A Novel Strategy for SARS-CoV-2 Mass-Screening Using Quantitative Antigen Testing of Saliva

Background: Development of innovative testing strategies to facilitate mass-screening of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent need for the prevention of coronavirus disease-19 outbreaks. The current standard polymerase chain reaction (PCR) testing using nasopharyngeal swab samples requires medical personnel and is time-consuming. Recently, a novel chemiluminescent enzyme immunoassay (CLEIA) has been developed to detect SARS-CoV-2 nucleoproteins within 30 minutes.Methods: We performed a prospective cohort study to develop an efficient mass-screening strategy of salivary detection of SARS-CoV-2 by CLEIA in persons at health centers and international airports. Performance of CLEIA was evaluated in comparison with PCR using self-collected saliva.Findings: Self-collected saliva was obtained from 2,056 persons. Results of CLEIA and PCR were concordant in 2,020 (98·2%) of samples demonstrating high correlation (Kendall’s W=0·99). Probabilities of CLEIA-positivity given PCR-positivity and CLEIA-negativity given PCR-negativity were 76% (90% credible interval (CI): 68-83%) and 99·24% (90%CI: 98·83-99·49%), respectively, at the cutoff value of 0·67 pg/ml. Two-step testing strategy with initial CLEIA using two thresholds (negative and positive cutoffs at 0·19 pg/ml and 4·0 pg/ml, respectively), with PCR as a second test only for intermediate results by CLEIA yielded 85% (90%CI: 78-90%) CLEIA-positivity given PCR-positivity and 100·00% (90%CI: 99·85-100·00%) CLEIA-negativity given PCR-negativity. Interpretation: CLEIA testing using self-collected saliva is simple and yields results quickly, thus suitable for testing en masse. To improve accuracy, we propose a strategy of two-step screening with initial CLEIA followed by confirmatory PCR for intermediate range concentrations, varying positive and negative thresholds depending on the local prevalence. Mass-screening by this strategy have expedited passenger processing at Japanese airports and may apply to other large-scale mass-screening initiatives.Funding Statement: Health, Labour and Welfare Policy Research Grants 20HA2002.Declaration of Interests: The authors declare no competing interests.Ethics Approval Statement: This study was approved by the Institutional Ethics Board (Hokkaido University Hospital Division of Clinical Research Administration Number: 020-0116) and informed consent was obtained from all individuals.