COVID-19 rapid antigen tests or RATs, also frequently called COVID-19 lateral flow tests or LFTs, are rapid antigen tests used to detect SARS-CoV-2 infection (COVID-19). They are quick to implement with minimal training, cost a fraction of other forms of COVID-19 testing, and give users a result within 5–30 minutes. RATs have been used in several countries as part of mass testing or population-wide screening approaches. Many RATs can be used for self-testing, in which an individual "collects their own specimen… and interpret[s] their test result themselves".

False positives are very rare; the tests' specificity is 98%-99%. However, the tests have a sensitivity of 70%-72%, which is lower than COVID-19 polymerase chain reaction (PCR) tests' sensitivity of 88%-96%. Despite this, COVID-19 RATs remain valuable in finding people who would otherwise not know they were infected, helping to prevent further transmission. The tests are more sensitive in the symptomatic and transmissive stages of disease when the viral load is higher.

Uses

Use in diagnosis COVID-19 rapid antigen tests (RATs) have been widely used for diagnosis of COVID-19. The World Health Organization (WHO) COVID-19 Case Definition states that a person with a positive RAT (also known as an antigen rapid diagnostic test or Antigen-RDT) can be considered a "confirmed case of SARS-CoV-2 infection" in two ways. First, the person with a positive Antigen-RDT could meet a "probable case definition" such as having recent loss of smell or taste without any known cause, or could meet certain "suspect criteria" such as having a severe acute respiratory illness. Second, the person with a positive Antigen-RDT could be asymptomatic but a "contact of a probable or confirmed case." Nevertheless, individual countries may have different case definitions of COVID-19; for example, in New Zealand a positive PCR test (not just a RAT) is necessary for a person to be considered a "confirmed case."

Use in screening Between 2020 and 2021, studies using mathematical models estimated the benefit of frequent RATs in screening populations for COVID-19. Paltiel et al studied a hypothetical college campus with 5000 students. Screening all students every two days with a "low-sensitivity, high-specificity test" (such as a RAT) would be able to control an outbreak of COVID-19. Mina et al theorized that higher-frequency screening using lower-sensitivity RATs may be more useful than lower-frequency screening using higher-sensitivity PCR tests because the former would "capture most infections while they are still infectious." The quick results of RATs would serve to limit asymptomatic spread. Larremore et al simulated various COVID-19 population screening strategies. The researchers found that "effective screening depends largely on frequency of testing and speed of reporting and is only marginally improved by high test sensitivity."

Humanitarian uses In addition to routine community use, rapid tests have also been utilised as part of humanitarian efforts during the pandemic. Following the flooding in Jakarta in Indonesia on 2 December 2020, rapid tests were made available in flood shelters. Furthermore, following the closure of national borders in Europe following the emergence of the Alpha variant just before Christmas 2020, nearly 6,000 lorry drivers were stranded without food, effectively stopping Christmas food deliveries. Rapid tests were deployed by French firefighters within 24 hours at the Channel. Rapid tests enabled lorries to get on the road and complete their deliveries and return to their families for Christmas, demonstrating the potential global utility of having an easily implementable COVID-19 test. Médecins Sans Frontières strongly endorsed the use of rapid tests in lower- and middle-income countries, noting "COVID-19 antigen tests can deliver rapid and actionable results, ensuring timely identification of people infected with the virus at the community level".

Use for "return to normal" Spain became the first country to use rapid tests to facilitate a return-to-normal with rapid tests being widely available in pharmacies in December 2020, and a free music concert held in Barcelona for individuals who took a rapid test. A similar approach was taken in Albania to enable music festivals. However, many experts were unsure of this approach believing that "rapid tests are not the solution to restart normal life" but might be used in conjunction with other infection control techniques.

Concerns about use

False negatives (low sensitivity) Although the specificity of RATs are high (98%-99%), in 2020 RATs were criticized for having a sensitivity as low as 50%; that is, if people with COVID-19 as determined by a positive PCR test were also tested with a RAT, about half the time the RAT would be negative. As of 2022, systematic reviews determined that the pooled sensitivities of RATs were 70%-72%. In one systematic review, the range of sensitivities across studies was 37%-90%. As the World Health Organization (WHO) recommends RATs with "≥ 80% sensitivity", many RATs do not meet the WHO recommendation.

In the systematic reviews, the sensitivity was higher for symptomatic people (76%-82%) than for asymptomatic people (57%-68%). RATs were more sensitive when samples had more viral load, as measured by a low PCR "cycle threshold," and less sensitive when the samples had less viral load.

A 2022 study followed 225 adults and children with COVID-19 over 15 days using PCR tests, viral cultures, and home RATs. It found that the sensitivity of the RAT (Quidel QuickVue) increased from 0% two days prior to symptom onset or first positive PCR test to 77% four days after symptom onset or first positive PCR test, with an overall sensitivity of 50%. Compared with PCR tests collected the same day, the RAT sensitivity was 64%; compared with viral cultures collected the same day, the RAT sensitivity was 84%. The sensitivity of the RAT was lower in persons who were vaccinated against COVID-19 than in persons who were not vaccinated against COVID-19.

