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The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject.
The use of rapid antigen tests has gained widespread acceptance as an alternative method for diagnosis of COVID-19 outside of health care settings. As of January 2022, every household in the U.S. is eligible to order four free at-home rapid antigen tests by mail using covidtests.gov.
These tests differ from molecular tests such as RT-PCR because they are designed to detect the presence of viral proteins using simple immunochromatography methods, commonly referred to as lateral flow assays. Rapid antigen tests target the SARS-CoV-2 nucleocapsid protein, the most abundant protein expressed by the virus. They directly assess for the presence of viral proteins, making them different from serology tests, which look for antibodies produced by the host in response to the infection. Thus, rapid antigen tests assess for acute infection only, not prior infection or response to vaccination.
Rapid antigen tests offer a number of advantages over molecular assays. Testing can be deployed outside of hospital laboratories, and many can be performed by members of the general public. They are relatively inexpensive relative to RT-PCR and simple to interpret. They have a turnaround time as fast as 15 minutes, allowing for testing prior to entrance into congregate care facilities or other public settings. They are compatible with samples taken from the anterior nares rather than the nasopharynx, making them more comfortable for serial testing.
In October 2021, FDA prioritized making at-home over-the-counter SARS-CoV-2 antigen testing more readily available. This will allow for earlier identification of cases and proactive separation from susceptible hosts. The first test approved through this initiative is ACON Laboratories’ FlowFlex SARS-CoV-2 Antigen Rapid Test, which showed a sensitivity of 92% relative to PCR when performed in individuals within one week of symptoms and asymptomatic individuals, with a specificity of 100% (FINDDx.org, October 2021).
Comparison to RT-PCR
A major difference between rapid antigen tests and RT-PCR is the difference in the analytic sensitivity of the assay. Typically, the sensitivity of antigen tests is 30% to 40% lower than for RT-PCR, depending on whether tested subjects were symptomatic or asymptomatic (Cochrane Library, March 2021). However, lower sensitivity has both disadvantages and benefits. The primary disadvantage is a risk of falsely negative results in people with low viral loads who may be early in their infection, and who go on to spread it to others in subsequent days. In practice, this subpopulation represents just a small fraction of those tested, and risk can be mitigated through serial testing algorithms. There is also a slightly elevated rate of false positives relative to molecular tests, though the rate is dependent on the prevalence of disease and the proportion of people who are symptomatic. For many commonly-used rapid antigen tests, the negative predictive value (e.g., the likelihood someone with a negative test is truly negative for infection) is greater than 98% (Boum, August 2021). A major advantage of these assays is the lower likelihood of detecting residual viral nucleic acid left over from a remote infection in recovered individuals (Mina, November 2020). This reduces the chance of unnecessary initiation of isolation and quarantine precautions and subsequent rounds of testing.
Rapid antigen tests are subject to the same considerations as molecular tests with respect to factors that affect clinical sensitivity. These include the quality of sampling and the timing of testing relative to the onset of infection. They have been noted to have diminished performance in the asymptomatic population, which may be related to the lower levels of virus in this group relative to those with symptoms, rather than characteristics of the tests themselves (Pray, January 2021).
Use cases for rapid antigen testing
Rapid antigen tests for SARS-CoV-2 are in widespread use, but the optimal setting for their deployment remains undefined. Given the rapid tests’ lower sensitivities and specificities, programs generally deploy confirmatory RT-PCR for positive antigen tests in asymptomatic (low pretest probability) individuals and for negative antigen tests in symptomatic individuals and close contacts of positive cases (high pretest probability) settings. Serial testing is also helpful to improve sensitivity and identify infection during the critical early transmission period. A study performed at two universities in Wisconsin using the Quidel Sofia 2 SARS-CoV-2 antigen assay with mid-turbinate swabs reported a sensitivity of 79% in symptomatic people and 44% in asymptomatic people relative to RT-PCR (Ford, April 2021; Pray, January 2021). The majority of false negative results occurred in people with low amounts of the virus, inferred by high cycle threshold (Ct) values on RT-PCR. A multicenter descriptive study from Spain evaluating the Abbott PanBio COVID-19 Rapid Ag test reported a sensitivity of 45% in symptomatic children, suggesting reduced performance relative to adults, an important consideration for school-based testing programs. The extent to which PCR-positive/antigen-negative individuals carry live transmissible virus is not yet fully known.
