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1.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-333091

ABSTRACT

Coronavirus disease 2019 (COVID-19)-related pneumonia challenges clinical practice. We explore the potential diagnostic benefit of positron emission tomography/computed tomography (PET/CT) in order to establish the underlying inflammatory or fibrotic repair processes in prolonged structural lung abnormalities in COVID-19 patients. Methods: : Six post-COVID-19 patients suspected for pulmonary fibrosis were scheduled for dual tracer PET/CT with 18 F-FDG (fluorodeoxyglucose) and 68 Ga-fibroblast activation protein inhibitor (FAPI)-46. The uptake of 68 Ga FAPI-46 in the involved lung was compared to a control group of nine non COVID-19 patients. Clinical data and PET/CT imaging were collected and analysed. Results: : PET/CT revealed in all six pulmonary impaired patients the reduced glucose avidity on 18 F-FDG and clear positivity on 68 Ga-FAPI-46 PET/CT in comparison to the control group. Conclusion: Indicating fibrotic repair mechanisms, 68 Ga-FAPI PET/CT may enhance non-invasive clinical diagnostic performance, drive therapeutic interventions, and facilitate therapeutic response monitoring in patients with long-term CT-abnormalities after severe COVID-19.

2.
Front Med (Lausanne) ; 9: 792881, 2022.
Article in English | MEDLINE | ID: covidwho-1775691

ABSTRACT

Background: Coronavirus Disease-19 (COVID-19) convalescents are at risk of developing a de novo mental health disorder or worsening of a pre-existing one. COVID-19 outpatients have been less well characterized than their hospitalized counterparts. The objectives of our study were to identify indicators for poor mental health following COVID-19 outpatient management and to identify high-risk individuals. Methods: We conducted a binational online survey study with adult non-hospitalized COVID-19 convalescents (Austria/AT: n = 1,157, Italy/IT: n = 893). Primary endpoints were positive screening for depression and anxiety (Patient Health Questionnaire; PHQ-4) and self-perceived overall mental health (OMH) and quality of life (QoL) rated with 4 point Likert scales. Psychosocial stress was surveyed with a modified PHQ stress module. Associations of the mental health and QoL with socio-demographic, COVID-19 course, and recovery variables were assessed by multi-parameter Random Forest and Poisson modeling. Mental health risk subsets were defined by self-organizing maps (SOMs) and hierarchical clustering algorithms. The survey analyses are publicly available (https://im2-ibk.shinyapps.io/mental_health_dashboard/). Results: Depression and/or anxiety before infection was reported by 4.6% (IT)/6% (AT) of participants. At a median of 79 days (AT)/96 days (IT) post-COVID-19 onset, 12.4% (AT)/19.3% (IT) of subjects were screened positive for anxiety and 17.3% (AT)/23.2% (IT) for depression. Over one-fifth of the respondents rated their OMH (AT: 21.8%, IT: 24.1%) or QoL (AT: 20.3%, IT: 25.9%) as fair or poor. Psychosocial stress, physical performance loss, high numbers of acute and sub-acute COVID-19 complaints, and the presence of acute and sub-acute neurocognitive symptoms (impaired concentration, confusion, and forgetfulness) were the strongest correlates of deteriorating mental health and poor QoL. In clustering analysis, these variables defined subsets with a particularly high propensity of post-COVID-19 mental health impairment and decreased QoL. Pre-existing depression or anxiety (DA) was associated with an increased symptom burden during acute COVID-19 and recovery. Conclusion: Our study revealed a bidirectional relationship between COVID-19 symptoms and mental health. We put forward specific acute symptoms of the disease as "red flags" of mental health deterioration, which should prompt general practitioners to identify non-hospitalized COVID-19 patients who may benefit from early psychological and psychiatric intervention. Clinical Trial Registration: [ClinicalTrials.gov], identifier [NCT04661462].

