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Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design

Version 3 2024-06-11, 06:10
Version 2 2024-01-09, 07:54
Version 1 2023-12-28, 06:36
journal contribution
revised on 2024-06-11, 06:03 and posted on 2024-06-11, 06:10 authored by Houssein H Ayoub, Milan Tomy, Hiam Chemaitelly, Heba N Altarawneh, Peter Coyle, Patrick Tang, Mohammad R Hasan, Zaina Al Kanaani, Einas Al Kuwari, Adeel A Butt, Andrew Jeremijenko, Anvar Hassan Kaleeckal, Ali Nizar Latif, Riyazuddin Mohammad Shaik, Gheyath K Nasrallah, Fatiha M Benslimane, Hebah A Al Khatib, Hadi M Yassine, Mohamed G Al Kuwari, Hamad Eid Al Romaihi, Hanan F Abdul-Rahim, Mohamed H Al-Thani, Abdullatif Al Khal, Roberto Bertollini, Laith J Abu-Raddad

The COVID-19 pandemic has highlighted the need to use infection testing databases to rapidly estimate effectiveness of prior infection in preventing reinfection (PEs) by novel SARS-CoV-2 variants. Mathematical modeling was used to demonstrate a theoretical foundation for applicability of the test-negative, case-control study design to derive PEs. Apart from the very early phase of an epidemic, the difference between the test-negative estimate for PEs and true value of PEs was minimal and became negligible as the epidemic progressed. The test-negative design provided robust estimation of PEs and its waning. Assuming that only 25% of prior infections are documented, misclassification of prior infection status underestimated PEs, but the underestimate was considerable only when >50% of the population was ever infected. Misclassification of latent infection, misclassification of current active infection, and scale-up of vaccination all resulted in negligible bias in estimated PEs. The test-negative design was applied to national-level testing data in Qatar to estimate PEs for SARS-CoV-2. PEs against SARS-CoV-2 Alpha and Beta variants was estimated at 97.0% (95% CI: 93.6-98.6) and 85.5% (95% CI: 82.4-88.1), respectively. These estimates were validated using a cohort study design. The test-negative design offers a feasible, robust method to estimate protection from prior infection in preventing reinfection.

Other Information

Published in: American Journal of Epidemiology
See article on publisher's website:


Open Access funding provided by the Qatar National Library.

Qatar University collaborative grant (QUCG-CAS-23/24-114).

Marubeni grant (M-QJRC-2020-5).

Qatar National Research Fund (NPRP 9-040-3-008).

Qatar National Research Fund (NPRP 12S-0216-190094).



  • English


Oxford University Press

Publication Year

  • 2023

License statement

This Item is licensed under the Creative Commons Attribution 4.0 International License.

Institution affiliated with

  • Qatar University
  • College of Arts and Sciences - QU
  • Biomedical Research Center - QU
  • Qatar University Health - QU
  • Weill Cornell Medicine - Qatar
  • WHO Collaborating Centre for Disease Epidemiology Analytics on HIV/AIDS, Sexually Transmitted Infections, and Viral Hepatitis - WCM-Q
  • Hamad Medical Corporation
  • Hamad General Hospital - HMC

Geographic coverage


Related Datasets

Ayoub, H. H., Tomy, M., Chemaitelly, H., Altarawneh, H. N., Coyle, P., Tang, P., Hasan, M. R., Kanaani, Z. A., Kuwari, E. A., Butt, A. A., Jeremijenko, A., Kaleeckal, A. H., Latif, A. N., Shaik, R. M., Nasrallah, G. K., Benslimane, F. M., Khatib, H. A. A., Yassine, H. M., Kuwari, M. G. A., … Abu-Raddad, L. J. (2023). Estimating protection afforded by prior infection in preventing reinfection: Applying the test-negative study design. GitHub repository. Last modified 2022.

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