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1.
Crit Care Explor ; 2(6): e0139, 2020 Jun.
Article in English | MEDLINE | ID: covidwho-1795099

ABSTRACT

OBJECTIVES: The severe acute respiratory syndrome coronavirus 2 pandemic has stretched ICU resources in an unprecedented fashion and outstripped personal protective equipment supplies. The combination of a novel disease, resource limitations, and risks to medical personnel health have created new barriers to implementing the ICU Liberation ("A" for Assessment, Prevention, and Manage pain; "B" for Both Spontaneous Awakening Trials and Spontaneous Breathing Trials; "C" for Choice of Analgesia and Sedation; "D" for Delirium Assess, Prevent, and Manage; "E" for Early Mobility and Exercise; and "F" for Family Engagement and Empowerment [ABCDEF]) Bundle, a proven ICU care approach that reduces delirium, shortens mechanical ventilation duration, prevents post-ICU syndrome, and reduces healthcare costs. This narrative review acknowledges barriers and offers strategies to optimize Bundle performance in coronavirus disease 2019 patients requiring mechanical ventilation. DATA SOURCES STUDY SELECTION AND DATA EXTRACTION: The most relevant literature, media reports, and author experiences were assessed for inclusion in this narrative review including PubMed, national newspapers, and critical care/pharmacology textbooks. DATA SYNTHESIS: Uncertainty regarding coronavirus disease 2019 clinical course, shifts in attitude, and changes in routine behavior have hindered Bundle use. A domino effect results from: 1) changes to critical care hierarchy, priorities, and ICU team composition; 2) significant personal protective equipment shortages cause; 3) reduced/restricted physical bedside presence favoring; 4) increased depth of sedation and use of neuromuscular blockade; 5) which exacerbate drug shortages; and 6) which require prolonged use of limited ventilator resources. Other identified barriers include manageable knowledge deficits among non-ICU clinicians unfamiliar with the Bundle or among PICU specialists deploying pediatric-based Bundle approaches who are unfamiliar with adult medicine. Both groups have been enlisted to augment the adult ICU work force to meet demand. Strategies were identified to facilitate Bundle performance to liberate patients from the ICU. CONCLUSIONS: We acknowledge current challenges that interfere with comprehensive management of critically ill patients during the coronavirus disease 2019 pandemic. Rapid response to new circumstances precisely requires established safety mechanisms and protocols like the ABCDEF Bundle to increase ICU and ventilator capacity and help survivors maximize recovery from coronavirus disease 2019 as early as possible.

2.
J Clin Med ; 10(7)2021 Mar 25.
Article in English | MEDLINE | ID: covidwho-1753619

ABSTRACT

The real-world performance of a home telemonitoring strategy (ForeseeHome AMD Monitoring System®, Notal Vision, Inc.,Manassas VA, USA) was evaluated and compared to the device arm of the AREDS2-HOME study among patients with intermediate AMD (iAMD) who converted to neovascular AMD (nAMD). All patients with confirmed conversion to nAMD who used the home monitoring system from 10/2009 through 9/2018 were identified by Notal Vision Diagnostic Clinic's medical records. Selected outcome variables were evaluated, including visual acuity (VA) at baseline and at conversion, and change in visual acuity (VA) from baseline to time of conversion. In total, 8991 patients performed 3,200,999 tests at a frequency of 5.6 ± 3.2 times/week. The 306 eyes that converted from iAMD to nAMD over the study period (a 2.7% annual rate) were included in the analyses. There was a median (interquartile range) change of -3.0 (0.0-(-10.0)) letters among converted eyes, 81% [95% confidence interval (72-88%)] maintained a VA ≥ 20/40 at the time of conversion, while 69% of the conversion detections were triggered by system alerts. The real-world performance of an at-home testing strategy was similar to that reported for the device arm of the AREDS2-HOME study. The home telemonitoring system can markedly increase early detection of conversion to nAMD.

