https://doi.org/10.4046/trd.2021.

0033
ORIGINAL ARTICLE ISSN: 1738-3536(Print)/2005-6184(Online) • Tuberc Respir Dis 2021;84:226-236

Diagnostic Accuracy of the Quidel Sofia

Rapid Influenza Fluorescent Immunoassay
in Patients with Influenza-like Illness:
A Systematic Review and Meta-analysis

Jonghoo Lee, M.D., Ph.D.1,* , Jae-Uk Song, M.D., Ph.D.2,* and Yee Hyung Kim, M.D., Ph.D.3
1
Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Jeju, 2Division
of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan
University School of Medicine, Seoul, 3Department of Pulmonary and Critical Care Medicine, Kyung Hee University Hospital at
Gangdong, Kyung Hee University School of Medicine, Seoul, Republic of Korea

Background: Although the Quidel Sofia rapid influenza fluorescent immunoassay (FIA) is widely used to identify
influenza A and B, the diagnostic accuracy of this test remains unclear. Thus, the objective of this study was to determine
the diagnostic performance of this test compared to reverse transcriptase-polymerase chain reaction.
Methods: A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register.
Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary receiver-operating characteristic
curve (HSROC) of this test for identifying influenza A and B were determined using meta-analysis. A sensitivity subgroup
analysis was performed to identify potential sources of heterogeneity within selected studies.
Results: We identified 17 studies involving 8,334 patients. Pooled sensitivity, specificity, and DOR of the Quidel Sofia
rapid influenza FIA for identifying influenza A were 0.78 (95% confidence interval [CI], 0.71–0.83), 0.99 (95% CI, 0.98–
0.99), and 251.26 (95% CI, 139.39–452.89), respectively. Pooled sensitivity, specificity, and DOR of this test for identifying
influenza B were 0.72 (95% CI, 0.60–0.82), 0.98 (95% CI, 0.96–0.99), and 140.20 (95% CI, 55.92–351.54), respectively. The
area under the HSROC for this test for identifying influenza A was similar to that for identifying influenza B. Age was
considered a probable source of heterogeneity.
Conclusion: Pooled sensitivities of the Quidel Sofia rapid influenza FIA for identifying influenza A and B did not quite
meet the target level (≥80%). Thus, caution is needed when interpreting data of this study due to substantial between-
study heterogeneity.

Keywords: Influenza, Human; Diagnosis; Point-of-Care Testing; Fluorescence Polarization Immunoassay

Address for correspondence: Jonghoo Lee, M.D., Ph.D.

Department of Internal Medicine, Jeju National University Hospital, Jeju National University School of Medicine, Aran 13 gil 15, Jeju 63241, Republic of
Korea
Phone: 82-64-717-1601, Fax: 82-64-717-1131, E-mail: lovlet@jejunu.ac.kr
*These authors contributed equally to this work.
Received: Feb. 24, 2021, Revised: Apr. 4, 2021, Accepted: May. 3, 2021, Published online: May. 13, 2021

cc It is identical to the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/).

Copyright © 2021
The Korean Academy of Tuberculosis and Respiratory Diseases.

