Available online 7 March 2023

Author links open overlay panel, , , , , , AbstractIntroduction

Rapid qualitative antigen testing has been widely used for the laboratory diagnosis of COVID-19 with nasopharyngeal samples. Saliva samples have been used as alternative samples, but the analytical performance of those samples for qualitative antigen testing has not been sufficiently evaluated.

Methods

A prospective observational study evaluated the analytical performance of three In Vitro Diagnostics (IVD) approved COVID-19 rapid antigen detection kits for saliva between June 2022 and July 2022 in Japan using real-time reverse transcription polymerase chain reaction (RT-qPCR) as a reference. A nasopharyngeal sample and a saliva sample were simultaneously obtained, and RT-qPCR was performed.

Results

In total, saliva samples and nasopharyngeal samples were collected from 471 individuals (RT-qPCR-positive, n = 145) for the analysis. Of these, 96.6% were symptomatic. The median copy numbers were 1.7 × 106 copies/mL for saliva samples and 1.2 × 108 copies/mL for nasopharyngeal samples (p < 0.001). Compared with the reference, the sensitivity and specificity were 44.8% and 99.7% for ImunoAce SARS-CoV-2 Saliva, 57.2% and 99.1% for Espline SARS-CoV-2 N, and 60.0% and 99.1% for QuickChaser Auto SARS-CoV-2, respectively. The sensitivities of all antigen testing kit were 100% for saliva samples with a high viral load (>107 copies/mL), whereas the sensitivities were <70% for high-viral-load nasopharyngeal samples (>107 copies/mL).

Conclusion

COVID-19 rapid antigen detection kits with saliva showed high specificity, but the sensitivity varied among kits, and were also insufficient for the detection of symptomatic COVID-19 patients.

Section snippetsAuthorship statement

All authors meet the ICMJE authorship criteria. Norihiko Terada designed the study, collected samples, and drafted the manuscript. Yusaku Akashi made figures and performed the statistical analysis. Yuto Takeuchi collected samples and revised the manuscript. Shigeyuki Notake, Atsuo Ueda, and Koji Nakamura collected samples and operated the equipment. Hiromichi Suzuki drafted the manuscript, designed the study, and supervised the project. All authors contributed to the writing of the final

Method

This study was performed with samples submitted by both symptomatic and asymptomatic patients between June 8, 2022, and July 12, 2022, at a drive-through PCR center at Tsukuba Medical Center Hospital (TMCH), which intensively performed COVID-19 PCR evaluations with NP samples or saliva samples in the Tsukuba district of Tsukuba, Ibaraki Prefecture, Japan. People with and without symptoms were referred from 49 clinics and a local public health center during the study period. Asymptomatic

Results

In total, saliva samples and NP samples were collected from 471 individuals during the study period; 455 were from symptomatic individuals, and 16 were from asymptomatic individuals. In this study, both nasopharyngeal samples and saliva samples were successfully obtained from all individuals. No cases were excluded due to a sample volume that was insufficient for evaluation. Of the simultaneously obtained saliva samples and NP samples, 140 saliva samples and 143 NP samples were

Discussion

The current study revealed that each COVID-19 antigen detection kit for saliva had good specificity with infrequent false-positive findings; however, the sensitivity varied among the kits and was insufficient for the detection of symptomatic COVID-19 patients, probably due to the lower viral loads in saliva samples than in NP samples. In this study, high viral loads of SARS-CoV-2 were detected in NP samples in most COVID-19-positive patients, but there were many false-negative results with the

Declaration of competing interest

FUJIREBIO, Inc., and MIZUHO MEDY Co., Ltd., provided funds for research expenses and antigen kits without charge. Hiromichi Suzuki received advisory fees from MIZUHO MEDY Co., Ltd. The other authors have no conflicts of interest.

Acknowledgments

We thank Ms. Yoko Ueda, Ms. Mio Matsumoto, Ms. Mika Yaguchi, Ms. Yumiko Tanaka, Ms. Hiromi Tsuruta, Mr. Naoki Tanimura, and the staff of the Department of Clinical Laboratory of Tsukuba Medical Center Hospital for their support in this study. We thank all participating medical institutions for providing their patients' clinical information. Quick Chaser Auto SARS-CoV-2 was the same reagent as FUJI DRI-CHEM IMMUNO AG Cartridge COVID-19 Ag (Fujifilm, Tokyo, Japan), and is tailored for digital

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© 2023 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.