As the coronavirus disease 2019 (COVID-19) continues to circulate, testing strategies are of the utmost importance. Given national shortages of testing supplies, personal protective equipment, and other hospital resources, diagnostic stewardship is necessary to aid in resource management. We report the low utility of serial testing in a low-prevalence setting

Brett-Major, David

Broadhurst, M. Jana

Fey, Paul D.

Hewlett, Angela L

Rearigh, Lindsey M.

Rupp, Mark

Van Schooneveld, Trevor

English

University of Nebraska Medical Center Research: DigitalCommons@UNMC

University of Nebraska Medical Center DigitalCommons@UNMC Journal Articles: Epidemiology Epidemiology 2021 Utility of Repeat Testing for COVID-19: Laboratory Stewardship When the Stakes are High Lindsey M. Rearigh Angela L. Hewlett Paul D. Fey M. Jana Broadhurst David Brett-Major See next page for additional authors Follow this and additional works at: https://digitalcommons.unmc.edu/coph_epidem_articles  Part of the Epidemiology Commons Authors Lindsey M. Rearigh, Angela L. Hewlett, Paul D. Fey, M. Jana Broadhurst, David Brett-Major, Mark Rupp, and Trevor Van Schooneveld Concise CommunicationUtility of repeat testing for COVID-19: Laboratory stewardship whenthe stakes are highLindsey M. Rearigh DO1 , Angela L. Hewlett MD, MS1, Paul D. Fey PhD2, M. Jana Broadhurst MD, PhD2,David M. Brett-Major MD, MPH3, Mark E. Rupp MD1 and Trevor C. Van Schooneveld MD11Division of Infectious Diseases, University of Nebraska Medical Center, Omaha, Nebraska, 2Division of Pathology and Microbiology, University of NebraskaMedical Center, Omaha, Nebraska and 3Department of Epidemiology, University of Nebraska Medical Center, Omaha, NebraskaAbstractAs the coronavirus disease 2019 (COVID-19) continues to circulate, testing strategies are of the utmost importance. Given national shortagesof testing supplies, personal protective equipment, and other hospital resources, diagnostic stewardship is necessary to aid in resourcemanagement. We report the low utility of serial testing in a low-prevalence setting.(Received 4 May 2020; accepted 29 July 2020; electronically published 3 August 2020)Rapid and accurate testing for severe acute respiratory coronavirusvirus 2 (SARS-CoV-2) during the coronavirus disease 2019(COVID-19) pandemic is essential to limit transmission andto aid in appropriate management of hospitalized patients.Understanding of the performance of COVID-19 nucleic acidtesting in clinical settings is evolving. Many false-negativereverse transcription polymerase chain reaction (rt-PCR) testshave been reported, raising concerns regarding infection controland patient placement.1–3 Apprehension regarding transmissionprevention along with lack of data on test performance have ledto the ordering of serial tests for persons under investigation.We assessed the value of repeat testing for COVID-19 after an ini-tial negative result to evaluate test performance and to determinewhether repeat testing is necessary.MethodsWe retrospectively reviewed inpatient and outpatient test resultsamong patients who presented to our academic medical centerin Omaha, Nebraska, from March 10 through April 28, 2020.Patients with a negative or inconclusive COVID-19 rt-PCR test fol-lowed by at least 1 additional test were included. Patients who hadtesting separated by >14 days were excluded because there wassignificant risk of new exposure during that period, promptingtesting. Basic demographic information and clinician indicationfor testing were collected via electronic medical record review.Testing was performed with the cobas SARS CoV-2 on theRoche 6800 platform, and a second laboratory developed anRT-PCR test (NECoV19). The cobas SARS CoV-2 uses primersand probes that detect the ORF1a and E genes whereas theNECoV19 assay detects the E and N genes. Using the NECoV19assay, if the E-gene was detected, the same RNA sample wasretested with the E-gene and N-gene as targets. If either the E-geneor the N-gene or both were detected, the test was positive.However, if gene targets were inconsistently identified and neitherthe E-gene nor the N-gene was not detected by the repeat test, thetest was inconclusive.ResultsIn total, 275 patients with initially negative or inconclusive testresults (94% negative, 6% inconclusive) underwent at least 1 addi-tional test. Results of the second test were 98.5% (271 of 275) neg-ative, 0.5% positive (1 of 275), and 1% inconclusive (3 of 275).Furthermore, 40 patients (14.5%) underwent a third test, with97% negative results (39 of 