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1.
N Engl J Med ; 386(9): 815-826, 2022 03 03.
Article in English | MEDLINE | ID: covidwho-1721751

ABSTRACT

BACKGROUND: Whether the use of balanced multielectrolyte solution (BMES) in preference to 0.9% sodium chloride solution (saline) in critically ill patients reduces the risk of acute kidney injury or death is uncertain. METHODS: In a double-blind, randomized, controlled trial, we assigned critically ill patients to receive BMES (Plasma-Lyte 148) or saline as fluid therapy in the intensive care unit (ICU) for 90 days. The primary outcome was death from any cause within 90 days after randomization. Secondary outcomes were receipt of new renal-replacement therapy and the maximum increase in the creatinine level during ICU stay. RESULTS: A total of 5037 patients were recruited from 53 ICUs in Australia and New Zealand - 2515 patients were assigned to the BMES group and 2522 to the saline group. Death within 90 days after randomization occurred in 530 of 2433 patients (21.8%) in the BMES group and in 530 of 2413 patients (22.0%) in the saline group, for a difference of -0.15 percentage points (95% confidence interval [CI], -3.60 to 3.30; P = 0.90). New renal-replacement therapy was initiated in 306 of 2403 patients (12.7%) in the BMES group and in 310 of 2394 patients (12.9%) in the saline group, for a difference of -0.20 percentage points (95% CI, -2.96 to 2.56). The mean (±SD) maximum increase in serum creatinine level was 0.41±1.06 mg per deciliter (36.6±94.0 µmol per liter) in the BMES group and 0.41±1.02 mg per deciliter (36.1±90.0 µmol per liter) in the saline group, for a difference of 0.01 mg per deciliter (95% CI, -0.05 to 0.06) (0.5 µmol per liter [95% CI, -4.7 to 5.7]). The number of adverse and serious adverse events did not differ meaningfully between the groups. CONCLUSIONS: We found no evidence that the risk of death or acute kidney injury among critically ill adults in the ICU was lower with the use of BMES than with saline. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; PLUS ClinicalTrials.gov number, NCT02721654.).


Subject(s)
Acute Kidney Injury/prevention & control , Critical Illness/therapy , Saline Solution/therapeutic use , Acute Kidney Injury/etiology , Adult , Aged , Critical Care/methods , Critical Illness/mortality , Double-Blind Method , Female , Fluid Therapy , Gluconates/adverse effects , Gluconates/therapeutic use , Humans , Intensive Care Units , Magnesium Chloride/adverse effects , Magnesium Chloride/therapeutic use , Male , Middle Aged , Potassium Chloride/adverse effects , Potassium Chloride/therapeutic use , Saline Solution/adverse effects , Sodium Acetate/adverse effects , Sodium Acetate/therapeutic use , Sodium Chloride/adverse effects , Sodium Chloride/therapeutic use , Treatment Outcome
2.
Sci Rep ; 11(1): 22548, 2021 11 19.
Article in English | MEDLINE | ID: covidwho-1628380

ABSTRACT

The objective of this study is to examine the IgG antibody response in critically ill patients with the Middle East respiratory syndrome (MERS) and to examine the association of early antibody response with mortality and viral clearance. We collected blood samples from 40 consecutive real-time reverse transcription-polymerase chain reaction (rRT-PCR) confirmed critically ill MERS patients on ICU days 1, 3, 7, 14 and 28. MERS-CoV antibodies were detected by enzyme-linked immunosorbent assay (ELISA), using wells coated with MERS-CoV S1 antigen. Patients were admitted to ICU after a median (Q1, Q3) of 9 (4, 13) days from onset of symptoms with an admission Sequential Organ Failure Assessment (SOFA) score of 11 (6.5, 12). Among the study cohort, 38 patients (95%) received invasive ventilation, 35 (88%) vasopressors, 21 (53%) renal replacement therapy and 17 (43%) corticosteroids. Median (Q1,Q3) ELISA optical density (OD) ratio significantly increased with time (p < 0.001) from 0.11 (0.07, 1.43) on day 1; to 0.69 (0.11, 2.08) on day 3, 2.72 (1.84, 3.54) on day 7, 2.51 (0.35, 3.35) on day 14 and 3.77 (3.70, 3.84) on day 28. Early antibody response (day 1-3) was observed in 13/39 patients (33%) and was associated with lower mortality (hazard ratio: 0.31, 95% CI 0.10, 0.96, p = 0.04) but was not associated with faster clearance of MERS-CoV RNA. In conclusion, among critically ill patients with MERS, early antibody response was associated with lower mortality but not with faster clearance of MERS-CoV RNA. These findings have important implications for understanding pathogenesis and potential immunotherapy.