226
The Quidel Sofia influenza FIA

Introduction of 2020 was performed. Search terms for influenza included

“Influenza, Human” [MeSh] OR “Influenza A virus” OR “In-
Influenza, an acute respiratory viral infection caused by fluenza B virus” OR “influenza” OR “flu”. Search terms for the
influenza A or B virus, occurs mainly in the winter months tests included “rapid test*” OR “rapid diagnos*” OR “point-of-
throughout the world. It causes significant morbidity and care test*” OR “immunoassay*” OR “immunochromatographic
mortality worldwide1,2. Adequate antiviral therapy can shorten test*” OR “influenza FIA” OR “Quidel Sofia Influenza” OR “Rapid
the time of illness and reduce the duration of hospitalization Detection Flu”. As this study was a systematic review of pub-
and the risk of complications from influenza infections3. Clini- lished articles, neither informed consent nor ethics approval
cal benefit of antiviral therapy is the greatest when it is started was required. A manual search of references listed in relevant
soon after the onset of influenza illness4. Therefore, rapid and review articles was also conducted.
accurate diagnosis of influenza infection is necessary in clini-
cal practice. 2. Study selection
Although polymerase chain reaction (PCR) has been used
as the reference standard for diagnosing viral infections, per- We included studies that met the following inclusion crite-
forming PCR is relatively expensive. In addition, it requires ria: (1) full-length reports published in peer-reviewed English
technical expertise5. Alternatively, point-of-care rapid influ- language journals; (2) studies that evaluated the performance
enza diagnostic tests (RIDTs) can detect viral antigens by im- of the Quidel Sofia rapid influenza FIA, compared to a refer-
munoassay and provide quick results within 30 minutes. They ence standard; (3) studies that included patients with influ-
can facilitate antiviral therapy, reduce additional diagnostic enza-like illness; and (4) studies that provided sufficient data
tests and hospitalization therapy, and induce appropriate to calculate absolute numbers of true-positive, false-positive,
infection control measures6,7. A recent systematic review and false-negative, and true-negative results. Review articles, case
meta-analysis for 162 diagnostic accuracy studies of RIDTs reports, commentaries, and studies reporting outcomes with-
has revealed that traditional RIDTs have specificities higher out raw data or peer review were excluded. Demographics
than 98% with poor sensitivities (54.4% for influenza A and and underlying diseases of participants were not restricted.
53.2% for influenza B)5. Two classes of RIDTs, automated Influenza-like illness was defined as fever ≥38°C and any
immunochromatographic antigen detection tests (digital im- signs/symptoms of respiratory tract infection (e.g., cough, spu-
munoassays [DIAs]) and rapid nucleic acid amplification tests tum, sore throat, wheezing, etc.). We allowed the followings
(NAATs), have been used since 20115. Pooled sensitivities for as specimens: nasopharyngeal aspirates, swabs, or washes;
DIAs (80.0% for influenza A and 76.8% for influenza B) and nasal aspirates, swabs, or washes; saliva; and throat swabs. A
rapid NAATs (91.6% for influenza A and 95.4% for influenza B) reference standard was either a commercial reverse transcrip-
are significantly higher than those for traditional RIDTs5. tase–polymerase chain reaction (RT-PCR) or a laboratory-
As a type of DIA, the Quidel Sofia rapid influenza fluores- developed RT-PCR.
cent immunoassay (FIA) (Quidel Corp., San Diego, CA, USA)
is a point-of-care test to detect influenza A and B in less than 3. Data extraction and quality assessment
15 minutes using a compact instrument (Sofia analyzer). Al-
though the performance characteristics of this test to detect Two authors independently reviewed potentially relevant
seasonal influenza virus strains have been established, the studies and each study according to predefined eligibility cri-
diagnostic accuracy of the Quidel Sofia rapid influenza FIA is teria, after which data were extracted. Any disagreements that
not yet fully known. Thus, the objective of this systematic re- arose during the process of study selection or data extraction
view and meta-analysis of clinical trial data was to investigate were resolved by discussion. A predefined form was used to
diagnostic properties of the Quidel Sofia rapid influenza FIA extract data from each study. The following data from each
in patients with influenza like illness. study included in the meta-analysis were extracted: author,
year of publication, study design, place of study, number of
participants, age, proportion of children, sex, study period,
Materials and Methods type of reference standard, type of specimens, and type of
population. As recommended by the Cochrane Collabora-
1. Data sources and search strategy tion, the Quality Assessment of Diagnostic Accuracy Studies
(QUADAS)-2 tool was used to assess the risk of bias in diag-
This meta-analysis is reported in accordance with the nostic test accuracy9. Discrepancies were resolved by consen-
Preferred Reporting Items for Systematic reviews and Meta- sus between the two authors.
Analyses of Diagnostic Test Accuracy Studies statement8. A
comprehensive search of three electronic databases (MED-
LINE, EMBASE, and the Cochrane Central Register) up to July

www.e-trd.org https://doi.org/10.4046/trd.2021.0033 227

 J Lee et al.

