Yesterday, the FDA has issued Emergency Use Authorization for Abbott’s point of care detection of COVID-19.
Abbott’s technology can deliver positive results in as little as 5 minutes and negative results in 15 minutes. This test utilizes the ID NOW platform, which is currently used for rapid detection of influenza, respiratory syncytial virus, and streptococcus pneumoniae. Using this technology, Abbott plans to delivery 50,000 COVID-19 tests per day. Press releases from Abbott are here and here. A video summary of the device is below.
In this post, I’ll summarize what we know about this technology.
Background of Nucleic Acid Amplification
The gold standard of nucleic acid amplification is polymerase chain reaction. This is also our current gold standard for detecting COVID-19 in a patient.. In this process, template DNA is denatured and split into two separate strands (Step 1: denaturation), primers are added that bind to the split strands (Step 2: annealing), and new nucleic acids are added which elongate from the primers and bind to the template DNA (Step 3: elongation). Steps 1, 2, and 3 are repeated to continuously amplify nucleic acids. This process works well, but is laborious, technically demanding, expensive, and takes hours to complete. It is also limited in scenarios with increased patient volumes, such as what we are seeing in the current COVID-19 pandemic.
The most laborious step of polymerase chain reaction is the constant denaturation and elongation steps which require different temperature ranges to function. To overcome this challenge, scientists have developed various isothermal nucleic acid amplification techniques to detect a specific nucleic acid sequence.
The mechanism is described in more detail in Bell et al. and Nie. et al, with a figure below. My understanding is that you first start with a template DNA strand, constructed using reverse transcriptase from viral RNA. Then specific nicking enzymes open the template strand which allow for DNA polymerase enzymes to create new DNA. However, each newly constructed DNA will also get nicked to allow for construction of another DNA strand. This process leads to exponential growth of DNA strands in minutes.
Sensitivity and Specificity compared to PCR
Abbott’s ID Now technology was previously shown to have over 96% sensitivty and specificity to detect influenza when compared to RT-PCR as the gold standard.
Results disclosed to the FDA show that the ID Now also is consistent with RT-PCR for detecting SARS-CoV-2. There was 100% agreement in detecting 30 samples of SARS-CoV-2 and not detecting the virus in 30 controls.
The limit of detection was 125 genome equivalents/mL which can be obtained >95% of the time with a standard nasopharyngeal swab.
Overall, this is a major breakthrough in our fight against COVID-19. We can quickly, safely, accurately detect COVID-19 in a massive scale.
One caveat is that we do know that the sensitivity of RT-PCR for detecting COVID-19 is variable across test kits. The sensitivity can be as low as 71% compared to a clinical suspicion of COVID-19 with positive chest CT findings (Source Fang et al. Radiology 2020). This means that there may be cases where the Abbott technology provides a false negative result. This may be more prevalent during early signs of disease, and this is why some people need two or more tests to confirm or rule out COVID-19. However, this is less of a problem for Abbott’s technology because it only takes ~10 minutes to run.