How to Read Sofia Strep Test Results Without the Analyzer
Diagnostic Operation of an Antigen Test with RT-PCR for the Detection of SARS-CoV-2 in a Hospital Setting — Los Angeles County, California, June–Baronial 2020
Auguste Brihn, DVM1 ,ii; Jamie Chang, Medicoiii; Kelsey OYong, MPH2; Sharon Balter, Docii; Dawn Terashita, Doctwo; Zach Rubin, Doctorii; Nava Yeganeh, Dr.2 (View author affiliations)
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Summary
What is already known about this topic?
Prompt and accurate diagnosis of SARS-CoV-2 infection is critical to containing the spread of COVID-19 in a infirmary setting.
What is added by this report?
The Quidel rapid antigen test had lower sensitivity in both asymptomatic (lx.5%) and symptomatic (72.1%) patients but a high specificity (98.seven% and 99.v% for symptomatic and asymptomatic patients, respectively) when compared with the contrary transcription–polymerase chain reaction (RT-PCR) examination.
What are the implications for public wellness practice?
Antigen tests have lower sensitivity compared with RT-PCR; negative antigen test results in persons with symptoms should be confirmed with an RT-PCR test, because a false-negative result might atomic number 82 to failures in infection command and prevention practices and cause delays in diagnosis, isolation, and treatment.
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Prompt and accurate detection of SARS-CoV-2, the virus that causes COVID-19, has been important during public health responses for containing the spread of COVID-xix, including in hospital settings (1–3). In vitro diagnostic nucleic acid amplification tests (NAAT), such as real-time reverse transcription–polymerase concatenation reaction (RT-PCR) can exist expensive, have relatively long turnaround times, and require experienced laboratory personnel.* Antigen detection tests can be speedily and more easily performed and are less expensive. The performance† of antigen detection tests, compared with that of NAATs, is an area of interest for the rapid diagnosis of SARS-CoV-2 infection. The Quidel Sofia ii SARS Antigen Fluorescent Immunoassay (FIA) (Quidel Corporation) received Food and Drug Administration Emergency Use Authorization for use in symptomatic patients within 5 days of symptom onset (4). The reported test positive percentage understanding§ between this test and an RT-PCR test issue is 96.7% (95% conviction interval [CI] = 83.3%–99.iv%), and the negative percentage agreement is 100.0% (95% CI = 97.nine%–100.0%) in symptomatic patients.¶ However, performance in asymptomatic persons in a university setting has shown lower sensitivity (v); assessment of performance in a clinical setting is ongoing. Data collected during June 30–Baronial 31, 2020, were analyzed to compare antigen test operation with that of RT-PCR in a hospital setting. Among 1,732 paired samples from asymptomatic patients, the antigen test sensitivity was threescore.v%, and specificity was 99.five% when compared with RT-PCR. Among 307 symptomatic persons, sensitivity and specificity were 72.1% and 98.7%, respectively. Health care providers must remain enlightened of the lower sensitivity of this test among asymptomatic and symptomatic persons and consider confirmatory NAAT testing in loftier-prevalence settings because a simulated-negative effect might lead to failures in infection control and prevention practices and cause delays in diagnosis, isolation, and treatment.
During a menses of high community COVID-nineteen prevalence,** the Los Angeles County Section of Public Health collaborated with hospital A, a tertiary medical heart serving a large urban population in central Los Angeles, to evaluate the performance of the Quidel Sofia two SARS Antigen FIA (antigen test) compared with that of the Fulgent COVID-xix RT-PCR (Fulgent Genetics) (RT-PCR test) for screening of all patients admitted to the hospital through the ED during June thirty–August 31. Albeit orders included requests for both tests to enable prompt inpatient cohorting. Each admitted patient had 2 simultaneously collected samples for SARS-CoV2 testing by ED nursing staff members: an inductive nasal swab successively swabbing both nostrils with i swab and a nasopharyngeal swab. Nasopharyngeal swab specimens were candy and sent past courier to a Clinical Laboratory Comeback Amendments–certified laboratory for RT-PCR testing. Results were available 24–48 hours after specimen drove. Test cycle threshold (Ct) values for N1 and N2 nucleocapsid viral gene targets were reported. N1 and N2 targets with Ct values <40 were used to define a positive RT-PCR issue, per manufacturer instructions.†† Because differences between N1 and N2 targets were negligible, for this analysis, N1 target Ct values were used. The anterior nasal swab specimens were processed for antigen testing using calibrated Sofia 2 analyzers in the ED.
