How mass testing can keep a lid on COVID-19 — plus a list of the tests in commercial development

The rapid spread of COVID-19 across the world has exposed major gaps in the abilities of most countries to respond to a virulent new pathogen.

The extraordinary success of Singapore, Taiwan and Hong Kong in limiting the impact of the sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrates that it is possible to mount an effective response to an outbreak by major investment in pandemic preparedness. Despite their proximity to China, these three regions have managed to keep case numbers and fatalities low. By learning from previous coronavirus outbreaks where these territories bore the brunt, they were able to rapidly deploy widespread testing, combine it with digital surveillance to trace individuals’ movements, and impose strict quarantines in suspect cases, in addition to building large stockpiles of personal protective equipment.

In the rest of the world, most countries have been completely unprepared for the onslaught of the virus. As a result, many healthcare systems have faced community transmission before adequate testing was in place to allow isolation and tracking. Despite public health authorities’ often draconian measures and isolation tactics, many were caught flat-footed in validating, implementing and distributing SARS-CoV-2 diagnostic tests and in establishing decentralized point-of-care (POC) testing. Now that picture is starting to change, with the first shipments of such tests (Table 1). What’s more, the present crisis could be a defining moment for diagnostics based on CRISPR technology — the first diagnostic test based on CRISPR gene editing technology may only be weeks away. To stop the virus spreading, however, will take a massive effort to scale up the production of easy-to-use POC tests and then to deploy them widely.

So far, the frontline response to the SARS-CoV-2 outbreak has been polymerase chain reaction (PCR) testing. PCR is the gold standard for diagnosing an infectious agent, and it has the advantage that the primers needed for such tests can be produced with relative speed as soon as the viral sequence is known. The first quantitative reverse-transcriptase-based PCR (RT-PCR) tests for detecting SARS-CoV2 were designed and distributed in January by the World Health Organization (WHO), soon after the virus was identified. The test protocol is complex and expensive, however, and is mainly suited to large, centralized diagnostic laboratories. Tests typically take 4–6 hours to complete, but the logistical requirement to ship clinical samples means the turnaround time is 24 hours at best. In the United States, the US Centers for Disease Controls opted to develop its own test rather than adopt the WHO test. Foot-dragging by the US Food and Drug Administration in authorizing public health or hospital labs to run the tests, a glitch in one of the reagents used in the initial RT-PCR test developed and distributed by the Centers for Disease Controls in early February, and a shortage of RNA extraction reagents has further delayed the rollout of testing nationwide.

Despite these shortcomings, multiplex RT-PCR, which tests for multiple target sequences simultaneously, will remain the backbone of testing, particularly in centralized laboratories. Large providers such as Roche Diagnostics, Thermo Fisher Scientific, Qiagen (soon to be acquired by Thermo Fisher) and Quest Diagnostics are ramping up the capacity to perform such tests by rolling out automated SARS-CoV-2 testing systems and services.

POC tests are needed as well to accelerate clinical decision-making and to take some of the workload off centralized test laboratories. Rapid POC tests for use at community level were identified by a WHO expert group convened in Geneva last month as the first of eight research priorities. The Foundation for Innovative New Diagnostics (FIND), a Geneva-based not-for-profit that supports the development and delivery of diagnostics to low-income countries, is aiding that broad effort by inviting assay developers to submit their products for independent evaluation. It has received 220 submissions, which are being assessed, and qualifying manufacturers will be contacted by the end of this month. FIND has also compiled an extensive list of SARS-CoV-2 diagnostic developers, which is dominated by companies developing PCR-based nucleic acid detection tests or immunoassays. The Saw Swee Hock School of Public Health at the National University of Singapore is also closely tracking diagnostics development, in both commercial companies and academic labs.

Immunoassays can provide historic information about viral exposure, as well as diagnostic evidence. They exploit antibody–antigen recognition, either by using monoclonal antibodies (mAbs) to detect viral antigens in clinical samples or by using cloned viral antigens to detect patient antibodies directed against the virus. The lateral flow assay format — essentially a dipstick encased in a cassette — contains the capture reagents (either an mAb directed at a viral antigen or a viral antigen that is recognized by patients’ antibodies) immobilized at defined locations on a nitrocellulose membrane, as well as labelled detector mAbs that recognize the same target. A positive result, which is triggered by binding between the analyte and capture mAb and binding by the detector mAb, is visible as a colored line. Two drops of blood from a pinprick is enough to detect a virus. They’re essentially the same as home pregnancy kits.

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