3.
Ann Med ; 53(1): 402-409, 2021 12.
Article in English | MEDLINE | ID: covidwho-1574118

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) has a high burden on the healthcare system. Prediction models may assist in triaging patients. We aimed to assess the value of several prediction models in COVID-19 patients in the emergency department (ED). METHODS: In this retrospective study, ED patients with COVID-19 were included. Prediction models were selected based on their feasibility. Primary outcome was 30-day mortality, secondary outcomes were 14-day mortality and a composite outcome of 30-day mortality and admission to medium care unit (MCU) or intensive care unit (ICU). The discriminatory performance of the prediction models was assessed using an area under the receiver operating characteristic curve (AUC). RESULTS: We included 403 patients. Thirty-day mortality was 23.6%, 14-day mortality was 19.1%, 66 patients (16.4%) were admitted to ICU, 48 patients (11.9%) to MCU, and 152 patients (37.7%) met the composite endpoint. Eleven prediction models were included. The RISE UP score and 4 C mortality scores showed very good discriminatory performance for 30-day mortality (AUC 0.83 and 0.84, 95% CI 0.79-0.88 for both), significantly higher than that of the other models. CONCLUSION: The RISE UP score and 4 C mortality score can be used to recognise patients at high risk for poor outcome and may assist in guiding decision-making and allocating resources.


Subject(s)
COVID-19/mortality , Emergency Service, Hospital/statistics & numerical data , Aged , COVID-19/diagnosis , Feasibility Studies , Female , Hospital Mortality , Humans , Length of Stay/statistics & numerical data , Logistic Models , Male , Middle Aged , Netherlands/epidemiology , Prognosis , ROC Curve , Retrospective Studies , Risk Assessment/methods , SARS-CoV-2/isolation & purification
4.
J Med Internet Res ; 23(2): e23390, 2021 02 22.
Article in English | MEDLINE | ID: covidwho-1574113

ABSTRACT

BACKGROUND: The initial symptoms of patients with COVID-19 are very much like those of patients with community-acquired pneumonia (CAP); it is difficult to distinguish COVID-19 from CAP with clinical symptoms and imaging examination. OBJECTIVE: The objective of our study was to construct an effective model for the early identification of COVID-19 that would also distinguish it from CAP. METHODS: The clinical laboratory indicators (CLIs) of 61 COVID-19 patients and 60 CAP patients were analyzed retrospectively. Random combinations of various CLIs (ie, CLI combinations) were utilized to establish COVID-19 versus CAP classifiers with machine learning algorithms, including random forest classifier (RFC), logistic regression classifier, and gradient boosting classifier (GBC). The performance of the classifiers was assessed by calculating the area under the receiver operating characteristic curve (AUROC) and recall rate in COVID-19 prediction using the test data set. RESULTS: The classifiers that were constructed with three algorithms from 43 CLI combinations showed high performance (recall rate >0.9 and AUROC >0.85) in COVID-19 prediction for the test data set. Among the high-performance classifiers, several CLIs showed a high usage rate; these included procalcitonin (PCT), mean corpuscular hemoglobin concentration (MCHC), uric acid, albumin, albumin to globulin ratio (AGR), neutrophil count, red blood cell (RBC) count, monocyte count, basophil count, and white blood cell (WBC) count. They also had high feature importance except for basophil count. The feature combination (FC) of PCT, AGR, uric acid, WBC count, neutrophil count, basophil count, RBC count, and MCHC was the representative one among the nine FCs used to construct the classifiers with an AUROC equal to 1.0 when using the RFC or GBC algorithms. Replacing any CLI in these FCs would lead to a significant reduction in the performance of the classifiers that were built with them. CONCLUSIONS: The classifiers constructed with only a few specific CLIs could efficiently distinguish COVID-19 from CAP, which could help clinicians perform early isolation and centralized management of COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Community-Acquired Infections/diagnosis , Machine Learning , Pneumonia/diagnosis , SARS-CoV-2/pathogenicity , Area Under Curve , COVID-19/blood , COVID-19/virology , Community-Acquired Infections/blood , Female , Humans , Laboratories , Leukocyte Count , Logistic Models , Male , Middle Aged , Pneumonia/blood , Procalcitonin/blood , ROC Curve , Retrospective Studies
6.
Intern Med J ; 51(11): 1810-1815, 2021 11.
Article in English | MEDLINE | ID: covidwho-1526370

