National polymerase chain reaction (PCR) testing indication guidance for COVID-19
Preamble
The first version of the *National laboratory testing indication guidance for COVID-19- document was developed at the onset of the COVID-19 pandemic. The original guidance document was finalized and approved by the Special Advisory Committee on April 16, 2020, and updated again in May 2020.
As part of the commitment to ongoing re-evaluation of testing guidance, an update was completed in September 2020. Distinct areas of testing requiring specific guidance were identified: (1) the core guidance for molecular, reverse transcription polymerase chain reaction (RT-PCR) testing is contained within the present document; (2) and guidance for the use of newer testing technologies (e.g., antigen tests) is presented in the document entitled *Interim Guidance on the Use of Rapid Antigen Detection Tests for the Identification of SARS-CoV-2 Infection*. 
Purpose
To facilitate a consistent national approach to PCR testing, acknowledging regional variations in COVID-19 epidemiology and that testing requirements are expected to vary over time.
Objectives
- To outline the elements of a national approach to PCR testing for SARS-CoV-2 for consideration by Canadian provinces and territories (PTs);
- To support identification of triggers for public health actions.
Context
At present, the performance of a validated PCR test on a clinically appropriate sample (e.g., nasopharyngeal, lower respiratory tract sample obtained via bronchoalveolar lavage) collected by a trained health care provider is considered the gold standard for the diagnosis of SARS-CoV-2 infection.
The overall performance of SARS-CoV-2 PCR tests in distinguishing between individuals who do and do not have SARS-CoV-2 infection depends on both test attributes and epidemiological considerations.
Test attributes include the sensitivity (the ability of the test to correctly identify those who truly are infected with SARS-CoV-2) and the specificity (the ability of the test to correctly identify those who truly are not infected with SARS-CoV-2) at the time the clinical specimen was collected for laboratory analysis. Since the sensitivity and specificity of PCR testing for SARS-CoV-2 varies with viral load, test performance varies during the course of illness. False negative results can occur if the patient is not shedding sufficient virus at the time or at the site of specimen collection, or if the specimen is not collected properly. While rare, PCR tests can generate false positive results, such as when cross-contamination occurs during sample processing or in situations when there is non-specific amplification near the limit of detection. The observation of prolonged detection of SARS-CoV-2 RNA beyond the resolution of symptoms due to non-infectious viral fragments rather than infectious virus also complicates the interpretation of results showing a low viral load.
Epidemiological considerations include the pre-test likelihood of SARS-CoV-2 being truly present in a given population being considered for testing (prevalence). The proportion of false positive tests increases as the prevalence of SARS-CoV-2 in the population decreases, and any test result thought to be a false positive should be investigated further (e.g., sample tested again or lab processes checked for possible contamination). Interpreting a negative test result should be done with caution since, in situations where the clinical index of suspicion is high (high pre-test likelihood), a negative test does not rule out disease (due to the factors noted above). For those with a recent exposure, there is no defined time after exposure when a negative test excludes disease, since incubation can last for up to 14 days following contact with an infectious case.
It is recognized that there will be variation in how PTs implement this guidance, depending on resources, local epidemiology, and other considerations.
Approach
Overall, the recommended approach for PCR testing is to prioritize symptomatic individuals (including those with mild symptoms) for purposes of case identification, clinical treatment and contact tracing. This approach is consistent with the Infectious Diseases Society of America testing guidelines. Due to the non-specific nature of many COVID-19 symptoms, the set of symptoms used to determine the indication for testing will need to be considered in relation to local epidemiology, testing capacity and guidance from public health authorities. Yield of testing is highest in symptomatic individuals. The overall effectiveness of testing to identify SARS-CoV-2 infection is dependent on individuals who are likely to have been exposed to SARS-CoV-2 coming forward and being able to access the appropriately offered testing in a timely manner. Should testing resources become constrained, consideration for matching testing resources to public health objectives may become necessary.

# Consideration for PCR testing of individuals who are asymptomatic
It has been recognized that a significant proportion of SARS-CoV-2 infected patients can be asymptomatic. As a result, the value of broad-based asymptomatic testing has been a topic of frequent discussion in Canada. While the value of such programmes remain unclear, a number of pilot projects of testing asymptomatic people with no known exposure have been completed in Canada during the spring and summer of 2020. These have demonstrated low utility and limited yield so far, but this may change if community transmission increases significantly.
Furthermore, untargeted asymptomatic testing can displace capacity for the timely testing of symptomatic individuals, and this will likely become an even greater issue during the fall and winter seasons when colds, influenza, and other respiratory viral illnesses co-circulate. While there are limitations to asymptomatic testing, there are circumstances where it may be warranted and these are outlined below, with a distinction made between asymptomatic testing following a known exposure to a confirmed case and those who did not have an exposure.