40) and 3% positive results (1 of 39).Also, 10 patients (1.5%) underwent >3 tests, with no positiveresults. Patient characteristics, indications for testing, and samplesources are outlined in Table 1. Median time from symptom onsetto initial test was 3 days, with 69% of initial tests performed in thefirst week of illness and 17% performed on asymptomatic patients(primarily preprocedural screening). All samples were obtainedfrom the respiratory tract. The most testing was performed vianasopharyngeal (NP) swab, although lower respiratory tract (LRT)sampling was more common with repeat testing. Median timebetween testing was longer among second and third tests com-pared to first and second tests (3.8 days vs 1 day). The mostcommon indication for repeat testing was signs and symptomsconcerning for COVID-19 infection or evidence of LRT infectionon imaging via either chest CT or x-ray: 58% for the second testingindication and 50% for the third testing indication.DiscussionWe found that repeat testing in patients who had initially testednegative had very low utility. Of 275 patients tested, 2 testedAuthor for correspondence:Dr Trevor C. Van Schooneveld, E-mail: tvanscho@unmc.edu Or Lindsey M. Rearigh, E-mail: lindsey.rearigh@unmc.edu.Cite this article: Rearigh LM, et al. (2021). Utility of repeat testing for COVID-19:Laboratory stewardship when the stakes are high. Infection Control & HospitalEpidemiology, 42: 338–340, https://doi.org/10.1017/ice.2020.397© 2020 by The Society for Healthcare Epidemiology of America. All rights reserved. This is an Open Access article, distributed under the terms of the Creative Commons Attributionlicence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.Infection Control & Hospital Epidemiology (2021), 42, 338–340doi:10.1017/ice.2020.397positive from an NP swab on serial testing after an initial negativeresult. However, there was a high clinical suspicion for COVID-19infection in both cases due to bilateral ground glass consolidationsseen on chest CT. Patient 1 presented 6 days from symptom onsetafter traveling in a high-prevalence area. Patient 2 presented 5 daysfrom symptom onset after a high-risk exposure to a knownCOVID-19–positive patient. Decreased sensitivity in NP samplinghas been demonstrated in studies, particularly later in the diseasecourse and if pneumonia is present.4,5 This decreased sensitivity isthought to be due to waning viral load levels in the upper respira-tory region.6–8Diagnostic stewardship is essential to improving the efficiencyof the testing process and to conserve testing supplies and personalprotective equipment (PPE) given critical national shortages.9Patient flow and bed availability are also affected by duplicate test-ing, which can delay patient transfer out of isolation rooms as wellas increase PPE utilization while test results are pending. Furtherpatient work-up and definitive diagnoses can also be delayed due tophysician anchoring and confirmation biases. Equipment such asswabs and reagents to perform testing are limited, emphasizing theneed to safely limit testing particularly in low-prevalence areas toallocate resources were more testing is necessary.Based on our findings, we modified our testing recommenda-tions to state that a single appropriately obtained NP swab per-formed within the first 7 days of illness is generally adequate torule out COVID-19. If clinical suspicion persists due to high-riskexposure or classic clinical presentation, additional testing shouldbe obtained. Patients presenting with pneumonia may benefit fromrepeat testing utilizing specimens from the LRT. Preference for col-lection of LRT specimens in patients with pneumonia is in line withboth the World Health Organization and Centers for DiseaseControl recommendations.10,11 Our guideline revision was imple-mented via education of our COVID teams and ID physicians. Ourcurrent practice of determining the need for additional testinginvolves patient review by a multidisciplinary team, including aninfectious diseases physician with experience in managing patientswith COVID-19. The ID physician leading this team generallydetermines whether additional testing is needed after input fromthe primary team.Limitations of this study include a relatively low COVID-19community prevalence (average 7% of tests positive), which limitsits generalizability to high-prevalence settings. Testing in ourfacility utilized 2 assays that demonstrated similar performancefor COVID-19 detection, but these results may not be applicableto other assays. Repeat