Subject(s)
Antibodies, Viral/immunology , Coronavirus Infections/immunology , Coronavirus Infections/mortality , Critical Illness/mortality , Middle East Respiratory Syndrome Coronavirus/immunology , Adult , Aged , Antibodies, Viral/blood , Antibody Formation , Cohort Studies , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Humans , Immunoglobulin G/blood , Immunoglobulin G/immunology , Intensive Care Units , Kinetics , Male , Middle Aged , Organ Dysfunction Scores , Renal Replacement Therapy , Survival Analysis
3.
Biomolecules ; 12(2)2022 02 08.
Article in English | MEDLINE | ID: covidwho-1674482

ABSTRACT

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28-44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99-52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04-53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/urine , COVID-19/diagnosis , COVID-19/urine , Critical Illness/mortality , Acute Kidney Injury/complications , Acute Kidney Injury/mortality , Adult , Aged , Biomarkers/urine , COVID-19/complications , COVID-19/mortality , Female , Humans , Insulin-Like Growth Factor Binding Proteins/urine , Kaplan-Meier Estimate , Lipocalin-2/urine , Longitudinal Studies , Male , Middle Aged , Prospective Studies , Risk Factors , Tissue Inhibitor of Metalloproteinase-2/urine
4.
PLoS One ; 17(1): e0261958, 2022.
Article in English | MEDLINE | ID: covidwho-1622349

ABSTRACT

INTRODUCTION: Multicenter studies involving patients with acute kidney injury (AKI) associated with the disease caused by the new coronavirus (COVID-19) and treated with renal replacement therapy (RRT) in developing countries are scarce. The objectives of this study were to evaluate the demographic profile, clinical picture, risk factors for mortality, and outcomes of critically ill patients with AKI requiring dialysis (AKI-RRT) and with COVID-19 in the megalopolis of São Paulo, Brazil. METHODS: This multicenter, retrospective, observational study was conducted in the intensive care units of 13 public and private hospitals in the metropolitan region of the municipality of São Paulo. Patients hospitalized in an intensive care unit, aged ≥ 18 years, and treated with RRT due to COVID-19-associated AKI were included. RESULTS: The study group consisted of 375 patients (age 64.1 years, 68.8% male). Most (62.1%) had two or more comorbidities: 68.8%, arterial hypertension; 45.3%, diabetes; 36.3%, anemia; 30.9%, obesity; 18.7%, chronic kidney disease; 15.7%, coronary artery disease; 10.4%, heart failure; and 8.5%, chronic obstructive pulmonary disease. Death occurred in 72.5% of the study population (272 patients). Among the 103 survivors, 22.3% (23 patients) were discharged on RRT. In a multiple regression analysis, the independent factors associated with death were the number of organ dysfunctions at admission and RRT efficiency. CONCLUSION: AKI-RRT associated with COVID-19 occurred in patients with an elevated burden of comorbidities and was associated with high mortality (72.5%). The number of organ dysfunctions during hospitalization and RRT efficiency were independent factors associated with mortality. A meaningful portion of survivors was discharged while dependent on RRT (22.3%).


Subject(s)
Acute Kidney Injury/complications , COVID-19/complications , Acute Kidney Injury/epidemiology , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Aged , Brazil/epidemiology , COVID-19/epidemiology , COVID-19/mortality , COVID-19/therapy , Critical Illness/epidemiology , Critical Illness/mortality , Critical Illness/therapy , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Renal Replacement Therapy , Retrospective Studies , Risk Factors , SARS-CoV-2/isolation & purification
5.
J Korean Med Sci ; 36(44): e309, 2021 Nov 15.
Article in English | MEDLINE | ID: covidwho-1593105

ABSTRACT

BACKGROUND: We assessed maternal and neonatal outcomes of critically ill pregnant and puerperal patients in the clinical course of coronavirus disease 2019 (COVID-19). METHODS: Records of pregnant and puerperal women with polymerase chain reaction positive COVID-19 virus who were admitted to our intensive care unit (ICU) from March 2020 to August 2021 were investigated. Demographic, clinical and laboratory data, pharmacotherapy, and neonatal outcomes were analyzed. These outcomes were compared between patients that were discharged from ICU and patients who died in ICU. RESULTS: Nineteen women were included in this study. Additional oxygen was required in all cases (100%). Eight patients (42%) were intubated and mechanically ventilated. All patients that were mechanically ventilated have died. Increased levels of C-reactive protein (CRP) was seen in all patients (100%). D-dimer values increased in 15 patients (78.9%); interleukin-6 (IL-6) increased in 16 cases (84.2%). Sixteen patients used antiviral drugs. Eleven patients were discharged from the ICU and eight patients have died due to complications of COVID-19 showing an ICU mortality rate of 42.1%. Mean number of hospitalized days in ICU was significantly lower in patients that were discharged (P = 0.037). Seventeen patients underwent cesarean-section (C/S) (89.4%). Mean birth week was significantly lower in patients who died in ICU (P = 0.024). Eleven preterm (57.8%) and eight term deliveries (42.1%) occurred. CONCLUSION: High mortality rate was detected among critically ill pregnant/parturient patients followed in the ICU. Main predictors of mortality were the need of invasive mechanical ventilation and higher number of days hospitalized in ICU. Rate of C/S operations and preterm delivery were high. Pleasingly, the rate of neonatal death was low and no neonatal COVID-19 occurred.


