Effective screening strategies for detection of asymptomatic COVID-19 travelers at airport quarantine stations: Exploratory findings in Japan

Abstract

The quantitative reverse transcription polymerase chain reaction method using nasopharyngeal swabs (NPS RT-qPCR) is regarded as the reference standard for diagnosing coronavirus disease 2019 (COVID-19). However, when using NPS RT-qPCR at busy airport quarantine stations, there are constraints on testing capacity, time, travelers' tolerance, and availability of personal protective equipment for quarantine officers. A feasible alternative is therefore needed to test incoming travelers, especially when passenger numbers increase with the resumption of business, tourism, and economic activities. To explore alternatives to NPS RT-qPCR, we collected nasopharyngeal, anterior nasal, and saliva samples chronologically over days 1-7 from asymptomatic COVID-19 air travelers who were under quarantine at a designated facility, and we then compared test results for 9 different methods, comprising RT-qPCR (including the reference method), loop-mediated isothermal amplification (LAMP), and qualitative and quantitative antigen testing. We evaluated sensitivity for 97 person-day samples independently to evaluate asymptomatic travelers regardless of their testing date and period of asymptomatic status upon entry. Sensitivity of the different tests varied from 46.6% to 81.0%, but this was improved from 72.7% to 100.0% when the viral load was > 10 4 copies/sample on NPS RT-qPCR. Thus, most high-risk asymptomatic travelers with higher viral load would be detected by the tests evaluated. Quantitative antigen testing using saliva samples showed 90.9% sensitivity and provided quicker results, and should be an acceptable alternative to NPS RT-qPCR at busy airport quarantine stations. We discuss the implications of our exploratory findings for establishing a comprehensive and feasible testing strategy for COVID-19 among air passengers.

Reduced Relative Sensitivity of the Elecsys SARS-CoV-2 Antigen Assay in Saliva Compared to Nasopharyngeal Swabs

“…Our results show a clear advantage of NPS as a specimen in combination with the probed antigen test. This is in concordance with other antigen test systems which, in general, have shown lower sensitivity compared to NPS [ 35 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. One of the automated antigen tests previously evaluated for saliva samples is the Lumipulse G SARS-CoV-2 Ag assay, a chemiluminescent enzyme immunoassay which received the CE marking for qualitative and quantitative detection of the SARS-CoV-2 N antigen on both saliva and NPS samples.…”

“…One of the automated antigen tests previously evaluated for saliva samples is the Lumipulse G SARS-CoV-2 Ag assay, a chemiluminescent enzyme immunoassay which received the CE marking for qualitative and quantitative detection of the SARS-CoV-2 N antigen on both saliva and NPS samples. Sensitivities relative to the corresponding molecular reference test ranged from 41.3% to 88.9%; specificities were reported in four of the five studies and ranged from 96.9% to 98.6% [ 42 , 43 , 44 , 46 , 51 ]. It has to be noted, however, that in the study reporting the highest sensitivity (i.e., 88.9%), only nine RT-PCR-positive saliva samples were evaluated.…”

“…As we showed, conducting head-to-head comparisons of NPS and saliva for both PCR and antigen test is critical to dissect if matrix effects in saliva exist. As only few studies have assessed saliva in the context of SARS-CoV-2 antigen tests, and those that have, recorded variable results [ 35 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ], it can currently not be excluded that antigen tests generally show a reduced sensitivity across diverse tests systems. Alternatively, these effects may be test-dependent and can be modest enough to allow application in mass testing as a recent study suggests [ 41 ].…”

Self-testing for the detection of SARS-CoV-2 infection with rapid antigen tests for people with suspected COVID-19 in the community

“…Since the sensitivity is not optimal, self-testing should not be used as diagnostic tool for severely ill patients to guide possible therapies in a hospital setting. The poorer sensitivity of self-testing using RDT's as compared to qRT-PCR on nasopharyngeal swabs taken by health care professionals is probably both due to the intrinsic lesser sensitivity of RDT's when compared to qRT-PCR and poorer self-sampling and self-test performance (18). However, the test characteristics are suitable for large scale preventive testing programs to open up specific activities in society.…”

An accurate model for SARS-CoV-2 pooled RT-PCR test errors

“…One major application of this technology is the rapid testing of contacts of positive individuals in order to cut transmission chains. Moreover, in some countries, RT-PCR testing has become a routine procedure of surveillance, testing incoming air passengers in airports [ 1 , 2 ], school students [ 3 ], or even the entire adult population [ 4 ].…”