Rapid near patient testing for both current and past infection is urgently required.
Test, test, test was the mantra of the World Health Organisation and is the key to controlling the spread of SARS-CoV-2 and its clinical manifestation COVID-19.
However, three months after the notification of the novel coronavirus infection in China there is still inadequate access to appropriate diagnostic tests globally and confusion amongst health professionals and the public about prioritisation of testing and interpretation of results.
As we know, the virus is spread by the respiratory route, primarily by droplets and contact with contaminated surfaces and by aerosol formation during invasive respiratory procedures. The virus is also found in urine, faeces and saliva. Asymptomatic shedding seems to be common especially in children and can spread infection.
The incubation period from infection to first symptom is typically 5 to 7 days with a range of about 4 to 14 days. The diagnosis of current infection relies on tests to detect the virus in the various body fluids. Antibody tests on blood are used to confirm past infection and presumed immunity, although the duration and effectiveness of such protection is not yet known.
It is felt that respiratory shedding of a virus peaks at the end of the first week after infection, just before and as symptoms are developing. It is thought that it can be intermittent so a single negative swab result can be misleading and tests may need to be repeated. Swabs need to be taken correctly and transported in the appropriate viral transport medium.
Nasopharyngeal swabs are more sensitive than the oropharyngeal swabs and are best taken when the symptoms first emerge. However, swabs from both sites are often combined to increase sensitivity.
The gold standard test for diagnosis is detection of viral RNA by molecular methods typically known as the reverse transcription polymerase chain reaction RT-PCR or PCR for short.
Antibody tests are primarily used to determine if a person has already had COVID-19. Specific IgM and IgG antibodies should start to become detectable after about four to five days with a positive IgM antibody in 70% of symptomatic patients by days 8 to 14 and 90% of total antibody tests positive by days 11 to 24. IgG reactivity is thought to reach greater than 98% after several more weeks. The duration of this antibody response is not yet known.
These antibody tests require knowledge of the proteins that form the viral coat, specifically the proteins to which the immune system responds and thus is triggered with the production of antibodies that flag or neutralise the virus.
The sections of the viral protein coat need to be then produced in the laboratory and included in immunoassays. These will form the basis of home testing kits for people who think they have had COVID-19 but their development takes time and the right protein has to be used.
The viral spike protein, which one has seen on the depictions of the virus, is the one that is commonly used and this is thought to be the sole protein on the viral surface that is responsible for entry into the host’s i.e. the human, cells. However, there are various different parts of the spike protein and it is difficult to know which one should be used.
The uniqueness of the spike protein is important in terms of the specificity of the antibody tests. The more unique it is, the lower the odds of having a false positive with reactions to other coronaviruses. Four coronaviruses cause the common cold and it is essential that a test for COVID antibodies does not cross react with the common cold coronaviruses giving false positives.
It is generally thought that reports of re-infection with COVID-19 are more likely due to false negative or erroneous PCR tests. Martin Hibberd, Professor of Emerging Infectious Diseases at the London School of Hygiene & Tropical Medicine feels that once people produce antibodies against a particular coronavirus, they probably have immunity for life. A laboratory in China has investigated how long immunity against the SARS and Middle East respiratory syndrome coronavirus lasts and 17 years later, a SARS survivor was still found to have neutralising antibodies. This is of course reassuring for governments that intend to deploy antibody tests to establish which healthcare workers are immune.
Conventional ELISA tests can deliver results in less than 20 minutes from a few drops of blood obtained by finger prick. The usually combined tests for IgM and IgG may not become positive until the second week in the infection and sensitivity may be lower after asymptomatic infection. Antibody detection tests are also limited by poor specificity and patients can be wrongly identified as having been infected and thus have a false sense of security.
Interpretation of these tests depends on the biological site and timing of samples and recognition of both intermittent viral shedding and variation in sensitivity and specificity of different test instruments. New tests should be properly validated before use in any given setting. An unreliable test is worse than no test. However, tests cannot be interpreted if they are not available, so it is important that regulatory bodies are able to identify and validate tests as soon as possible.
This is why The London General Practice feels that any testing of any patient should be performed by a clinician with full pre and post discussion of the implications of the test and clearly the understanding of the result.
To learn more about testing options available at The London General Practice contact us on 0207 935 1000 or email firstname.lastname@example.org