SARS-CoV-2/COVID-19 Testing: The Tower of Babel

SARS-CoV-2/COVID-19 Testing: The Tower of Babel

Authors

  • Chiara Reno Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna
  • Jacopo Lenzi Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna
  • Davide Golinelli Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna
  • Davide Gori Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna
  • Carlo Signorelli Università Vita-Salute San Raffaele; Dipartimento di Medicina e Chirurgia, Università degli Studi di Parma
  • John Kraemer Department of Health Systems Administration, Georgetown University
  • Michael A. Stoto Department of Health Systems Administration, Georgetown University; Emergency Preparedness Research, Evaluation and Practice (EPREP) Program, Harvard T.H. Chan School of Public Health
  • Elisa Avitabile Dipartimento di Farmacia e Biotecnologie, Alma Mater Studiorum - Università di Bologna
  • Maria Paola Landini IRCCS Istituto Ortopedico Rizzoli; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Alma Mater Studiorum - Università di Bologna
  • Tiziana Lazzarotto Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Alma Mater Studiorum - Università di Bologna, Bologna
  • Maria Carla Re Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Alma Mater Studiorum - Università di Bologna
  • Paola Rucci Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna
  • Gloria Taliani Dipartimento di Medicina Traslazionale e di Precisione, Università degli Studi di Roma "La Sapienza"
  • Davide Trerè Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Alma Mater Studiorum - Università di Bologna
  • Caterina Vocale IRCCS Azienda Ospedaliero-Universitaria "Policlinico Sant'Orsola-Malpighi" di Bologna
  • Maria Pia Fantini Dipartimento di Scienze Biomediche e Neuromotorie, Alma Mater Studiorum - Università di Bologna

Keywords:

COVID-19, SARS-CoV-2, Pandemic, Molecular Diagnostic Techniques, Rapid Antigen Test, Pooling Test, Predictive Value of Tests, Public Health Surveillance, Screening

Abstract

Background and aim: Testing represents one of the main pillars of public health response to SARS-CoV-2/COVID-19 pandemic. This paper shows how accuracy and utility of testing programs depend not just on the type of tests, but on the context as well.

Methods: We describe the testing methods that have been developed and the possible testing strategies; then, we focus on two possible methods of population-wide testing, i.e., pooled testing and testing with rapid antigen tests. We show the accuracy of split-pooling method and how, in different pre-test probability scenarios, the positive and negative predictive values vary using rapid antigen tests.

Results: Split-pooling, followed by retesting of negative results, shows a higher sensitivity than individual testing and requires fewer tests. In case of low pre-test probability, a negative result with antigen test could allow to rule out the infection, while, in case of a positive result, a confirmatory molecular test would be necessary.

Conclusions: Test performance alone is not enough to properly choose which test to use; goals and context of the testing program are essential. We advocate the use of pooled strategies when planning population-wide screening, and the weekly use of rapid tests for close periodic monitoring in low-prevalence populations.

References

European Centre for Disease Prevention and Control. Using face masks in the community. Stockholm: ECDC; 2020.

Pasquarella C, Colucci ME, Bizzarro A, et al. Detection of SARS-CoV-2 on hospital surfaces. Acta Biomed. 2020;91(9-S):76-78.

European Centre for Disease Prevention and Control. Population-wide testing of SARS-CoV-2: country experiences and potential approaches in the EU/EEA and the UK Stockholm: ECDC; 2020

Food & Drug Administration. Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised). May 11, 2020. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-coronavirus-disease-2019-tests-during-public-health-emergency-revised (accessed Nov 6, 2020)

European Commission. COMMUNICATION FROM THE COMMISSION: Guidelines on COVID-19 in vitro diagnostic tests and their performance. April 15, 2020. https://eur-lex.europa.eu/legal-content/EN/TXT/?uri=CELEX:52020XC0415(04) (accessed Nov 6, 2020)

European Commission. Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices. https://eur-lex.europa.eu/legal-content/EN/ALL/?uri=CELEX%3A31998L0079 October 27, 1998 (accessed Nov 6, 2020)

Centers for Disease Control and Prevention. Interim Guidance for Rapid Antigen Testing for SARS-CoV-2. September 4, 2020. https://www.cdc.gov/coronavirus/2019-ncov/lab/resources/antigen-tests-guidelines.html (accessed Nov 6, 2020)

Istituto Superiore di Sanità. Report ISS 29 maggio. May 29, 2020. https://www.epicentro.iss.it/coronavirus/pdf/rapporto-covid-19-11-2020.pdf (accessed Nov 6, 2020)

Riccò M, Ferraro P, Gualerzi G, et al. Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data. J Clin Med. 2020;9(5):1515.