4. Data synthesis and statistical analysis vs. non-specific season), and study population (children vs.
adult). Pooled sensitivity and specificity estimates were calcu-
For diagnostic meta-analysis, random effects meta-analyses lated for each covariate. To investigate the effect of study qual-
were performed to generate pooled estimates with 95% con- ity, sensitivity analyses were performed. A p-value <0.05 was
fidence intervals (CIs). Numbers of patients were extracted considered statistically significant. All statistical analyses were
with true-positive, false-positive, false-negative, and true nega- performed with Stata statistical software version 14.2 (Stata
tive test results either directly or indirectly through a recalcula- Corp LP, College Station, TX, USA) and Review Manager ver-
tion based on reported measures of accuracy in combination sion 5.3 (Nordic Cochrane Centre, The Cochrane Collabora-
with the prevalence and sample size of the included study. tion, Copenhagen, Denmark).
Pooled sensitivity and specificity, positive likelihood ratio
(PLR), negative likelihood ratio (NLR), diagnostic odds ratio
(DOR), and area under the receiver-operating characteristic Results
curve (AUC) were calculated as pooled estimates with a 95%
CI10. Hierarchical summary receiver-operating characteristic 1. Study search, characteristics of included studies, and
curves (HSROCs) were also constructed. The heterogeneity quality of included studies
was evaluated using the Higgins I2 statistics on a scale of 0–1.
An I2>0.5 indicated a substantial level of between-study het- The literature search process is shown in Figure 1. Initially,
erogeneity. To assess effects of potential sources of heteroge- 432 articles from PubMed, 1,310 articles from EMBASE, 356
neity, subgroup analyses were performed using the following articles from the Cochrane library, and an additional article
covariates to the model: study design (single vs. multicenter), from hand-searching were identified. After removing dupli-
number of participants (≥250 vs. <250), study period (influenza cate articles, 1,664 potentially eligible articles were screened.

2,098 Records identified through database searching

432 PubMed
1,310 EMBASE
356 Cochrane Central Register

435 Records owing to duplication

1 Additional article identified from

hand searching

1,664 Records screened

1,629 Records excluded after screening

titles and abstracts

35 Full-text articles assessed

for eligibility

15 Full-text articles excluded with following

reasons

8 Other fluorescent immunoassay as index test

2 Other reference standard other than RT-PCR
1 Absence of control
4 Abstract

20 Studies included in qualitative synthesis

3 Construction of 2 2 tables impossible

Figure 1. Flow diagram showing the
identification of eligible studies. RT-PCR:
17 Studies included in quantitative reverse transcription polymerase chain
synthesis/meta-analysis
reaction.

228 Tuberc Respir Dis 2021;84:226-236 www.e-trd.org

 Table 1. Characteristics of studies included in the meta-analysis
No. of Age (yr) Proportion
Male Reference Type of
Study Design Country partici­ (mean or of children Study period Population

www.e-trd.org
(%) standard specimens
pants median) (%)
Bruning11, 2014 Single Netherlands 68 NA 100 NA December 2013 RT-PCR NP swabs or Children (aged
center to February aspirates 0–16 years old)
study 2014 with symptoms of
respiratory illness
The Quidel Sofia influenza FIA

admitted to either
pediatric ICU or infant
ward
Busson12, 2017 Multi- Belgium 267 3.5 66.8 46.6 January 2015 to RT-PCR NP swabs, NP Children and adult
center March 2015 aspirates, patients admitted with
study broncho- suspected influenza
alveolar
lavages
Dunn13, 2014 Single USA 240 NA NA NA January 2013 to RT-PCR Nasal wash Symptomatic patients
center April 2013 under 18 years of age

https://doi.org/10.4046/trd.2021.0033
study
Gomez14, 2016 Single Spain 1,065 NA NA NA November 2013 RT-PCR NP swabs, NP Adult (80.6%)
center to April 2014 aspirates and pediatric
study (19.4%) patients
with respiratory
tract symptoms
hospitalized
Hazelton15, Single Australia 202 56 0 NA NA RT-PCR NP swabs Patients ≥16 yr with an
2015 center influenza-like illness
study
Hazelton16, Single Australia 209 56 0 NA NA RT-PCR Throat swabs, Patients with an
2015 center NP swabs, or influenza-like illness
study nose swabs
Kammerer17, Multi- USA 871 NA 90.0 NA 2012 to 2014 RT-PCR Nasal swabs Patients with an
2016 center influenza-like illness
study (>70% of patients were
under the age of 25
years)
Lee18, 2012 Single South Korea 169 27.7 NA 56.4 December 2011 RT-PCR and NP swabs Patients with an
center to February virus culture influenza-like illness
study 2012
Continued