The RT-PCR examination was used as the standard. Results were considered concordant if they were positive for both tests or negative for both, and discordant if one was positive and the other was negative. Persons were categorized equally having COVID-19–compatible symptoms if they had a temperature ≥100.four°F (38°C) at triage, or reported respiratory distress, shortness of breath, cough, flu-similar symptoms, nausea, vomiting, diarrhea, or headache. Signs and symptoms (ED chief complaints and vital signs) were categorized into those more commonly reported by COVID-19 patients (6) (i.e., fever, respiratory distress or shortness of jiff, and cough) and those less commonly reported (i.e., flu-similar symptoms, nausea or vomiting, diarrhea, and headache). Symptoms were retrospectively ascertained through medical record abstraction using the ED triage assessment. Hospital service codes and vital signs were evaluated for patients without an ED primary complaint. Patients who went to a not-ED location (due east.thousand., labor and delivery), might non have an ED main complaint and were classified every bit asymptomatic for this analysis. Additional information regarding symptoms was obtained from the hospital's electronic medical records system for patients with discordant antigen and RT-PCR test results.
Data were managed and analyzed using SAS software (version ix.4; SAS Institute). Sensitivity, specificity, negative predictive value, and positive predictive value were calculated for antigen testing and compared with those of RT-PCR. N1 Ct values for antigen-positive and antigen-negative symptomatic and asymptomatic groups were compared using t-tests; p-values <0.05 were considered statistically significant. Signs and symptoms, demographic characteristics, and underlying medical weather for the grouping of patients with discordant results were compared using chi-square or Fisher's exact tests. Odds ratios were calculated for each of the more common or less common symptoms and overall. This investigation was reviewed by the Los Angeles Canton Institutional Review Board and CDC and was conducted consistent with applicable federal police force and CDC policy.§§
During June 30–August 31, hospital A tested 2,039 patients admitted through the ED with paired antigen and RT-PCR tests. Median patient historic period was 56 years (range = 16–107 years); ane,126 (55%) were female person, and 913 (45%) were male. The mean exam turnaround time for RT-PCR was 28.2 hours. Overall, 307 (15%) patients had COVID-19–compatible symptoms (Tabular array 1). Among the 307 symptomatic patients, 120 (39%) had a positive exam result past either test, including 52 (17%) by antigen and 68 (22%) by RT-PCR. Positive examination result by both the antigen and the RT-PCR tests were reported for 49 (16%) patients. Hateful N1 Ct values were significantly lower among patients with a positive antigen event (mean Ct = 21.iii) than among patients with a negative antigen issue (mean Ct = 28.5; p<0.001).
Amongst the one,732 asymptomatic patients, 139 (8%) had a positive test issue by either test (58 [three%] past antigen and 81 [v%] past RT-PCR). Mean N1 Ct values did non differ significantly between samples from patients who were symptomatic (hateful Ct = 23.5) and those who were asymptomatic (mean Ct = 23.9). Amid asymptomatic and symptomatic patients, the specificity of the antigen test was 99.v% and 98.7%, respectively, and the sensitivity was 60.v% and 72.1%, respectively. The diagnostic functioning between the 2 groups did non differ significantly, with the exception of negative predictive value (p<0.001). Sensitivity of the discordant antigen test results from patients who were symptomatic and asymptomatic was assessed beyond a range of Ct values. Antigen test sensitivity increased in symptomatic and asymptomatic persons equally N1 Ct values decreased (sensitivity 75% for Ct ≤30 and sensitivity xc.vii% for Ct ≤25).
