Health care
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B r i e f r e p o r t
Clinical Infectious Diseases
BRIEF REPORT • cid 2021:XX (XX XXXX) • 1
Self-Collected Oral Fluid and Nasal
Swabs Demonstrate Comparable
Sensitivity to Clinician Collected
Nasopharyngeal Swabs for Coronavirus
Disease 2019 Detection
N. Kojima,1, F. Turner,2 V. Slepnev,2 A. Bacelar,2 L. Deming,2 S. Kodeboyina2 and
J.D. Klausner3
1Department of Medicine, University of California Los Angeles, Los Angeles, California, USA,
2Curative Inc., Menlo Park, California, USA, and 3Department of Epidemiology, Fielding School
of Public Health, University of California Los Angeles, Los Angeles, CA
We compared self-collected oral fluid swab specimens with
and without clinician supervision, clinician-supervised
self-collected anterior nasal swab specimens, and clinician-
collected nasopharyngeal swab specimens for the detection
of severe acute respiratory syndrome coronavirus 2 (SARS-
CoV-2). Supervised oral fluid and nasal swab specimens per-
formed similarly to clinician-collected nasopharyngeal swab
specimens. No sample type could detect SARS-CoV-2 infec-
tions amongst all positive participants.
Keywords. COVID19; SARS-CoV-2; oral; nasal;
pharyngeal.
The 2019 severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2), which causes coronavirus disease-19 (COVID-
19), was first detected in Wuhan, China in late 2019 [1]. On
January 20, 2020, the first case of COVID-19 was reported in
the United States [2]. After more than 118 000 cases were de-
tected in 114 countries with over 4000 deaths, the World Health
Organization declared COVID-19 pandemic [3].
The ideal specimen for the detection of SARS-CoV-2 is un-
known. Currently, trained health care professionals and special-
ized collection devices are recommended for the collection of
nasopharyngeal swab specimens [4]. That requires staffing of
health care workers, who could be performing other duties, and
the use of personal protective equipment (PPE), during a se-
vere shortage. Additionally, patients report discomfort during
nasopharyngeal swab specimen collection, which may deter pa-
tients from being tested [5]. The use of anterior nasal swab and
oral fluid specimens could greatly increase health worker safety
and the number of persons tested. We recruited participants re-
cently tested for SARS-CoV-2 to assess differences in specimen
types and collection methods for SARS-CoV-2 testing.
METHODS
We recruited participants who had recently tested for SARS-
CoV-2 at a CLIA-certified, high-complexity laboratory. The pa-
tient population and recruitment methods are described below.
Testing Population
We recruited nonhospitalized persons tested for SARS-CoV-2
in Los Angeles County, California, that included symptomatic
adults older than 65 years of age, those with a chronic disease,
first responders, and law enforcement officers who may have
been exposed to SARS-CoV-2. We aimed to recruit 30 persons
who tested negative for SARS-CoV-2 and 30 persons who tested
positive. Participants were contacted via telephone or email and
provided with details of the study. Participants were given a
study information sheet and gave verbal informed consent.
Specimen Collection Methods
We obtained unsupervised self-collected oral fluid swab speci-
mens, clinician-supervised self-collected oral fluid swab speci-
mens, clinician-supervised self-collected anterior nasal swab
specimens, and clinician-collected posterior nasopharyngeal
swab specimens.
For the unsupervised self-collected oral fluid swab speci-
mens, we provided written instructions with the testing kit,
which included a sterile swab and a tube with an RNA preserva-
tive media (DNA/RNA Shield™ solution, Zymo Research Corp.,
Irvine, CA). Participants were instructed to cough deeply 3 to
5 times collecting any phlegm or secretions in their mouth, rub
the swab on the inside of both cheeks, above and below the
tongue, on both outer [gums], and on the hard palate for a total
of 20 seconds to ensure the swab was saturated with oral fluid.
