Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Severe Acute Respiratory Syndrome , COVID-19 , Humans , SARS-CoV-2ABSTRACT
BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None.
Subject(s)
Betacoronavirus , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Occupational Diseases/diagnosis , Pneumonia, Viral/diagnosis , Point-of-Care Systems , Adult , COVID-19 , COVID-19 Testing , Coronavirus Infections/epidemiology , Coronavirus Infections/virology , Enzyme-Linked Immunosorbent Assay/statistics & numerical data , Female , Health Personnel , Humans , Immunoassay/statistics & numerical data , Male , Middle Aged , Occupational Diseases/epidemiology , Occupational Diseases/virology , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Predictive Value of Tests , Prospective Studies , Reproducibility of Results , SARS-CoV-2 , Sensitivity and Specificity , Seroepidemiologic Studies , United Kingdom/epidemiologyABSTRACT
Atherosclerosis is a significant cause of morbidity and mortality globally. Many animal models have been developed to study atherosclerosis, and permit experimental conditions, diet and environmental risk factors to be carefully controlled. Pathophysiological changes can be produced using genetic or pharmacological means to study the harmful consequences of different interventions. Experiments using such models have elucidated its molecular and pathophysiological mechanisms, and provided platforms for pharmacological development. Different models have their own advantages and disadvantages, and can be used to answer different research questions. In the present review article, different species of atherosclerosis models are outlined, with discussions on the practicality of their use for experimentation.