Scant data exist on changes in performance for antigen tests in vaccinated individuals, but there is a theoretical risk that receipt of a COVID-19 vaccine could result in lower viral loads, which would reduce the assay’s sensitivity. However, recent data published regarding the delta variant suggest that viral loads may be similar in vaccinated and unvaccinated individuals (Brown, August 2021).
IDSA guidelines make no recommendations for or against using rapid tests (i.e., result time ≤1 hour) versus standard nucleic acid amplification testing (e.g. RT-PCR) in symptomatic individuals suspected of having COVID-19, citing knowledge gaps.
Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection (Dinnes, August 2020)
Overall, in this Cochrane review of rapid tests for SARS-CoV-2, the snesitiity of antigen tests across was variable, and the average sensitivtity was low at 56.2%. For rapid molecular tests the sensitivity across studies was more consistent, and the aevrage sensitivity was 95.2%. it is unclear how the tests evaluated in this review will perform in clinical practice.
- 18 study cohorts of people with suspected current SARS‐CoV‐2 infection, known to have, or not to have SARS‐CoV‐2 infection, or where tests were used to screen for infection.
- There were 3198 unique samples, of which 1775 had confirmed SARS‐CoV‐2 infection.
- Ten studies took place in North America, two in South America, four in Europe, one in China, and one was conducted internationally.
- To assess the diagnostic accuracy of point‐of‐care antigen and molecular‐based tests to determine if a person presenting in the community or in primary or secondary care has current SARS‐CoV‐2 infection.
- For antigen tests, sensitivity varied from 0% to 94%; the average sensitivity was 56.2% (95% CI 29.5 to 79.8%) and average specificity was 99.5% (95% CI 98.1% to 99.9%.
- Data for individual antigen tests were limited with no more than two studies for any test.
- For rapid molecular tests, sensitivity showed was more consistent than in antigen tests (from 68% to 100%).
- Average sensitivity was 95.2% (95% CI 86.7% to 98.3%) and specificity 98.9% (95% CI 97.3% to 99.5%).
- The authors did not find any studies at low risk of bias for all quality domains and had concerns about applicability of results across all studies.
- The authors note their confidence in the literature evaluated was limited. because many studies did not follow the test manufacturers’ instructions
- The studies frequently did not use the most reliable methods or did not report enough information for us to judge their methods.
- The evaluations were largely based on remnant laboratory samples.
Comparison of Abbott ID Now (IDNCOV) and Abbott m2000 Methods for the Detection of SARS-CoV-2 from Nasopharyngeal and Nasal Swabs from Symptomatic Patients (Harrington, August 2020).
- 524 paired nasal swabs (NS) tested on Abbot ID NOW (IDNCOV) compared with nasopharyngeal swabs from symptomatic patients meeting criteria for a diagnosis of COVID-19.
- To compare Abbot ID Now (IDNCOV), with the Abbott RealTime SARS-CoV-2 (ACOV) assay performed on the Abbott m2000 system.
- The overall positivity rate in this sample collection was 35%.
- The overall positive agreement was 75% (95% CI, 67.74% - 80.67%) and 99% negative agreement (95% CI, 97.64% - 99.89%) between IDNCOV and ACOV for all specimens tested.
- No information is given about length of symptoms before testing or Ct values, both of which may impact the sensitivity of rapid tests and the test performance seen in this study.
Rapid detection of COVID-19 Coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform (Yu, July 2020).
- 248 samples from COVID-19 patients diagnosed in Shenyang province, China.
- To evaluate a LAMP-based assay for the detection of SARS-CoV-2.
- This LAMP-based assay had a sensitivity of 89.9%, with 25 false negatives due to relatively low viral loads.
Rapid and visual detection of 2019 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal amplification assay (Yan, June 2020).
- 130 specimens (a mixture of upper and lower tract) from patients with clinically suspected SARS-CoV-2 infection.
- To evaluate a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for detection of SARS-CoV-2, and compare it with RT-PCR.
- Based on 58 positive and 72 negative samples compared to RT-PCR.