RT-PCR–positive and antigen-positive examination results were compared with patients' signs and symptoms at the time of admission. Symptoms associated with a positive RT-PCR test result included fever, respiratory distress or shortness of jiff, cough, and flu-similar symptoms (Table 2). Shortness of breath was the nigh unremarkably reported symptom among persons with a positive RT-PCR test issue (28%) and among both discordant groups (RT-PCR–positive/antigen-negative = 39%; RT-PCR–negative/antigen-positive = v of 12 patients) (Table three). No COVID-xix–compatible symptoms occurred in 27 (53%) patients with RT-PCR positive/antigen-negative test results and 6 of 12 patients with RT-PCR negative/antigen-positive test results. Some patients with RT-PCR–positive/antigen-negative test results had underlying medical weather condition recorded in medical records (10% reporting having diabetes and 18% having hypertension) and were at higher run a risk for severe COVID-xix–associated illness.¶¶
Discussion
In this analysis of RT-PCR and antigen testing of asymptomatic and symptomatic patients at the fourth dimension of a third hospital admission through the ED, the sensitivity of the Quidel Sofia 2 SARS Antigen FIA examination was 66% (72% and 61% in symptomatic and asymptomatic patients, respectively) using the Fulgent COVID-19 RT-PCR test as the standard; specificity was high overall (>99%). The antigen test'southward sensitivity increased in specimens with lower Ct values, consequent with college virus titers in the specimen. Proper estimation of the antigen exam results should consider the patient's signs, symptoms, and exposure history, the prevalence of COVID-nineteen in the community, and the test's performance characteristics.*** The lower sensitivity of antigen tests compared with RT-PCR testing supports the strategy of using a more than sensitive NAAT exam if there is high clinical suspicion for COVID-xix. COVID-19–compatible symptoms in this study were associated with positive RT-PCR test results. A positive antigen exam result with a high pretest probability, either because of symptoms, exposure to an active case, or residence in an area of high community prevalence, could enable early on isolation and receipt of medical intendance. This assay did not identify any statistical difference between N1 Ct values in the study samples nerveless from symptomatic and asymptomatic persons. Findings bespeak that although sensitivity of the antigen test does increase with lower Ct values, sensitivity is still lower at Ct values <thirty and even at Ct values <25 in symptomatic and asymptomatic persons.
The findings in this report are bailiwick to at to the lowest degree four limitations. First, this community and tertiary medical heart represent a convenience sample and are not representative of all U.S. customs and medical eye settings. Second, data regarding whatever COVID-19–uniform symptoms reported were non collected beyond the ED chief complaint for the concordant grouping; therefore, the number of symptomatic persons might be underestimated. Tertiary, exposure history was non evaluated. Finally, RT-PCR is an imperfect standard for comparison considering it detects the presence of viral RNA, which includes "dead" virus and might not be correlated with manual.
Overall, this evaluation of the performance of a rapid antigen test among symptomatic and asymptomatic persons suggests cautious interpretation of rapid antigen test results given its lower sensitivity. A imitation-negative antigen examination effect in health care settings might atomic number 82 to failures in infection control and prevention practices and cause delays in diagnosis, isolation, and treatment. Persons with COVID-19–compatible symptoms and negative Quidel Sofia 2 SARS Antigen FIA antigen examination results should have an additional sample confirmed with a NAAT test. While pending confirmation, measures to prevent SARS-CoV-2 transmission are recommended, including the utilize of personal protective equipment, source control for the patient, adherence to infection prevention protocols, and avoidance of cohorting these patients with others who exercise not have confirmed or suspected COVID-19 infection.†††
Acknowledgments
Jaime Reyes, CHA Hollywood Presbyterian Medical Heart; Sarah Guerry, Paul Simon, Los Angeles County Department of Public Health, California.
oneEpidemic Intelligence Service, CDC; twoLos Angeles County Section of Public Health, California; threeCHA Hollywood Presbyterian Medical Center, California.
All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of involvement. No potential conflicts of interest were disclosed.
