Why covid-19 antibody tests are not the game changer the UK government claimsBMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m2469 (Published 24 June 2020) Cite this as: BMJ 2020;369:m2469
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Systematic reviews on diagnostic accuracy of antibody tests for SARS-CoV-2: a bonus for Health Technology Assessment Re: Why covid-19 antibody tests are not the game changer the UK government claims
We read with interest Stephen Armstrong recount and comment (1) on the Cochrane systematic review of studies on covid-19 antibody tests (2), which we were eagerly awaiting for, having ourselves just published a EUnetHTA Rapid Collaborative Review on the same topic (3). The two reports were published only three days apart and the timing of the two independently developed works represents a remarkable opportunity for comparing results and seeking an indirect feedback on one’s own work.
The EUnetHTA report on the role of antibody tests for novel coronavirus SARS-CoV-2 (3) is the first output of the collaborative effort to meet decision makers’ urgent needs for trustworthy scientific information on the safety and effectiveness of the health technologies adopted for the management of the pandemic. Our review addressed five research questions, corresponding to the five health policy questions emerged from a consultation with EUnetHTA partners: whether antibody tests can be reliably used for (1) surveillance and early detection of new asymptomatic cases of SARS-CoV-2 acute infection in the general population and/or specific subpopulations; (2) diagnosis of acute infection in patients presenting symptoms suggestive of SARS-CoV-2 infection; (3) measuring seroprevalence in communities; (4) ruling out risk of transmission in patients who recovered from SARS-CoV-2 infection; (5) assessing protective immunity in subjects with past and resolved SARS-CoV-2 infection.
The first two questions matched those of the diagnostic accuracy review on asymptomatic and symptomatic subject, carried out by J. Deeks and colleagues (1). Despite some slight differences in studies inclusion criteria, the two reviews provide consistent results on diagnostic accuracy estimates and on the strong dependency of these estimates on time since symptom onset. In line with the Cochrane review, our statistical meta-analysis showed that diagnostic accuracy of antibody tests used in symptomatic patients increases with time since infection or symptom onset. Both IgM and IgG resulted adequately detected only from the second week of symptom onset, but molecular tests RT-PCR appeared to perform better than any type of serological test in both time windows. These results on timing of detection can be informative also for the use of antibody tests in asymptomatic people (for whom no sufficient data was retrieved), suggesting that detection of asymptomatic individuals would be more accurate at least two weeks after infection, making isolation measures much belated with respect to their time of infectivity. By contrast, the test may less accurately identify subjects close to infection and with longer time to infect others, hindering early detection and prompt isolation of new cases.
As Health Technology Assessment (HTA) institutions, our target audience consist in public health decision makers who - when this review was undertaken - were struggling to complement molecular tests for the deployment of testing, isolation and contact tracing widely recommended policy (4). We therefore made specific and explicit references to the correct use of test results and to the impact they have on the individuals and on public health for a comprehensive risk-benefit evaluation.
If these preliminary results might dampen the hope for an immediate and attractive alternative to molecular testing, the remaining three questions deserve a continuous monitoring of the upcoming evidence. The seventeen seroprevalence studies we included in our review were highly heterogeneous and we could only provide descriptive results. From the studies mainly conducted in Europe from end of March to middle of April 2020, we found seroprevalence estimates in general population ranging from 1.5% (95%CI 1.1-2.0) to 25.9% (95%CI 22.6-29.4), in blood donors from 1.0 (95%CI 0.4-2.5) to 3.1 (95%CI 2.7-3.6) and in health care workers from 4.5% (95%CI 1.8-10.5) to 17.2% (95%CI 14.6-20.2). We will continue to surveil the literature for data from the large populations studies currently on-going in many countries, to assess their contribution in understanding the full spread of the infection. Similarly, the issue of whether discharged and recovered patients re-testing positive after few weeks from recovery can still transmit the infection is an important public health concern (5). Finally, we hope that research on antibody concentration over time and on disease recurrence will not be prematurely abandoned, as similar research on SARS and MERS unfortunately was.
For the time being, the near simultaneous completion and publication of the two systematic reviews on the diagnostic accuracy of antibody tests for SARS-CoV-2 is – from an HTA perspective – an unexpected bonus when decision making is in such need for scientific evidence.
EUnetHTA is a network of European Health Technology Assessment organizations co-funded by the European Commission.
01. Armstrong Stephen. Why covid-19 antibody tests are not the game changer the UK government claims BMJ 2020; 369 :m2469
02. Deeks JJ, Dinnes J, Takwoingi Y, et al . Antibody tests for identification of current and past infection with SARS-CiV-2. Cochrane Database Syst Rev2020;6:CD013652. Google Scholar
03. EUnetHTA RCRC01 Authoring Team. The current role of antibody tests for novel coronavirus SARS-CoV-2 in the management of the pandemic. Collaborative Assessment. Diemen (The Netherlands): EUnetHTA; 2020 23rd of June. Nº144 pages. Report No.:RCR01. Available from: https //www.eunethta.eu
04. World Health Organization. Critical preparedness, readiness and response actions for COVID-19. 2020. https://www.who.int/publications/i/item/critical-preparedness-readiness-...
05. World Health Organization. Criteria for releasing COVID-19 patients from isolation.https://www.who.int/publications/i/item/criteria-for-releasing-covid-19-...
Competing interests: No competing interests