Potential for false negative results due to new variants In November 2020, a new, marginally more infectious strain of SARS-CoV-2 was identified in the United Kingdom, the SARS-CoV-2 Alpha variant. The strain rapidly spread around the world. With widespread global use of this form of COVID-19 testing, there was a concern that this variant would render rapid testing obsolete. As part of the UK's accelerated technology evaluation of lateral flow, within 24 hours Public Health England laboratories were able to confirm that RATs in global development were not affected (i.e., that they could identify the new variant). This was because rapid test generally targets the capsid protein and not the spike protein. Some strains have been identified with a nucleocapsid mutation (D399N) that does decrease the sensitivity of at least one RAT (Quidel Sofia 2) up to 1,000-fold. Fortunately, the frequency of mutation D399N was still relatively low globally at ~0.02% as of May 2021. A study published in 2022 found that the sensitivities of six rapid antigen detection tests were 70.0%-92.9% for the Delta variant and 69.6%-78.3% for the Omicron variant across a range of viral loads; however, for Omicron samples with a low viral load, the sensitivities were 0.0%-23.1%.

False positive results when instructions not followed If a COVID-19 RAT is used outside manufacturer recommendations, the result can be false positive. Beginning in December 2020, TikTok videos demonstrated how to use soft drinks to create false positive COVID-19 RAT results. Later, researchers found that introducing fruit juices, alcoholic beverages, bottled water, and other products directly into an Abbott Panbio COVID-19 RAT without the manufacturer's recommended buffer solution produced false positives. In contrast, a different RAT (BD Veritor) produced no false positive results under the same conditions.

Slow deployment and uptake Some have raised concerns about the slow deployment and uptake of RATs, and the potential loss of life that might have occurred as a result. A modelling study in Canada estimated that half the deaths in care homes in British Columbia in 2020 could have been prevented if rapid testing had been available.

Toxicity of components Various concerns have been raised related to the safety of chemical components contained within RAT kits, which can be toxic to humans if not properly used. On 24 February 2022, Health Canada issued a public advisory warning that there had been a recent increase in calls to poison control centers associated with RATs, which contained the preservatives sodium azide and ProClin.

Methods

An antigen is a foreign molecule or molecular structure that can cause an immune response. COVID-19 rapid antigen tests (RATs) detect antigenic proteins on the surface of or in the interior of the SARS-CoV-2 coronavirus. Of the COVID-19 RATs that had received an emergency use authorization (EUA) from the US Food and Drug Administration (FDA) by January 2022, all detected nucleocapsid proteins, and one also detected the receptor-binding domain of the coronavirus spike protein. Similarly, almost all tests on the European Union common list of COVID-19 RATs target nucleocapsid proteins.

A typical COVID-19 RAT is a lateral flow test (LFT). For an LFT, a liquid sample (such as from a nasal swab) is placed on a pad at one end of a porous paper-like strip. The liquid is pulled through the strip by wicking (capillary action), encountering different chemically-enhanced regions embedded within the strip.

First, at a "conjugate pad," soluble antibodies with gold nanoparticles are picked up by the liquid, attaching to any SARS-CoV-2 antigens present in the sample. Then, at the test line (which may be labelled "T"), antibodies specific to SARS-CoV-2 are anchored to the strip; these bind to any SARS-CoV-2 antigens, capturing the associated nanoparticles. Finally at the control line (which may be labelled "C"), antibodies that can attach to the antibodies with nanoparticles are anchored, capturing the remaining nanoparticles.

If there are no SARS-CoV-2 antigens present, then the gold nanoparticles are carried by the liquid, continue through the test line, and then captured at the control line, showing a single indicating a negative test. However, if there are antigens present, then some of the nanoparticles will be stopped at the test line and the rest will be stopped at the control line, showing two lines indicating a positive test.

History of development and deployment

2020

In May 2020, the US Food and Drug Administration (FDA) issued the first emergency use authorization (EUA) for a COVID-19 RAT, the Sofia 2 test manufactured by Quidel.

In August 2020, the United States Department of Health and Human Services announced that the US government would be purchasing 150 million BinaxNOW RATs produced by Abbott Laboratories "to expand strategic, evidence-based testing." Later the agency announced that 100 million of the tests were to be sent to governors to use "at their discretion," for example to reopen schools.

By September 2020, it was reported that the United Kingdom's Moonshot program would be investing £100 billion to systematically assess, develop and implement new technologies for COVID-19 testing, including RATs for COVID-19. In that month, the World Health Organization (WHO) released interim guidance on COVID-19 "antigen-detecting rapid diagnostic tests" (Ag-RDTs) including recommendations for their use, selection, and implementation. The interim guidance noted that Ag-RDTs were easier to implement and less expensive than nucleic acid amplification tests (NAATs). The World Health Organization (WHO) recommended the use of Ag-RDTs in outbreaks, in monitoring disease trends, and in early identification of cases.