That is the maxim from the WHO Director General, affirming that we “cannot fight this pandemic blindfolded.” For many countries across the world, testing for SARS-CoV-2, the virus responsible for COVID-19, has become the cornerstone of controlling the pandemic. Certainly, in Australia, testing rates have been some of the best in the world.

Australia has the benefit of a world class system of public and private laboratories. This is supported by a robust regulatory framework at a national level to ensure that all laboratories conducting COVID-19 tests are meeting the highest standards of testing rigour.

But why are we testing, what are we testing, and what are the limitations of the tests we are using? Furthermore, how do these concepts translate to the education, consent, and management of our patients whom are undergoing a SARS-CoV-2 test?

The roles of testing

In the COVID-19 pandemic, there are a great many roles for testing. In Australia the main focus thus far has been on testing people most likely to have COVID-19, so as to isolate and contact trace. This has been done with a view to reducing the basic reproductive number of the virus below one. For this reason, testing guidelines have focussed on identifying ‘suspected cases’ based on symptoms and risk assessment. As Australia now moves into the next phase of the pandemic, with decreased transmission and incidence, we are beginning to see broadening of the testing criteria to ensure no case is missed. It is estimated that, overall, Australia is detecting approximately 92% of all symptomatic cases.¹ Beyond diagnosis, testing also has an important role in ‘de-isolation’ of positive cases, to ensure that the case no longer has detectable viral shedding in their upper respiratory tract. For reasons we will explore, testing in both diagnosis and de-isolation is best conducted by looking for the virus directly – the nucleic acid PCR tests.

The role for testing at a population level, including testing of asymptomatic individuals, has yet to be determined. This is the area where serology testing may become useful. Serology tests look for indirect evidence of SARS-CoV-2 infection by detecting the antibodies produced as the body mounts its immune response. Since the antibody response follows the viral infection by days to weeks, these tests are more likely to give false negatives when the patient is in the acute stages of infection, and serology does not currently have a role in the diagnosis of COVID-19 during the acute illness. Furthermore, these tests may throw up ‘false positives’ by detection of antibodies previously raised in response to other, non-SARS-CoV-2, human coronaviruses. However, serology tests may be helpful for the diagnosis of past cases allowing for broad-based surveillance, assessment of vaccine efficacy, and research activities.²

The PCR test

As we have alluded to, the nature of a test will vary depending on its desired purpose. In the case of COVID-19, for example, screening for population exposure requires different testing strategies to testing individuals for the purpose of diagnosis. At the clinician–patient level in the diagnosis of acute illness, nucleic acid testing (NAT) using polymerase chain reaction (PCR) is the method of choice. This test looks for direct evidence of the virus in the nasopharynx, by nucleic acid amplification and detection.

The limitations of the PCR test

No test is perfect, and there is an inherent trade-off between sensitivity (the ability to pick up true positives) and specificity (the ability pick up true negatives). The SARS-CoV-2 PCR test is no different.

Given the extraordinary speed at which the PCR tests have been developed, and the absence of a gold-standard comparator, we don’t know the true sensitivity of the PCR tests, but there is likely to be a small number of ‘false negatives’ – people who truly do have COVID-19 but whom the test fails to detect as a positive case.

While we are not sure what contributes to ‘false negatives’, the following factors are likely to contribute:

The ramifications of a ‘false negative’ result

A negative test result is, of course, reassuring for both the patient and for the healthcare system, but this reassurance should perhaps be tempered by the small but not insignificant chance of a false negative. We must be cognisant of the fact that a patient with a negative swab will likely be less strict in self-isolation or social distancing, even if symptoms persist. This has implications for onwards transmission. Further, false reassurance may make the patient more complacent with worsening symptoms and dissuade them appropriately reaching out to emergency services if they become more unwell.

False positive test results

The false positive rate is determined by the test’s specificity, and we are not certain exactly how specific the PCR test is. However, even if the specificity of the test is extremely high, false positive test results may make up an increasing proportion of total positive test results as the prevalence of the SARS-CoV-2 virus in the population falls. As we have already seen in one high-profile case in Australia, a false-positive result can cause anxiety, distress, and sets in motion a significant public health response. Thus, as with false negatives, having an idea of the pre-test probability of infection is essential.

How can we translate this knowledge into safe, effective, patient-focused testing for COVID-19?