3.
Eur J Neurol ; 29(6): 1685-1696, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1759178

ABSTRACT

BACKGROUND AND PURPOSE: Neurological sequelae from coronavirus disease 2019 (COVID-19) may persist after recovery from acute infection. Here, the aim was to describe the natural history of neurological manifestations over 1 year after COVID-19. METHODS: A prospective, multicentre, longitudinal cohort study in COVID-19 survivors was performed. At a 3-month and 1-year follow-up, patients were assessed for neurological impairments by a neurological examination and a standardized test battery including the assessment of hyposmia (16-item Sniffin' Sticks test), cognitive deficits (Montreal Cognitive Assessment < 26) and mental health (Hospital Anxiety and Depression Scale and Post-traumatic Stress Disorder Checklist 5). RESULTS: Eighty-one patients were evaluated 1 year after COVID-19, out of which 76 (94%) patients completed a 3-month and 1-year follow-up. Patients were 54 (47-64) years old and 59% were male. New and persistent neurological disorders were found in 15% (3 months) and 12% (10/81; 1 year). Symptoms at 1-year follow-up were reported by 48/81 (59%) patients, including fatigue (38%), concentration difficulties (25%), forgetfulness (25%), sleep disturbances (22%), myalgia (17%), limb weakness (17%), headache (16%), impaired sensation (16%) and hyposmia (15%). Neurological examination revealed findings in 52/81 (64%) patients without improvement over time (3 months, 61%, p = 0.230) including objective hyposmia (Sniffin' Sticks test <13; 51%). Cognitive deficits were apparent in 18%, whereas signs of depression, anxiety and post-traumatic stress disorders were found in 6%, 29% and 10% respectively 1 year after infection. These mental and cognitive disorders had not improved after the 3-month follow-up (all p > 0.05). CONCLUSION: Our data indicate that a significant patient number still suffer from neurological sequelae including neuropsychiatric symptoms 1 year after COVID-19 calling for interdisciplinary management of these patients.


Subject(s)
COVID-19 , Anosmia/diagnosis , Anosmia/etiology , COVID-19/complications , COVID-19/diagnosis , Cohort Studies , Female , Humans , Longitudinal Studies , Male , Middle Aged , Prospective Studies , SARS-CoV-2
4.
Eur J Neurol ; 28(10): 3348-3359, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1607398

ABSTRACT

BACKGROUND AND PURPOSE: To assess neurological manifestations and health-related quality of life (QoL) 3 months after COVID-19. METHODS: In this prospective, multicenter, observational cohort study we systematically evaluated neurological signs and diseases by detailed neurological examination and a predefined test battery assessing smelling disorders (16-item Sniffin Sticks test), cognitive deficits (Montreal Cognitive Assessment), QoL (36-item Short Form), and mental health (Hospital Anxiety and Depression Scale, Posttraumatic Stress Disorder Checklist-5) 3 months after disease onset. RESULTS: Of 135 consecutive COVID-19 patients, 31 (23%) required intensive care unit (ICU) care (severe), 72 (53%) were admitted to the regular ward (moderate), and 32 (24%) underwent outpatient care (mild) during acute disease. At the 3-month follow-up, 20 patients (15%) presented with one or more neurological syndromes that were not evident before COVID-19. These included polyneuro/myopathy (n = 17, 13%) with one patient presenting with Guillain-Barré syndrome, mild encephalopathy (n = 2, 2%), parkinsonism (n = 1, 1%), orthostatic hypotension (n = 1, 1%), and ischemic stroke (n = 1, 1%). Objective testing revealed hyposmia/anosmia in 57/127 (45%) patients at the 3-month follow-up. Self-reported hyposmia/anosmia was lower (17%) at 3 months, however, improved when compared to the acute disease phase (44%; p < 0.001). At follow-up, cognitive deficits were apparent in 23%, and QoL was impaired in 31%. Assessment of mental health revealed symptoms of depression, anxiety, and posttraumatic stress disorders in 11%, 25%, and 11%, respectively. CONCLUSIONS: Despite recovery from the acute infection, neurological symptoms were prevalent at the 3-month follow-up. Above all, smelling disorders were persistent in a large proportion of patients.


Subject(s)
COVID-19 , Stroke , Cohort Studies , Humans , Prospective Studies , Quality of Life , SARS-CoV-2
5.
Clin Infect Dis ; 2021 Nov 26.
Article in English | MEDLINE | ID: covidwho-1545917

ABSTRACT

BACKGROUND: Long COVID, defined as presence of COVID-19 symptoms 28 days or more after clinical onset, is an emerging challenge to healthcare systems. The objective of this study was to explore recovery phenotypes in non-hospitalized COVID-19 individuals. METHODS: A dual cohort, online survey study was conducted between September 2020 and July 2021 in the neighboring European regions Tyrol (TY, Austria, n = 1157) and South Tyrol (STY, Italy, n = 893). Data on demographics, comorbidities, COVID-19 symptoms and recovery adult outpatients were collected. Phenotypes of acute COVID-19, post-acute sequelae and risk of protracted recovery were explored by semi-supervised clustering and multi-parameter LASSO modeling. RESULTS: Working age subjects (TY: 43 yrs (IQR: 31 - 53), STY: 45 yrs (IQR: 35 - 55)) and females (TY: 65.1%, STY: 68.3%) predominated the study cohorts. Nearly half of the participants (TY: 47.6%, STY: 49.3%) reported symptom persistence beyond 28 days. Two acute COVID-19 phenotypes were discerned: the non-specific infection phenotype and the multi-organ phenotype (MOP). Acute MOP symptoms encompassing multiple neurological, cardiopulmonary, gastrointestinal and dermatological complaints were linked to elevated risk of protracted recovery. The major subset of long COVID individuals (TY: 49.3%, STY: 55.6%) displayed no persistent hyposmia or hypogeusia but high counts of post-acute MOP symptoms and poor self-reported physical recovery. CONCLUSION: The results of our two-cohort analysis delineated phenotypic diversity of acute and post-acute COVID-19 manifestations in home-isolated patients which needs to be considered for predicting protracted convalescence and allocation of medical resources.

