46 research outputs found
Antibody tests for identification of current and past infection with SARS-CoV-2
Background
The diagnostic challenges associated with the COVIDâ19 pandemic resulted in rapid development of diagnostic test methods for detecting SARSâCoVâ2 infection. Serology tests to detect the presence of antibodies to SARSâCoVâ2 enable detection of past infection and may detect cases of SARSâCoVâ2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARSâCoVâ2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARSâCoVâ2 epidemiology.
Objectives
To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARSâCoVâ2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARSâCoVâ2. Sources of heterogeneity investigated included: timing of test, test method, SARSâCoVâ2 antigen used, test brand, and reference standard for nonâSARSâCoVâ2 cases.
Search methods
The COVIDâ19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Coâordinating Centre (EPPIâCentre) âCOVIDâ19: Living map of the evidenceâ and the Norwegian Institute of Public Health âNIPH systematic and living map on COVIDâ19 evidenceâ. We did not apply language restrictions.
Selection criteria
We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RTâPCR test. Small studies with fewer than 25 SARSâCoVâ2 infection cases were excluded. We included any reference standard to define the presence or absence of SARSâCoVâ2 (including reverse transcription polymerase chain reaction tests (RTâPCR), clinical diagnostic criteria, and preâpandemic samples).
Data collection and analysis
We use standard screening procedures with three reviewers. Quality assessment (using the QUADASâ2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for metaâanalysis, we fitted univariate randomâeffects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the randomâeffects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria.
Main results
We included 178 separate studies (described in 177 study reports, with 45 as preâprints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARSâCoVâ2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARSâCoVâ2 infection were most commonly hospital inpatients (78/178, 44%), and preâpandemic samples were used by 45% (81/178) to estimate specificity. Over twoâthirds of studies recruited participants based on known SARSâCoVâ2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARSâCoVâ2 vaccines and present data for naturally acquired antibody responses. Seventyânine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzymeâlinked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%).
Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies.
Average sensitivities for current SARSâCoVâ2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot.
Average specificities were consistently high and precise, particularly for preâpandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies).
Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescentâphase infection) and specific (preâpandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spikeâprotein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescentâphase infection.
Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity.
In a lowâprevalence (2%) setting, where antibody testing is used to diagnose COVIDâ19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARSâCoVâ2 infection.
In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days postâsymptom onset or postâpositive PCR) of SARSâCoVâ2 infection.
Authors' conclusions
Some antibody tests could be a useful diagnostic tool for those in whom molecularâ or antigenâbased tests have failed to detect the SARSâCoVâ2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with postâacute sequelae of COVIDâ19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for seroâepidemiological purposes. The applicability of results for detection of vaccinationâinduced antibodies is uncertain
The Foster method: rapid and non-invasive detection of clinically significant American Foulbrood disease levels using eDNA sampling and a dual-target qPCR assay, with its potential for other hive pathogens
Clinical signs of American Foulbrood (AFB) can be difficult to diagnose and thus disease is often missed and leads to further spread. Diagnosis is centred on the beekeeperâs skill in recognising clinical symptoms â a highly subjective and time-consuming activity. Previous testing methods have relied on sampling that necessitates dismantling the hive and/or requires multiple visits to retrieve passive samples. The Foster method is a novel environmental DNA (eDNA) sampling method using colony entrance swabs together with a dual-target qPCR for Paenibacillus larvae: the causative bacteria of AFB disease. The quantification data generated can be used to detect hives with clinically significant infections, even before visual symptoms are apparent. The testing method shows promise for other bee pathogens and incursion pests.</p
Optimized cloaking design in moving fluid based on the scattering analysis method
This work develops a theoretical framework that can analyze acoustic cloak's scattering in a moving fluid. The equivalent sound source induced by the moving fluid local to the cloak is analytically constructed and is then estimated using Born approximation. Far field radiations can thereafter be obtained using the associated Green's function of convected wave equation. The results demonstrate that the proposed analytical method, which might be helpful in the designs and evaluations of cloaking systems, effectively elucidates the key characteristics of relevant physics. The optimized cloaking design based on the theoretical analysis is obtained that can greatly suppress the acoustic scattering.EI