ABSTRACT

BACKGROUND: COVID-19 long-term sequelae are ill-defined since only a few studies have explored the long-term consequences of this disease so far. AIMS: To evaluate the 6-month respiratory outcome and exercise capacity of COVID-19 acute respiratory failure (ARF) patients treated with continuous positive airway pressure (CPAP) during the first wave of the ongoing COVID-19 pandemic. METHODS: A retrospective observational study included COVID-19 patients with ARF. Interventions included CPAP during hospitalisation and 6-month follow up. Frailty assessment was carried out through frailty index (FI), pO2 /FiO2 during hospitalisation and at follow up, respiratory parameters, 6-min walking test (6MWT) and the modified British Medical Research Council (mMRC) and Borg scale at follow up. RESULTS: More than half of the patients had no dyspnoea according to the mMRC scale. Lower in-hospital pO2 /FiO2 correlated with higher Borg scale levels after 6MWT (ρ 0.27; P 0.04) at the follow-up visit. FI was positively correlated with length of hospitalisation (ρ 0.3; P 0.03) and negatively with the 6MWT distance walked (ρ -0.36; P 0.004). CONCLUSIONS: Robust and frail patients with COVID-19 ARF treated with CPAP outside the intensive care unit setting had good respiratory parameters and exercise capacity at 6-month follow up, although more severe patients had slightly poorer respiratory performance compared with patients with higher PaO2 /FiO2 and lower FI.


Subject(s)
COVID-19 , Respiratory Insufficiency , Continuous Positive Airway Pressure , Exercise Tolerance , Humans , Pandemics , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/therapy , Retrospective Studies , SARS-CoV-2
7.
Ann Hepatol ; 25: 100350, 2021.
Article in English | MEDLINE | ID: covidwho-1525673

ABSTRACT

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.


Subject(s)
COVID-19/epidemiology , Hospitalization , Liver Cirrhosis/epidemiology , Body Mass Index , Comorbidity , Female , Follow-Up Studies , Humans , Liver Cirrhosis/diagnosis , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , South America/epidemiology , Survival Rate/trends
8.
PLoS One ; 15(12): e0243342, 2020.
Article in English | MEDLINE | ID: covidwho-1388895

ABSTRACT

INTRODUCTION: In numerous countries, large population testing is impossible due to the limited availability of RT-PCR kits and CT-scans. This study aimed to determine a pre-test probability score for SARS-CoV-2 infection. METHODS: This multicenter retrospective study (4 University Hospitals) included patients with clinical suspicion of SARS-CoV-2 infection. Demographic characteristics, clinical symptoms, and results of blood tests (complete white blood cell count, serum electrolytes and CRP) were collected. A pre-test probability score was derived from univariate analyses of clinical and biological variables between patients and controls, followed by multivariate binary logistic analysis to determine the independent variables associated with SARS-CoV-2 infection. RESULTS: 605 patients were included between March 10th and April 30th, 2020 (200 patients for the training cohort, 405 consecutive patients for the validation cohort). In the multivariate analysis, lymphocyte (<1.3 G/L), eosinophil (<0.06 G/L), basophil (<0.04 G/L) and neutrophil counts (<5 G/L) were associated with high probability of SARS-CoV-2 infection but no clinical variable was statistically significant. The score had a good performance in the validation cohort (AUC = 0.918 (CI: [0.891-0.946]; STD = 0.014) with a Positive Predictive Value of high-probability score of 93% (95%CI: [0.89-0.96]). Furthermore, a low-probability score excluded SARS-CoV-2 infection with a Negative Predictive Value of 98% (95%CI: [0.93-0.99]). The performance of the score was stable even during the last period of the study (15-30th April) with more controls than infected patients. CONCLUSIONS: The PARIS score has a good performance to categorize the pre-test probability of SARS-CoV-2 infection based on complete white blood cell count. It could help clinicians adapt testing and for rapid triage of patients before test results.


Subject(s)
COVID-19/diagnosis , COVID-19/genetics , Reagent Kits, Diagnostic , Reverse Transcriptase Polymerase Chain Reaction , SARS-CoV-2/genetics , Adult , Aged , Aged, 80 and over , COVID-19/epidemiology , Female , Humans , Male , Middle Aged , Probability , Retrospective Studies , Sensitivity and Specificity
9.
Brain ; 144(4): 1263-1276, 2021 05 07.
Article in English | MEDLINE | ID: covidwho-1313840

