Each year influenza causes significant morbidity and mortality including up to 647,000 hospitalizations and 61,200 deaths during the 2018-19 respiratory season in the United States alone. Because symptoms of different respiratory diseases often overlap, influenza diagnostic testing plays an important role in the differential diagnosis and clinical management of these patients. Moreover, prompt diagnosis is vital to effective pharmaceutical interventions, infection control, and addressing underlying medical conditions in high risk-patient populations. Rapid diagnosis also plays an important role in facilitating patient flow through healthcare facilities during active respiratory seasons and pandemics.
Given these challenges, various rapid diagnostic platforms have been developed for the diagnosis of influenza infections. Here we describe the performance of Quidel’s Sofia Influenza A+B FIA when used on Sofia 2 Fluorescent Immunoassay Analyzer. As shown below, this CLIA-waived assay* provides objective results for influenza A or B in as early as 3 minutes, and never longer than 15 minutes.
To accomplish this, the Sofia 2 scans the test cassette at 3, 5, 8, 10, or 15 minutes and provides a positive result when first detected at any of these timepoints. In this ongoing clinical study, we analyzed the time-to-result (TTR) distribution for positive specimens obtained over the two most recent respiratory seasons (9/1/17 to 5/10/19) at two (2) urgent cares and eleven (11) community health centers. Nasal swabs were collected from patients presenting with acute respiratory infections (ARI) and directly tested in the WALK AWAY mode as defined in the Sofia 2 User Manual. Two thousand eight hundred and eighty-one (2,881) ARI patient specimens were tested for Influenza A or B, and 727/2881 cases (25.2%) were positive. For a subset of patients, the number of days post symptom onset were recorded, and remnant Sofia-extracted specimens were tested using the CDC’s Influenza A+B RT-PCR.
The distribution of time-to-result (TTR) for positive patients relative to their ages is shown in Table 1.
Of 727 positive test results, 326 were reported by Sofia 2 in 3 minutes—44.8% of the total number of positives identified! As shown in the last two columns in Table 1, a total of 574 positive results had been identified by 5 minutes (79.0%), 645 by 8 minutes (88.7%), 677 within 10 minutes (93.1%), and 50 more (only 6.9% of the positives) at 15 minutes. All negatives (2,204) were reported at 15 minutes.
Especially noteworthy were the following:
- Relationship of time of post symptom onset to time-to-result (TTR). The post symptom-onset was recorded for 488 patients, of which 97 were positive for influenza A or B. Of these positive results, 46 (47.4%) were obtained in three minutes, with an average of 2.37 days post symptom onset for these patients, and 34 (35.1%) were obtained in five minutes for patients with an average of 3.54 days post symptom onset.
- Relationship of PCR Ct values to TTR. PCR results were obtained for 965 remnant samples, of which 153 were positive by both PCR and Sofia. Ninety-two (92) of these Sofia-positive results were obtained in 3 minutes and nearly 60% of these (54) had PCR Ct values <30, compared to only 15 of the Sofia-positive results obtained in 5 minutes.
- Rapid TTR for Children, Infant to <12 Years of Age. Three hundred and thirty-eight (338) children tested positive for influenza. Notably, 276 of these children tested positive in five minutes or less (and 175 of these in 3 minutes or less)!
- Association of TTR for Patients of All Ages Examined. As shown in Table 1, although the sample number of more aged patients is small, the trend holds. Even 82% of patients 65 years or older who tested positive were detected within 5 minutes or less.
During the peak influenza season, moving patients promptly through the busy clinics and waiting rooms is a serious challenge for healthcare facilities. This is especially true during severe influenza epidemics, as experienced during the 2017-2018 respiratory season, and even more dramatically important during pandemic years such as 2009. Also important is timely administration of antiviral treatment for influenza-positive patients, especially those at high risk. Influenza antiviral medications are authorized for use and deemed most effective when administered within 48 hours of onset of symptoms, which further emphasizes the importance of early diagnosis. Moreover, identification of influenza infections in the hospital setting becomes critical in the context of hospital admissions, inpatient care, and infection control.
This study shows that Sofia 2 and the Sofia Influenza A+B FIA detect approximately 80% of influenza-positive nasal swab specimens in 5 minutes or less. In light of these findings, Sofia 2 provides timely identification of most patients with influenza infections, allowing for effective clinical management, and expedited patient flow through healthcare facilities.
*Sofia Influenza A+B FIA meets and exceeds the new FDA reclassification requirements for marketing in the United States.