Recommendations For National SARS-CoV-2 Testing Strategies and Diagnostic Capacities

Key points

• Diagnostic testing for SARS-CoV-2 is a critical component to the overall prevention and control strategy for COVID19.

• Countries should have a national testing strategy in place with clear objectives that can be adapted according to changes in the epidemiological situation, available resources and tools, and country specific context.

• It is critical that all SARS-CoV-2 testing is linked to public health actions to ensure appropriate clinical care and support and to carry out contact tracing to break chains of transmission.

• All individuals meeting the suspected case definition for COVID-19 should be tested for SARS-CoV-2, regardless of vaccination status or disease history.

• Individuals meeting the suspected case definition for COVID-19 should be prioritized for testing. If resources are constrained and it is not possible to test all individuals meeting the case definition, the following cases should be prioritized for testing: o individuals who are at risk of developing severe disease o health workers o inpatients in health facilities o the first symptomatic individual or subset of symptomatic individuals in a closed setting (e.g. long-term care facilities) in the setting of a suspected outbreak.

• Nucleic acid amplification tests (NAAT) are the reference standard for diagnosis of acute SARS-CoV-2 infection.

• Countries can use high quality antigen-detection lateral flow or rapid diagnostic tests (Ag-RDTs), which are simple to use and offer rapid results, to achieve high coverage of testing, ideally testing all symptomatic individuals meeting the COVID-19 case definition as soon as possible from disease onset (within the first week of illness). Information on the use of Ag-RDTs can be found here.  Interim guidance on the use of Ag-RDTs can be found here.

• Testing of asymptomatic individuals with NAAT or Ag-RDTs is currently recommended only for specific groups including contacts of confirmed or probable COVID-19 cases and frequently exposed groups such as health care workers and long-term care facility workers.

• Widespread screening of asymptomatic individuals is not a currently recommended strategy due to the significant costs associated with it and the lack of data on its operational effectiveness.

• Considerations for the use of self-testing should include improved access to testing and potential risks that may affect outbreak control. The potential benefits and harms of self-testing with SARS-CoV-2 Ag-RDTs will be addressed in a separate guidance document.

• Mutation-detecting NAAT assays may be used as a screening tool for SARS-CoV-2 variants, but the presence of a specific variant should be confirmed through sequencing. Such tests should be appropriately validated for their purpose.

• The network of SARS-CoV-2 testing facilities should leverage and build on existing capacities and capabilities, be able to integrate new diagnostic technologies and adapt capacity according to the epidemiological situation, available resources and country specific context.

Version Control 

This interim guidance replaces the WHO guidance entitled “Laboratory testing strategy recommendations for COVID-19”, originally published on 21 March 2020. Updates from previous version This version provides updated guidance on diagnostic testing strategy in the context of updated transmission classifications, public health and social measures, public health surveillance and the WHO case definitions for COVID-19. The use of new tools such as antigen detection rapid diagnostic tests (Ag-RDTs) and considerations for testing vaccinated individuals and testing for genetic mutations associated with variants have been integrated. Annexes including a compilation of relevant resources and the 10 components of expansion of subnational testing have also been developed for this version.

Background

COVID-19 has put enormous demand on laboratory infrastructure and required an unprecedented rapid scale-up of testing capacity for its causative agent, SARS-CoV-2, at all levels of the health care system. 

More recently, the identification of variants with mutations that may confer changes in phenotypic properties, designated as variants of interest (VOIs) or variants of concern (VOCs), further highlights how detection of SARS-CoV-2 remains a critical element in the global strategy to control COVID-19 . More information on variants can be found on the WHO website here. Laboratory capacity is one of the core capacities required to detect, assess, notify and report public health events under the International Health Regulations (IHR) 2005 (4). Testing is a critical tool in detecting the etiological agent, understanding virus transmission, and guiding and monitoring public health control measures and the clinical management of patients. Several different diagnostic techniques for SARS-CoV-2 are available, as follows:

i. Detection of viral RNA, through manual or automated nucleic acid amplification tests (NAAT), such as real time reversetranscription polymerase chain reaction (rRT-PCR);

ii.Detection of viral antigens through immunodiagnostic techniques, such as lateral flow assays (LFAs), commonly called rapid diagnostic tests or Ag-RDTs.

iii. Detection of host antibodies through serological techniques, such as LFAs, enzyme linked immunosorbent assays (ELISAs), or chemiluminescent immunoassays (CLIAs). 

WHO interim guidance on the technical requirements of diagnostic testing for SARS-CoV-2 can be found here. NAAT is the most sensitive and specific and is therefore recommended as the reference standard. Ag-RDTs offer an opportunity to increase the availability and speed of testing in appropriate scenarios. Full guidance on the use of Ag-RDTs can be found here. Antibody detection is not recommended for diagnosis of COVID-19, as it may take up to two weeks for host antibodies to be produced, but it plays an important role in the detection of past infection for research and surveillance (6-9). More information on natural immunity to SARS-CoV-2 can be found here (10).

