The effectiveness of tests to detect the presence of SARS-CoV-2 virus, and antibodies to SARS-CoV-2, to inform COVID-19 diagnosis: a rapid systematic review
Authors: Jarrom David , Elston Lauren , Washington Jennifer , Prettyjohns Matthew , Cann Kimberley , Myles Susan , Groves Peter 
Published: August 2020

STRUCTURED ABSTRACT

Objectives

We undertook a rapid systematic review with the aim of identifying evidence that could be used to answer the following research questions: (1) What is the clinical effectiveness of tests that detect the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to inform COVID-19 diagnosis? (2) What is the clinical effectiveness of tests that detect the presence of antibodies to the SARS-CoV-2 virus to inform COVID-19 diagnosis?

Design

systematic review and meta-analysis of studies of diagnostic test accuracy. We systematically searched for all published evidence on the effectiveness of tests for the presence of SARS-Cov-2 virus, or antibodies to SARS-CoV-2, up to 4 May 2020, and assessed relevant studies for risks of bias using the QUADAS-2 framework.

Main outcome measures

measures of diagnostic accuracy (sensitivity, specificity, positive/negative predictive value) were the main outcomes of interest. We also included studies that reported influence of testing on subsequent patient management, and that reported virus/antibody detection rates where these facilitated comparisons of testing in different settings, different populations, or using different sampling methods.

Results

38 studies on SARS-CoV-2 virus testing and 25 studies on SARS-CoV-2 antibody testing were identified. We identified high or unclear risks of bias in the majority of studies, most commonly as a result of unclear methods of patient selection and test conduct, or because of the use of a reference standard that may not definitively diagnose COVID-19. The majority were in hospital settings, in patients with confirmed or suspected COVID-19 infection. Pooled analysis of 16 studies (3818 patients) estimated a sensitivity of 87.8% (95% confidence interval 81.5% to 92.2%) for an initial reverse-transcriptase polymerase chain reaction test. For antibody tests, ten studies reported diagnostic accuracy outcomes: sensitivity ranged from 18.4% to 96.1% and specificity 88.9% to 100%. However, the lack of a true reference standard for SARS-CoV-2 diagnosis makes it challenging to assess the true diagnostic accuracy of these tests. Eighteen studies reporting different sampling methods suggest that for virus tests, the type of sample obtained/type of tissue sampled could influence test accuracy. Finally we searched for, but did not identify, any evidence on how any test influences subsequent patient management.

Conclusions

Evidence is rapidly emerging on the effectiveness of tests for COVID-19 diagnosis and management, but important uncertainties about their effectiveness and most appropriate application remain. Estimates of diagnostic accuracy should be interpreted bearing in mind the absence of a definitive reference standard to diagnose or rule out COVID-19 infection. More evidence is needed about the effectiveness of testing outside of hospital settings and in mild or asymptomatic cases. Implementation of public health strategies centred on COVID-19 testing provides opportunities to explore these important areas of research.

SUMMARY BOX

What is already known about this subject?

Tests for the presence of the SARS-CoV-2 virus, and antibodies to the virus, are being deployed rapidly and at scale as part of the global response to COVID-19.

At the outset of this work (March 2020), no high-quality evidence reviews on the effectiveness of SARS-CoV-2 virus or antibody tests were available.

High-quality evidence reviews are required to help decision makers deploy and interpret these tests effectively.

What are the new findings?

Here, we synthesise evidence on the diagnostic accuracy of all known tests for SARS-CoV-2, as well as tests for antibodies to SARS-CoV-2.

We also systematically summarise evidence on the influence of tissue sample site on virus test detection rates, and the influence of test timing relative to disease course on antibody detection. The results suggest that both these factors could influence test results.

We conclude that evidence on SARS-CoV-2 virus and antibody tests is nascent and significant uncertainties remain in the evidence base regarding their clinical and public health application. We also note that potential risks of bias exist within many of the available studies.

How might it impact on clinical practice in the foreseeable future?

In a rapidly developing pandemic, the widespread use of testing is an essential element in the development of effective public health strategies, but it is important to acknowledge the gaps and limitations that exist in the current evidence base and that, where possible, these should be addressed in future studies.

In particular, more evidence is needed on the performance of point-of-care or near-patient tests compared to their laboratory equivalents, and results of testing in people with no or minimal symptoms in community-based settings needs further analysis.