A group of researchers led by Britain’s University of Birmingham have led what they claim is the most comprehensive test of its kind investigating the accuracy evidence for COVID-19 antibody tests published up until the end of April. The results are discouraging: these test results are not accurate enough to actually verify if an individual has been infected with COVID-19 if used within the first two weeks once symptoms appear. Rather, the accuracy of most tests depend on the timing of the analysis. Tests are more likely to be useful evaluating SARS-CoV-2 if conducted at least 14 days after the onset of symptoms; such test scenarios will miss 1 in 10 COVID-19 cases. The studies were small, poorly reported and weren’t necessarily the optimal patient group size. Testing product manufacturers need to open up and make all of their findings accessible; transparency is of paramount importance during a pandemic or not.
The ability to accurately test for COVID-19 represents a key goal moving forward. That a government, for example, can identify how many people in a given community have been infected with SARS-CoV-2, the virus behind the COVID-19 pandemic, enables health care officials and agencies to understand how the disease has spread and what are optimal interventions. Moreover, researchers are on a quest to understand whether an individual infected builds an immunity to the pathogen.
The COVID-19 testing field is new and rapidly unfolding, hence this represents a novel and dynamic situation. As new test studies are launched and completed, researchers will study and publish the results. Moreover, the researchers at University of Birmingham suggest, “the design, execution and reporting of studies of the accuracy of COVID-19 tests requires considerable improvement.” Consequently, measures need to be taken by government authorities to ensure that the results of ongoing tests are available in the public domain and “not withheld by test manufacturers.” Transparency and accessibility represents TrialSite News’ mission and critical concepts for researchers and medical communities to better understand COVID-19 testing.
Antibody tests involve different methods for testing for COVID-19 from the use of venous blood and specialist laboratory equipment to a simple finger prick generating samples on disposable devices similar to pregnancy tests for example.
Key Test Data: Immune Response
People infected with COVID-19 respond to the infection by producing cells that can fight the virus called antibodies that operate in the blood. Tests to detect antibodies in individual’s blood can reveal whether they currently have COVID-19 or whether they had it in the past.
The body actually produces three classes of antibody including (1) IgA, (2) IgG and (3) IgM. Currently the majority of antibody tests measure both IgG and IgM however some can measure a single antibody while others can measure combinations of the three antibodies. With the infection’s intensity and associated timing, the presence of antibodies rises and falls. The University of Birmingham reports that the IgG antibody is associated with a high point a few weeks post infection.
It is by utilizing antibody tests that researchers can start to get a handle on a number of fundamental questions, such as who in a community has been infected for example.
In the study titled, ‘Antibody tests for identification of current and past infection with SARS-CoV-2,’ the UK-based research team analyzed over 11,000 publications covering COVID-19 and identified 54 relevant studies from Asia, Europe and America that measured the accuracy of antibody tests used to detect current or past COVID-19 infection, from both hospital and community settings. The studies produced 16,000 real-world results.
The University of Birmingham-led team found that all tests evidenced low sensitivity (the ability to detect disease) during the first week after symptoms begin (detecting less than 30% of cases of disease); but in the second week and hitting the peak of accuracy in the third week. For sensitivity sources, visit the University of Birmingham’s write up of the study.
Interestingly, in scenarios where an estimated 50% of people may have contracted SARS-CoV-2 (e.g. health care workers who have suffered respiratory symptoms), the researchers now forecast that there will be 7 false positives and 43 false negatives for every 1,000 people undergoing combined IgG and IgM testing at days 15 to 21 after COVID-19 symptoms first surface.
The research team suspects that accuracy issues could persist at the community testing level where most tests were assessed while used on hospitalized patients which preclude whether the tests can detect lower antibody levels associated with milder and asymptomatic COVID-19 disease, reports the University of Birmingham.
Research Comments on Timing of Testing
The head of the Test Evaluation Group at the University of Birmingham, Jon Deeks, Professor of Biostatistics commented on the team’s findings, “We’ve analyzed all available data from around the world and discovered clear patterns telling is that timing is vital in using these tests. Use them at the wrong time and they don’t work.”
Deeks continued that some of the tests show promise but candidly currently there is a lack of evidence to identify the best tests yet. What is needed is ongoing and refined analyses of data derived from non-clinical settings where individuals display less symptoms with more longitudinal data.
About University of Birmingham & The Study Group
Ranked among the world’s top 100 research institutions, the University of Birmingham attracts talented students, professors and researchers from over 150 nations.
The Cochrane COVID DTA reviews team harnesses worldwide expertise in test evaluation from key expert groups around the world. The team is led by Prof Jon Deeks working with 18 colleagues in the Test Evaluation Research Group at the University of Birmingham; collaborating with teams at the Universities of Liverpool (UK), Amsterdam (Netherlands), Utrecht (Netherlands), Leuven (Belgium), and Ottawa (Canada); the Foundation for Innovative Diagnostics (FIND) and the World Health Organization (WHO) in Geneva (Switzerland). Currently, the work of the team is largely funded from local institutional resources. The Birmingham team receives support funding from the NIHR Birmingham Biomedical Research Centre and has worked closely with colleagues at University Hospital Birmingham. The team has been approved by Cochrane as free from commercial conflicts of interest.
Professor Jon Deeks, PhD, CStat; Deeks, a Professor of Biostatistics, leads the Biostatistics, Evidence Synthesis and Test Evaluation Research Group in the Institute of Applied Health Research. Note, several other authors contributed to this important study and can be viewed here.