While molecular testing can play an important role in preventing transmission of SARS-CoV-2, especially among healthcare workers, data published in The Lancet Infectious Diseases suggests that at current levels of population immunity no single strategy will reduce the effective reproduction number (R) below 1.
Increased testing for SARS-CoV-2 is being encouraged by the World Health Organization (WHO), but countries are taking different approaches, and the effectiveness of each strategy is unknown. Therefore, investigators developed a mathematical model of SARS-CoV-2 transmission based on infectiousness and polymerase chain reaction (PCR) test sensitivity over time since infection, in order to evaluate various testing and isolation strategies.
The reduction in R due to testing and isolating symptomatic individuals, regular screening of high-risk groups irrespective of symptoms, and quarantine of contacts of laboratory-confirmed cases identified through test-and-trace protocols was estimated and the effectiveness of a strategy defined as the percentage reduction in R. Data on the performance of antibody tests reported by the Foundation for Innovative New Diagnostics was also reviewed and their implications for the use of “immunity passports” examined.
According to the modelling data, if persons with symptoms compatible with coronavirus disease 2019 (COVID-19) self-isolated, and if this isolation was 100% effective in reducing further transmission, this strategy would result in a reduction in R of 47% (95% uncertainty interval [UI], 32-55). Identifying infections via PCR soon after symptom onset could reduce the number of individuals needing to isolate, but would reduce the effectiveness of self-isolation as roughly 10% would be false negatives. In another strategy, investigators implemented PCR-based weekly screenings of healthcare workers and other high-risk groups (regardless of symptoms) and estimated a reduction in transmission of 23% (95% UI, 16-40). This would be on top of the reductions achieved by self-isolation following symptoms, assuming results are available at 24 hours.
The effectiveness of test and trace, investigators noted, is strongly dependent on coverage and the timeliness of contact tracing, potentially reducing R by 26% (95% UI, 14-35). This would be on top of reductions gained by self-isolation following symptoms, if 80% of cases and contacts are identified and there is immediate testing following symptom onset and quarantine of contacts within 24 hours. Investigators also found that performance has been highly variable among currently available antibody tests. Specificity for rapid diagnostic tests is around 90% or lower and 95% to 99% for laboratory-based ELISA and chemiluminescent assays.
The continued uncertainty surrounding the contribution of asymptomatic infections to transmission is a notable limitation to this work, reported investigators, but attempts were made to address this through the sensitivity analysis. They further pointed out that “data on the implementation and impact of test-and-trace strategies and on the contribution of health-care workers to nosocomial transmission are also needed.” Adding that, as these strategies are implemented in the UK and elsewhere, it will be important to collect high-quality data for improving models and to refine testing strategies.
Regarding the so-called immunity passports, investigators raised several challenges to the implementation of such a strategy. Poor specificity could result in non-immune persons being put at risk and poor sensitivity would compromise the strategy’s effectiveness and result in individuals with acquired immunity being ineligible for an immunity passport. It also remains unclear whether “detectable antibody or PCR evidence of infection indicate protection against COVID-19, and if so, for how long.”
According to investigators, PCR and antibody testing are certainly required for surveillance and will play an important role in informing the lifting or reimposing of physical distancing interventions. They can also directly impact the prevention of transmission, but this is strongly dependent on coverage and speed to results. Investigators also report that the strategy of immunity passports currently faces substantial technical, legal, and ethical challenges. “Now is the time to invest in testing capacity, policy, and planning to maximize their contribution to the fight against COVID-19,” the researchers concluded.
Grassly NC, Pons-Salort M, Parker EPK, White PJ; for the Ferguson NM, Imperial College COVID-19 Response Team. Comparison of molecular testing strategies for COVID-19 control: a mathematical modelling study [published online August 18, 2020]. Lancet Infect Dis. doi: 10.1016/S1473-3099(20)30630-7