Review highlights differences in accuracy of COVID-19 rapid tests

Cochrane researchers have published an updated systemic review assessing rapid tests for the detection of SARS-CoV-2 infection. The review included 78 study cohorts, mainly from the U.S. and Europe, that assessed 16 antigen and five molecular assays. It shows that rapid antigen tests are better at correctly identifying COVID-19 in symptomatic (72%) vs asymptomatic individuals (58%). Among uninfected people, antigen tests correctly ruled out infection in 99.5% of people with COVID-19-like symptoms and 98.9% of uninfected people without symptoms. The percentage of people identified with COVID-19 varied by brand and how well user instructions for the tests were followed. For symptomatic people, accurate detection ranged from 34% for Coris Bioconcept sprl’s assay, to 58% for Innova Medical Group Inc.’s assay and 88% for SD Biosensor Inc.’s Standard Q assay. Nearly a third of the studies involved rapid molecular tests, and here again sensitivities varied by test brand. For example, Abbott Laboratories’ ID Now COVID-19 test had an average sensitivity of 73% and average specificity of 99.7%. For Cepheid’s Xpert Xpress SARS-CoV-2 test, average sensitivity was 100% and average specificity was 97.2%. The review also found wide variations in the accuracy of different COVID-19 test brands, with few meeting the WHO’s minimum acceptable performance standards. To meet those standards, a test must correctly detect at least 80% of infected individuals and exclude infection in 97% of uninfected people. Antigen tests that are accurate enough to replace RT-PCR “would be most useful when quick decisions are needed about patient care, or if RT-PCR is not available,” the authors wrote, citing opportunities such as identifying outbreaks or identifying symptomatic people for further testing with PCR. While several point-of-care molecular tests demonstrated “very high accuracy and potential for use, … more evidence of their performance when evaluated in real life settings is required.” To truly understand the value of rapid tests, “We need more evidence on rapid testing in people without symptoms, on the accuracy of repeated testing, testing in non-healthcare settings such as schools (including self-testing), and direct comparisons of test brands, with testers following manufacturers’ instructions.”

Likelihood of disease from hidden genetic defects

Researchers from Hebrew University of Jerusalem, Radboud University Medical Center and Maastricht University Medical Center+ have gained new insight into how often hidden genetic defects that can result in disease are present in individuals in the European population. The team screened nearly 6,500 people in the Netherlands and Estonia and found that every person averages two to four hidden genetic defects. A European couple’s risk of having a child who becomes sick due to two such defects is about 1%. In consanguineous couples, such as cousins, about a fifth of couples appeared to be at increased risk, according to work published March 18, 2021, in The American Journal of Human Genetics. In a separate study, the researchers performed exome sequencing (ES) on 100 consanguineous couples, selecting rare variants could lead to biallelic variants in offspring. These variants were filtered against a gene pool of roughly 2,000 genes associated with known autosomal recessive (AR) disorders. Among the 100 biologically related couples, 28% had likely pathogenic defects and variants previously unknown in the couple’s family, putting their offspring at 25% risk of being affected. “ES-based PCT provides a powerful diagnostic tool to identify AR disease carrier status in consanguineous couples,” the researchers said, adding that “outcomes provided significant reproductive choices for a higher proportion of these couples than previous tests.” The study was published online March 19, 2021, in Genetics in Medicine.

Confocal PET enables color differentiation of PET tracers in preclinical imaging

Preclinical imaging tools such as positron emission tomography (PET) scanners are invaluable in studying disease and evaluating potential therapies, especially in mice. Confocal PET technology developed by Dutch med-tech company Milabs BV magnifies all beneficial photons emitted from PET tracers to provide images with enhanced resolution and can do so for multiple PET tracers simultaneously, a recent study shows. This spectral PET enables simultaneous detection of dual isotopes, such as 18F/89Zr and 124I/18F, while rejecting unwanted photons that cause noise background, improving signal-to-noise contrast of images. A team of researchers at Delft University of Technology used the Milabs’ VECTor scanner to demonstrate multi-isotope and sub-millimeter resolution PET of isotopes with several mm positron range by employing prompt gamma photons that are typically overlooked. “Image quantification in phantoms with reservoirs filled with both 124I and 18F showed excellent separation of isotopes and high quantitative accuracy. Mouse imaging showed uptake of 124I in tiny thyroid parts and simultaneously injected 18F-NaF in bone structures,” the authors wrote. “The ability to obtain PET images at sub-mm resolution both for isotopes with several mm positron range and for multi-isotope PET adds to many other unique capabilities of VECTor's clustered pinhole imaging, including simultaneous sub-mm PET-SPECT and theranostic high energy SPECT.” Their findings appeared in the March 5, 2021, online issue of Physics in Medicine & Biology.