References
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- Fauci AS, Lane HC, Redfield RR. Covid-19—navigating the uncharted. N Engl J Med 2020;382:1268–9. https://doi.org/10.1056/NEJMe2002387external icon PMID:32109011external icon
- Del Rio C, Malani PN. COVID-19—new insights on a rapidly changing epidemic. JAMA 2020;323:1339–40. https://doi.org/x.1001/jama.2020.3072external icon PMID:32108857external icon
- Food and Drug Assistants. In vitro diagnostics EUAs. Silver Spring, Dr.: The states Section of Health and Human Services, Nutrient and Drug Administration; 2020. https://world wide web.fda.gov/medical-devices/coronavirus-disease-2019-covid-nineteen-emergency-use-authorizations-medical-devices/in-vitro-diagnostics-euasexternal icon
- Pray IW, Ford L, Cole D, et al. ; CDC COVID-19 Surge Laboratory Group. Functioning of an antigen-based examination for asymptomatic and symptomatic SARS-CoV-2 testing at two university campuses—Wisconsin, September–October 2020. MMWR Morb Mortal Wkly Rep 2021;69:1642–7. https://doi.org/10.15585/mmwr.mm695152a3external icon PMID:33382679external icon
- Guan WJ, Ni ZY, Hu Y, et al. ; Red china Medical Treatment Expert Grouping for Covid-19. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med 2020;382:1708–xx. https://doi.org/ten.1056/NEJMoa2002032external icon PMID:32109013external icon
| Exam diagnostic characteristic | All patients (N = two,039) | Symptomatic patients (northward = 307) | Asymptomatic patients (n = 1,732) | p-value† |
|---|---|---|---|---|
| Positive RT-PCR examination results, no. (%) | 149 (seven.iii) | 68 (22.ii) | 81 (4.7) | — |
| Positive antigen exam results, no. (%)§ | 110 (5.4) | 52 (sixteen.9) | 58 (3.4) | — |
| Sensitivity of antigen exam, % (95% CI) | 65.8 (57.6–73.three) | 72.1 (61.4–82.7) | 60.5 (49.9–71.1) | 0.16 |
| Specificity of antigen test, % (95% CI) | 99.4 (98.9–99.7) | 98.seven (97.three–100.0) | 99.5 (99.1–99.8) | 0.19 |
| Positive predictive value of antigen test, % (95% CI) | 89.1 (81.seven–94.2) | 94.2 (87.9–100.0) | 83.0 (75.two–93.8) | 0.13 |
| Negative predictive value of antigen test, % (95% CI) | 97.iv (96.5–98.0) | 92.6 (89.three–95.eight) | 98.1 (97.4–98.7) | <0.001 |
Abbreviations: CI = confidence interval; RT-PCR = contrary transcription–polymerase chain reaction.
* Quidel Sofia ii SARS Antigen Fluorescent Immunoassay test characteristics (sensitivity, specificity, positive predictive value, and negative predictive value) were based on comparing with the Fulgent COVID-19 RT-PCR exam.
† Chi-square and Fisher'southward verbal p-value comparison symptomatic patients with asymptomatic patients.
§ At hospital A, the Quidel Sofia 2 SARS Antigen Fluorescent Immunoassay was used for qualitative detection of nucleocapsid poly peptide from SARS-CoV-two.
| Patient's main complaint | No. (%) | OR (95% CI) for RT-PCR–positive results† | |
|---|---|---|---|
| RT-PCR–positive results (due north = 138) | RT-PCR–negative results (n = one,529) | ||
| More common COVID-nineteen–like signs and symptoms | |||
| Fever/Chills | 11 (8.0) | 31 (two.0) | 4.two (2.1–8.5) |
| Respiratory distress/Shortness of jiff | 39 (28.0) | 150 (x.0) | iv.i (2.8–half dozen.1) |
| Coughing | half dozen (4.0) | eight (0.5) | 9.9 (iii.four–28.8) |
| Less common signs and symptoms | |||
| Flu-similar symptoms | 10 (vii.0) | 5 (0.three) | 27.1 (9.1–lxxx.half-dozen) |
| Nausea/Airsickness | i (0.seven) | 29 (ii.0) | 0.4 (0.1–iii.2) |
| Diarrhea | ane (0.7) | 5 (0.3) | 2.v (0.3–21.nine) |
| Headache | 0 (—) | 11 (0.7) | 0 (—) |
| Met case definition§ | 68 (49.0) | 239 (xvi.0) | five.2 (iii.7–7.five) |
Abbreviations: CI = confidence interval; OR = odds ratio; RT-PCR = opposite transcription–polymerase chain reaction.
