key: cord-0910351-2wmricsf
authors: George, Blessen; McGee, James; Giangrasso, Eileen; Finkelstein, Sheila; Wu, Susan; Glatt, Aaron E
title: What Is the Predictive Value of a Single Nasopharyngeal SARS-CoV-2 PCR Swab Test in a Patient with COVID-like Symptoms and / or Significant COVID-19 Exposure?
date: 2020-09-01
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofaa399
sha: 9a54c7d17a02870a193b65899f3612b2d2b50d7c
doc_id: 910351
cord_uid: 2wmricsf

Utilizing results of PCR testing and subsequent antibody titers, we report on the test characteristics of screening PCR test for Severe acute respiratory syndrome coronavirus-2 among hospital-workers. The PCR-test was found to be 87% sensitive, 97% specific, a positive predictive value of 0.98, and a negative predictive value of 0.80.

A c c e p t e d M a n u s c r i p t INTRODUCTION Since the first case of pneumonia was reported from Wuhan, China in December 2019 1 , hospital workers have been at risk for exposure to the novel coronavirus currently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2 . During the early days of this pandemic, testing was administered selectively to identify and isolate those infected. Little objective evidence was available to determine pre-test probability and predictive value of these tests. We report a retrospective, cross sectional, observational study analyzing SARS-CoV-2 healthcare worker testing at a tertiary care hospital in Long Island, NY.

From March 1 -April 30, 2020, Mount Sinai South Nassau tested healthcare workers with "COVID-19 like" symptoms or significant exposure (defined as at least 15 minutes in close proximity) to a SARS-CoV-2 patient without wearing personal protective equipment using an established reverse transcription polymerase chain reaction (RT-PCR) test on a nasopharyngeal specimen. Due to the limited availability of testing supplies, only symptomatic employees were offered on-site testing. No "Patient Consent Statement" specific for this testing was obtained as this was part of routine care that all patients were receiving. This RT-PCR was showed that the neutralizing antibody titers significantly correlated with the numbers of specific T cell response to the virus 5 . In turn, the SARS-CoV-2 antibody titers were correlated with invitro viral neutralization with a specificity of 100%. All staff also completed a questionnaire self-reporting symptoms experienced before the initial RT-PCR screening test using a questionnaire (See Figure 1) . We analyzed data including date and result of SARS-CoV-2 PCR, symptoms on presentation, and date and result of antibody testing.

Symptoms reported were aggregated and compared with SARS-CoV-2 PCR and antibody tests. Symptoms were compared via two-tailed z-test with the threshold for significance defined as a p-value of 0.05.

A c c e p t e d M a n u s c r i p t workers with a negative SARS-CoV-2 PCR test, 9 (20.5%) were subsequently found to have antibody. Quantitative titers showed that 94% of subjects developed a robust immune response with a titer >1:320 (chosen as the level accepted by mount Sinai for plasma donation). At the time of SARS-CoV-2 PCR testing, 76 healthcare workers reported symptoms, including fevers, chills, cough, dyspnea, wheezing, myalgia, pain, nausea, vomiting, diarrhea, fatigue, anosmia, throat pain, otalgia, tachycardia and hypersomnia. Statistical analysis of a larger group of employees (n= 461, total tested for antibody including these 105 employees) revealed cough and myalgia to be the two symptoms significantly different between those with and without antibody (see Table 1a ). The most common symptom reported was cough. The SARS-CoV-2 PCR test via nasopharyngeal swab was found to be 87% sensitive and 97% specific. The PCR test was also found to have a positive predictive value (PPV) of 0.98 and a negative predictive value (NPV) of 0.80 (see table 1b) among symptomatic patients.

Determining likelihood of COVID illness using diagnostic PCR testing has not been fully determined. The lack of availability of adequate SARS-CoV-2 testing, reports of high false negative tests 6 and variability of symptoms on presentation 7 hinder accurate diagnosing. The high PPV seen is this study reinforces the rationale for PCR testing to identify new active cases. However, one fifth (20.5%) of symptomatic or significantly exposed staff were incorrectly labeled as not having SARS-CoV-2 after a single negative nasopharyngeal swab. This could be due to sub-detectable viral load at the time of screening, poor collection technique, and quality of specimen collected (depth of swab, and quality of sweep of nasopharyngeal region).

Our study had some notable limitations. Symptoms were self-reported thus failed to preclude recall bias and lacked objective verification. Antibody titers were thus not correlated by symptoms due to the subjective nature of symptoms reporting. The calculated specificity was dependent on the assumption that employees did not become infected between the screening test and antibody testing and applies only to symptomatic employees. However, our study showed the value and the limitations of relying on a single PCR nasopharyngeal swab to diagnose SARS-CoV2 illness. 

Clinical features of patients infected with

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Roche Diagnostics. (n.d). cobas ® SARS-CoV-2 Test (for the COVID-19 Coronavirus

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals

Evaluating the accuracy of different respiratory specimens in the laboratory diagnosis and monitoring the viral shedding of 2019-nCoV infections

Clinical Characteristics of Coronavirus Disease 2019 in China

ACKNOWLEDGEMENTS Financial support. None reported.

Patient Consent specific for this testing was not obtained as all care was provided as part of routine patient care.

M a n u s c r i p t 7 A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t 9 Figure 1