September 2020 | Recent medical releases
Since the beginning of the COVID-19 pandemic, three basic types of laboratory tests have been developed and used.
Nucleic-acid amplification tests (NAAT, including RT-PCR, TMA and LAMP) evaluate the presence or absence of the CoV-2 genome, generally in samples from the airways (nasopharyngeal and oropharyngeal swabs). PCR and equivalent nucleic-acid tests are currently considered the most accurate way of determining if a person is carrying CoV-2. A positive result indicates that the viral genome is present, but does not definitively establish if the person is contagious or not.
Serological tests detect the presence of antibodies (specific immune response) against CoV-2 antigenic proteins, in a blood sample. A positive result shows that the person has been exposed to CoV-2 in the past, but gives little or no information on their current infection status. In the future it is hoped that serological test will provide information on immunity to CoV-2 infection, but this is not at present the case.
Antigen tests measure the presence or absence of the viral proteins (antigens) themselves, most commonly the abundant nucleocapsid protein. The preferred sample type is again nasopharyngeal or oropharyngeal swabs. Like with nucleic acid-based tests, there is hope that saliva or mouthwash will provide a viable alternative, but at present this appears less accurate.
In the past weeks, there has been much discussion about rapid antigen tests for SARS-CoV-2.
Rapid tests have the advantages that they have a time-to-result in minutes rather than hours and can be performed almost anywhere, for example at the bedside, in a waiting room, or in a business setting. They do still require swabs as samples and so must be collected by healthcare professionals.
The most recent generation of these tests, available from several different suppliers, are expected to perform well in patients with high viral loads. This is usually the case approximately 3-10 days after infection with the virus, when the person is contagious, and may be asymptomatic or in the first days of symptoms.
It is therefore hoped that rapid antigen tests can support diagnosis of COVID-19 in people who have the first symptoms. In the USA, some tests have received authorization for diagnostic testing in symptomatic individuals, within 5-7 days from the onset of symptoms i.
Rapid antigen tests have a lower sensitivity* than NAAT (84-97.6%), and in particular are much more likely to give false-negative results in individuals with lower amounts of virus. This makes them unreliable in individuals in the first days of infection, later than 5-7 days after onset of symptoms, and above all in asymptomatic infected individuals. Negative results should be treated with caution and confirmation by a second test, ideally NAAT, should be considered.
*Probability that a carrier of the virus will test positive.
In some situations, testing only symptomatic individuals does not lead to the highest level of safety. This is especially the case when the aim of testing is to ensure safety at the workplace (or occupational safety) or to screen people entering at-risk situations (e.g. at sporting events or when travelling). Recent findings show that the virus’ transmission rate can be high before the onset of symptoms and that isolating symptomatic patients alone is not sufficient to contain the spread of the virus ii iii.
The suggestion that rapid antigen tests might only miss weaker positives that are unlikely to be contagious is not evidence-based, as precise correlation between viral load and contagiousness has not yet been ascertained. In contrast, transmission by asymptomatic carriers has been clearly established iv. Furthermore, antigen tests can miss individuals in the first few days after infection, just before entering the most contagious period.
Consequently, there is a risk of failing to control new chains of infection when using rapid antigen tests outside of their specific intended purpose. Therefore, these tests should not be used for the screening of larger groups to rule out infections (e.g. at events, in offices, at airports, etc.). In these cases, where the presence of asymptomatic carriers must also be detected, a more sensitive testing with NAAT (RT-PCR or equivalent) is important.
The past weeks have shown rising interest towards rapid tests and their performance. Roche has announced that it will launch a Rapid Antigen Test in September for markets accepting the CE mark. As they state, the test simply intends to give aid to the initial screening of patients showing clinical symptoms: https://www.roche.com/media/releases/med-cor-2020-09-01b.htm.
Abbott has brought the Panbio™ COVID-19 Ag Rapid Test Device on the market to provide preliminary screening opportunities: https://www.globalpointofcare.abbott
Similarly, LumiraDx has also brought a SARS-CoV-2 Ag Test to the market that detects nucleocapsid proteins in nasal swab specimens from patients suspected of COVID-19. Their product insert equally specifies that “Negative results do not rule out SARS-CoV-2 infection and should not be used as the sole basis for treatment or patient management decisions, including infection control decisions.” https://www.lumiradx.com/assets/images/new/pdf/sars-cov-2-ag-test-strip-product-insert-eua.pdf.
On 11 September 2020, the World Health Organization published Interim Guidance on antigen detection v.
They recommend that rapid antigen tests can be used to diagnose CoV-2 infection, where NAAT are unavailable or where reduced turnaround-time is clinically necessary. They also suggest that the tests could be used for contract tracing and testing of asymptomatic cases, but warn concerning the reduced sensitivity. Repeated testing or preferably confirmatory testing (NAAT) of negatives should be performed whenever possible. Equally, they note that a negative Ag-RDT should not remove a contact from quarantine requirements.
According to the Interim Guidance, antigen tests are not recommended in settings or populations with low expected prevalence of disease. They list the following specific scenarios where rapid antigen tests should not be used:
U.S. Food and Drug Administration (FDA) similarly informs that healthcare providers may order a NAAT to confirm a negative antigen test result vi.
The graph below explains why the RT-PCR or equivalent method is still the most reliable way to test and discover contagious individuals before the onset of symptoms:
SYNLAB provides testing to support safety at work, at sports events and universities, and when travelling or crossing borders. The aim is to identify potentially contagious individuals as early as possible, which means also detecting the virus in pre-symptomatic or asymptomatic carriers – for which the RT-PCR or an equivalent NAAT is essential.
i CDC 4.9.2020, Interim Guidance for Rapid Antigen Testing for SARS-CoV-2. www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html
ii Arons et al. (2020) Presymptomatic SARS-CoV-2 Infections and Transmission in a Skilled Nursing Facility. The New England Journal of Medicine. 382(22).
iii Chang et al. (2020) Contact Tracing Assessment of COVID-19 Transmission Dynamics in Taiwan and Risk at Different Exposure Periods Before and After Symptom Onset. JAMA Intern Med.
iv Zhao et al (2020) COVID-19: asymptomatic carrier transmission is an underestimated problem. Epidemiology and Infection 148, e116, 1–3.
v WHO, 09.11.2020. Antigen-detection in the diagnosis of SARS-CoV-2 infection using rapid immunoassays: Interim guidance. WHO/2019-nCoV/Antigen_Detection/2020.1.
vi FDA, 16.07.2020. Coronavirus testing basics: www.fda.gov/consumers/consumer-updates/coronavirus-testing-basics
The spread of SARS-CoV-2 has become a serious challenge for public health, economy and social life in Europe and other regions of the world. To flatten the curve of new infections, not only social distancing and restrictions in public life but also fast and reliable testing plays an essential role.
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