COVID-19 Testing: Frequency Wins over Sensitivity in Control of Disease Transmission

Abstract

Emerging pathogens have no known therapies or vaccines and therefore can only be controlled via traditional methods of contact tracing, quarantine and isolation that require rapid and widespread testing. The most recent outbreak from an emerging pathogen is due to the highly transmissible SARS-CoV-2 virus causing COVID-19 disease, which is associated with no symptoms or mild symptoms in 80–90% of the infected individuals, while in the remainder of the patients it exhibits severe illness that can be lethal or persist for several weeks to months after infection. The first tests to diagnose infection by SARS-CoV-2 were developed soon after the genome of the virus became known, and use probes to measure viral RNA by reverse transcriptase-polymerase chain reaction (RT-PCR). These tests are highly sensitive and specific but can require several days to return results, which makes contact tracing and more generally efforts to control the spread of the infection very difficult. Furthermore, the sensitivity threshold is orders of magnitude below the viral load necessary for transmission; therefore, individuals recovering from the infection may still be have a positive test and be required to isolate unnecessarily while they are no longer infectious. Antigen tests were subsequently developed that use antibodies mostly targeted to the nucleocapsid protein of the virus. These tests are about 100 times less sensitive than RT-PCR, yes they detect viral loads that are about 1/10 that needed for transmission. Furthermore, such tests are potentially much cheaper than RT-PCR and yield results in 15 min or less. Antibody, also known as serological testing, is available and can provide useful information to understand the extent to which a population has been exposed to the virus; however, it is not a good indicator of current infection and not useful for infection control. Viral transmission models that incorporate testing and contact tracing show that infection control is much more readily achieved by increasing testing frequency than by using higher sensitivity testing. For example, compared to no testing at all, testing once every other week has a marginal benefit, while testing weekly can decrease the number of infections to 20–40%, and testing twice weekly or more can bring about a 95%[Formula: see text] reduction in infections. These lessons learned from dealing from the COVID-19 pandemic should guide future planning against potential emerging viruses.