Following that, participants were instructed to place the swab
into the tube, secure the lid, invert the tube 3 to 5 times, and
place the capped tube into a collection bag. Unsupervised spec-
imen collection was observed by a clinician but from a greater
distance than the supervised collections, and the clinician did
not provide any feedback to the participant. For the clinician-
supervised self-collected oral fluid swab specimens, the same
instructions were provided and a clinician provided real time
feedback. Without clinician feedback, some unsupervised pa-
tients did not cough before self-collecting their sample.
For the clinician-supervised self-collected nasal swab spec-
imen, a kit was provided that included a flocked swab (Copan
Diagnostics, Murrieta, CA) and the same collection media as
Received 15 May 2020; editorial decision 19 June 2020; published online 19 October 2020.
Correspondence: N. Kojima, Department of Medicine at UCLA, 10833 Le Conte Ave, Los
Angeles, CA 90095 (nkojima@ucla.edu).
Clinical Infectious Diseases® 2021;XX(XX):1–4
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
DOI: 10.1093/cid/ciaa1589
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mailto:nkojima@ucla.edu?subject=
2 • cid 2021:XX (XX XXXX) • BRIEF REPORT
described above The participant was verbally instructed to in-
sert the swab into each nostril to the depth of 3–4 cm, rotate
the swab for 5–10 seconds, place the swab into the collection
tube, invert the tube 3–5 times, and place the capped tube into
a collection bag. Posterior nasopharyngeal swab specimens
were collected by a clinician with the recommended medical
technique using nasopharyngeal swabs (Becton Dickinson and
Company, Franklin Lakes, NJ) [6].
Surveying and Sampling
We collected samples in private areas of participant homes.
We collected symptom data immediately prior to sampling.
Sampling methods are detailed above. For each patient, all sam-
ples were collected within a 30-minute window. Unsupervised
self-collected oral fluids samples were collected first, followed
by supervised self-collected oral fluid samples, supervised
self-collected nasal specimens, and lastly clinician-collected NP
swab specimens. Samples were transported to the laboratory at
ambient temperature for testing on the day of collection.
Specimen Extraction and Testing
We processed samples from the specimen collection tubes. We
lysed and extracted RNA from samples (RNA Purification Kit,
Norgen Biotek Corp., Thorold, ON, Canada) using an auto-
mated instrument (Resolvex A200, Tecan Group Ltd, Zürich,
Switzerland) on a 96-well plate. We used a reverse transcription-
quantitative polymerase chain reaction (RT-qPCR) assay that
utilized a single color TaqMan probe with a modified version
of the qualitative detection of SARS-CoV-2 (N1, N2 primer/
probe assay) designed and validated by the Centers for Disease
Control and Prevention (CDC) (Integrated DNA Technologies,
Coralville, IA) [7]. We recorded cycle threshold values for tests.
We detected human Ribonuclease P RNA with an additional
single color TaqMan assay, in a parallel reaction using an ali-
quot of the extracted participant specimen to serve as a con-
trol for specimen extraction, specimen adequacy, and RT-PCR
inhibition. We ran samples on an RT-qPCR System (CFX 96™
Touch RT-PCR Detection System or CFX 96™ Connect RT-PCR
Detection System, Bio-Rad, Hercules, CA).
Ethics Statement
The Institutional Review Board of the University of California
Los Angeles reviewed and approved the study (reference
number 20-000545).
RESULTS
We recruited 45 participants. The median age of study partici-
pants was 42 years (Interquartile range [IQR], 31 to 52 years). Of
the participants, 29 tested positive for SARS-CoV-2 viral RNA
in at least one specimen. All 29 participants that tested positive
for SARS-CoV-2 in at least one specimen had prior symptoms.
Of the participants, 23 (51%) of 45 participants reported active
symptoms; 21 of those 23 had COVID-19. Symptoms and likely
transmission source are documented in the Supplemental Table.
Overall, we collected 180 specimens from 45 participants. Of
those specimens, one specimen was lost and two specimens had
insufficient sample for laboratory analysis. Therefore, 177 spe-
cimens yielded results (Table 1). Clinician-supervised oral fluid
swab specimens detected 26 (90%) of 29 infected individuals,
clinician-supervised anterior nasal swab specimens detected
23 (85%) of 27, clinician-collected posterior nasopharyngeal
swab specimens detected 23 (79%) of 29, and unsupervised
self-collected oral fluid swab specimens detected 19 (66%) of
29. There was no difference in testing performance when com-
paring those with and without active symptoms.