1. Pick the right test

   At present, only nucleic acid testing (NAT) using polymerase chain reaction (PCR) is recommended. These are available in both centralised laboratory and point of care modalities. Serology (antibody) testing is not recommended for the diagnosis of acute illness, and indeed some states have gone so far as to place prohibitions on their supply or conditions on their use, and the Therapeutic Goods Administration (TGA) has banned advertising of the tests to consumers see: TGA.

2. Have an awareness of the pre-test probability

   This will help you decide both who to test, and how to interpret the test result.

   Public health units across the country are identifying ‘hotspot’ areas of high prevalence or outbreaks of COVID-19. In these areas of higher pre-test probability, it may be appropriate to have a lower threshold for testing individuals with even the mildest of symptoms. Be alert to national and local guidelines which will help guide testing decisions.

   Equally, if a person with a high pre-test probability of COVID-19 (e.g. strongly suggestive clinical symptoms, with a known contact) tests negative, it would be prudent to consider the possibility of a false negative. Current CDNA guidelines advise that “a risk assessment should be undertaken for suspect cases who initially test negative for SARS-CoV-2. If there is no alternative diagnosis and a high index of suspicion remains that such cases may have COVID-19, consideration should be given to continued isolation and use of the recommended infection control precautions, pending further testing.”⁴

3. Be aware of, and attempt to ameliorate, the limitations of the test

   Ensure good swabs of both the deep nasal and oropharynx areas, to maximise the chances of viral collection.

   Be mindful of where the patient is in their clinical course, and that this may affect the sensitivity of the test.

4. Communicate with your patient

   A patient being tested for SARS-CoV-2 is likely to be anxious. Reasonably so; this is an unprecedent pandemic with phenomenal media attention. A positive result carries the real prospect of illness or death, notwithstanding the need for quarantine, distancing from loved ones, cessation of work, and a possible (and perhaps underappreciated) stigma associated with being a COVID-19 case. Doctors need to be mindful of these stressors in patients suspected of COVID-19, while also recognising that testing is not foolproof and ensuring appropriate education is given to the patient to minimise the consequences of false-negative results:

   • The need to remain isolated while awaiting test results
   • The need to remain isolated while symptoms persist
   • The need to be attentive to evolution of symptoms and be aware of the red flags such as increasing shortness of breath that should prompt contact with the emergency department.

5. Formalise this communication into consent

   As with any test or investigation we perform on patients, we should be getting at least verbal consent before performing SARS-CoV-2 tests. The Medical Board’s ‘Good Medical Practice’ states that it is incumbent on doctors to provide ‘information to patients in a way that they can understand before asking for their consent’. This entails a person’s voluntary decision made with knowledge and understanding of the benefits and risks involved. The communication and education discussed in the previous point will need to be incorporated into this consent process. This may be aided by aided by patients being provided with, or directed to, the Department of Health’s fact sheets.

6. Stay up to date

   The CDNA guidelines provide advice on suspected case definitions and testing. However, as each of Australia’s states and territories begins to experience different extents and mechanisms of transmission, it is important to be aware of local guidelines on testing.

Screening tests before elective surgery

Currently, routine testing of all patients prior to elective surgery is not being advised. Indeed, the Australian Health Protection Principal Committee (AHPPC) highlighted as a risk of restoration of elective surgery the ‘increased burden on testing regime presented by some individual clinicians conducting pre-operative testing as a perceived risk mitigation strategy, leading to undermining of the surveillance activities of Public Health Units’.

An appropriate approach would be to thoroughly risk assess all patients before elective surgery, with testing of any patient suspected of COVID-19, and deferral of their surgery if possible.

The medico legal aspects of testing

Avant has produced FAQs on testing, covering such topics as:

• Who should be tested?
• Can I compel a patient to be tested

Conclusion

Australia is in a strong position, with the benefit of a robust network of pathology laboratories, strong regulatory frameworks to ensure quality testing, and plentiful supplies of testing kits. This makes SARS-CoV-2 testing one of our most powerful tools as we strive to contain COVID-19. However, as is clear to us all by now, our response to COVID-19 cannot be static. Understanding the fundamental principles of testing – the different roles, types, strengths and weaknesses – is essential if we doctors are to evolve our practice in line with the evolution of the pandemic itself.

References

1. Australian Health Protection Principal Committee (AHPPC) coronavirus (COVID-19) statement on 16 April 2020
2. PHLN guidance on laboratory testing for SARS-CoV-2 (the virus that causes COVID-19)
3. Temporal dynamics in viral shedding and transmissibility of COVID-19
4. CDNA National guidelines for public health units

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