SARS-CoV-2 testing for public health use: core principles and considerations for defined use settings
Authors: Catharina Boehme, Emma Hannay, Rangarajan Sampath
Journal: The Lancet Global Health (2021)

With many regions of the world seeing a rise in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases, borders, schools, and workplaces are partially or fully closed, and physical interactions are restricted. Although vaccine roll-out has begun in numerous countries,1British Broadcasting CompanyCovid-19 vaccine: first person receives Pfizer jab in UK.https://www.bbc.co.uk/news/uk-55227325Date accessed: December 15, 2020Google Scholar it will take many months to complete. Meanwhile, communities are reliant on diagnostic testing in conjunction with other public health measures to keep facilities open. Until now, testing for SARS-CoV-2 has been mostly limited to use for clinical confirmation and care, but some countries are now implementing widespread testing for public health use and risk management. However, there is little guidance available to policy makers on how to translate the scientific information on SARS-CoV-2 diagnostic tests into practical policies for widespread testing in non-clinical settings. The development of rapid antigen tests, which can be used outside of the laboratory with fast turnaround times, has made widespread testing feasible. Although there were initial concerns about test performance, emerging evidence suggests that the most sensitive tests can detect 97% of infectious cases, based on the relationship between viral load and infectiousness.2van Beek J Igloi Z Boelsums T et al.From more testing to smart testing: data-guided SARS-CoV-2 testing choices.medRxiv. 2020; (published online Oct 14.) (preprint)https://doi.org/10.1101/2020.10.13.20211524Google Scholar Moreover, modelling analyses show that frequency of testing and speed of reporting have a greater influence than test sensitivity on the effectiveness of SARS-CoV-2 infection surveillance.3Larremore DB Wilder B Lester E et al.Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance.medRxiv. 2020; (published online June 27.) (preprint)https://doi.org/10.1101/2020.06.22.20136309PubMed Google Scholar Although the nasopharyngeal specimens required for many antigen tests are challenging to obtain, tests that utilise alternative sampling methods, such as nasal or saliva specimens, are becoming available and could provide the ease of use necessary for widespread testing.4Lindner AK Nikolai O Kausch F et al.Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with self-collected anterior nasal swab versus professional-collected nasopharyngeal swab.Eur Respir J. 2020; (published online Dec 10.)https://doi.org/10.1183/13993003.03961-2020Crossref PubMed Scopus (104) Google Scholar, 5Azzi L Baj A Alberio T et al.Rapid salivary test suitable for a mass screening program to detect SARS-CoV-2: a diagnostic accuracy study.J Infect. 2020; 81: e75-e78Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar These core principles (ie, the importance of fast test turnaround times, the relationship between test positivity and infectivity, and the ease of use for sample colletion) are applicable to all SARS-CoV-2 testing policies for public health use, along with cost considerations relating to high-volume testing. Beyond the core principles, several factors specific to the setting in which the test is to be used should be considered when designing testing policies. Settings can be defined according to patterns of contact and level of exposure, and include: points of entry, where people transit across defined borders; semi-closed communities, where the same people come together repeatedly; and random exposure settings, where people meet for a single exposure and then disperse (figure). The testing intensity required for entry points differs according to the level of risk of spread, which varies according to the frequency and distance of travel, and the prevalence of disease. The mode of travel strongly influences its frequency; air travel is usually planned and less frequent, whereas land crossings are more spontaneous and regular, even occurring daily. Prevalence of disease has a greater impact on risk when individuals cross from a higher prevalence area into a lower prevalence area, compared with similar prevalence areas. Long distance journeys have additional risk associated with the period of travel, as they are likely to entail means of transport involving many people (eg, aeroplanes, buses, or trains). Additionally, quarantine restrictions might need to be more flexible for commercial vehicles than for non-commercial vehicles, for economic reasons. Currently, strategies for reducing transmission in semi-closed communities are reliant on public health measures, such as physical distancing and mask wearing, supplemented by testing symptomatic individuals and contacts in health-care settings in line with country policies. There is still a potential for outbreaks in these communities, leading to quarantines or temporary closures. Strategies for additional proactive testing to detect asymptomatic infections and prevent spread can range from testing of individuals who are at high risk of being exposed to the virus (eg, those in frontline roles), to mass-testing the whole community. Testing in semi-closed communities is more effective at preventing outbreaks when done frequently, especially for individuals with a high risk of exposure,3Larremore DB Wilder B Lester E et al.Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance.medRxiv. 2020; (published online June 27.) (preprint)https://doi.org/10.1101/2020.06.22.20136309PubMed Google Scholar, 6Park SY Kim YM Yi S et al.Coronavirus disease outbreak in call center, South Korea.Emerg Infect Dis. 2020; 26: 1666-1670Crossref PubMed Scopus (339) Google Scholar but the optimal frequency of testing is dependent on community-specific factors, such as total population, proportion of the population who consistently wear masks, and presence of a contact tracing programme. Random exposure settings are particularly susceptible to the cluster-based superspreader events characteristic of COVID-19. Risk can be reduced by preventing the virus from entering the three Cs: crowded places, close contact settings, and confined and enclosed spaces.7WHOCoronavirus disease (COVID-19) advice for the public.https://www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-publicDate accessed: November 30, 2020Google Scholar However, risk limitation becomes more challenging as the size of a gathering increases, because physical distancing becomes more difficult in a large crowd and individuals are likely to have travelled from areas with a higher prevalence of infection.8Centers for Disease Control and PreventionConsiderations for events and gatherings.https://www.cdc.gov/coronavirus/2019-ncov/community/large-events/considerations-for-events-gatherings.htmlDate accessed: November 30, 2020Google Scholar Practically, reducing amplification events in these settings would need participants to be tested before arrival, which would require diagnostic tests to be readily available to the public outside of usual health-care settings. Although communities are progressing towards decentralised testing,9United States Food and Drug AdministrationLucira COVID-19 All-In-One Test Kit.https://www.fda.gov/media/143810/downloadDate accessed: November 26, 2020Google Scholar current tools are not sufficiently reliable or affordable for routine and repeated use. Additionally, a test for use outside of a health-care setting would need to incorporate a method of presenting results, with certification to ensure authenticity (especially in light of an already emerging market for fake SARS-CoV-2 test certificates10The ConnexionGroup caught making fake Covid test results at Paris airport.https://www.connexionfrance.com/French-news/Group-caught-making-fake-Covid-test-results-at-Paris-airportDate accessed: December 8, 2020Google Scholar). Digital integration would be crucial to such a strategy. Ultimately, commoditised and reliable home-based testing available at low cost would be key to allowing population-level mass testing. Robust strategies for widespread testing should take into account the core principles relating to diagnostic testing, and specific considerations for each defined use. Evidence suggests that rapid antigen tests are relevant for a wide set of uses, but there is still a need to invest in the development of novel diagnostics for commoditised use beyond the health-care system. CB convenes to and EH manages the ACT-Accelerator Diagnostics Pillar on behalf of FIND and the Global Fund. RS declares no competing interests. We thank Rachel Wright, PhD, Rachel Wright Medical Communications (Crewe, UK)for providing medical writing services, funded by Foundation for Innovative New Diagnostics (FIND), in accordance with Good Publication Practice (GPP3).