229
230
Table 1. Continued
No. of Age (yr) Proportion
Male Reference Type of
Study Design Country partici­ (mean or of children Study period Population
(%) standard specimens
pants median) (%)
Leonardi19, Single USA 141 NA 48.0 NA Influenza RT-PCR NP swabs Frozen original
2013 center seasons influenza-positive
study from 2006 to specimens and
2011 and the prospective
2011–2012 specimens
Lewandrowski20, Multi- USA 2,047 NA 93.1 52.9 NA RT-PCR or virus Nasal swabs Patients with an
2013 center culture and NP swabs influenza-like illness
study or aspirates
Noh21, 2015 Multi- South Korea 391 40 NA 37.6 December 2012 RT-PCR NP swabs Adult patients with
center to April 2013 influenza-like illness
study
Ryu22, 2016 Single South Korea 314 30.4 NA 51.9 January 2014 to RT-PCR NP swabs Patients showing
center February 2015 influenza-like
study symptoms
Ryu23, 2018 Single South Korea 158 23.8 58.7 NA 2016 RT-PCR NP swabs Patients with an
center influenza-like illness
study between neonates
and 90 years old
Selove24, 2016 Single USA 1,649 57 15.3 50 September 2014 RT-PCR Nasal aspirates Patients with an
center to May 2015 influenza-like illness
study
Tuttle25, 2015 Single Germany 686 3.5 for 100 55 December 2012 RT-PCR or virus NP or nasal Patients aged 0–18 years
center mean, 1.8 to April 2013 culture swabs with an influenza-like
study for me- illness
dian
Yang26, 2018 Single Taiwan 109 38.8 0 56.9 January 2012 RT-PCR and/or NP or throat Patients who presented
center to December virus culture swabs at out-patient clinics
study 2013 or the emergency

Tuberc Respir Dis 2021;84:226-236

department with
influenza-like illness
Yoon27, 2017 Single South Korea 385 46 NA 46.5 December 2014 RT-PCR NP swabs or Patients with an
center to April 2015 saliva influenza-like illness
study
NA: not available; RT-PCR: reverse transcription polymerase chain reaction; ICU: intensive care unit.