Subject(s)
COVID-19/mortality , Pregnancy Complications, Infectious/mortality , Puerperal Disorders/mortality , SARS-CoV-2 , Adult , Antiviral Agents/therapeutic use , COVID-19/blood , COVID-19/diagnostic imaging , COVID-19/therapy , Cesarean Section , Combined Modality Therapy , Critical Illness/mortality , Delivery, Obstetric/statistics & numerical data , Female , Hospital Mortality , Humans , Infant, Newborn , Intensive Care Units/statistics & numerical data , Length of Stay/statistics & numerical data , Lung/diagnostic imaging , Oxygen Inhalation Therapy , Pregnancy , Pregnancy Outcome , Respiration, Artificial , Retrospective Studies , Treatment Outcome , Young Adult
6.
JAMA ; 326(21): 2161-2171, 2021 Dec 07.
Article in English | MEDLINE | ID: covidwho-1596653

ABSTRACT

IMPORTANCE: The effect of high-flow oxygen therapy vs conventional oxygen therapy has not been established in the setting of severe COVID-19. OBJECTIVE: To determine the effect of high-flow oxygen therapy through a nasal cannula compared with conventional oxygen therapy on need for endotracheal intubation and clinical recovery in severe COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Randomized, open-label clinical trial conducted in emergency and intensive care units in 3 hospitals in Colombia. A total of 220 adults with respiratory distress and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen of less than 200 due to COVID-19 were randomized from August 2020 to January 2021, with last follow-up on February 10, 2021. INTERVENTIONS: Patients were randomly assigned to receive high-flow oxygen through a nasal cannula (n = 109) or conventional oxygen therapy (n = 111). MAIN OUTCOMES AND MEASURES: The co-primary outcomes were need for intubation and time to clinical recovery until day 28 as assessed by a 7-category ordinal scale (range, 1-7, with higher scores indicating a worse condition). Effects of treatments were calculated with a Cox proportional hazards model adjusted for hypoxemia severity, age, and comorbidities. RESULTS: Among 220 randomized patients, 199 were included in the analysis (median age, 60 years; n = 65 women [32.7%]). Intubation occurred in 34 (34.3%) randomized to high-flow oxygen therapy and in 51 (51.0%) randomized to conventional oxygen therapy (hazard ratio, 0.62; 95% CI, 0.39-0.96; P = .03). The median time to clinical recovery within 28 days was 11 (IQR, 9-14) days in patients randomized to high-flow oxygen therapy vs 14 (IQR, 11-19) days in those randomized to conventional oxygen therapy (hazard ratio, 1.39; 95% CI, 1.00-1.92; P = .047). Suspected bacterial pneumonia occurred in 13 patients (13.1%) randomized to high-flow oxygen and in 17 (17.0%) of those randomized to conventional oxygen therapy, while bacteremia was detected in 7 (7.1%) vs 11 (11.0%), respectively. CONCLUSIONS AND RELEVANCE: Among patients with severe COVID-19, use of high-flow oxygen through a nasal cannula significantly decreased need for mechanical ventilation support and time to clinical recovery compared with conventional low-flow oxygen therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04609462.


Subject(s)
COVID-19/complications , Intubation, Intratracheal/statistics & numerical data , Oxygen Inhalation Therapy/methods , Oxygen/therapeutic use , Respiratory Insufficiency/therapy , Aged , Aged, 80 and over , COVID-19/therapy , Critical Illness/mortality , Critical Illness/therapy , Female , Humans , Intensive Care Units , Intubation, Intratracheal/adverse effects , Male , Middle Aged , Oxygen Inhalation Therapy/instrumentation , Respiration, Artificial , Respiratory Insufficiency/etiology , Respiratory Insufficiency/mortality , SARS-CoV-2 , Time Factors , Treatment Outcome
7.
Diabetes Metab Syndr ; 16(1): 102373, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1587938

ABSTRACT

BACKGROUND AND AIMS: Obesity has been reported to be one of the most frequent comorbidities in COVID-19 patients and associated with higher rates of in-hospital mortality compared to non-obese patients. Acute kidney injury (AKI) is also known to be a complication associated with obesity in critically-ill COVID-19 patients. We aimed to investigate whether obesity was associated with increased risk of in-hospital mortality and AKI among patients with COVID-19 treated with corticosteroids. METHODS: We utilized 9965 hospitalized COVID-19 patient data and divided patients who were treated with corticosteroids into 6 groups by body mass index (BMI) (less than 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 kg/m2 or greater). The association between BMI and in-hospital mortality and between BMI and incidence rate of AKI during admission among COVID-19 patients receiving corticosteroids were retrospectively investigated. RESULTS: There were 4587 study participants receiving corticosteroids (mean age 66.5 ± 15.5 years, men 56.6%, mean BMI 29.0 ± 7.2 kg/m2). The smooth spline curve suggested a J-shape association between BMI and in-hospital mortality. Patients with BMI above 40 kg/m2 exhibited a higher in-hospital mortality and higher incidence rate of AKI during admission compared to patients with BMI between 25 and 30 kg/m2. The differences in in-hospital mortality and the rate of AKI were larger among patients with severe COVID-19. CONCLUSIONS: Class III obesity was associated with high in-hospital mortality and AKI in patients with COVID-19 treated by corticosteroids. Clinicians must stay vigilant on the impact of class III obesity and development of AKI to disease trajectory of COVID-19 patients.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19 , Hospital Mortality , Obesity , Adult , Aged , Aged, 80 and over , Body Mass Index , COVID-19/complications , COVID-19/drug therapy , COVID-19/mortality , Comorbidity , Critical Illness/mortality , Female , Humans , Incidence , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Obesity/epidemiology , Retrospective Studies , Risk Factors , United States/epidemiology
8.
Ann Med ; 53(1): 295-301, 2021 12.
Article in English | MEDLINE | ID: covidwho-1575822