ABSTRACT

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into the focus of interest. In this prospective cohort study, we assessed neurological and cognitive symptoms in hospitalized coronavirus disease-19 (COVID-19) patients and aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because of non-neurological complications were screened between 20 April 2020 and 12 May 2020. Patients (age > 18 years) were included in our cohort when presenting with at least one new neurological symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment and/or pathological findings on clinical neurological examination). Patients with ≥2 new symptoms were eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI and 18fluorodeoxyglucose (FDG) PET as soon as infectivity was no longer present. Exclusion criteria were: premorbid diagnosis of cognitive impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 COVID-19 inpatients screened, 29 patients (65.2 ± 14.4 years; 38% female) in the subacute stage of disease were included in the register. Most frequently, gustation and olfaction were disturbed in 29/29 and 25/29 patients, respectively. Montreal Cognitive Assessment performance was impaired in 18/26 patients (mean score 21.8/30) with emphasis on frontoparietal cognitive functions. This was confirmed by detailed neuropsychological testing in 15 patients. 18FDG PET revealed pathological results in 10/15 patients with predominant frontoparietal hypometabolism. This pattern was confirmed by comparison with a control sample using voxel-wise principal components analysis, which showed a high correlation (R2 = 0.62) with the Montreal Cognitive Assessment performance. Post-mortem examination of one patient revealed white matter microglia activation but no signs of neuroinflammation. Neocortical dysfunction accompanied by cognitive decline was detected in a relevant fraction of patients with subacute COVID-19 initially requiring inpatient treatment. This is of major rehabilitative and socioeconomic relevance.


Subject(s)
COVID-19/metabolism , Cerebral Cortex/metabolism , Cognitive Dysfunction/metabolism , Glucose/metabolism , Mental Status and Dementia Tests , Aged , Aged, 80 and over , COVID-19/diagnostic imaging , COVID-19/psychology , Cerebral Cortex/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/psychology , Cohort Studies , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Positron-Emission Tomography/methods
10.
AJR Am J Roentgenol ; 217(3): 623-632, 2021 09.
Article in English | MEDLINE | ID: covidwho-1311346

ABSTRACT

BACKGROUND. Chest radiographs (CXRs) are typically obtained early in patients admitted with coronavirus disease (COVID-19) and may help guide prognosis and initial management decisions. OBJECTIVE. The purpose of this study was to assess the performance of an admission CXR severity scoring system in predicting hospital outcomes in patients admitted with COVID-19. METHODS. This retrospective study included 240 patients (142 men, 98 women; median age, 65 [range, 50-80] years) admitted to the hospital from March 16 to April 13, 2020, with COVID-19 confirmed by real-time reverse-transcriptase polymerase chain reaction who underwent chest radiography within 24 hours of admission. Three attending chest radiologists and three radiology residents independently scored patients' admission CXRs using a 0- to 24-point composite scale (sum of scores that range from 0 to 3 for extent and severity of disease in upper and lower zones of left and right lungs). Interrater reliability of the score was assessed using the Kendall W coefficient. The mean score was obtained from the six readers' scores for further analyses. Demographic variables, clinical characteristics, and admission laboratory values were collected from electronic medical records. ROC analysis was performed to assess the association between CXR severity and mortality. Additional univariable and multivariable logistic regression models incorporating patient characteristics and laboratory values were tested for associations between CXR severity and clinical outcomes. RESULTS. Interrater reliability of CXR scores ranged from 0.687 to 0.737 for attending radiologists, from 0.653 to 0.762 for residents, and from 0.575 to 0.666 for all readers. A composite CXR score of 10 or higher on admission achieved 53.0% (35/66) sensitivity and 75.3% (131/174) specificity for predicting hospital mortality. Hospital mortality occurred in 44.9% (35/78) of patients with a high-risk admission CXR score (≥ 10) versus 19.1% (31/162) of patients with a low-risk CXR score (< 10) (p < .001). Admission composite CXR score was an independent predictor of death (odds ratio [OR], 1.17; 95% CI, 1.10-1.24; p < .001). composite CXR score was a univariable predictor of intubation (OR, 1.23; 95% CI, 1.12-1.34; p < .001) and continuous renal replacement therapy (CRRT) (OR, 1.15; 95% CI, 1.04-1.27; p = .007) but was not associated with these in multivariable models (p > .05). CONCLUSION. For patients admitted with COVID-19, an admission CXR severity score may help predict hospital mortality, intubation, and CRRT. CLINICAL IMPACT. CXR may assist risk assessment and clinical decision-making early in the course of COVID-19.