www.e-trd.org
J Lee et al.
The Quidel Sofia influenza FIA

After reviewing titles and ab­stracts, 1,629 search records were 2. Diagnostic accuracy of the Quidel Sofia rapid
removed and the remaining 35 articles were eligible for full influenza FIA to identify influenza A and B
text reading. Fifteen articles were excluded for reasons shown
in Figure 1. With quantitative synthesis, seventeen studies Figures 3 and 4 show paired forest plots of sensitivity and
were included in our final analysis11-27. specificity of the Quidel Sofia rapid influenza FIA for detecting
Features of included studies are summarized in Table 1. For influenza A and B. The pooled sensitivity across studies of the
influenza A, we identified 17 studies involving 8,334 partici- Quidel Sofia rapid influenza FIA for identifying influenza A
pants. For influenza B, sixteen studies involving 7,909 subjects was 0.78 (95% CI, 0.71–0.83), with a pooled specificity of 0.99
met the defined inclusion criteria. One study assessed influ- (95% CI, 0.98–0.99). The pooled PLR and NLR were 56.99 (95%
enza A infection only21. The number of patients in each trial CI, 31.87–101.90) and 0.23 (95% CI, 0.18–0.29), respectively.
ranged from 68 to 1,649. All studies were published between The DOR for influenza A was 251.26 (95% CI, 139.39–452.89).
2012 and 2018. Most studies evaluated combined populations The pooled sensitivity across studies for identifying influ-
of adults and children. enza B was 0.72 (95% CI, 0.60–0.82), with a pooled specificity
Results of the QUADAS-2 assessment are shown in Figure of 0.98 (95% CI, 0.96–0.99). The pooled PLR and NLR were
2. For patient selection, the index test, and the reference stan- 40.08 (95% CI, 17.26–93.07) and 0.29 (95% CI, 0.19–0.42),
dard domain, more than 50% of included studies were judged respectively. The DOR for influenza B was 140.20 (95% CI,
to have a low risk of bias. However, for the study flow and the 55.92–351.54). The pooled sensitivity and specificity of the
timing domain, the risk of bias was high or unclear for 52.9% Quidel Sofia rapid influenza FIA for identifying influenza A
of the included studies because of unclear intervals between and B were not significantly different (p=0.341 for sensitivity
the index test and the reference standard. Considering our and p=0.206 for specificity). Figure 5 shows HSROCs for the
inclusion criteria, we had little concern for the applicability of index test. AUCs of the Quidel Sofia rapid influenza FIA for
results from selected studies for each domain. identifying influenza A and influenza B were similar (0.96 with
95% CI of 0.94–0.98 for influenza A vs. 0.95 with 95% CI of
0.92–0.96 for influenza B, p=0.166).

A Applicability B
Risk of bias concerns
Patient selection
Reference standard

Reference standard

Index test
Patient selection

Patient selection

Reference standard
Flow and timing

Flow and timing

Index test

Index test

0% 25% 50% 75% 100% 0% 25% 50% 75% 100%

Risk of bias Applicability concerns

Bruning High Unclear Low

Busson
Dunn
Gomez
Hazelton (A)
Hazelton (B)
Kammerer
Lee
Leonardi
Lewandrowski
Noh
Ryu (A)
Ryu (B)
Selove
Tuttle
Yang
Yoon
Figure 2. (A) Summary of risk of bias in included studies. (B) Risk of
High Unclear Low bias graph for included studies.

www.e-trd.org https://doi.org/10.4046/trd.2021.0033 231

 J Lee et al.

Study, year No. TP FP FN TN Sensitivity (95% CI) Specificity (95% CI)

11
Bruning , 2014 68 6 2 3 57 0.67 (0.30 0.93) 0.97 (0.88 1.00)
Busson12, 2017 267 41 1 17 208 0.71 (0.57 0.82) 1.00 (0.97 1.00)
Dunn13, 2014 240 46 17 2 175 0.96 (0.86 0.99) 0.91 (0.86 0.95)
Gomez14, 2016 1,057 244 10 80 723 075 (0.70 0.80) 0.99 (0.98 0.99)
Hazelton15, 2015 209 21 3 8 177 0.71 (0.54 0.85) 0.98 (0.95 1.00)
Hazelton16, 2015 202 25 3 10 164 0.72 (0.53 0.87) 0.98 (0.95 1.00)
Kammerer17, 2016 871 115 19 36 701 0.76 (0.69 0.83) 0.97 (0.96 0.98)
Lee18, 2012 169 60 0 13 96 0.82 (0.71 0.90) 1.00 (0.96 1.00)
Leonardi19, 2013 141 72 0 18 51 0.80 (0.70 0.88) 1.00 (0.93 1.00)
Lewandrowski20, 2013 1,461 260 7 73 1,121 0.78 (0.73 0.82) 0.99 (0.99 1.00)
Noh21, 2015 391 145 9 51 186 0.74 (0.67 0.80) 0.95 (0.91 0.98)
Ryu22, 2016 314 66 0 23 225 0.74 (0.64 0.83) 1.00 (0.98 1.00)
Ryu23, 2017 158 69 2 4 83 0.95 (0.87 0.98) 0.98 (0.92 1.00)
Selove24, 2016 1,649 103 11 145 1,390 0.42 (0.35 0.48) 0.99 (0.99 1.00)
Tuttle25, 2015 643 50 4 12 577 0.81 (0.69 0.90) 0.99 (0.98 1.00)
Yang26, 2017 109 27 8 6 68 0.82 (0.65 0.93) 0.89 (0.80 0.95)
Yoon27, 2017 385 89 0 31 265 0.74 (0.65 0.82) 1.00 (0.99 1.00)