When comparing cycle threshold values, clinician-collected
posterior nasopharyngeal swab specimens had an average
cycle threshold value of 25.88 (standard deviation (SD): 5.90;
Supplemental Figure 1), clinician-supervised self-collected ante-
rior nasal swab specimens had an average cycle threshold value
of 30.49 (SD: 5.59), clinician-supervised self-collected oral fluid
swab specimens had an average cycle threshold value of 34.13
(SD: 3.63), and unsupervised self-collected oral fluid swab spe-
cimens had an average cycle threshold value of 33.48 (SD: 3.26).
DISCUSSION
We found that clinician-supervised self-collected specimens
for SARS-CoV-2 detection were sensible and feasible. No single
specimen type identified all participants with SARS-CoV-2. The
performance of clinician-supervised self-collected oral fluid
and nasal swab specimens was similar to clinician-collected na-
sopharyngeal swab specimens. Unsupervised self-collected oral
fluid swab specimens performed worse in this study sample.
The CDC currently recommends the use of nasopharyngeal
or oropharyngeal swab specimens either collected by a health
care worker or self-collected mid-turbinate or anterior nares
samples in symptomatic patients in a health care setting, in-
cluding a supervised drive-through setting, if nasopharyngeal
swab specimens are not available [4]. Prior studies reported
that SARS-CoV-2 detection was similar among oral fluid and
nasal swab specimens when compared to nasopharyngeal
swabs specimens [8, 9]. It was found in one of those studies that
multiple anatomic site testing may improve clinical sensitivity
and reduce false-negative test results.
There is an urgent need to validate reliable specimen collection
methods for the detection of SARS-CoV-2 to increase access to
safe and easy testing. Our findings support that clinician-collected
posterior nasopharyngeal swab specimens have a similar clin-
ical sensitivity to clinician-supervised self-collected oral fluid
and clinician-supervised self-collected anterior nasal swab speci-
mens for the detection of SARS-CoV-2. Further research on other
supervised means of collection, such as video-based instructions
or observation and feedback via telehealth, is warranted.
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BRIEF REPORT • cid 2021:XX (XX XXXX) • 3
In our sample, there were 6 cases of SARS-CoV-2 detected
among oral fluid swab specimens, which were not detected in
clinician-collected nasopharyngeal swab specimens. It is pos-
sible that the detection of SARS-CoV-2 may differ at anatomic
sites based on the fidelity of collection and timing of infec-
tion [10, 11]. There were also 3 cases of SARS-CoV-2 detected
among nasopharyngeal specimens not detected in oral fluid
swab specimens. That suggests that testing any single anatomic
site may miss some cases of SARS-CoV-2, which is consistent
with a prior study [12]. We did not find significant differences
in cycle threshold values between specimen types. Prior studies
have found that oral fluid provides a similar sensitivity to
Table 1. SARS-CoV-2 Detection in Self-Collected Unsupervised and Clinician-Supervised Oral Fluid Swab Specimens, Clinician-Supervised Self-Collected
Anterior Nasal Swab Specimens, Clinician-Collected Posterior Nasopharyngeal Swab Specimens, and Pooled Results by Current Symptom Status
Symptomatic
Days of
symptoms
Unsupervised
Self-Collected
Oral Fluid
Supervised
Self-Collected
Oral Fluid
Supervised
Self-Collected
Nasal Specimen
Clinician-Collected
NP
Any
Positive
No 18 + + QNS + +
Yes 7 + + QNS + +
Yes 21 + + + + +
Yes 15 + + + + +
Yes 12 + + + + +
Yes 10 + + + + +
Yes 9 + + + + +
Yes 8 + + + + +
Yes 8 + + + + +
Yes 7 + + + + +
Yes 7 + + + + +
Yes 6 + + + + +
Yes 4 + + + + +
Yes 2 + + + + +
No 17 – + + + +
No 14 – + + + +
Yes 17 – + + + +
Yes 14 – + + + +
Yes 5 – + + + +
Yes 15 + – + + +
No 7 – – + + +
Yes 18 – + – + +
Yes 9 – – – + +
Yes 17 + + + – +
No 16 + + + – +
No N/A + + + – +
No 5 + + + – +
No N/A – + – – +
Yes 13 – + – – +
No N/A QNS – – – –
Yes 10 – – – – –
Yes 7 – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
No N/A – – – – –
Abbreviations: COVID-19, coronavirus disease 2019; QNS, Quantity Not Sufficient; +, positive; -, negative.
