Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Rationale: The development of serological testing has been mainly used to monitoring and responding to the pandemic including the restart of economic activities. This is based on the hope that antibodies to the SARS-Cov2 will provide protective and long lasting immunity and allow recovered individuals to resume their daily lives. However its not clear up to this point in time what the presence of antibodies signifies (for the individual or communities), how durable the antibodies will be and how much serologic variation to expect among different groups such those who had asymptomatic infection. 

Diagnostic tests for covid-19 fall into two main categories:  (a) molecular tests that detect viral RNA, and (b) serological tests that detect anti-SARS-CoV-2 immunoglobulins.

Reverse transcriptase polymerase chain reaction (RT-PCR), a molecular test, is widely used as the reference standard for diagnosis of covid-19; however, limitations include potential false negative results, changes in diagnostic accuracy over the disease course, and precarious availability of test materials.

Serological tests may provide an alternative or complement to RT-PCR in the diagnosis of acute infection, as some might be cheaper and easier to implement at the point of care. A clear advantage of these tests over RT-PCR is that they can identify individuals previously infected by SARS-CoV-2, even if they never underwent testing while acutely ill. As such, serological tests could be deployed as surveillance tools to better understand the epidemiology of SARS-CoV-2 and potentially inform individual risk of future disease.

There are three  types of antibody tests: (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), and chemiluminescent immunoassays (CLIAs)).

In the early months of the outbreak, the global market was flooded with antibody tests of unproven test performance, and various governments, including those of the UK and India, purchased large quantities of ineffective antibody tests. In the US, the FDA reversed course in May and mandated emergency use authorizations for all commercially available serologic test kits with a test performance of 90% or more sensitivity and 95% or more specificity, but the damage had been done and contributed to surveillance data of uneven quality. Critical independent evaluations of antibody tests are currently underway by the FDA and other organizations.

Sensitivities were consistently lower with the LFIA method compared with ELISA and CLIA methods. For each test method, the type of immunoglobulin being measured—IgM, IgG, or both—was not associated with diagnostic accuracy. Pooled sensitivities were lower with commercial kits and in the first and second week after symptom onset compared with the third week or later. Pooled specificities of each test method were high. However, stratified results suggested specificity was lower in individuals with suspected covid-19, and that other viral infections could lead to false positive results for the LFIA method. These observations indicate important weaknesses in the evidence on covid-19 serological tests, particularly those being marketed as point-of-care tests.

 

Conclusion: As this review makes clear, there is more work to do on serologic testing. Assays must be optimized further, independently validated, and used in an algorithm format to achieve the highest possible accuracy for decision making, especially at an individual level. Serologic assays for SARS-CoV-2 antibodies, especially point-of-care tests, are not ready for widespread use by clinicians, the general public, or policy makers.

LINK: Antibody testing for coronavirus disease 2019: not ready for prime time. BMJ 2020370 doi: https://doiorg.ezproxy.uws.edu.au/10.1136/bmj.m2655 (Published 03 July 2020)Cite this as: BMJ 2020;370:m2655

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