Subject(s)
COVID-19/diagnostic imaging , Lung/diagnostic imaging , Radiography, Thoracic , Severity of Illness Index , Aged , Aged, 80 and over , COVID-19/classification , COVID-19/diagnosis , COVID-19 Nucleic Acid Testing , Female , Hospital Mortality , Hospitalization , Humans , Male , Middle Aged , Prognosis , Reproducibility of Results , Retrospective Studies
11.
Otol Neurotol ; 42(5): 666-670, 2021 06 01.
Article in English | MEDLINE | ID: covidwho-1294812

ABSTRACT

OBJECTIVE: While COVID-19 symptoms impact rhinology (anosmia) and laryngology (airways), two major disciplines of the otolaryngology armamentarium, the virus has seemed to spare the auditory system. A recent study, however, reported changes in otoacoustic emission (OAE) signals measured in SARS-COV-2 positive patients. We sought to assess the effect of COVID-19 infection on auditory performance in a cohort of recovered SARS-COV-2 patients and controls. To avoid a potential bias of previous audiological dysfunction not related to SARS-COV-2 infection, the study encompasses patients with normal auditory history. We hypothesized that if SARS-COV-2 infection predisposes to hearing loss, we would observe subtle and early audiometric deficits in our cohort in the form of subclinical auditory changes. STUDY DESIGN: Cross-sectional study. SETTING: Tertiary referral center. PATIENTS: The Institutional Review Board approved the study and we recruited participants who had been positive for SARS-COV-2 infection, according to an Reverse Transcription Polymerase Chain Reaction (RT-PCR) test on two nasopharyngeal swabs. The patients included in this study were asymptomatic for the SARS-COV-2 infection and were evaluated following recovery, confirmed by repeated swab testing. The control group comprised healthy individuals matched for age and sex, and with a normal auditory and otologic history. INTERVENTIONS: The eligibility to participate in this study included a normal audiogram, no previous auditory symptoms, normal otoscopy examination with an intact tympanic membrane, and bilateral tympanometry type A. None of our volunteers reported any new auditory symptoms following SARS-COV-2 infection. Ototacoustic emissions (OAE) and auditory brainstem response (ABR) measurements were used to evaluate the auditory function. MAIN OUTCOME MEASURES: OAE and ABR measurements. RESULTS: We have found no significant differences between recovered asymptomatic SARS-COV-2 patients and controls in any of transitory evoked otoacoustic emission (TEOAE), distortion product otoacoustic emissions (DPOAE), or ABR responses. CONCLUSIONS: There is no cochlear dysfunction represented by ABR, TEOAE, and DPOAE responses in recovered COVID-19 asymptomatic patients. Retrocochlear function was also preserved as evident by the ABR responses. A long-term evaluation of a larger cohort of SARS-COV-2 patients will help to identify a possible contribution of SARS-COV-2 infection to recently published anecdotal auditory symptoms associated with COVID-19.


Subject(s)
COVID-19 , SARS-CoV-2 , Cross-Sectional Studies , Evoked Potentials, Auditory, Brain Stem , Humans , Otoacoustic Emissions, Spontaneous
12.
J Allergy Clin Immunol ; 148(1): 91-95, 2021 07.
Article in English | MEDLINE | ID: covidwho-1291943

ABSTRACT

BACKGROUND: The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause. OBJECTIVE: Our aim was to evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, and the BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccines in patients with a history of PEG allergy. METHODS: Three known individuals with PEG allergy and 3 healthy controls were recruited and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines, and to related compounds by skin testing and basophil activation, as measured by CD63 upregulation using flow cytometry. RESULTS: We found that the BNT162b2 vaccine induced positive skin test results in patients with PEG allergy, whereas the result of traditional PEG skin testing was negative in 2 of 3 patients. One patient was found to be cosensitized to both the BNT162b2 and AZD1222 vaccines because of cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGylated lipids within nanoparticles, but not PEG in its native state, are able to efficiently induce degranulation. CONCLUSIONS: Our findings implicate PEG, as covalently modified and arranged on the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis in response to BNT162b2, and highlight shortcomings of current skin testing protocols for allergy to PEGylated liposomal drugs.


Subject(s)
Anaphylaxis/immunology , Basophils/immunology , COVID-19 Vaccines/immunology , COVID-19/immunology , Doxorubicin/analogs & derivatives , Drug Hypersensitivity/immunology , Nanoparticles/adverse effects , Polyethylene Glycols/adverse effects , SARS-CoV-2/physiology , Adult , Cell Degranulation , Cells, Cultured , Doxorubicin/adverse effects , Doxorubicin/chemistry , Female , Humans , Lipids/chemistry , Male , Middle Aged , Nanoparticles/chemistry , Polyethylene Glycols/chemistry , Skin Tests , Young Adult
13.
EClinicalMedicine ; 31: 100683, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1291524