ABSTRACT

INTRODUCTION: Critically ill patients with COVID-19 are at increased risk of developing a hypercoagulable state due to haemostatic changes directly related to the SARS-CoV-2 infection or to the consequence of the cytokine storm. Anticoagulation is now recommended to reduce the thrombotic risk. Ilio-psoas haematoma (IPH) is a potentially lethal condition that can arise during the hospitalization, especially in intensive care units (ICUs) and frequently reported as a complication of anticoagulation treatment. MATERIALS AND METHODS: We report a case series of seven subjects with SARS-CoV-2 pneumonia complicated by Ilio-psoas haematomas (IPHs) at our COVID-Hospital in Rome, Italy. RESULTS: Over the observation period, 925 subjects with confirmed SARS-CoV-2 infection were admitted to our COVID-hospital. Among them, we found seven spontaneous IPHs with an incidence of 7.6 cases per 1000 hospitalization. All the reported cases had a severe manifestation of COVID-19 pneumonia, with at least one comorbidity and 5/7 were on treatment with low weight molecular heparin for micro or macro pulmonary thrombosis. CONCLUSIONS: Given the indications to prescribe anticoagulant therapy in COVID-19 and the lack of solid evidences on the optimal dose and duration, it is important to be aware of the iliopsoas haematoma as a potentially serious complication in COVID-19 inpatients. KEY MESSAGE Critically ill patients with COVID-19 are at increased risk of hypercoagulability state and anticoagulation therapy is recommended. Ilio-psoas haematoma (IPH) is found to be a complication of anticoagulation regimen especially in severe COVID-19 cases. An incidence of 7.6 cases per 1000 admission of IPHs was reported. Hypoesthesia of the lower limbs, pain triggered by femoral rotation, hypovolaemia and anaemia are the most common symptoms and signs of IPHs that should alert physician.


Subject(s)
Anticoagulants/adverse effects , COVID-19/complications , Hematoma/epidemiology , Psoas Muscles/diagnostic imaging , Thrombophilia/drug therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Female , Glucocorticoids/therapeutic use , Hematoma/chemically induced , Hematoma/diagnosis , Hematoma/drug therapy , Heparin, Low-Molecular-Weight , Hospital Mortality , Humans , Incidence , Intensive Care Units , Italy/epidemiology , Magnetic Resonance Imaging , Male , Middle Aged , Muscular Diseases , SARS-CoV-2/isolation & purification , SARS-CoV-2/pathogenicity , Severity of Illness Index , Thrombophilia/etiology , Tomography, X-Ray Computed , Treatment Outcome
9.
Br J Anaesth ; 128(3): 482-490, 2022 03.
Article in English | MEDLINE | ID: covidwho-1536454

ABSTRACT

BACKGROUND: Tracheostomy is performed in patients expected to require prolonged mechanical ventilation, but to date optimal timing of tracheostomy has not been established. The evidence concerning tracheostomy in COVID-19 patients is particularly scarce. We aimed to describe the relationship between early tracheostomy (≤10 days since intubation) and outcomes for patients with COVID-19. METHODS: This was a prospective cohort study performed in 152 centres across 16 European countries from February to December 2020. We included patients aged ≥70 yr with confirmed COVID-19 infection admitted to an intensive care unit, requiring invasive mechanical ventilation. Multivariable analyses were performed to evaluate the association between early tracheostomy and clinical outcomes including 3-month mortality, intensive care length of stay, and duration of mechanical ventilation. RESULTS: The final analysis included 1740 patients with a mean age of 74 yr. Tracheostomy was performed in 461 (26.5%) patients. The tracheostomy rate varied across countries, from 8.3% to 52.9%. Early tracheostomy was performed in 135 (29.3%) patients. There was no difference in 3-month mortality between early and late tracheostomy in either our primary analysis (hazard ratio [HR]=0.96; 95% confidence interval [CI], 0.70-1.33) or a secondary landmark analysis (HR=0.78; 95% CI, 0.57-1.06). CONCLUSIONS: There is a wide variation across Europe in the timing of tracheostomy for critically ill patients with COVID-19. However, we found no evidence that early tracheostomy is associated with any effect on survival amongst older critically ill patients with COVID-19. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04321265.