Combined 0.78 (0.71 0.83) 0.99 (0.98 0.99)

Q=177.06, Q=203.71,
df=16.00, df=16.00,
p=0.37 p<0.001
2 2
I =90.96 0.3 1.0 I =92.15 0.8 1.0
(87.75 94.18) (89.47 94.82)

Figure 3. Paired forest plots of sensitivity and specificity of the Quidel Sofia rapid influenza fluorescent immunoassay for detecting influenza A.
TP: true positive; FP: false positive; FN: false negative; TN: true negative; CI: confidence interval.

Study, year No. TP FP FN TN Sensitivity (95% CI) Specificity (95% CI)

11
Bruning , 2014 68 4 6 6 52 0.40 (0.12 0.74) 0.90 (0.79 0.96)
Busson12, 2017 267 6 3 5 253 0.55 (0.23 0.83) 0.99 (0.97 1.00)
Dunn13, 2014 240 51 55 1 133 0.98 (0.90 1.00) 0.71 (0.64 0.77)
Gomez14, 2016 1,057 8 79 8 962 0.50 (0.25 0.75) 0.91 (0.92 0.94)
Hazelton15, 2015 209 2 2 4 201 0.33 (0.10 0.65) 0.99 (0.97 1.00)
Hazelton16, 2015 202 4 1 8 189 0.33 (0.04 0.78) 0.99 (0.96 1.00)
Kammerer17, 2016 871 92 74 45 660 0.67 (0.59 0.75) 0.90 (0.88 0.92)
Lee18, 2012 168 56 0 16 96 0.78 (0.66 0.87) 1.00 (0.96 1.00)
Leonardi19, 2013 78 22 0 5 51 0.81 (0.62 0.94) 1.00 (0.93 1.00)
Lewandrowski20, 2013 1,461 211 19 34 1,197 0.86 (0.81 0.90) 0.98 (0.98 0.99)
Ryu22, 2016 314 85 0 18 211 0.83 (0.74 0.89) 1.00 (0.98 1.00)
Ryu23, 2017 145 55 4 5 81 0.92 (0.82 0.97) 0.95 (0.88 0.99)
Selove24, 2016 1,649 18 7 30 1,594 0.38 (0.24 0.53) 1.00 (0.99 1.00)
Tuttle25, 2015 686 64 6 25 591 0.72 (0.61 0.81) 0.99 (0.98 1.00)
Yang26, 2017 109 5 12 2 90 0.71 (0.29 0.96) 0.88 (0.80 0.94)
Yoon27, 2017 385 22 1 7 355 0.76 (0.56 0.90) 1.00 (0.98 1.00)

Combined 0.72 (0.60 0.82) 0.98 (0.96 0.99)

Q=116.12, Q=701.37,
df=15.00, df=15.00,
p<0.001 p<0.001
2 2
I =87.08 0.0 1.0 I =97.86 0.6 1.0
(81.82 92.34) (97.36 98.36)

Figure 4. Paired forest plots of sensitivity and specificity of the Quidel Sofia rapid influenza fluorescent immunoassay for detecting influenza B.
TP: true positive; FP: false positive; FN: false negative; TN: true negative; CI: confidence interval.

232 Tuberc Respir Dis 2021;84:226-236 www.e-trd.org

The Quidel Sofia influenza FIA

A B
1.0 1.0

0.8 0.8
Sensitivity

Sensitivity
0.6 0.6
Observed data Observed data
Summary operating point Summary operating point
0.4 Sensitivity=0.78 (0.71 0.83) 0.4 Sensitivity=0.72 (0.60 0.82) Figure 5. Hierarchical summary receiver
Specificity=0.99 (0.98 0.99) Specificity=0.98 (0.96 0.99)
HSROC curve HSROC curve
operating characteristic curves of the
0.2 AUC=0.96 (0.94 0.98)
0.2 AUC=0.95 (0.92 0.96) Quidel Sofia rapid influenza fluorescent
95% Confidence contour 95% Confidence contour immunoassay for detecting influenza
95% Prediction contour 95% Prediction contour A (A) and influenza B (B). HSROC: hi-
0.0 0.0 erarchical summary receiver-operating
1.0 0.8 0.6 0.4 0.2 0.0 1.0 0.8 0.6 0.4 0.2 0.0 characteristic curve; AUC: area under the
Specificity Specificity receiver-operating characteristic curve.