ABSTRACT

BACKGROUND: The medium-term effects of Coronavirus disease (COVID-19) on organ health, exercise capacity, cognition, quality of life and mental health are poorly understood. METHODS: Fifty-eight COVID-19 patients post-hospital discharge and 30 age, sex, body mass index comorbidity-matched controls were enrolled for multiorgan (brain, lungs, heart, liver and kidneys) magnetic resonance imaging (MRI), spirometry, six-minute walk test, cardiopulmonary exercise test (CPET), quality of life, cognitive and mental health assessments. FINDINGS: At 2-3 months from disease-onset, 64% of patients experienced breathlessness and 55% reported fatigue. On MRI, abnormalities were seen in lungs (60%), heart (26%), liver (10%) and kidneys (29%). Patients exhibited changes in the thalamus, posterior thalamic radiations and sagittal stratum on brain MRI and demonstrated impaired cognitive performance, specifically in the executive and visuospatial domains. Exercise tolerance (maximal oxygen consumption and ventilatory efficiency on CPET) and six-minute walk distance were significantly reduced. The extent of extra-pulmonary MRI abnormalities and exercise intolerance correlated with serum markers of inflammation and acute illness severity. Patients had a higher burden of self-reported symptoms of depression and experienced significant impairment in all domains of quality of life compared to controls (p<0.0001 to 0.044). INTERPRETATION: A significant proportion of patients discharged from hospital reported symptoms of breathlessness, fatigue, depression and had limited exercise capacity. Persistent lung and extra-pulmonary organ MRI findings are common in patients and linked to inflammation and severity of acute illness. FUNDING: NIHR Oxford and Oxford Health Biomedical Research Centres, British Heart Foundation Centre for Research Excellence, UKRI, Wellcome Trust, British Heart Foundation.

14.
Infect Dis Ther ; 10(3): 1505-1518, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1274999

ABSTRACT

BACKGROUND: Quantitative serological assays detecting response to SARS-CoV-2 are needed to quantify immunity. This study analyzed the performance and correlation of two quantitative anti-S1 assays in oligo-/asymptomatic individuals from a population-based cohort. METHODS: In total, 362 plasma samples (108 with reverse transcription-polymerase chain reaction [RT-PCR]-positive pharyngeal swabs, 111 negative controls, and 143 with positive serology without confirmation by RT-PCR) were tested with quantitative assays (Euroimmun Anti-SARS-CoV-2 QuantiVac enzyme-linked immunosorbent assay [EI-S1-IgG-quant]) and Roche Elecsys® Anti-SARS-CoV-2 S [Ro-RBD-Ig-quant]), which were compared with each other and confirmatory tests, including wild-type virus micro-neutralization (NT) and GenScript®cPass™. Square roots R of coefficients of determination were calculated for continuous variables and non-parametric tests were used for paired comparisons. RESULTS: Quantitative anti-S1 serology correlated well with each other (true positives, 96%; true negatives, 97%). Antibody titers decreased over time (< 30 to > 240 days after initial positive RT-PCR). Agreement with GenScript-cPass was 96%/99% for true positives and true negatives, respectively, for Ro-RBD-Ig-quant and 93%/97% for EI-S1-IgG-quant. Ro-RBD-Ig-quant allowed distinct separation between positives and negatives, and less non-specific reactivity versus EI-S1-IgG-quant. Raw values (95% CI) ≥ 28.7 U/mL (22.6-36.4) for Ro-RBD-Ig-quant and ≥ 49.8 U/mL (43.4-57.1) for EI-S1-IgG-quant predicted NT > 1:5 in 95% of cases. CONCLUSIONS: Our findings suggest both quantitative anti-S1 assays (EI-S1-IgG-quant and Ro-RBD-Ig-quant) may replace direct neutralization assays in quantitative measurement of immune protection against SARS-CoV-2 in certain circumstances. However, although the mean antibody titers for both assays tended to decrease over time, a higher proportion of Ro-RBD-Ig-quant values remained positive after 240 days.

15.
Eur J Clin Microbiol Infect Dis ; 40(9): 1983-1997, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1263157

ABSTRACT

SARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.


