Fighting The COVID-19 Fire With Molecular Diagnostics Innovations
"You cannot fight a fire blindfolded. And we cannot stop this pandemic if we don't know who is infected. We have a simple message for all countries: test, test, test. Test every suspected case" ---- Dr Tedros Adhanom Ghebreyesus, Director-General, World Health Organization (WHO)
Viruses were once known as "contagious living fluids", strange infectious substances capable of slipping through the finest of filters unnoticed. SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic is indeed slipping through every layer of society, leaving behind severe public health and economic crises. Unlike in the influenza pandemic in 1918, today we are better equipped to identify the elusive bug, with the toolbox of molecular diagnostics and lateral flow assays.
Since the full genome sequencing of the SARS-CoV-2, many national laboratories have identified, in record time, regions of the genome amenable for genetic testing. The golden standard adopted by national laboratories around the world following the WHO protocol to detect the virus in individuals, is based on detecting genetic material specific to SARS-CoV-2 viruses in a person's nasopharyngeal secretions. The main tool for such genetic tests is the Reverse Transcription Polymerase Chain Reaction (RT-PCR). Primer strands that hybridise specifically to the SARS-CoV-2 genome, together with fluorescent probes, help amplify and detect the viral load present in a patient. RT-PCR, normally performed in a real-time quantitative qRT-PCR machine for live fluorescent read-out, constitutes the core element of the testing effort being deployed at the moment across the globe. Clinical laboratories with the necessary equipment and technical know-how to perform RT-PCR are leading this diagnosis effort.
However, not all countries are prepared, neither logistically or with enough equipment and capacity to perform mass testing. An important bottleneck is the short supply of certain ancillary reagents needed to prepare samples for RT-PCR test. RNA extraction kits, for example, are needed for extracting the viral RNA from the sample. The shortage of such supplies, the long processing time and the need to become self-sufficient, has led to many laboratories to try to circumvent some steps in the protocol and to come up with new approaches to reach the testing targets that have been set by policymakers and healthcare officials.
The need for universal and massive testing across the population has led to a race for technology innovations for COVID-19 diagnostics. The newly launched IDTechEx report, "COVID-19 Diagnostics", surveys the technology landscape, with an in-depth analysis of the technology innovations that are enabling a quick access to COVID-19 diagnosis in response to the global pandemic.
Point-of-care molecular diagnostics (POC MDx) are portable devices that perform molecular diagnosis away from central labs. Microfluidics is the key technology behind POC MDx, which controls the motion of small amounts of fluids in microchannels. Microfludic cartridges enable the miniaturisation of devices and introduces automation in the sample handling and detection processes. Some POC MDx devices use isothermal amplification of nucleic acid as an alternative to PCR devices. Isothermal amplifaction bypasses the need of thermal cycling and reduces the detection time from around 2 hours to just 5 min (Abbott ID Now system). Various isothermal amplifaction methods have been adopted for COVID-19 diagnostics. Complex design and unspecific amplification hinder the widespread use of this method. "COVID-19 Diagnostics" provides a deep insight and comparison into the technologies, innovations and current progress on POC MDx and isothermal amplification.
Apart from the time consuming thermal cycling, real-time fluorescent detection is another limitation for low-cost and portable diagnosis tools. Lateral flow assays (both fluorescent or colorimetric), electrochemical detection and microbead-based arrays are integrated with thermal cyclers (PCR reaction) to detect the amplified genetic products. These hybrid systems enable faster, cheaper and palm-size devices for COVID-19 detection at the expense of sensitivity and specificity. More recently, CRISPR-Cas (gene-editing tool based on specific gene recognition) and DNA sequencing techniques show the potential for highly sensitive and selective hybrid systems, as highlighted in "COVID-19 Diagnostics", for more information on this report, please visit www.IDTechEx.com/COVID.
Resonating with the message of the WHO director general: "test, test and test", these innovations offer the tools to stop the current outbreak, as well as to prevent future outbreaks, by effective diagnostics and surveillance testing.