Subject(s)
COVID-19/mortality , COVID-19/therapy , Critical Care/methods , Critical Care/statistics & numerical data , Critical Illness/mortality , Tracheostomy/mortality , Tracheostomy/statistics & numerical data , Aged , Correlation of Data , Europe , Female , Humans , Intensive Care Units/statistics & numerical data , Length of Stay , Male , Prospective Studies , Respiration, Artificial , Survival Rate/trends , Time Factors , Treatment Outcome
10.
Clin Transl Sci ; 14(6): 2146-2151, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526353

ABSTRACT

Tocilizumab is an IL-6 receptor antagonist with the ability to suppress the cytokine storm in critically ill patients infected with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We evaluated patients treated with tocilizumab for a SARS-CoV-2 infection who were admitted between March 13, 2020, and April 16, 2020. This was a multicenter study with data collected by chart review both retrospectively and concurrently. Parameters evaluated included age, sex, race, use of mechanical ventilation (MV), usage of steroids and vasopressors, inflammatory markers, and comorbidities. Early dosing was defined as a tocilizumab dose administered prior to or within 1 day of intubation. Late dosing was defined as a dose administered > 1 day after intubation. In the absence of MV, the timing of the dose was related to the patient's date of admission only. We evaluated 145 patients. The average age was 58.1 years, 64% were men, 68.3% had comorbidities, and 60% received steroid therapy. Disposition of patients was 48.3% discharged and 29.3% died, of which 43.9% were African American. MV was required in 55.9%, of which 34.5% died. Avoidance of MV (P = 0.002) and increased survival (P < 0.001) was statistically associated with early dosing. Tocilizumab therapy was effective at decreasing mortality and should be instituted early in the management of critically ill patients with coronavirus disease 2019) COVID-19).


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19/drug therapy , COVID-19/therapy , Cytokine Release Syndrome/therapy , Respiration, Artificial/statistics & numerical data , COVID-19/immunology , COVID-19/mortality , COVID-19/virology , Critical Illness/mortality , Critical Illness/therapy , Cytokine Release Syndrome/immunology , Cytokine Release Syndrome/mortality , Cytokine Release Syndrome/virology , Female , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies , SARS-CoV-2/immunology , Severity of Illness Index , Time Factors , Time-to-Treatment , Treatment Outcome
11.
Cytokine ; 149: 155727, 2022 01.
Article in English | MEDLINE | ID: covidwho-1506763

ABSTRACT

BACKGROUND: Although pneumonia is the hallmark of coronavirus disease 2019 (COVID-19), multiple organ failure may develop in severe disease. TNFα receptors in their soluble form (sTNFR) are involved in the immune cascade in other systemic inflammatory processes such as septic shock, and could mediate the inflammatory activation of distant organs. The aim of this study is to analyse plasma levels of sTNFR 1 and 2 in association with organ failure and outcome in critically ill patients with COVID-19. METHODS: After informed consent, we included 122 adult patients with PCR-confirmed COVID-19 at ICU admission. Demographic data, illness severity scores, organ failure and survival at 30 days were collected. Plasma sTNFR 1 and 2 levels were quantified during the first days after ICU admission. Twenty-five healthy blood donors were used as control group. RESULTS: Levels of sTNFR were higher in severe COVID-19 patients compared to controls (p < 0.001). Plasma levels of sTNFR were associated to illness severity scores (SAPS 3 and SOFA), inflammation biomarkers such as IL-6, ferritin and PCT as well as development of AKI during ICU stay. sTNFR 1 higher than 2.29 ng/mL and? sTNFR 2 higher than 11.7 ng/mL were identified as optimal cut-offs to discriminate survivors and non-survivors 30 days after ICU admission and had an area under the curve in receiver operating characteristic curve of 0.75 and 0.67 respectively. CONCLUSION: Plasma levels of sTNFR 1 and 2 were higher in COVID-19 patients compared to controls and were strongly associated with other inflammatory biomarkers, severity of illness and acute kidney injury development during ICU stay. In addition, sTNFR 1 was an independent predictor of 30-day mortality after adjustment for age and respiratory failure.


Subject(s)
Acute Kidney Injury/blood , Acute Kidney Injury/mortality , COVID-19/blood , COVID-19/mortality , Critical Illness/mortality , Receptors, Tumor Necrosis Factor/blood , Biomarkers/blood , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Multiple Organ Failure/blood , Multiple Organ Failure/mortality , Organ Dysfunction Scores , Prospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index
12.
Anesthesiology ; 135(6): 1076-1090, 2021 12 01.
Article in English | MEDLINE | ID: covidwho-1507118