Subject(s)
Antibodies, Viral/blood , Bacterial Infections/diagnosis , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Respiratory Tract Infections/diagnosis , Antibodies, Bacterial/blood , Bacterial Infections/blood , COVID-19/blood , COVID-19/virology , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin A/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Respiratory Tract Infections/blood , SARS-CoV-2/immunology , Sensitivity and Specificity , Spike Glycoprotein, Coronavirus/immunology
16.
J Oral Maxillofac Surg ; 79(8): 1629-1642, 2021 08.
Article in English | MEDLINE | ID: covidwho-1248986

ABSTRACT

PURPOSE: Approximately 3-15% of COVID-19 patients will require prolonged mechanical ventilation thereby requiring consideration for tracheotomy. Guidelines for tracheotomy in this cohort of patients are therefore required with assessed outcomes of tracheotomies. PATIENTS AND METHODS: A retrospective chart review was performed of COVID-19 patients undergoing tracheotomy. Inclusion criteria were the performance of a tracheotomy in COVID-19 positive patients between March 11 and December 31, 2020. Exclusion criteria were lack of consent, extubation prior to the performance of a tracheotomy, death prior to the performance of the tracheotomy, and COVID-19 patients undergoing tracheotomy who tested negative twice after medical treatment. The primary predictor variable was the performance of a tracheotomy in COVID-19 positive patients and the primary outcome variable was the time to cessation of mechanical ventilation with the institution of supplemental oxygen via trach mask. RESULTS: Seventeen tracheotomies were performed between 4-25 days following intubation (mean = 17 days). Seven patients died between 4 and 16 days (mean = 8.7 days) following tracheotomy and 10 living patients realized cessation of mechanical ventilation from 4 hours to 61 days following tracheotomy (mean = 19.3 days). These patients underwent tracheotomy between 4 and 22 days following intubation (mean = 14 days). The 7 patients who died following tracheotomy underwent the procedure between 7 and 25 days following intubation (mean = 18.2 days). Seven patients underwent tracheotomy on or after 20 days of intubation and 3 survived (43%). Ten patients underwent tracheotomy before 20 days of intubation and 7 patients survived (70%). Significant differences between the mortality groups were detected for age (P = .006), and for P/F ratio at time of consult (P = .047) and the time of tracheotomy (P = .03). CONCLUSIONS: Tracheotomies are safely performed in COVID-19 patients with a standardized protocol. The timing of tracheotomy in COVID-19 patients is based on ventilator parameters, P/F ratio, patient prognosis, patient advanced directives, and family wishes.


Subject(s)
COVID-19 , Tracheotomy , Humans , Respiration, Artificial , Retrospective Studies , SARS-CoV-2 , Tracheostomy
17.
Int J Endocrinol ; 2021: 5563960, 2021.
Article in English | MEDLINE | ID: covidwho-1247434

ABSTRACT

Although the numbers of aged populations have risen considerably in the last few decades, the current coronavirus disease 2019 (COVID-19) has revealed an extensive vulnerability among these populations. Sarcopenia is an age-related disorder that increases hospitalization, dependencies, and mortality in older adults. It starts to develop in midlife or even earlier as a result of unbalanced diet/poor nutrition and low levels of physical activity, in addition to chronic disorders such as obesity and diabetes mellitus. Given that social isolation is adopted as the most protective measure against COVID-19, the level of physical activity and the intake of adequate diet have considerably declined, especially among older adults-denoting an increased possibility for developing sarcopenia. Research also shows a higher vulnerability of sarcopenic people to COVID-19 as well as the development of wasting disorders such as sarcopenia and cachexia in a considerable proportion of symptomatic and recovering COVID-19 patients. Muscular wasting in COVID-19 is associated with poor prognosis. Accordingly, early detection and proper management of sarcopenia and wasting conditions in older adults and COVID-19 patients may minimize morbidity and mortality during the current COVID-19 crisis. This review explored different aspects of screening for sarcopenia, stressing their relevance to the detection of altered muscular structure and performance in patients with COVID-19. Current guidelines recommend prior evaluation of muscle strength by simple measures such as grip strength to identify individuals with proven weakness who then would be screened for muscle mass loss. The latter is best measured by MRI and CT. However, due to the high cost and radiation risk entailed by these techniques, other simpler and cheaper techniques such as DXA and ultrasound are given preference. Muscle loss in COVID-19 patients was measured during the acute phase by CT scanning of the pectoralis muscle simultaneously during a routine check for lung fibrosis, which seems to be an efficient evaluation of sarcopenia among those patients with no additional cost. In recovering patients, muscle strength and physical performance have been evaluated by electromyography and traditional tests such as the six-minute walk test. Effective preventive and therapeutic interventions are necessary in order to prevent muscle loss and associated physical decline in COVID-19 patients.