3. Subgroup and sensitivity analyses for the Quidel pected influenza5. For diagnosis of influenza A and B, pooled
Sofia rapid influenza FIA to identify influenza A and sensitivities of DIAs and the Quidel Sofia rapid influenza FIA
B were 80.0% and 76.8%, respectively5. In the present study,
compared to RT-PCR, the pooled sensitivity of the Quidel So-
The Higgins I2 statistics proved significant heterogeneity for fia rapid influenza FIA to identify influenza A and B were 78%
both the sensitivity (0.91 with 95% CI of 0.88–0.94 for influen- and 72%, respectively. Our findings did not quite reach the
za A and 0.87 with 95% CI of 0.82–0.92 for influenza B) (Figure target level of sensitivity required by the FDA. Therefore, some
3) and specificity (0.92 with 95% CI of 0.90–0.95 for influenza patients with negative results on the Quidel Sofia rapid influ-
A and 0.98 with 95% CI of 0.97–0.98 for influenza B) (Figure 4). enza FIA might still need be confirmed to have an influenza
Subgroup analyses were also performed to investigate poten- infection by an alternative diagnostic method that is more
tial sources of heterogeneity (Table 2). The sensitivity of the sensitive.
Quidel Sofia rapid influenza FIA was significantly increased Influenza type could affect the accuracy of RIDTs. A previ-
when tests were performed in children (0.86 with 95% CI of ous meta-analysis has revealed that overall RIDTs show an
0.78–0.92 for influenza A and 0.79 with 95% CI of 0.71–0.85 for increased sensitivity for detecting influenza A than for detect-
influenza B) than when tests were performed in adults (0.74 ing influenza B (64.6% vs. 52.2%; p=0.05)29. Influenza A virus
with 95% CI of 0.67–0.79 for influenza A and 0.33 with 95% CI can cause more severe disease, higher influenza-associated
of 0.10–0.65 for influenza B). hospitalization, and more death than influenza B virus 29.
In sensitivity analysis to investigate the influence of each Higher virulence of influenza A might lead to higher viral bur-
individual study on the overall analysis estimate, one study den, which can result in a relatively higher sensitivity19. In the
had a significantly different sensitivity than other studies on present study, although the pooled sensitivity of the Quidel
influenza A24. Even after exclusion of that study24, the pooled Sofia rapid influenza FIA for identifying influenza A tended to
sensitivity across studies on influenza A was similar to that be higher than that for identifying influenza B, the difference
of overall studies (0.79 with 95% CI of 0.75–0.82). Instead, the between the two was not statistically significant.
heterogeneity decreased (0.51 with 95% CI of 0.23–0.79). The type of specimen might also lead to difference in diag-
nostic performances. Although we tried to perform subgroup
analyses according to specimens, we could only find two
Discussion suitable studies26,27. One study compared the results of test-
ing throat and NP swabs specimens26. The sensitivity for each
According to the rule set by the Food and Drug Adminis- type of specimens was 72% and 100% for detecting influenza
tration (FDA), RIDTs for influenza A and B are required to A and 71% and 100% for detecting influenza B, respectively26.
have a sensitivity of at least 80% and a specificity of at least In the other study, sensitivities of the Quidel Sofia rapid in-
95% compared to an FDA-cleared nucleic acid based-test or fluenza FIA with saliva specimens were comparable to those
other currently appropriate tests and FDA accepted compara- with NP swabs specimens27. The sensitivity of the test with NP
tor methods other than a correctly performed viral culture swabs samples was significantly higher than that with saliva
method28. A recent systematic review and meta-analysis per- samples for detecting influenza A (74.2% vs. 59.2%, p=0.014)
formed a search up to May 2017 and compared accuracies of and similar between two samples in influenza B (75.9% vs.
traditional RIDTs, rapid NAATs, and DIAs in patients with sus- 65.5%, p=0.387)27. Based on results of these two studies regard-

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 J Lee et al.