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4 • cid 2021:XX (XX XXXX) • BRIEF REPORT
nasopharyngeal swabs [10, 13–15], particularly when combined
with coughing before specimen collection to provide an upper
respiratory tract sample.
We found that unsupervised self-collected oral fluid swab
specimens detected SARS-CoV-2 in fewer patients than other
specimen types, and this discrepancy was unexpected. We ob-
served that without feedback, some unsupervised participants
did not cough before self-collecting their sample. A pre-printed
study reported that after bronchoalveolar lavage fluid, which is
not feasible in the outpatient setting, sputum samples showed
the highest positivity in all stages following a SARS-CoV-2 in-
fection, followed by nasal swabs [16]. Coughing was included
as part of our specimen collection protocol and may provide
a sputum specimen in the oral fluid specimen in addition to
saliva. Laboratory studies and a case series have indicated that
oral fluid collected after a participant coughs are reliable spe-
cimens [13, 15]. Our findings suggest that coughing may be a
critical step when collecting oral fluid swab specimens for the
detection of SARS-CoV-2.
Our report has several strengths. We were able to perform
self-collected specimen collection for SARS-CoV-2 testing.
We studied multiple sample types and collection methods, in-
cluding unsupervised self-collected specimens and clinician-
supervised self-collected specimens. Clinician-collected
nasopharyngeal specimens were collected in all patients for
comparison. All samples were tested at a CLIA-certified,
high-complexity laboratory with a validated FDA-authorized
SARS-CoV-2 assay.
However, our study had a limited sample size due to the cur-
rent shortage of testing supplies. Our study was not designed to
detect statistical differences between specimen types or collec-
tion methods. Given the urgency of obtaining results, recruit-
ment took place over a short period.
CONCLUSIONS
Supervised self-collected oral fluid and anterior nasal swab
specimens performed similarly to clinician-collected nasopha-
ryngeal swab specimens for the detection of SARS-CoV-2. No
sample type captured all infections. Supervised self-collected
methods were feasible and could enable widespread access to
testing by removing the need for a healthcare professional to
collect each sample, reducing potential exposure for healthcare
professionals and reducing the amount of PPE used for testing.
Supplementary Data
Supplementary materials are available at Clinical Infectious Diseases online.
Consisting of data provided by the authors to benefit the reader, the posted
materials are not copyedited and are the sole responsibility of the authors, so
questions or comments should be addressed to the corresponding author.
Notes
Acknowledgments. The authors thank the staff of University of California
Los Angeles, TKSL, Curative Inc. and Korva-Labs Inc. F. T. and V. S. devel-
oped a viral assay for the detection of SARS-CoV-2.
Disclaimer. The content is solely the responsibility of the authors and
does not necessarily represent the official views of the NIH or UCGHI.
Potential conflicts of interest. V. S. is the CSO of Curative Inc. and holds
stock in the company. N. K. reports working as a research consultant for
Curative Inc. F.T. is the CEO of Curative Inc. and holds stock in the com-
pany. Dr. Klausner has served as Medical Director of Curative Inc. during
the study period. All other authors have no potential conflicts. All authors
have submitted the ICMJE Form for Disclosure of Potential Conflicts of
Interest. Conflicts that the editors consider relevant to the content of the
manuscript have been disclosed.
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