6.
Qual Life Res ; 31(5): 1401-1414, 2022 May.
Article in English | MEDLINE | ID: covidwho-1439744

ABSTRACT

PURPOSE: To assess patient characteristics associated with health-related quality of life (HR-QoL) and its mental and physical subcategories 3 months after diagnosis with COVID-19. METHODS: In this prospective multicentre cohort study, HR-QoL was assessed in 90 patients using the SF-36 questionnaire (36-item Short Form Health Survey), which consists of 8 health domains that can be divided into a mental and physical health component. Mental health symptoms including anxiety, depression, and post-traumatic stress disorders were evaluated using the Hospital Anxiety and Depression Scale (HADS) and Post-traumatic Stress Disorder Checklist-5 (PCL-5) 3 months after COVID-19. Using descriptive statistics and multivariable regression analysis, we identified factors associated with impaired HR-QoL 3 months after COVID-19 diagnosis. RESULTS: Patients were 55 years of age (IQR, 49-63; 39% women) and were classified as severe (23%), moderate (57%), or mild (20%) according to acute disease severity. HR-QoL was impaired in 28/90 patients (31%). Younger age [per year, adjOR (95%CI) 0.94 (0.88-1.00), p = 0.049], longer hospitalization [per day, adjOR (95%CI) 1.07 (1.01-1.13), p = 0.015], impaired sleep [adjOR (95%CI) 5.54 (1.2-25.61), p = 0.028], and anxiety [adjOR (95%CI) 15.67 (3.03-80.99), p = 0.001) were independently associated with impaired HR-QoL. Twenty-nine percent (n = 26) scored below the normal range on the mental health component of the SF-36 and independent associations emerged for anxiety, depression, and self-reported numbness. Impairments in the physical health component of the SF-36 were reported by 12 (13%) patients and linked to hypogeusia and fatigue. CONCLUSION: Every third patient reported a reduction in HR-QoL 3 months after COVID-19 diagnosis and impairments were more prominent in mental than physical well-being.


Subject(s)
COVID-19 , Anxiety/epidemiology , COVID-19/epidemiology , COVID-19 Testing , Cohort Studies , Depression/epidemiology , Depression/psychology , Female , Humans , Male , Prospective Studies , Quality of Life/psychology
7.
Infection ; 50(1): 263-267, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1372830

ABSTRACT

BACKGROUND: There are substantial concerns about fibrotic and vascular pulmonary sequelae after coronavirus disease 2019 (COVID-19) associated acute respiratory distress syndrome (ARDS).AQ1 Histopathology reports of lung biopsies from COVID-19 survivors are scarce. CASE: We herein report results of functional and histopathological studies in a 70 year-old man undergoing a co-incidental tumor lobectomy six months after long-term mechanical ventilation for COVID-19 pneumonia. CONCLUSION: Despite several unfavorable risk factors, this case presentation shows a completed pulmonary recovery process within a few months.


Subject(s)
COVID-19 , Respiratory Distress Syndrome , Aged , Humans , Lung , Male , Respiration, Artificial , SARS-CoV-2
9.
EBioMedicine ; 67: 103348, 2021 May.
Article in English | MEDLINE | ID: covidwho-1201238

ABSTRACT

BACKGROUND: Antibody tests are essential tools to investigate humoral immunity following SARS-CoV-2 infection or vaccination. While first-generation antibody tests have primarily provided qualitative results, accurate seroprevalence studies and tracking of antibody levels over time require highly specific, sensitive and quantitative test setups. METHODS: We have developed two quantitative, easy-to-implement SARS-CoV-2 antibody tests, based on the spike receptor binding domain and the nucleocapsid protein. Comprehensive evaluation of antigens from several biotechnological platforms enabled the identification of superior antigen designs for reliable serodiagnostic. Cut-off modelling based on unprecedented large and heterogeneous multicentric validation cohorts allowed us to define optimal thresholds for the tests' broad applications in different aspects of clinical use, such as seroprevalence studies and convalescent plasma donor qualification. FINDINGS: Both developed serotests individually performed similarly-well as fully-automated CE-marked test systems. Our described sensitivity-improved orthogonal test approach assures highest specificity (99.8%); thereby enabling robust serodiagnosis in low-prevalence settings with simple test formats. The inclusion of a calibrator permits accurate quantitative monitoring of antibody concentrations in samples collected at different time points during the acute and convalescent phase of COVID-19 and disclosed antibody level thresholds that correlate well with robust neutralization of authentic SARS-CoV-2 virus. INTERPRETATION: We demonstrate that antigen source and purity strongly impact serotest performance. Comprehensive biotechnology-assisted selection of antigens and in-depth characterisation of the assays allowed us to overcome limitations of simple ELISA-based antibody test formats based on chromometric reporters, to yield comparable assay performance as fully-automated platforms. FUNDING: WWTF, Project No. COV20-016; BOKU, LBI/LBG.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Coronavirus Nucleocapsid Proteins/immunology , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Binding Sites , CHO Cells , COVID-19/immunology , Cricetulus , Early Diagnosis , HEK293 Cells , Humans , Immunoglobulin G/blood , Middle Aged , Sensitivity and Specificity , Young Adult
10.
Clin Chem Lab Med ; 59(8): 1453-1462, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1175446