18.
JRSM Open ; 12(5): 20542704211011837, 2021 May.
Article in English | MEDLINE | ID: covidwho-1241097

ABSTRACT

OBJECTIVES: To compare the performance of chest computed tomography (CT) scan versus reverse transcription polymerase chain reaction (RT-PCR) as the reference standard in the initial diagnostic assessment of coronavirus disease 2019 (COVID-19) patients. DESIGN: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. A search of electronic information was conducted using the following databases: MEDLINE, EMBASE, EMCARE, CINAHL and the Cochrane Central Register of Controlled Trials. SETTING: Studies that compared the diagnostic performance within the same patient cohort of chest CT scan versus RT-PCR in COVID-19 suspected patients. PARTICIPANTS: Thirteen non-randomised studies enrolling 4092 patients were identified. MAIN OUTCOME MEASURES: Sensitivity, specificity and accuracy were primary outcome measures. Secondary outcomes included other test performance characteristics and discrepant findings between both investigations. RESULTS: Chest CT had a median sensitivity, specificity and accuracy of 0.91 (range 0.82-0.98), 0.775 (0.25-1.00) and 0.87 (0.68-0.99), respectively, with RT-PCR as the reference. Importantly, early small, China-based studies tended to favour chest CT versus later larger, non-China studies. CONCLUSIONS: A relatively high false positive rate can be expected with chest CT. It is possible it may still be useful to provide circumstantial evidence, however, in some patients with a suspicious clinical presentation of COVID-19 and negative initial Severe Acute Respiratory Syndrome Coronavirus 2 RT-PCR tests, but more evidence is required in this context. In acute cardiorespiratory presentations, negative CT scan and RT-PCR tests is likely to be reassuring.

19.
NPJ Digit Med ; 4(1): 87, 2021 May 21.
Article in English | MEDLINE | ID: covidwho-1238021

ABSTRACT

As predicting the trajectory of COVID-19 is challenging, machine learning models could assist physicians in identifying high-risk individuals. This study compares the performance of 18 machine learning algorithms for predicting ICU admission and mortality among COVID-19 patients. Using COVID-19 patient data from the Mass General Brigham (MGB) Healthcare database, we developed and internally validated models using patients presenting to the Emergency Department (ED) between March-April 2020 (n = 3597) and further validated them using temporally distinct individuals who presented to the ED between May-August 2020 (n = 1711). We show that ensemble-based models perform better than other model types at predicting both 5-day ICU admission and 28-day mortality from COVID-19. CRP, LDH, and O2 saturation were important for ICU admission models whereas eGFR <60 ml/min/1.73 m2, and neutrophil and lymphocyte percentages were the most important variables for predicting mortality. Implementing such models could help in clinical decision-making for future infectious disease outbreaks including COVID-19.

20.
Redox Biol ; 43: 101982, 2021 07.
Article in English | MEDLINE | ID: covidwho-1237864

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is involved in a global outbreak affecting millions of people who manifest a variety of symptoms. Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is increasingly associated with cardiovascular complications requiring hospitalizations; however, the mechanisms underlying these complications remain unknown. Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitters that regulate key cardiovascular functions. METHODS: Blood samples were obtained from 68 COVID-19 patients and 33 controls and NO and H2S metabolites were assessed. H2S and NO levels were compared between cases and controls in the entire study population and subgroups based on race. The availability of gasotransmitters was examined based on severity and outcome of COVID-19 infection. The performance of H2S and NO levels in predicting COVID-19 infection was also analyzed. Multivariable regression analysis was performed to identify the effects of traditional determinants of gasotransmitters on NO and H2S levels in the patients with COVID-19 infection. RESULTS: Significantly reduced NO and H2S levels were observed in both Caucasian and African American COVID-19 patients compared to healthy controls. COVID-19 patients who died had significantly higher NO and H2S levels compared to COVID-19 patients who survived. Receiver-operating characteristic analysis of NO and H2S metabolites in the study population showed free sulfide levels to be highly predictive of COVID-19 infection based on reduced availability. Traditional determinants of gasotransmitters, namely age, race, sex, diabetes, and hypertension had no effect on NO and H2S levels in COVID-19 patients. CONCLUSION: These observations provide the first insight into the role of NO and H2S in COVID-19 infection, where their low availability may be a result of reduced synthesis secondary to endotheliitis, or increased consumption from scavenging of reactive oxygen species.


Subject(s)
COVID-19 , Gasotransmitters , Hydrogen Sulfide , Humans , Nitric Oxide , SARS-CoV-2
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