Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial

Ellie McDonald; Laure F Pittet; Marc Bonten; Anthony Byrne; John Campbell; Julio Croda; Margareth Dalcolmo; A J Davidson; Glauce Dos Santos; Kaya Gardiner; Amanda Gwee; Bruno Jardim; Marcus Lacerda; Michaela Lucas; David J Lynn; Laurens Manning; Helen Marshall; Kirsten P Perrett; Cristina Prat-Aymerich; Marco Antonio Moreira Puga; Peter Richmond; Jesús Rodríguez-Baño; Ushma Wadia; Adilia Warris; Nicholas Wood; Nigel Curtis; Nicole L Messina

doi:10.1186/s12879-026-13128-6

Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial

Ellie McDonald
, Laure F Pittet
, Marc Bonten
, Anthony Byrne
, John Campbell
, Julio Croda
, Margareth Dalcolmo
, A J Davidson
, Glauce Dos Santos
, Kaya Gardiner
, Amanda Gwee
, Bruno Jardim
, Marcus Lacerda
, Michaela Lucas
, David J Lynn
, Laurens Manning
, Helen Marshall
, Kirsten P Perrett
, Cristina Prat-Aymerich
, Marco Antonio Moreira Puga

Peter Richmond, Jesús Rodríguez-Baño, Ushma Wadia, Adilia Warris, Nicholas Wood, Nigel Curtis, Nicole L Messina^*,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND: Accurately identifying COVID-19 episodes was crucial during the pandemic for evaluating interventions. Results from diagnostic tools like PCR, rapid antigen test (RAT) and serology are affected by factors such as timing of tests and vaccination status. The BRACE trial developed an algorithm integrating these diagnostic tools for illness episode classification.

METHODS: In the BRACE trial, 3988 participants reported 5512 febrile/respiratory illness episodes and provided longitudinal blood samples over one year. SARS-CoV-2 diagnosis relied on a three-component algorithm: (1) a serology algorithm assessing anti-SARS-CoV-2 nucleocapsid antibody seroconversion, (2) a PCR/RAT algorithm, and (3) an episode interpretation algorithm combining serology and PCR/RAT results to categorise episodes as COVID-19, Not COVID-19 or Uncertain. The algorithms accounted for vaccination status and timing of testing relative to symptom onset to refine episode classifications.

RESULTS: Of 5512 illness episodes, 890 (16%) were classified as COVID-19, 3852 (70%) as Not COVID-19, and 770 (14%) as Uncertain. Compared to relying solely on PCR/RAT results, integrating serology in the algorithm reduced the proportion of Uncertain classifications by more than half. Among the COVID-19 episodes, 89% were identified by positive PCR/RAT results, and the remaining 11% (with missing or negative PCR/RAT tests) were identified by serology. Discordance between PCR/RAT and serology occurred in 9% of episodes.

CONCLUSIONS: An algorithm integrating PCR/RAT and serology results in the context of test timing and vaccine status enabled the accurate identification of COVID-19 episodes and minimised the number of episodes that would otherwise have been classified as Uncertain.

TRIAL REGISTRATION: The BRACE trial: BCG vaccination to reduce the impact of COVID-19 in healthcare workers.

CLINICALTRIALS: gov NCT04327206, Registration date:27 March 2020.

Original language	English
Journal	BMC Infectious Diseases
Volume	26
Issue number	1
DOIs	https://doi.org/10.1186/s12879-026-13128-6
Publication status	Published - 7 Apr 2026

Keywords

Humans
COVID-19/diagnosis
SARS-CoV-2/immunology
Algorithms
COVID-19 Serological Testing/methods
Male
Middle Aged
Female
Adult
Antibodies, Viral/blood
Polymerase Chain Reaction/methods

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s12879-026-13128-6Final published version, 1.44 MBLicence: CC BY

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McDonald, E., Pittet, L. F., Bonten, M., Byrne, A., Campbell, J., Croda, J., Dalcolmo, M., Davidson, A. J., Dos Santos, G., Gardiner, K., Gwee, A., Jardim, B., Lacerda, M., Lucas, M., Lynn, D. J., Manning, L., Marshall, H., Perrett, K. P., Prat-Aymerich, C. (2026). Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial. BMC Infectious Diseases, 26(1). https://doi.org/10.1186/s12879-026-13128-6