Veronesi L, Colucci ME, Pasquarella C, et al. Virological surveillance of SARS-CoV-2 in an Italian northern area: comparison of Real Time RT PCR cycle threshold (Ct) values in three epidemic periods. Acta Biomed. 2020;91(9-S):19-21.

Sethuraman N, Jeremiah SS, Ryo A. Interpreting Diagnostic Tests for SARS-CoV-2. JAMA. 2020;323(22):2249–2251.

Kucirka LM, Lauer SA, Laeyendecker O, Boon D, Lessler J. Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction-Based SARS-CoV-2 Tests by Time Since Exposure. Ann Intern Med. 2020 Aug 18;173(4):262-267.

Wyllie AL, Fournier J, Casanovas-Massana A, et al. Saliva or Nasopharyngeal Swab Specimens for Detection of SARS-CoV-2. N Engl J Med. 2020;10.1056/NEJMc2016359.

Food & Drug Administration. Coronavirus (COVID-19) Update: FDA Issues Emergency Use Authorization to Yale School of Public Health for SalivaDirect, Which Uses a New Method of Saliva Sample Processing. August 15, 2020 https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-issues-emergency-use-authorization-yale-school-public-health (accessed Nov 6, 2020)

SalivaDirect https://publichealth.yale.edu/salivadirect/ (accessed Nov 6, 2020)

Dinnes J, Deeks JJ, Adriano A, Berhane S, Davenport C, Dittrich S, et al. Cochrane COVID-19 Diagnostic Test Accuracy Group. Rapid, point-of-care antigen and molecular-based tests for diagnosis of SARS-CoV-2 infection. Cochrane Database Syst Rev. 2020 Aug 26;8:CD013705.

Piltch-Loeb, R.N., Jeong, K.Y., Lin, K., Kraemer, J.D., Stoto, M.A. Interpreting COVID-19 test results in clinical settings: it depends! Journal of the American Board of Family Medicine, published online ahead of print on October 9, 2020.

Stoto M.A., Wynia, M.K. Assessing Morbidity and Mortality Associated with the COVID-19 Pandemic: A Case Study Illustrating the Need for the Recommendations in this Report. In National Academies of Sciences, Engineering, and Medicine, A Framework for Assessing Mortality and Morbidity After Large-Scale Disasters, 2020. (https://www.nap.edu/read/25863/chapter/11)

Piltch-Loeb R, Kraemer J, Lin KW, Stoto MA. Public Health Surveillance for Zika Virus: Data Interpretation and Report Validity. Am J Public Health. 2018 Oct;108(10):1358-1362.

Rosenberg ES, Hall EW, Rosenthal EM, et al. Monitoring Coronavirus Disease 2019 (COVID-19) Through Trends in Influenza-like Illness, Laboratory-confirmed Influenza, and COVID-19—New York State, Excluding New York City, 1 January 2020–12 April 2020. Clin Infect Dis. 2020; 4-7.

Gudbjartsson DF, Helgason A, Jonsson H, et al. Spread of SARS-CoV-2 in the Icelandic population. N Engl J Med. 2020;382(24):2302-2315.

Stringhini S, Wisniak A, Piumatti G, et al. Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Geneva, Switzerland (SEROCoV-POP): a population-based study. Lancet. 2020;396(10247):313-319.

Pollán M, Pérez-Gómez B, Pastor-Barriuso R, Oteo J, Hernán MA, Pérez-Olmeda et al. ENE-COVID Study Group. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020 Aug 22;396(10250):535-544.

ISTAT. Primi risultati dell’indagine di sieroprevalenza sul SARS-CoV-2. Italian Institute of Statistics. August 2020. https://www.istat.it/it/files/2020/08/ReportPrimiRisultatiIndagineSiero.pdf

(accessed October 30, 2020)

Perico L, Tomasoni S, Peracchi T, Perna A, Pezzotta A, Remuzzi G, Benigni A. COVID-19 and lombardy: TESTing the impact of the first wave of the pandemic. EBioMedicine. 2020 Oct 22;61:103069.

Anand S, Montez-Rath M, Han J, et al. Prevalence of SARS-CoV-2 antibodies in a large nationwide sample of patients on dialysis in the USA: a cross-sectional study. Lancet. 2020;6736(20):1-10.