ABSTRACT

BACKGROUND: Mortality in critically ill COVID-19 patients remains high. Although randomized controlled trials must continue to definitively evaluate treatments, further hypothesis-generating efforts to identify candidate treatments are required. This study's hypothesis was that certain treatments are associated with lower COVID-19 mortality. METHODS: This was a 1-yr retrospective cohort study involving all COVID-19 patients admitted to intensive care units in six hospitals affiliated with Yale New Haven Health System from February 13, 2020, to March 4, 2021. The exposures were any COVID-19-related pharmacologic and organ support treatments. The outcome was in-hospital mortality. RESULTS: This study analyzed 2,070 patients after excluding 23 patients who died within 24 h after intensive care unit admission and 3 patients who remained hospitalized on the last day of data censoring. The in-hospital mortality was 29% (593 of 2,070). Of 23 treatments analyzed, apixaban (hazard ratio, 0.42; 95% CI, 0.363 to 0.48; corrected CI, 0.336 to 0.52) and aspirin (hazard ratio, 0.72; 95% CI, 0.60 to 0.87; corrected CI, 0.54 to 0.96) were associated with lower mortality based on the multivariable analysis with multiple testing correction. Propensity score-matching analysis showed an association between apixaban treatment and lower mortality (with vs. without apixaban, 27% [96 of 360] vs. 37% [133 of 360]; hazard ratio, 0.48; 95% CI, 0.337 to 0.69) and an association between aspirin treatment and lower mortality (with vs. without aspirin, 26% [121 of 473] vs. 30% [140 of 473]; hazard ratio, 0.57; 95% CI, 0.41 to 0.78). Enoxaparin showed similar associations based on the multivariable analysis (hazard ratio, 0.82; 95% CI, 0.69 to 0.97; corrected CI, 0.61 to 1.05) and propensity score-matching analysis (with vs. without enoxaparin, 25% [87 of 347] vs. 34% [117 of 347]; hazard ratio, 0.53; 95% CI, 0.367 to 0.77). CONCLUSIONS: Consistent with the known hypercoagulability in severe COVID-19, the use of apixaban, enoxaparin, or aspirin was independently associated with lower mortality in critically ill COVID-19 patients.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Critical Illness/mortality , Critical Illness/therapy , Aged , Aged, 80 and over , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anticoagulants/administration & dosage , Antiviral Agents/administration & dosage , Cohort Studies , Factor Xa Inhibitors/administration & dosage , Female , Humans , Male , Middle Aged , Mortality/trends , Retrospective Studies , Treatment Outcome
13.
Aging (Albany NY) ; 13(21): 23895-23912, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1498164

ABSTRACT

The coronavirus disease 2019 (COVID-19) is presently the most pressing public health concern worldwide. Cytokine storm is an important factor leading to death of patients with COVID-19. This study aims to characterize serum cytokines of patients with severe or critical COVID-19. Clinical records were obtained from 149 patients who were tested at the Sino-French New City Branch of Tongji Hospital from 30 January to 30 March 2020. Data regarding the clinical features of the patients was collected and analyzed. Among the 149, 45 (30.2%) of them had severe conditions and 104 (69.8%) of that presented critical symptoms. In the meantime, 80 (53.7%) of that 149 died during hospitalization. Of all, male patients accounted for 94 (69.1%). Compared with patients in severe COVID-19, those who in critical COVID-19 had significantly higher levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-8, and IL-10. Moreover, the passed-away patients had considerably higher levels of TNF-α, IL-6, IL-8, and IL-10 than those survived from it. Regression analysis revealed that serum TNF-α level was an independent risk factor for the death of patient with severe conditions. Among the proinflammatory cytokines (IL-1ß, TNF-α, IL-8, and IL-6) analyzed herein, TNF-α was seen as a risk factor for the death of patients with severe or critical COVID-19. This study suggests that anti-TNF-α treatment allows patients with severe or critical COVID-19 pneumonia to recover.


Subject(s)
COVID-19 , Critical Illness , Interleukins/blood , Pneumonia, Viral , Tumor Necrosis Factor-alpha/blood , COVID-19/diagnosis , COVID-19/immunology , COVID-19/mortality , COVID-19/therapy , China/epidemiology , Critical Illness/mortality , Critical Illness/therapy , Female , Hospital Mortality , Humans , Immunologic Tests/methods , Male , Middle Aged , Mortality , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/etiology , Predictive Value of Tests , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Tomography, X-Ray Computed/methods , Tumor Necrosis Factor Inhibitors/therapeutic use
14.
Nutrients ; 13(10)2021 Oct 12.
Article in English | MEDLINE | ID: covidwho-1477977

ABSTRACT

BACKGROUND: Vitamin C is a water-soluble antioxidant vitamin. Oxidative stress and its markers, along with inflammatory markers, are high during critical illness. Due to conflicting results of the published literature regarding the efficacy of vitamin C in critically ill patients, and especially the concerns for nephrotoxicity raised by some case reports, this meta-analysis was carried out to appraise the evidence and affirmation regarding the role of vitamin C in critically ill patients. METHODS: We searched the database thoroughly to collect relevant studies that assessed intravenous vitamin C use in critically ill patients published until 25 February 2021. We included randomized controlled trials and observational studies with 20 or more critically ill patients who have received intravenous ascorbic acid (vitamin C). After screening 18,312 studies from different databases, 53 were included in our narrative synthesis, and 48 were included in the meta-analysis. We used the Covidence software for screening of the retrieved literature. Review Manager (RevMan) 5.4 was used for the pooling of data and Odds Ratios (OR) and Mean difference (MD) as measures of effects with a 95% confidence interval to assess for explanatory variables. RESULTS: Pooling data from 33 studies for overall hospital mortality outcomes using a random-effect model showed a 19% reduction in odds of mortality among the vitamin C group (OR, 0.81; 95% CI, 0.66-0.98). Length of hospital stay (LOS), mortality at 28/30 days, ICU mortality, new-onset AKI and Renal Replacement Therapy (RRT) for AKI did not differ significantly across the two groups. Analysis of data from 30 studies reporting ICU stay disclosed 0.76 fewer ICU days in the vitamin C group than the placebo/standard of care (SOC) group (95% CI, -1.34 to -0.19). This significance for shortening ICU stay persisted even when considering RCTs only in the analysis (MD, -0.70; 95% CI, -1.39 to -0.02). CONCLUSION: Treatment of critically ill patients with intravenous vitamin C was relatively safe with no significant difference in adverse renal events and decreased in-hospital mortality. The use of vitamin C showed a significant reduction in the length of ICU stays in critically ill patients.


