DOI: 10.5061/dryad.kwh70rz5r
title: Data from: Detection of silent SARS-CoV-2 infection (S1 File)

description: Background: To control COVID-19 pandemic is of critical importance to the
 global public health. To capture the prevalence in an accurate and timely
 manner and to understand the mode of nosocomial infection are essential
 for its preventive measure. Methods: We recruited 685 healthcare workers
 (HCW’s) at Tokyo Shinagawa Hospital prior to the vaccination with COVID-19
 vaccine. Sera of the subjects were tested by assays for the titer of IgG
 against S protein’s receptor binding domain (IgG (RBD)) or IgG against
 nucleocapsid protein (IgG (N)) of SARS-CoV-2. Together with PCR data, the
 positive rates by these methods were evaluated. Results: Overall positive
 rates among HCW’s by PCR, IgG (RBD), IgG (N) with a cut-off of 1.4 S/C
 (IgG (N)1.4), and IgG (N) with a cut-off of 0.2 S/C (IgG (N)0.2) were
 3.5%, 9.5%, 6.1%, and 27.7%, respectively. Positive rates of HCW’s working
 in COVID-19 ward were significantly higher than those of HCW’s working in
 non-COVID-19 ward by all the four methods. Concordances of IgG (RBD), IgG
 (N)1.4, and IgG (N)0.2 against PCR were 97.1%, 71.4%, and 88.6%,
 respectively. By subtracting the positive rates of PCR from that of IgG
 (RBD), the rate of overall silent infection and that of HCW’s in COVID-19
 ward were estimated to be 6.0% and 21.1%, respectively.
 Conclusions:  For the prevention of nosocomial infection of
 SARS-CoV-2, identification of silent infection is essential. For the
 detection of ongoing infection, periodical screening with IgG (RBD) in
 addition to PCR would be an effective measure. For the surveillance of
 morbidity in the population, on the other hand, IgG (N)0.2 could be the
 most reliable indicator among the three serological tests.
description: <strong>Study design</strong> This
 study was conducted at Tokyo Shinagawa Hospital. The study protocol
 conformed to the ethical guidelines of the 1975 Declaration of Helsinki
 and was approved by the Ethics Committee at Tokyo Shinagawa Hospital
 (approval no. 20-A-34) prior to the start of the study. 685 HCW’s at Tokyo
 Shinagawa Hospital were included in this study after obtaining written
 informed consent. Sera were obtained from the subjects for the test of IgG
 against S protein’s receptor binding domain (IgG (RBD)) and IgG against
 nucleocapsid protein (IgG (N)) of SARS-CoV-2. None of them had been
 vaccinated with COVID-19 vaccine prior to the specimen collection. Subject
 information including age, sex, height, weight, job category in the
 hospital, history of SARS-CoV-2 infection diagnosed by PCR, and
 co-morbidity were obtained and anonymized before analyses.
 Tokyo Shinagawa Hospital started accommodating COVID-19 patients
 in March 2020. All the HCW’s were provided with full personal protective
 equipment (PPE). Especially, all frontline HCW’s wore long-sleeved gowns,
 N95 respirators, gloves, goggles or face shields when treating patients.
 SARS-CoV-2 testing by PCR was promptly carried out for HCW’s who showed
 symptoms suggestive of COVID-19 including fever, dry cough, respiratory
 distress, loss of smell, or dysgeusia.
 <strong>Clinical and laboratory
 tests</strong> Sera from the subjects were drawn
 during March and April 2021 and were tested with IgG (RBD) and IgG (N)
 assays. The titer of IgG (RBD) was measured by an ARCHITECT SARS-CoV-2 IgG
 II Quant assay on Architect i2000 CS5100 (Abbott Laboratories, Abbott
 Park, IL, USA) and that of IgG (N) was measured by an ARCHITECT SARS-CoV-2
 IgG assay on Architect i2000 CS5100 (Abbott Laboratories, Abbott Park, IL,
 USA). According to the package insert of IgG (RBD) assay, the cut-off
 index is 50.0 AU/mL and lowest concentration at which CV% is within 20% is
 7.8 AU/mL. Narasimhan et al. reported that the specificity of the IgG
 (RBD) assay was 100% while sensitivity of the IgG (RBD) exceeded 96% after
 15 days from symptom onset by applying the cut-off of 50.0 AU/mL [5].
 According to the package insert of IgG (N) assay, the cut-off index is 1.4
 S/C and CV% at a mean index of 0.04 S/C of 50 negative controls is 5.9%.
 According to a report by Bryan et al., sensitivity and specificity of the
 IgG (N) assay assessed with series of specimens from 125 patients were
 both 100% after 17 days from symptom onset with the cut-off of 1.4 S/C
 [6]. In addition to this cut-off, we used 0.2 S/C as one of the candidate
 cut-offs for the long-term assessment of the history of SARS-CoV-2
 infection by referring to the preceding literatures [7, 8, 9,
 10].  PCR was performed on QuantStudio™ 5 Real-Time PCR
 System (Thermo Fisher SCIENTIFIC, Waltham, MA, USA) which targets N1 and
 N2 regions of SARS-CoV-2. The PCR result was defined as positive when
 cycle threshold (Ct) was equal to or less than 40. Nasopharyngeal swabs
 for the PCR were collected by nurses who had ample experience of routine
 swab collections from fever outpatients and hospitalized
 patients. <strong>Statistical
 analysis</strong> We used JMP 15.1.0 (SAS
 Institute Inc., Cary, NC, USA) for Pearson’s chi-square test in Table 3 in
 which antibody titers below the cut-off were categorized as “0” while
 those equal to or above the cut-off were categorized as “1”. P-value of
 &lt;0.01 was considered significant. 
description: 0 = no, 1 = yes
 NA: not applicable Date:
 yyyy/mm/dd