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How can we improve detection?

In this article Rosanna Peeling, Professor of Diagnostics Research and Director of the International Diagnostics Centre (IDC) at the London School of Hygiene and Tropical Medicine gives an overview of diagnostic testing for COVID-19.

What is a diagnostic test?

A diagnostic test for an infectious disease can be used to demonstrate the presence or absence of infection, or to detect evidence of a previous infection.

Demonstration of the presence of the bacteria or virus causing the infection is important for effective patient management and for guiding treatment of infection and informing any public health measures required.

How are diagnostic tests used in an outbreak?

In any outbreak situation, a triad of diagnostic tests are needed:

  1. A highly sensitive (chance of test detecting those with the disease) and specific (chance of test detecting those without the disease) molecular test to detect the virus to confirm clinically suspected cases, and guide public health measures, such as isolation or quarantine. Such tests have to be performed in a laboratory by trained laboratory staff using specialised equipment. It typically takes more than an hour before the results are available.

  2. A rapid simple-to-use test to triage suspected cases at the point-of-care, or in community settings. These tests for detecting viral proteins can be performed by anyone who can follow simple instructions, and the results can be ready in 10-15 minutes.

  3. A (serological) test that can be used to detect current and past exposure, to assess the true extent of an outbreak, and inform prevention and control strategies. These can be done in batches in a laboratory or individually in community settings.

What test should be used and when?

For molecular testing, viruses are usually detected for a few days after the onset of symptoms, but in some instances may be detected before.

For serological testing, five days after the onset of symptoms, patients develop an antibody response. The first antibodies to appear in response to infections are IgM antibodies, which may persist for a few months. High levels of IgM antibody are suggestive of an active infection. As IgM antibodies subside, IgG antibody levels start to rise. These antibodies may persist for a long time. If a sample is taken from a patient in both the acute and convalescent stage of an infection, a four-fold rise in IgG antibodies is evidence of confirmed infection. Types of available tests used should therefore be related to the patient’s stage of infection.

For COVID-19, who should be tested?

Since the sequence of the novel coronavirus (SARS CoV-2) causing COVID-19 was published on January 12 2020, more than 20 different molecular tests have become available to detect genetic material of the virus (ribo-nucleic acid / RNA). As the symptoms of COVID-19 are relatively common in many infections (e.g. fever, cough), tests to detect the virus are useful in confirming patients who fulfil the clinical and epidemiologic case definition for COVID-19. This enables public health measures such as isolation or quarantine to be introduced. Case definitions from the World Health Organization are available: https://www.who.int/publications-detail/global-surveillance-for-human-infection-with-novel-coronavirus-(2019-ncov).

For COVID-19, what specimens should be taken for testing?

For molecular diagnostic testing for SARS CoV-2 causing COVID-19, current United Kingdom guidelines are to collect and test the following:

  • upper respiratory tract specimens: nasopharyngeal AND oropharyngeal swabs

  • lower respiratory tract specimens: sputum, if possible, for those patients with a productive cough, or bronchoalveolar lavage (BAL)

  • For patients who have been admitted to hospital: collect blood samples All specimens collected in clinics without laboratories need to be packaged and sent to a central or reference laboratory which has the reagents and equipment to perform testing for evidence of COVID-19 disease.

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Poster from Public Health England, available at https://www.gov.uk/government/publications/wuhan-novel-coronavirus-guidance-for-clinical-diagnostic-laboratories

What do the results from the molecular tests for COVID-19 mean?

  • Positive result: confirmed COVID-19 infection

  • Negative result: may mean the patient is not infected with the virus causing COVID-19, or that the patient has been tested too early, and may test positive later. In that case, the patient may need to be re-tested if the patient continues to show symptoms or deteriorates

  • Preliminary positive result not confirmed – possible detection of the novel coronavirus or other coronaviruses not related to the outbreak

How can we improve testing for COVID-19?

If simple, rapid (point of care) tests detecting viral proteins were available for triaging suspected cases in community settings, then we would be able to have a better understanding of the extent of active infection and possibly location of hotspots in the community. This would inform public health control strategies to interrupt transmission within a community.

If simple antibody tests (serological tests) to detect current and past infections were available, they could be used to assess the true extent of the outbreak over time and give us a better understanding of the natural history of infection, secondary attack rates and risk of adverse outcomes.

What has been done to build diagnostic capacity for COVID-19?

Laboratory infrastructure is limited in many countries. In February 2020, work began with the Africa Centres for Disease Control and Prevention and the Institut Pasteur Dakar to organise training workshops for laboratory scientists in more than 30 reference laboratories in Africa to learn how to detect COVID-19 RNA using a protocol published by the Charite, Berlin, Germany. The European Virus Archive provided all the reagents, including positive and negative controls for the workshop, and 200 sets of reagents for participants to take back to their home country, to begin testing as soon as they returned.

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COVID-19: Tackling the Novel Coronavirus

London School of Hygiene & Tropical Medicine

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