Subject(s)
Ascorbic Acid/pharmacology , Critical Illness , Acute Kidney Injury/therapy , Clinical Trials as Topic , Critical Illness/mortality , Hospital Mortality , Humans , Intensive Care Units , Length of Stay , Renal Replacement Therapy
15.
Crit Care Med ; 49(10): e1037-e1039, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1475866

ABSTRACT

OBJECTIVES: To determine if a restrictive visitor policy inadvertently lengthened the decision-making process for dying inpatients without coronavirus disease 2019. DESIGN: Regression discontinuity and time-to-event analysis. SETTING: Two large academic hospitals in a unified health system. PATIENTS OR SUBJECTS: Adult decedents who received greater than or equal to 1 day of ICU care during their terminal admission over a 12-month period. INTERVENTIONS: Implementation of a visit restriction policy. MEASUREMENTS AND MAIN RESULTS: We identified 940 adult decedents without coronavirus disease 2019 during the study period. For these patients, ICU length of stay was 0.8 days longer following policy implementation, although this effect was not statistically significant (95% CI, -2.3 to 3.8; p = 0.63). After excluding patients admitted before the policy but who died after implementation, we observed that ICU length of stay was 2.9 days longer post-policy (95% CI, 0.27-5.6; p = 0.03). A time-to-event analysis revealed that admission after policy implementation was associated with a significantly longer time to first do not resuscitate/do not intubate/comfort care order (adjusted hazard ratio, 2.2; 95% CI, 1.6-3.1; p < 0.0001). CONCLUSIONS: Policies restricting family presence may lead to longer ICU stays and delay decisions to limit treatment prior to death. Further policy evaluation and programs enabling access to family-centered care and palliative care during the ongoing coronavirus disease 2019 pandemic are imperative.


Subject(s)
COVID-19/mortality , Decision Making , Health Policy , Visitors to Patients/statistics & numerical data , Adult , Aged , COVID-19/complications , COVID-19/psychology , Critical Illness/mortality , Critical Illness/therapy , Female , Humans , Male , Middle Aged , Terminal Care/methods , Terminal Care/psychology , Terminal Care/standards
16.
PLoS One ; 16(9): e0258018, 2021.
Article in English | MEDLINE | ID: covidwho-1443853

ABSTRACT

BACKGROUND: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant. METHODS: In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality. RESULTS: Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course.


Subject(s)
COVID-19/blood , COVID-19/mortality , Adult , Aged , Arterial Pressure/physiology , Blood Physiological Phenomena , Blood Pressure/physiology , Cohort Studies , Critical Illness/mortality , Female , Germany/epidemiology , Hospital Mortality/trends , Humans , Hydrogen-Ion Concentration , Intensive Care Units/trends , Male , Middle Aged , Mortality/trends , Prognosis , Retrospective Studies , Risk Factors , SARS-CoV-2/pathogenicity
17.
Crit Care ; 25(1): 344, 2021 09 23.
Article in English | MEDLINE | ID: covidwho-1438302

ABSTRACT

BACKGROUND: The primary aim of this study was to assess the outcome of elderly intensive care unit (ICU) patients treated during the spring and autumn COVID-19 surges in Europe. METHODS: This was a prospective European observational study (the COVIP study) in ICU patients aged 70 years and older admitted with COVID-19 disease from March to December 2020 to 159 ICUs in 14 European countries. An electronic database was used to register a number of parameters including: SOFA score, Clinical Frailty Scale, co-morbidities, usual ICU procedures and survival at 90 days. The study was registered at ClinicalTrials.gov (NCT04321265). RESULTS: In total, 2625 patients were included, 1327 from the first and 1298 from the second surge. Median age was 74 and 75 years in surge 1 and 2, respectively. SOFA score was higher in the first surge (median 6 versus 5, p < 0.0001). The PaO2/FiO2 ratio at admission was higher during surge 1, and more patients received invasive mechanical ventilation (78% versus 68%, p < 0.0001). During the first 15 days of treatment, survival was similar during the first and the second surge. Survival was lower in the second surge after day 15 and differed after 30 days (57% vs 50%) as well as after 90 days (51% vs 40%). CONCLUSION: An unexpected, but significant, decrease in 30-day and 90-day survival was observed during the second surge in our cohort of elderly ICU patients. The reason for this is unclear. Our main concern is whether the widespread changes in practice and treatment of COVID-19 between the two surges have contributed to this increased mortality in elderly patients. Further studies are urgently warranted to provide more evidence for current practice in elderly patients. TRIAL REGISTRATION NUMBER: NCT04321265 , registered March 19th, 2020.