# Testing individuals who are asymptomatic with known exposure to a confirmed case
The following groups of individuals without symptoms should be considered for testing for reasons of contact tracing or outbreak management:
- Close contacts of a case in the community;
- Health care workers and staff who work in health care facilities with reported outbreaks;
- Residents and workers in high-risk congregate living settings (e.g., long-term care facilities, correctional facilities, homeless shelters, other temporary shelters, single-room occupancy residences and work camps) with reported outbreaks;
- Work settings where physical distancing cannot be maintained (e.g., meat and poultry-processing facilities) and where there are reported outbreaks;
- Other outbreak or cluster investigations.

# Testing of individuals who are asymptomatic with no known exposure to a confirmed case
There is limited evidence regarding the utility of testing individuals who are asymptomatic with no known exposure to a case and is not generally recommended at this time. Evidence from a number of pilots suggests that the yield of asymptomatic testing is low in the context of limited community transmission. The utility of asymptomatic testing in the context of significant community transmission is unknown at this time. At present, testing of individuals who are asymptomatic with no known exposure to a case is best done in the context of research activities to generate the knowledge needed to make future evidence-informed decisions. As the epidemiology of COVID-19 and evidence evolves, the criteria for when asymptomatic testing adds value to the prevention and control of SARS-CoV-2 transmission will become clearer. Additionally, as new technologies, such as antigen testing, become available with good test performance characteristics, they may extend capacity into areas where asymptomatic testing using PCR methods is not feasible at present. Please see the *Interim Guidance on the Use of Rapid Antigen Detection Tests for the Identification of SARS-CoV-2 Infection- for further details.
PCR testing of asymptomatic individuals with no known exposure may be considered in certain limited situations, depending on local context and judgement by regional public health authorities, such as the following:
- Individuals upon admission to hospital in areas with high community prevalence of COVID-19 (note that individuals with symptoms or know exposure will be tested as per recommendations noted above);
- Immunocompromised individuals prior to admission to hospital, regardless of community prevalence of COVID-19;
- Individuals undergoing immunosuppressive procedures or major time-sensitive surgery that cannot be safely delayed;
- Travellers to certain remote locations, as defined by local public health authorities, where infection rates are low and where the capacity to deal with increased cases is especially limited;
- Deceased individuals with no known cause of death, but where COVID-19 is possible and where public health action would be taken if COVID-19 were the cause of death.
Previous versions of this guidance document had specific mention of testing asymptomatic workers and residents in both high risk (e.g., congregate living, correctional facilities) and vulnerable settings (e.g., long-term care facilities). The value of testing asymptomatic individuals prior to working in or admission to these settings using PCR is unknown but could be considered, particularly if there is significant community transmission and assessment of exposure risk is difficult. Repeat testing using NP swabs is of low yield in situations of low community transmission and consideration for the value of repeat testing using alternative technologies, such as antigen testing, is discussed in the *Interim Guidance on the Use of Rapid Antigen Detection Tests for the Identification of SARS-CoV-2 Infection.*

## Special considerations
- Asymptomatic pregnant women could be tested in the antepartum period according to local epidemiology, guidelines, and availability of testing, although little is known about the utility and yield of this approach at this time.
- Asymptomatic individuals who require testing prior to international travel. This requirement for testing is established by foreign national governments or international airline/travel organizations. At this time, the value of pre-travel testing is unknown and the mechanism to access this testing may vary by jurisdiction.
Other PCR testing modalities
Most PCR testing needs can be efficiently and effectively delivered by high throughput lab capacity, resulting in a turnaround time that enables timely public health action. While these laboratories are able to support remote, rural, isolated and/or Indigenous communities, the delays introduced due to sample shipment and transit times can increase turnaround time significantly. In these settings, the deployment of point-of-care (PoC) PCR testing is strongly recommended. PoC and other rapid tests will be useful in other situations where quick turnaround times are important, and the allocation of limited resources to locations where such devices will have the most beneficial impact is recommended. A variant of PCR, LAMP (loop-mediated isothermal amplification), is technology that may offer similar performance characteristics to PCR and can be considered using the same principles as outlined above.
In some situations, the inconvenience or intolerability of a nasopharyngeal swab (e.g., in children) may be a barrier to PCR testing. The development of alternative sampling methods, such as swish/gargle for saliva or sampling the anterior nares, will help improve overall access to and uptake of PCR tests, and may impact testing recommendations.
Forward planning
This guidance was created in collaboration with the provincial and territorial public health authorities and will continue to be reviewed and updated as necessary.
Endnotes
Hanson KE, Caliendo AM, Arias CA, et al. Infectious Diseases Society of America Guidelines on the Diagnosis of COVID-19. IDSA 2020. Accessed 8 September 2020. Available at: /.
An outbreak is defined according to local epidemiology and context, and may be a single case.