Table 2. Subgroup analysis for the diagnostic performance of the Quidel Sofia rapid influenza fluorescent immunoassay
No. of No. of Sensitivity Specificity
Variable
studies patients Adjusted (95% CI) p-value Adjusted (95% CI) p-value
Studies that evaluated influenza A
Study design
Single center 13 5,344 0.79 (0.72–0.85) 0.583 0.99 (0.98–1.00) 0.574
Multicenter 4 2,990 0.75 (0.63–0.87) 0.99 (0.97–1.00)
No. of participants
≥250 9 7,038 0.72 (0.65–0.79) 0.173 0.99 (0.98–1.00) 0.114
<250 8 1,296 0.84 (0.77–0.90) 0.97 (0.95–0.99)
Study period
Influenza season 11 3,784 0.79 (0.73–0.86) 0.440 0.99 (0.98–1.00) 0.610
Non-specific season 6 4,550 0.74 (0.64–0.85) 0.99 (0.97–1.00)
Population
Children 3 951 0.86 (0.78–0.92) 0.019 0.97 (0.96–0.98) 0.332
Adults 2 593 0.74 (0.67–0.79) 0.97 (0.94–0.98)
Studies that evaluated influenza B
Study design
Single center 13 5,310 0.72 (0.59–0.84) 0.937 0.98 (0.97–1.00) 0.228
Multicenter 3 2,599 0.73 (0.48–0.97) 0.97 (0.93–1.00)
No. of participants
≥250 8 6,690 0.69 (0.53–0.84) 0.730 0.99 (0.97–1.00) 0.432
<250 8 1,219 0.75 (0.60–0.90) 0.97 (0.94–1.00)
Study period
Influenza season 10 3,372 0.76 (0.63–0.89) 0.403 0.98 (0.96–1.00) >0.999
Non-specific season 6 4,537 0.65 (0.45–0.85) 0.98 (0.96–1.00)
Population
Children 3 994 0.79 (0.71–0.85) <0.001 0.92 (0.90–0.94) 0.005
Adults 1 202 0.33 (0.10–0.65) 0.99 (0.97–1.00)
CI: confidence interval.

ing different specimens used for detection, the sensitivity of In the present study, pooled sensitivities of the Quidel Sofia
the Quidel Sofia rapid influenza might be lower for detecting rapid influenza FIA were significantly higher in children (by
influenza A and B viruses using oropharynx or saliva samples. approximately 12% higher for influenza A and 46% higher for
The Quidel Sofia rapid influenza FIA has advantages of be- influenza B) than in adults. The duration of influenza virus
ing simple, fast, and easy for viral testing. The pooled specific- shedding is commonly measured from the time of symptom
ity of this tool in our study was approximately 98%, above the onset to the time of shedding cessation. Children have been
target level for detecting both influenza A and B. From these reported to have a tendency to shed the virus for a longer du-
findings, we believe that clinicians could diagnose influenza ration than adults31. Longer duration of influenza virus shed-
with assurance on the basis of a positive result from the Quidel ding in children might be associated with a higher sensitivity
Sofia rapid influenza FIA. of this test in children than in adults. However, because the
Large heterogeneities are commonly reported for system- number of studies that distinguished children from adults was
atic reviews of studies on diagnostic test accuracy30. Substan- very small, our findings should be interpreted with caution.
tial between-study heterogeneity among enrolled studies was The sensitivity observed in one study24 was significantly
also observed in the present study. Age is a probable source lower than that observed in most studies. In that study, an
of heterogeneity for between-studies in pooled estimates. older patient population (median age of 57 years) and a study

234 Tuberc Respir Dis 2021;84:226-236 www.e-trd.org

The Quidel Sofia influenza FIA

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