Cox, R.J., Brokstad, K.A. Not just antibodies: B cells and T cells mediate immunity to COVID-19. Nat Rev Immunol 20, 581–582 (2020).

Walke HT, Honein MA, Redfield RR. Preventing and Responding to COVID-19 on College Campuses. JAMA. 2020;324(17):1727-1728

Mina MJ, Parker R, Larremore DB. Rethinking Covid-19 Test Sensitivity - A Strategy for Containment. N Engl J Med. 2020 Sep 30.

Paltiel AD, Zheng A, Walensky RP. Assessment of SARS-CoV-2 screening strategies to permit the safe reopening of college campuses in the United States. JAMA Network Open 2020; 3(7): e2016818.

Weis S, Sherag A, Baier M, Kiehntopf M, Kamradt Y, Kolanos S, et al. Seroprevalence of SARS-CoV-2 antibodies in an entirely PCR-sampled and quarantined community after a COVID-19 outbreak - the CoNAN study. medRxiv 2020.07.15.20154112; doi: https://doi.org/10.1101/2020.07.15.20154112

European Center for Disease Control. Diagnostic testing and screening for SARS-CoV-2. June 11, 2020 Stockholm: ECDC; 2020 https://www.ecdc.europa.eu/en/covid-19/latest-evidence/diagnostic-testing (accessed Nov 6, 2020)

Gandhi M, Yokoe DS, Havlir DV. Asymptomatic Transmission, the Achilles' Heel of Current Strategies to Control Covid-19. N Engl J Med. 2020 May 28;382(22):2158-2160.

European Center for Disease Control. COVID-19 in children and the role of school settings in COVID-19 transmission. August 6, 2020. Stockholm: ECDC; 2020.

Lavezzo, E., Franchin, E., Ciavarella, C. et al. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’. Nature 584, 425–429 (2020).

European Centre for Disease Prevention and Control. Methodology for estimating point prevalence of SARSCoV-2 infection by pooled RT-PCR testing. Stockholm: ECDC; 2020.

Saarland University. Virologists show that sample pooling can massively increase coronavirus testing capacity. April 28, 2020. https://www.eurekalert.org/pub_releases/2020-04/su-vst042820.php (accessed October 30, 2020)

Dorfman R. The detection of defective numbers of large populations. Ann Math Stat.

;14:436-440

Litvak E, Tu XM, Pagano M. Screening for the Presence of a Disease by Pooling Sera Samples. Journal of the American Statistical Association 1994:89(426):424-434.

Mahase E. Covid-19: Universities roll out pooled testing of students in bid to keep campuses open BMJ 2020; 370 :m3789

Carlson C. How will Syracuse University test 20,000 students for coronavirus? By pooling their saliva. July 08, 2020 https://www.syracuse.com/coronavirus/2020/07/how-will-syracuse-university-test-20000-students-for-coronavirus-by-pooling-their-saliva.html (accessed October 30, 2020)

LOMT - Laboratory Optimizer for Mass Testing https://lomt.jetware.org/ (accessed October 30, 2020)

Results Manager. https://www.results-manager.com/ (accessed October 30, 2020)

Guglielmi G. Fast coronavirus tests: what they can and can’t do. Nature 585, 496-498 (2020)

Scondotto S, Bisceglia L, Bauleo L, et al. Associazione Italiana di Epidemiologia. COVID-19: strumenti per decisioni politiche fondate sulle prove. October 28, 2020. https://www.epidemiologia.it/wp-content/uploads/2020/10/COVID-19_strumenti-per-decisioni-politiche-fondate-sulle-prove_AIE.pdf (accessed November 6, 2020)

Watson J. Interpreting a covid-19 test result. BMJ 2020;369:m1808

INAIL. Test di laboratorio per SARS-CoV-2e loro uso in sanità pubblica. https://www.inail.it/cs/internet/docs/alg-test-laboratorio-sar-covid.pdf (accessed October 30, 2020)

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Published

09-11-2020

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Section

ORIGINAL INVESTIGATIONS/COMMENTARIES - SPECIAL COVID19

How to Cite

1.
Reno C, Lenzi J, Golinelli D, Gori D, Signorelli C, Kraemer J, et al. SARS-CoV-2/COVID-19 Testing: The Tower of Babel. Acta Biomed [Internet]. 2020 Nov. 9 [cited 2024 Jul. 5];91(4):e2020144. Available from: https://mattioli1885journals.com/index.php/actabiomedica/article/view/10911