- The sensitivity of the RT-LAMP assay was 100% (95% CI 92.3%–100%).
- Specificity was 100% (95% CI 93.7%–100%).
- The RT-LAMP assay showed no cross-reactivity with other respiratory pathogens.
- 103 complete genomes of SARS-CoV-2 were obtained from four databases when designing the primers. These genomes may not have shown mutations occurring at the primer sequence region of the target gene.
- Some specimens were from bronchiolar lavage, but the authors do not say how many. Given the higher sensitivity with RT-PCR in this sample type, these findings may limit generalizability to settings where only nasopharyngeal swabs are used.
Evaluation of a novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples (Porte, June 2020)
Overall, in this retrospective study, a novel rapid antigen detection test had high sensitivity and specificity in patients who primary were tested within 2 days of symptoms. The test performed better in samples with higher viral loads.
- 127 nasopharyngeal and oropharyngeal samples derived from patients with respiratory symptoms and/or fever and an epidemiological risk factor for SARS-CoV-2 infection at a private medical center in Chile
- 82 of the samples were positive for SARS-CoV-2 RNA by RT-PCR
- Median patient age was 38 years, and 53.5% were male
- 93.7% samples were from the first week after symptom onset.
- To evaluate a novel antigen-based RDT for the detection of SARS-CoV-2 in respiratory specimens from suspected COVID-19 cases.
- The median duration of symptoms was 2 days (IQR 1–4 days)
- The median Ct value of RT-PCR-positive samples was 17.7 (IQR 14.2–25.1)
- Overall sensitivity and specificity were 93.9% (95% confidence interval 86.5–97.4%) and 100% (95% confidence interval 92.1–100%), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads.
- The sample type used in the study was not a type recommended by the test manufacturer
- The study was conducted during the summer, when other respiratory viruses were in low circulation. In the setting of other respiratory viruses, the test may have a different sensitivity/specificity
Low performance of rapid antigen detection test as frontline testing for COVID-19 diagnosis (Scohy, August 2020).
- 148 nasopharyngeal swabs tested by RT-PCR and rapid antigen testing.
- To determine the sensitivity and specificity of the Coris COVID-19 Ag Respi-Strip test, a rapid immunochromatographic test for the detection of SARS-CoV-2 antigen, in comparison to RT-qPCR.
- According to RT-qPCR results, 42 samples were negative and 106 were positive, with a Ct value of 33 (mean: 31.4; range: 16–38).
- The median time of symptom duration before the sampling date was 4 days (mean: 6.6; range: 0–34).
- 106 of samples were positive by RT-PCR; 32 were detected with the antigen test (30.2% sensitivity).
- For samples with Ct < 25 (n = 10), <30 (n = 34) and <35 (n = 64), 1.8 × 105, 9.4 × 103 and 494.8 copies/mL respectively, COVID-19 Ag Respi-Strip had a sensitivity of 100%, 70.6% and 46.9%.
- The median time of symptom duration was 4 days, which may have contributed to the poorer sensitivity of the antigen test. If utilized earlier, sensitivity may have been higher.
- The median cycle threshold was fairly high; it is possible the antigen test would have performed better at lower thresholds (higher viral loads).
Performance of Abbott ID Now COVID-19 Rapid Nucleic Acid Amplification Test Using Nasopharyngeal Swabs Transported in Viral Transport Media and Dry Nasal Swabs in a New York City Academic Institution (Basu, July 2020). In this comparison of the test performance of the Cepheid-Xpert-Xpress SARS-CoV-2 and the Abbot ID NOW rapid tests, the sensitivity of Abbott ID NOW COVID-19 for dry swabs of nares and nasopharynx was 51.6% and 66.7%, compared to Xpert Xpress platform.
Clinical Evaluation of Self-Collected Saliva by Quantitative Reverse Transcription-PCR (RT-qPCR), Direct RT-qPCR, Reverse Transcription–Loop-Mediated Isothermal Amplification, and a Rapid Antigen Test To Diagnose COVID-19 (Nagura-Ikeda, September 2020). In this study of saliva samples from 103 known-positive COVID-19 cases, SARS-CoV-2 was detected in 50.5-81.6% of cases with molecular assays and 11.7% of cases with rapid antigen testing.