

ABSTRACT

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). At present, the COVID-19 has been prevalent worldwide for more than a year and caused more than four million deaths. Liver injury was frequently observed in patients with COVID-19. Recently, a new definition of metabolic dysfunction associated fatty liver disease (MAFLD) was proposed by a panel of international experts, and the relationship between MAFLD and COVID-19 has been actively investigated. Several previous studies indicated that the patients with MAFLD had a higher prevalence of COVID-19 and a tendency to develop severe type of respiratory infection, and others indicated that liver injury would be exacerbated in the patients with MAFLD once infected with COVID-19. The mechanism underlying the relationship between MAFLD and COVID-19 infection has not been thoroughly investigated, and recent studies indicated that multifactorial mechanisms, such as altered host angiotensin converting enzyme 2 (ACE2) receptor expression, direct viral attack, disruption of cholangiocyte function, systemic inflammatory reaction, drug-induced liver injury, hepatic ischemic and hypoxic injury, and MAFLD-related glucose and lipid metabolic disorders, might jointly contribute to both of the adverse hepatic and respiratory outcomes. In this review, we discussed the relationship between MAFLD and COVID-19 based on current available literature, and summarized the recommendations for clinical management of MAFLD patients during the pandemic of COVID-19.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , COVID-19/complications , Chemical and Drug Induced Liver Injury/complications , Hypoxia/complications , Liver/metabolism , Non-alcoholic Fatty Liver Disease/complications , SARS-CoV-2/pathogenicity , Age Factors , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/drug therapy , COVID-19/pathology , COVID-19/virology , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/virology , Cytokines/genetics , Cytokines/metabolism , Dipeptides/therapeutic use , Gene Expression Regulation , Glucose/metabolism , Glycyrrhizic Acid/therapeutic use , Humans , Hypoxia/drug therapy , Hypoxia/pathology , Hypoxia/virology , Liver/drug effects , Liver/pathology , Liver/virology , Lung/drug effects , Lung/metabolism , Lung/pathology , Lung/virology , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Receptors, Virus/genetics , Receptors, Virus/metabolism , Severity of Illness Index
SELECTION OF CITATIONS
SEARCH DETAIL
...