key: cord-0277768-zzyibdy7
authors: Adamson, B. J.; Sikka, R.; Wyllie, A. L.; Premsrirut, P. K.
title: Discordant SARS-CoV-2 PCR and Rapid Antigen Test Results When Infectious: A December 2021 Occupational Case Series
date: 2022-01-05
journal: nan
DOI: 10.1101/2022.01.04.22268770
sha: f49a9c149f14ddf0f6278b16dc18ba5964d9de69
doc_id: 277768
cord_uid: zzyibdy7

The performance of Covid-19 diagnostic tests must continue to be reassessed with new variants of concern. The objective of this study was to describe the discordance in saliva SARS-CoV-2 PCR and nasal rapid antigen test results during the early infectious period. We identified a high-risk occupational case cohort of 30 individuals with daily testing during an Omicron outbreak in December 2021. Based on viral load and transmissions confirmed through epidemiological investigation, most Omicron cases were infectious for several days before being detectable by rapid antigen tests.

The median time from first positive PCR to first detectable antigen positive was 3 days (95% Confidence Interval: 2-NA). After infection was detected, a subgroup (n=5) who received daily saliva PCR, nasal swab PCR, and nasal swab rapid antigen testing showed viral load peaked in saliva 1-2 days before nasal tests (Supplemental Table 1 ). All individuals in the cohort developed symptoms within two days of the first PCR positive test.

We found that rapid antigen tests lagged in the ability to detect Covid-19 during an early period of disease when most individuals were infectious with Omicron and four transmissions were confirmed. The policy implication is that rapid antigen tests may not be as fit-for-purpose in routine workplace screening to prevent asymptomatic spread of Omicron, compared to prior variants, 6 given the shorter time from exposure to infectiousness and lower infectious doses sufficient for transmission. These findings are consistent with population-level Omicron epidemiology studies showing shorter serial intervals between cases and faster rates of community spread. Despite the small numbers of individuals included in this study, the findings are uniquely valuable because of the early detection of Omicron infection in frequent workplace Covid-19 testing to prevent spread. In real-world antigen testing, the limit of detection was substantially lower than manufacturers have reported to the FDA based on laboratory validation.

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No funding was received to support this study.

BJA reports receiving consultancy fees for safety advising several workplaces included in this study;

serving as an unpaid board member, SalivaDirect; being a paid employee of Flatiron Health, outside the submitted work. RS reports serving as an unpaid board member, SalivaDirect, outside of this work. ALW reports serving as an unpaid board member of SalivaDirect, outside of this work. PP reports being a paid employee of Mirimus Laboratory.

We thank the COVID-19 Sports and Society Working Group, workplace COVID Safety Managers, Harlan Krumholz, MD and Nathan Grubaugh, PhD from Yale University, and the operational team, including Charlene Speyer and Lisa Kussell from Infectious Economics.

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The copyright holder for this preprint this version posted January 5, 2022. 6 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

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Shown are Cycle Threshold (Ct) counts and rapid antigen test results from paired samples of infected patients (Panel A). Also shown is the Kaplan Meier analysis of time from positive PCR to positive rapid

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The data reported here represent a convenience sample of employees at a selection of workplaces that partner with Infectious Economics LLC for Covid-19 prevention, including corporate offices, entertainment, retail trade, and manufacturing. The study period ran December 1, 2021 to December 31, 2021. Clinical samples were obtained by self-collection observed by a trained COVID Safety Manager.

Employer-provided testing was preventatively provided to enable in-person workplace safety during times of high community prevalence and/or recent COVID exposures in the workplace. Because the sensitivity of tests may vary during the course of an infection, we evaluated concordance of PCR and rapid antigen test results in matched samples over time.

In accordance with the guidelines, this work with de-identified samples was approved for research not involving human subjects by the SUNY Downstate Institutional Review Board & Privacy Board (1603504-6) under the title "Pilot program for instituting massive COVID19 surveillance screening in schools and the workplace."

All de-identified data and the code for analysis is available on GitHub at https://github.com/blythejane/covid_safety.

The rapid antigen tests kits used were Quidel QuickVue At-Home OTC COVID-19 Test and Abbott BinaxNOW COVID-19 Antigen Self-Test. PCR to detect SARS-CoV-2 RNA was the ThermoFisher 8 . CC-BY 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted January 5, 2022. ; https://doi.org/10.1101/2022.01.04.22268770 doi: medRxiv preprint Combo Kit, allowing for the ability to detect an S-gene dropout. The time from specimen collection to results returned was <30 minutes for antigen tests and ranged 6-12 hours for PCR. A subset of specimens received whole genome sequencing in a broader epidemiology investigation of clusters to further improve workplace safety policies. Samples were classified as Omicron or Delta based on whole genome sequencing data, diagnostic PCR target failures, and sampling dates. In whole genome sequencing, RNA was extracted and confirmed as SARS-CoV-2 positive by RT-qPCR with the Thermo Fisher TaqPath SARS-CoV-2 assay. Next Generation Sequencing with the Illumina COVIDSeq ARTIC primer set2 was used for viral amplification.

The primary outcome of interest was concordance between PCR and rapid antigen test results, dependent on time and Ct values corresponding to infectiousness. We defined the index as the specimen collection date for the first PCR test with detectable SARS-CoV-2 with Ct <35, the event being the first positive rapid antigen test result, and censoring at the most recent antigen test date. Based on observed transmission events in these workplaces that were confirmed by contact tracing and genomic epidemiology investigation, we defined infectious viral load as corresponding to Ct values <29 in this analysis.

A Kaplan Meier analysis was performed to estimate the median time from PCR positive to rapid antigen positive and time-dependent probability of a false negative rapid antigen test. We defined the index as the specimen collection date for the first PCR test with detectable SARS-CoV-2 with Ct <35, the event being the first positive rapid antigen test result, and censoring at the most recent antigen test date. Analyses were conducted in R 4.1.2.

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The copyright holder for this preprint this version posted January 5, 2022. Notes: Cases are ordered from lowest to highest peak Ct among discordant paired tests. *Individual with confirmed transmissions during the period of false negative antigen testing. **High risk flag indicates an individual day when a person was observed to have infectious viral load and/or confirmed transmission event while testing negative on rapid antigen test. The index date (Day 0) was defined as the date of specimen collection for the first positive PCR test for an individual. The index date for Case S was based on symptom onset one day prior to first positive PCR. Dark shading indicates a "high risk" discordant matched pair of results having a negative antigen test during infectious viral load (saliva N-gene Ct <29); pale shading indicates a discordant matched pair of results with a negative antigen test and a positive PCR with viral load considered not to be infectious. PCR was the ThermoFisher Combo Kit. Some individuals additionally had nasal swabs collected for PCR testing and for those individuals the nasal Ct is also available to contextualize the saliva Ct.

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