* 372 patients (11 RT-PCR–positive and 361 RT-PCR–negative) with missing emergency department chief complaint information were excluded.
† Among patients with and without symptoms.
§ Instance was defined as symptomatic if patient had a chief complaint of more common or less mutual COVID-xix–compatible signs and symptoms.
| Discordant group characteristic | No. (%) | ||
|---|---|---|---|
| RT-PCR–positive§/Antigen-negative (northward = 51) | RT-PCR–negative/Antigen-positive¶ (n = 12) | Full (N = 63) | |
| Signs and symptoms at emergency department admission | |||
| Fever/Chills | eighteen (35) | 1 (8) | 19 (xxx) |
| Cough | xv (29) | 0 (0) | 15 (24) |
| Shortness of breath | twenty (39) | v (42) | 25 (40) |
| Fatigue | 6 (12) | 0 (—) | 6 (ten) |
| Muscle aches | 9 (eighteen) | 0 (—) | 9 (14) |
| Headache | 0 (0) | one (8) | 1 (2) |
| Loss of gustation or aroma | 1 (two) | 1 (8) | 2 (three) |
| Sore throat | 3 (6) | 0 (—) | 3 (5) |
| Congestion | five (9) | 0 (—) | 5 (8) |
| Nausea/Vomiting | 7 (xiii) | 1 (8) | eight (xiii) |
| Diarrhea | 5 (10) | 0 (—) | 5 (8) |
| No symptoms** | 27 (53) | 6 (50) | — |
| Temperature >100.four°F (38°C) | 5 (10) | 5 (42) | 5 (8) |
| Demographic characteristic | |||
| Sex activity | |||
| Female | 25 (49) | 8 (67) | 35 (56) |
| Male person | 24 (47) | 4 (33) | 28 (44) |
| Race †† | |||
| Asian | vii | v | 12 |
| White | 6 | — | 6 |
| Black | iii | 1 | four |
| Other | 32 | vi | 41 |
| Unknown | vi | — | — |
| Age, yrs, mean (range) | 59 (20–98) | 67 (28–100) | threescore (21–100) |
| Underlying medical condition | |||
| Diabetes | v (x) | ane (eight) | 6 (10) |
| Obesity | 2 (4) | 0 (—) | 2 (three) |
| Hypertension | 9 (18) | 2 (17) | 11 (18) |
| Heart disease | 2 (4) | three (25) | 5 (8) |
Abbreviation: RT-PCR = reverse transcription–polymerase chain reaction.
* Faux negative = antigen-negative and RT-PCR–positive; false positive = antigen-positive and RT-PCR–negative.
† 2,039 patients admitted through the emergency section were tested with paired SARS-CoV-2 antigen and RT-PCR tests.
§ The Fulgent COVID-xix by RT-PCR exam, a existent-time RT-PCR test intended for the qualitative detection of nucleic acid from SARS-CoV-ii in upper and lower respiratory specimens, was used.
¶ The Quidel Sofia 2 SARS Antigen Fluorescent Immunoassay was used for qualitative detection of the SARS-CoV-2 nucleocapsid protein.
** No symptoms identified through individual medical chart brainchild.
†† Ethnicity data were non nerveless for this analysis.
Suggested citation for this commodity: Brihn A, Chang J, OYong Grand, et al. Diagnostic Operation of an Antigen Test with RT-PCR for the Detection of SARS-CoV-2 in a Hospital Setting — Los Angeles County, California, June–August 2020. MMWR Morb Mortal Wkly Rep 2021;70:702–706. DOI: http://dx.doi.org/10.15585/mmwr.mm7019a3external icon.
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