Response plans and testing strategies should be adapted and responsive to evolving epidemiological situations, the addition of approved1 new diagnostic tests and available resources at national and local levels. Testing should always be linked to public health actions such as clinical care (11), isolation of cases (12), contact tracing (13), supported quarantine of contacts (14) and provision of information to the individual undergoing testing. Testing for SARS-CoV-2 should be carried out as part of a multi-layered public health response strategy and clear time bound consequences of testing should be defined. To be most effective, SARS-CoV-2 testing should be implemented within a strong national system comprising the public health laboratory network and clinical diagnostic laboratories, and include mechanisms to coordinate with other relevant sectors, such as veterinary, academic and private stakeholders. Although not directly linked to clinical management, leverage of existing sentinel surveillance sites and networks such as the Global Influenza Surveillance and Response System (GISRS) continues to play an important role in SARS-CoV-2 surveillance (15). This updated interim guidance aims to provide guidance to countries on testing strategies and the expansion and prioritization of national and subnational diagnostic testing capacity and capability for SARS-CoV-2 to meet existing and anticipated needs, while acknowledging resource constraints. It is primarily intended for laboratory and diagnostic stakeholders across Member States and national public health authorities involved in the scale up of SARS-CoV-2 testing and improvement of integrated testing services, particularly in resource constrained areas. 

Testing strategy recommendations

Testing is a critical element to the overall prevention and control strategy for COVID-19 (4). National testing strategies should set clear objectives and be adaptable according to the current and evolving epidemiological situation, available resources and the country specific context. By addressing these components, countries can develop a risk-based approach to the scaling up or focusing of testing, including a plan to consider the components of expansion of subnational testing described in Annex I and where and how additional testing capacity can be accessed or leveraged. Frequent reviews and changes to the testing strategy should be undertaken periodically or when there are situational changes. This process should be led by the national public health authority laboratory leadership and counterparts from epidemiological, surveillance and clinical management teams should be engaged when developing and implementing any testing strategy. WHO recommends that all individuals meeting the case definition for COVID-19, irrespective of vaccination or disease history, be tested for the presence of SARS-CoV-2 in respiratory specimens (1). 

While the testing of symptomatic individuals should be prioritized over testing asymptomatic individuals, testing of asymptomatic individuals can be informative in instances such as follow up of contacts of confirmed or probable cases or testing of health care and long-term care facility workers that are frequently exposed. Widespread testing of asymptomatic populations, including through self-testing, is not currently recommended, based on lack of evidence on impact and cost-effectiveness of such approaches and the concern that this approach risks diverting resources from higher priority testing indications. Member States that consider policies to test outside these recommendations should do so only if the following conditions are met:

• timely and reliable testing of suspected cases is maintained as the priority strategy

• there are available human and financial resources for testing, reporting, isolation, contact tracing and follow-up of all testpositive individuals If asymptomatic individuals are tested with Ag-RDTs and do not have an epidemiological link to a confirmed case or working in an area where COVID-19 patients are cared for, results should be treated as presumptive and ideally confirmed by NAAT.

More information on addressing screening of specific populations is available for contacts, healthcare workers, workplaces, long term care facilities, schools and travelers.

Confirmatory testing with NAAT

NAAT is considered as the reference standard for diagnosis of SARS-CoV-2 infection. Ag-RDTs are not meant to replace NAAT but can be implemented as a complementary strategy as there are many that are highly reliable (see WHO Emergency Use Listing), easy to use, and offer rapid turnaround of results. Ag-RDTs can be used where NAAT is not available or where results will be delayed by more than 48 hours. Ag-RDT uptake is encouraged to expand accessibility of testing and can be considered as follows:

• In symptomatic individuals in high prevalence settings confirmation of positive Ag-RDT results by NAAT is not necessary. Negative Ag-RDT results may be confirmed by NAAT at clinical discretion2 .

• In symptomatic individuals in low prevalence settings confirmation of negative Ag-RDT results by NAAT is not necessary. Positive Ag-RDT results may be confirmed by NAAT at clinical discretion2 .

• In asymptomatic individuals that are contacts of confirmed cases or are frequently exposed, such as health care and longterm care facility workers, Ag-RDT results are not required to be confirmed by NAAT but may be confirmed using NAAT, at clinical discretion.Epidemiological situation Different testing strategies should be considered according to differing epidemiological situations, availability of resources and other factors such as very remote or hard to access areas . The extent of transmission of SARS-CoV-2 in the population being tested will affect the positive and negative predictive values (PPV and NPV) of the tests. In populations with few or no cases, it is preferable to use the reference standard NAAT to diagnose cases, as it is the most specific. Where the number of cases is increasing and laboratories and health facilities are under heavy burden, it may be more effective to use tests that can be carried out closer to the patients and are less resource intensive, such as Ag-RDTs. Scale-up of testing should be accompanied by increased capacity to manage the clinical care, contact tracing and isolation measures associated with test results. If testing is being done in a setting with widespread community transmission, the priority may be to reduce transmission through cluster detection and implementation of public health and social measures (PHSM). In a setting with limited transmission, the goal may be more targeted to the early detection of cases and identification of their contacts, such as in the reintroduction of the virus through imported cases to areas that had previously suppressed transmission. Capacity for COVID-19 surveillance and SARS-CoV2 testing should be retained during periods of low or no transmission in case of a resurgence of cases and rapid increase in demand. Once new sporadic cases or clusters are detected the priority is to limit further transmission and reduce the spread of the virus through public health interventions. More information on how high and low prevalence affects interpretation of test results can be found in Annex I of the Ag-RDT guidance here.

Please see the full article here:  Recommendations for national SARS-CoV-2 testing strategies and diagnostic capacities – Interim guidance 25 June 2021