Subject(s)
COVID-19/mortality , Critical Illness/mortality , Pneumonia, Viral/mortality , Aged , Aged, 80 and over , Comorbidity , Europe/epidemiology , Female , Frail Elderly , Humans , Intensive Care Units , Male , Organ Dysfunction Scores , Pandemics , Pneumonia, Viral/virology , Prospective Studies , SARS-CoV-2 , Survival Analysis
18.
PLoS One ; 16(9): e0256203, 2021.
Article in English | MEDLINE | ID: covidwho-1435605

ABSTRACT

OBJECTIVES: We conducted the present multicenter, retrospective study to assess the epidemiological, clinical, laboratory, and radiological characteristics associated with critical illness among patients with COVID-19 from Egypt. METHODS: The present study was a multicenter, retrospective study that retrieved the data of all Egyptian cases with confirmed COVID-19 admitted to hospitals affiliated to the General Organization for Teaching Hospitals and Institutes (GOTHI) through the period from March to July 2020. The diagnosis of COVID-19 was based on a positive reverse transcription-polymerase chain reaction (RT-PCR) laboratory test. RESULTS: This retrospective study included 2724 COVID-19 patients, of whom 423 (15.52%) were critically ill. Approximately 45.86% of the critical group aged above 60 years, compared to 39.59% in the non-critical group (p = 0.016). Multivariate analysis showed that many factors were predictors of critically illness, including age >60 years (OR = 1.30, 95% CI [1.05, 1.61], p = 0.014), low oxygen saturation (OR = 0.93, 95% CI [0.91, 0.95], p<0.001), low Glasgow coma scale (OR = 0.75, 95% CI [0.67, 0.84], p<0.001), diabetes (OR = 1.62, 95% CI [1.26, 2.08], p<0.001), cancer (OR = 2.47, 95% CI [1.41, 4.35], p = 0.002), and serum ferritin (OR = 1.004, 95% CI [1.0003, 1.008], p = 0.031). CONCLUSION: In the present report, we demonstrated that many factors are associated with COVID-19 critical illness, including older age groups, fatigue, elevated temperature, increased pulse, lower oxygen saturation, the preexistence of diabetes, malignancies, cardiovascular disease, renal diseases, and pulmonary disease. Moreover, elevated serum levels of ALT, AST, and ferritin are associated with worse outcomes. Further studies are required to identify independent predictors of mortality for patients with COVID-19.


Subject(s)
COVID-19/complications , COVID-19/mortality , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Critical Illness/mortality , Egypt , Female , Hospital Mortality , Hospitalization , Humans , Infant , Infant, Newborn , Intensive Care Units , Male , Middle Aged , Risk Factors , SARS-CoV-2/pathogenicity , Young Adult
19.
Am J Otolaryngol ; 43(1): 103230, 2022.
Article in English | MEDLINE | ID: covidwho-1427502

ABSTRACT

PURPOSE: Tracheostomy is an aerosol-generating procedure, thus performing it during the COVID-19 pandemic arises considerations such as the most appropriate timing and the patients to whom it is suitable. Medical teams lack sufficient data to assist determining whether or not to conduct tracheostomy, its short- and long-term implications are not fully understood. This study aims to shed light on the critically ill COVID-19 patients that require tracheostomy, and to investigate its value. METHODS: A retrospective multicentral case-control study of 157 hospitalized critically ill COVID-19 patients, among whom 30 patients went through tracheostomy and consisted of our study group. RESULTS: The mean age was similar between study and control groups (68.9 ± 12.7 years vs 70.5 ± 15.8 years, p = 0.57), as well as comorbidity prevalence (56.7% vs 67.7%, p = 0.25). Patients in the study group were hospitalized for longer duration until defined critically ill (5 ± 4.3 vs 3 ± 3.9 days; p = 0.01), until admitted to the intensive care unit (6 ± 6.6 vs 2.5 ± 3.7 days respectively; p = 0.005), and until discharged (24 ± 9.7 vs 10.7 ± 9.1 days, p < 0.001). Mortality rate was lower in the study group (30% vs 59.8%, p = 0.003). Kaplan Meier survival analysis revealed a statistically significant difference in survival time between groups (Log rank chi-sq = 20.91, p < 0.001) with mean survival time of 41 ± 3.1 days vs 21 ± 2.2 days. Survival was significantly longer in the study group (OR = 0.37, p = 0.004). CONCLUSION: Tracheostomy allows for more prolonged survival for gradually deteriorating critically ill COVID-19 patients. This should be integrated into the medical teams' considerations when debating whether or not to conduct tracheostomy.


Subject(s)
COVID-19/therapy , Critical Illness/therapy , Pneumonia, Viral/therapy , Tracheostomy , Aged , COVID-19/mortality , Critical Illness/mortality , Female , Humans , Length of Stay/statistics & numerical data , Male , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , SARS-CoV-2 , Survival Rate
20.
PLoS Pathog ; 17(9): e1009804, 2021 09.
Article in English | MEDLINE | ID: covidwho-1416909

ABSTRACT

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49-14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08-18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 -a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention.


Subject(s)
COVID-19/immunology , COVID-19/mortality , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Antigens, CD/immunology , Antigens, Differentiation, T-Lymphocyte/immunology , B-Lymphocytes/immunology , Biomarkers/blood , Blood Proteins/metabolism , Cohort Studies , Critical Illness/mortality , Female , Humans , Immunophenotyping , Influenza, Human/immunology , Lectins, C-Type/immunology , Lymphocyte Activation , Male , Middle Aged , Mucosal-Associated Invariant T Cells/immunology , Patient Acuity
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