ABSTRACT

OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections cause coronavirus disease 2019 (COVID-19) and induce a specific antibody response. Serological assays detecting IgG against the receptor binding domain (RBD) of the spike (S) protein are useful to monitor the immune response after infection or vaccination. The objective of our study was to evaluate the clinical performance of the Siemens SARS-CoV-2 IgG (sCOVG) assay. METHODS: Sensitivity and specificity of the Siemens sCOVG test were evaluated on 178 patients with SARS-CoV-2-infection and 160 pre-pandemic samples in comparison with its predecessor test COV2G. Furthermore, correlation with virus neutralization titers was investigated on 134 samples of convalescent COVID-19 patients. RESULTS: Specificity of the sCOVG test was 99.4% and sensitivity was 90.5% (COV2G assay 78.7%; p<0.0001). S1-RBD antibody levels showed a good correlation with virus neutralization titers (r=0.843; p<0.0001) and an overall qualitative agreement of 98.5%. Finally, median S1-RBD IgG levels increase with age and were significantly higher in hospitalized COVID-19 patients (median levels general ward: 25.7 U/mL; intensive care: 59.5 U/mL) than in outpatients (3.8 U/mL; p<0.0001). CONCLUSIONS: Performance characteristics of the sCOVG assay have been improved compared to the predecessor test COV2G. Quantitative SARS-CoV-2 S1-RBD IgG levels could be used as a surrogate for virus neutralization capacity. Further harmonization of antibody quantification might assist to monitor the humoral immune response after COVID-19 disease or vaccination.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/diagnosis , Immunoglobulin G/immunology , Neutralization Tests , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/immunology , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , COVID-19/pathology , COVID-19/virology , Female , Humans , Immunoglobulin G/blood , Male , Middle Aged , Protein Subunits/immunology , Reagent Kits, Diagnostic , SARS-CoV-2/isolation & purification , Sensitivity and Specificity , Severity of Illness Index , Young Adult
12.
Clin Chem Lab Med ; 59(6): 1143-1154, 2021 05 26.
Article in English | MEDLINE | ID: covidwho-1067442

ABSTRACT

OBJECTIVES: Serological tests detect antibodies against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the ongoing coronavirus disease-19 (COVID-19) pandemic. Independent external clinical validation of performance characteristics is of paramount importance. METHODS: Four fully automated assays, Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, Siemens SARS-CoV-2 total (COV2T) and SARS-CoV-2 IgG (COV2G) were evaluated using 350 pre-pandemic samples and 700 samples from 245 COVID-19 patients (158 hospitalized, 87 outpatients). RESULTS: All tests showed very high diagnostic specificity. Sensitivities in samples collected at least 14 days after disease onset were slightly lower than manufacturers' claims for Roche (93.0%), Abbott (90.8%), and Siemens COV2T (90.3%), and distinctly lower for Siemens COV2G (78.8%). Concordantly negative results were enriched for immunocompromised patients. ROC curve analyses suggest a lowering of the cut-off index for the Siemens COV2G assay. Finally, the combination of two anti-SARS-CoV-2 antibody assays is feasible when considering borderline reactive results. CONCLUSIONS: Thorough on-site evaluation of commercially available serologic tests for detection of antibodies against SARS-CoV-2 remains imperative for laboratories. The potentially impaired sensitivity of the Siemens COV2G necessitates a switch to the company's newly filed SARS-CoV-2 IgG assay for follow-up studies. A combination of tests could be considered in clinical practice.


Subject(s)
Antibodies, Viral/blood , COVID-19 Serological Testing/methods , COVID-19/diagnosis , Immunoglobulin G/blood , Adult , Aged , Aged, 80 and over , Antibodies, Viral/immunology , COVID-19/blood , COVID-19/epidemiology , Female , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Pandemics , ROC Curve , SARS-CoV-2/immunology , Sensitivity and Specificity , Young Adult
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