Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing.

OptimisAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies (ADAPT study): a protocol for a prospective diagnostic accuracy study of multimodality testing in patients suspected of a treatable idiopathic inflammatory myopathy

IntroductionIdiopathic inflammatory myopathies (IIMs) excluding inclusion body myositis (IBM) are a group of heterogeneous autoimmune disorders characterised by subacute-onset and progressive proximal muscle weakness, which are frequently part of a multisystem autoimmune disorder. Reaching the diagnosis can be challenging, and no gold standard for the diagnosis of IIM exists. Diagnostic modalities include serum creatine kinase activity, muscle imaging (MRI or ultrasound (US)), electromyography (EMG), myositis autoantibody testing and muscle biopsy. Several diagnostic criteria have been developed for IIMs, varying in reported sensitivity and specificity.HypothesisWe hypothesise that an evidence-based diagnostic strategy, using fewer and preferably the least invasive diagnostic modalities, can achieve the accuracy of a complete panel of diagnostic tests, including MRI, US, EMG, myositis-specific autoantibody testing and muscle biopsy.Methods and analysisThe OptimizAtion of Diagnostic Accuracy in idioPathic inflammaTory myopathies study is a prospective diagnostic accuracy study with an over-complete study design. 100 patients suspected of an IIM excluding IBM will be included. A reference diagnosis will be assigned by an expert panel using all clinical information and all results of all ancillary tests available, including 6 months of follow-up. Several predefined diagnostic strategies will be compared against the reference diagnosis to find the optimal diagnostic strategy.Ethics and disseminationEthical approval was obtained from the medical ethics committee of the Academic Medical Centre, University of Amsterdam, The Netherlands (2019-814). The results will be distributed through conference presentations and peer-reviewed publications.Trial registration numberNetherlands trial register; NL8764.

Diagnostic Errors Are Common in Acute Pediatric Respiratory Disease: A Prospective, Single-Blinded Multicenter Diagnostic Accuracy Study in Australian Emergency Departments

Background: Diagnostic errors are a global health priority and a common cause of preventable harm. There is limited data available for the prevalence of misdiagnosis in pediatric acute-care settings. Respiratory illnesses, which are particularly challenging to diagnose, are the most frequent reason for presentation to pediatric emergency departments.Objective: To evaluate the diagnostic accuracy of emergency department clinicians in diagnosing acute childhood respiratory diseases, as compared with expert panel consensus (reference standard).Methods: Prospective, multicenter, single-blinded, diagnostic accuracy study in two well-resourced pediatric emergency departments in a large Australian city. Between September 2016 and August 2018, a convenience sample of children aged 29 days to 12 years who presented with respiratory symptoms was enrolled. The emergency department discharge diagnoses were reported by clinicians based upon standard clinical diagnostic definitions. These diagnoses were compared against consensus diagnoses given by an expert panel of pediatric specialists using standardized disease definitions after they reviewed all medical records.Results: For 620 participants, the sensitivity and specificity (%, [95% CI]) of the emergency department compared with the expert panel diagnoses were generally poor: isolated upper respiratory tract disease (64.9 [54.6, 74.4], 91.0 [88.2, 93.3]), croup (76.8 [66.2, 85.4], 97.9 [96.2, 98.9]), lower respiratory tract disease (86.6 [83.1, 89.6], 92.9 [87.6, 96.4]), bronchiolitis (66.9 [58.6, 74.5], 94.3 [80.8, 99.3]), asthma/reactive airway disease (91.0 [85.8, 94.8], 93.0 [90.1, 95.3]), clinical pneumonia (63·9 [50.6, 75·8], 95·0 [92·8, 96·7]), focal (consolidative) pneumonia (54·8 [38·7, 70·2], 86.2 [79.3, 91.5]). Only 59% of chest x-rays with consolidation were correctly identified. Between 6.9 and 14.5% of children were inappropriately prescribed based on their eventual diagnosis.Conclusion: In well-resourced emergency departments, we have identified a previously unrecognized high diagnostic error rate for acute childhood respiratory disorders, particularly in pneumonia and bronchiolitis. These errors lead to the potential of avoidable harm and the administration of inappropriate treatment.