testing was not systematically employedand cases may have potentially been missed, but at this time weare unaware of any missed COVID-19 cases in our facility.In conclusion, we found little benefit of repeat testing inpatients who presented early in their illness.We have adopted diag-nostic testing stewardship, limiting testing to a single nasopharyn-geal swab sample in most cases. Facilities should continuallyevaluate test performance and utilization to maximize the valueof such tests, especially when faced with limited resources.Acknowledgments. None.Financial support. No financial support was provided relevant to this article.Conflicts of interest.All authors report no conflicts of interest relevant to thisarticle.References1. Winichakoon P, Chaiwarith R, Liwsrisakun C, et al. Negative nasopharyn-geal and oropharyngeal swab does not rule out COVID-19. J Clin Microbiol2020. doi: 10.1128/JCM.00297-20.2. Zhang W, Du RH, Li B, et al. Molecular and serological investigation of2019-nCoV infected patients: implication of multiple shedding routes.Emerg Microbe Infect 2020;9:386–389.3. Lee TH, Lin RJ, Lin RTP, et al. Testing for SARS-CoV-2: can we stop at two?Clin Infect Dis 2020. doi: 10.1093/cid/ciaa459.4. Yang Y, Yang M, Shen C, et al. Laboratory diagnosis and monitoring theviral shedding of 2019-nCoV infections. medRxiv 2020. doi: 10.1101/2020.02.11.20021493.Table 1. Population Characteristics and Testing IndicationCharacteristicNo. (%)(N= 275)Median age, y (range) 62 (1–94)Male sex 143 (58)Median time between 1st and 2nd tests, d (range) 1.0 (0–14)Median time between 2nd and 3rd tests, d (range) 3.8 (1–14)Time to initial testing from symptom onset1–7 d 190 (69)8–14 d 27 (10)>14 d 10 (4)Screening da 48 (17)2nd test indicationbSymptoms suggestive of COVID-19 infection or evidenceof LRTI on imaging158 (58)Immunosuppressed patientc 55 (20)High-risk exposured 27 (10)Additional screening neededa 69 (25)Othere 21 (8)3rd test indicationb (N = 40)Symptoms suggestive of COVID-19 or evidence of LRTIon imaging20 (50)Immunosuppressed patientc 3 (7)High-risk exposured 2 (5)Additional screening neededa 19 (48)Sample source1st test (N = 275)Nasopharyngeal 272 (99)Tracheal aspirate/sputum 3 (1)2nd test (N = 275)Nasopharyngeal 255 (93)Tracheal aspirate/sputum 20 (7)3rd test (N = 40)Nasopharyngeal 31 (77)Tracheal aspirate/sputum 9 (23)aScreening was required for planned procedures, for patients residing in a group setting, andfor those with frequent contact with healthcare facilities. Additional screening was requiredprior to hospital discharge.bPatients could have >1 indication for 2nd and 3rd testing.cIncluded patients on immunosuppressive medications, transplant recipients, patients withactive cancer on chemotherapy, and patients with HIV with CD4 count <200.dIncludes exposure to a person who is a known positive or currently under investigation forCOVID-19.eReason not documented or clinician requesting additional testing.Infection Control & Hospital Epidemiology 3395. Zhao J, Yuan Q, Wang H et al. Antibody responses to SARS-CoV-2 inpatients of novel coronavirus disease 2019. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa344.6. Zou L, Ruan F, HuangM, et al. SARS-CoV-2 viral load in upper respiratoryspecimens of infected patients. N Engl J Med 2020;382:1177–1179.7. Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic features and clini-cal course of patients infected with SARS-CoV-2 in Singapore. JAMA2020;323:1488–1494.8. Yu F, Yan L, Wang N, et al. Quantitative detection and viral loadanalysis of SARS-CoV-2 in infected patients. Clin Infect Dis 2020;71:793–798.9. Artenstein AW. In pursuit of PPE. N Engl J Med 2020. doi: 10.1056/NEJMc2010025.10. Laboratory testing for coronavirus disease 2019 (COVID-19) in suspectedhuman cases: interim guidance, 2 March 2020. World Health Organizationwebsite. https://apps.who.int/iris/handle/10665/331329. Published March2, 2020. Accessed July 31, 2020.11. Interim guidelines for collecting, handling, and testing clinical specimensfrom persons for coronavirus disease 2019 (COVID-19). Centers forDisease Control and Prevention website. https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html. Published April 28, 2020.Accessed July 31, 2020.340 Lindsey M. Rearigh et al

Utility of Repeat Testing for COVID-19: Laboratory Stewardship When the Stakes are High

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Utility of Repeat Testing for COVID-19: Laboratory Stewardship When the Stakes are High

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