key: cord-0823819-1s20w22b
authors: Itoh, Kazuhiro; Kawamitsu, Toru; Osaka, Yoko; Sato, Kazuyo; Suzuki, Yusuke; Kiriba, Chiyo; Saito, Yumi; Hirose, Ryo; Ichihara, Hiroshi; Saito, Mitsugu; Mitsuke, Yasuhiko; Kuzumi, Kenichi; Miyashita, Hirofumi; Tsutani, Hiroshi
title: False positive results in severe acute respiratory coronavirus 2 (SARS-CoV-2) rapid antigen tests for inpatients
date: 2021-03-22
journal: J Infect Chemother
DOI: 10.1016/j.jiac.2021.03.011
sha: d8387b5b4aab0e46568ad617ff67b1ab9aaeaf8c
doc_id: 823819
cord_uid: 1s20w22b

Severe acute respiratory syndrome coronavirus 2 rapid antigen detection (RAD) test kits are widely used as primary screening test in Japan because rapid diagnosis of coronavirus disease 2019 (COVID-19) is critical for infection control. We report cases with RAD test false-positive results in a ward for patients with disabilities. RAD tests potentially evoke hospital operational risk. It is desirable that performing PCR test appropriately when patients admitted to a medical treatment ward with COVID-19 symptoms instead of RAD test.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) infection, has recently emerged and caused a pandemic.

COVID-19 outbreaks in hospitals or welfare facilities have become a significant social problem, such as the aggravation of inpatients and residents at risk of underlying diseases and old age and the difficulty of securing human resources because of staff infection [1] [2] [3] . In Japan, rapid antigen detection (RAD) test kits based on the immunochromatography method are widely used as primary screening test because early detection of COVID-19 is important for institutional infection control.

We very recently experienced false-positive cases detected by RAD tests used for febrile patients hospitalized in the ward of persons with disabilities.

J o u r n a l P r e -p r o o f Five patients hospitalized in the ward of disabled persons exhibited a fever for 2 days or more. These patients had been in reverse isolation for the last 7 months since the first wave of COVID-19 in Japan (Table 1) . After the onset of fever, tazobactam/piperacillin were empirically administered to all patients, and azithromycin hydrate and favipiravir were additionally administered to the three patients with SARS-CoV-2 RAD test positive. Favipiravir was discontinued after confirming SARS-CoV-2 PCR test negative. Four patients showed defervescence on day 3, but one patient had a persistent fever.

Specimens were collected from the innermost part of the nasal cavity according to the guidelines for the utilization of SARS-CoV-2 antigen detection kits and were prepared for assays according to the respective manufacturer's manual [4] . We have received a report that rhinoviruses were detected by direct sequencing in the remaining specimens from the PCR test by administrative testing. The rhinoviruses have been confirmed in four patients other than patient no. 4.

The RAD test result using the ESPLINE kit was judged to give false-positive results because patients were PCR-negative, and the occurrence of COVID-19 was clinically denied. We cannot say that there are no true COVID-19 cases in which the antigen test is positive, and the PCR test is negative.

However, we estimated that this case was with false positive, taking into account the reported specificity of both the antigen and PCR tests, the fact that there were no PCR test positive cases among the 69 patients and staff involved, and the prevalence situation in the area. In fact, rhinovirus infection was later reported by administrative testing using direct sequencing. Furthermore, because different lots of the ESPLINE kit yielded similar results, and the other two antigen test kits also gave negative results, we speculate that this was an issue specific to the ESPLINE kit.

The RAD test based on the immunochromatography method is widely used in Japan, and if the test is positive, the patient is diagnosed as having COVID-19. Although several reports have noted low sensitivity with RAD tests, and false positives have already been reported for quantitative tests such as Lumipulse®, to our knowledge, in qualitative tests no reports have described false-positive results [6] [7] [8] [9] . However, more recently, false-positive results from the RAD test have become a J o u r n a l P r e -p r o o f Funding None.

The authors have read the journal's policy on the disclosure of potential conflicts of interest and the journal's authorship agreement. The authors declare that they have neither conflicts of interest nor competing interests.

J o u r n a l P r e -p r o o f 

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Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington

Japanese Ministry of Health, Labor and Welfare. 2020. The guidelines for the utilization of the SARS-CoV-2 antigen detection kit. Japanese Ministry of Health, Labor and Welfare

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Another false-positive problem for a SARS-CoV-2 antigen test in Japan

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