@article{cd6d340bea914872a6133e4f471fecb5,

title = "Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial",

abstract = "BACKGROUND: Accurately identifying COVID-19 episodes was crucial during the pandemic for evaluating interventions. Results from diagnostic tools like PCR, rapid antigen test (RAT) and serology are affected by factors such as timing of tests and vaccination status. The BRACE trial developed an algorithm integrating these diagnostic tools for illness episode classification.METHODS: In the BRACE trial, 3988 participants reported 5512 febrile/respiratory illness episodes and provided longitudinal blood samples over one year. SARS-CoV-2 diagnosis relied on a three-component algorithm: (1) a serology algorithm assessing anti-SARS-CoV-2 nucleocapsid antibody seroconversion, (2) a PCR/RAT algorithm, and (3) an episode interpretation algorithm combining serology and PCR/RAT results to categorise episodes as COVID-19, Not COVID-19 or Uncertain. The algorithms accounted for vaccination status and timing of testing relative to symptom onset to refine episode classifications.RESULTS: Of 5512 illness episodes, 890 (16\%) were classified as COVID-19, 3852 (70\%) as Not COVID-19, and 770 (14\%) as Uncertain. Compared to relying solely on PCR/RAT results, integrating serology in the algorithm reduced the proportion of Uncertain classifications by more than half. Among the COVID-19 episodes, 89\% were identified by positive PCR/RAT results, and the remaining 11\% (with missing or negative PCR/RAT tests) were identified by serology. Discordance between PCR/RAT and serology occurred in 9\% of episodes.CONCLUSIONS: An algorithm integrating PCR/RAT and serology results in the context of test timing and vaccine status enabled the accurate identification of COVID-19 episodes and minimised the number of episodes that would otherwise have been classified as Uncertain.TRIAL REGISTRATION: The BRACE trial: BCG vaccination to reduce the impact of COVID-19 in healthcare workers.CLINICALTRIALS: gov NCT04327206, Registration date:27 March 2020.",

keywords = "Humans, COVID-19/diagnosis, SARS-CoV-2/immunology, Algorithms, COVID-19 Serological Testing/methods, Male, Middle Aged, Female, Adult, Antibodies, Viral/blood, Polymerase Chain Reaction/methods",

author = "Ellie McDonald and Pittet, \{Laure F\} and Marc Bonten and Anthony Byrne and John Campbell and Julio Croda and Margareth Dalcolmo and Davidson, \{A J\} and \{Dos Santos\}, Glauce and Kaya Gardiner and Amanda Gwee and Bruno Jardim and Marcus Lacerda and Michaela Lucas and Lynn, \{David J\} and Laurens Manning and Helen Marshall and Perrett, \{Kirsten P\} and Cristina Prat-Aymerich and Puga, \{Marco Antonio Moreira\} and Peter Richmond and Jes{\'u}s Rodr{\'i}guez-Ba{\~n}o and Ushma Wadia and Adilia Warris and Nicholas Wood and Nigel Curtis and Messina, \{Nicole L\}",

note = "{\textcopyright} 2026. The Author(s).",

year = "2026",

month = apr,

day = "7",

doi = "10.1186/s12879-026-13128-6",

language = "English",

volume = "26",

journal = "BMC Infectious Diseases",

issn = "1471-2334",

publisher = "BioMed Central Ltd.",

number = "1",

}

McDonald, E, Pittet, LF, Bonten, M, Byrne, A, Campbell, J, Croda, J, Dalcolmo, M, Davidson, AJ, Dos Santos, G, Gardiner, K, Gwee, A, Jardim, B, Lacerda, M, Lucas, M, Lynn, DJ, Manning, L, Marshall, H, Perrett, KP, Prat-Aymerich, C, Puga, MAM, Richmond, P, Rodríguez-Baño, J, Wadia, U, Warris, A, Wood, N, Curtis, N, Messina, NL 2026, 'Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial', BMC Infectious Diseases, vol. 26, no. 1. https://doi.org/10.1186/s12879-026-13128-6

TY - JOUR

T1 - Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing

T2 - insights from the BRACE trial

AU - McDonald, Ellie

AU - Pittet, Laure F

AU - Bonten, Marc

AU - Byrne, Anthony

AU - Campbell, John

AU - Croda, Julio

AU - Dalcolmo, Margareth

AU - Davidson, A J

AU - Dos Santos, Glauce

AU - Gardiner, Kaya

AU - Gwee, Amanda

AU - Jardim, Bruno

AU - Lacerda, Marcus

AU - Lucas, Michaela

AU - Lynn, David J

AU - Manning, Laurens

AU - Marshall, Helen

AU - Perrett, Kirsten P

AU - Prat-Aymerich, Cristina

AU - Puga, Marco Antonio Moreira

AU - Richmond, Peter

AU - Rodríguez-Baño, Jesús

AU - Wadia, Ushma

AU - Warris, Adilia

AU - Wood, Nicholas

AU - Curtis, Nigel

AU - Messina, Nicole L

PY - 2026/4/7

Y1 - 2026/4/7

N2 - BACKGROUND: Accurately identifying COVID-19 episodes was crucial during the pandemic for evaluating interventions. Results from diagnostic tools like PCR, rapid antigen test (RAT) and serology are affected by factors such as timing of tests and vaccination status. The BRACE trial developed an algorithm integrating these diagnostic tools for illness episode classification.METHODS: In the BRACE trial, 3988 participants reported 5512 febrile/respiratory illness episodes and provided longitudinal blood samples over one year. SARS-CoV-2 diagnosis relied on a three-component algorithm: (1) a serology algorithm assessing anti-SARS-CoV-2 nucleocapsid antibody seroconversion, (2) a PCR/RAT algorithm, and (3) an episode interpretation algorithm combining serology and PCR/RAT results to categorise episodes as COVID-19, Not COVID-19 or Uncertain. The algorithms accounted for vaccination status and timing of testing relative to symptom onset to refine episode classifications.RESULTS: Of 5512 illness episodes, 890 (16%) were classified as COVID-19, 3852 (70%) as Not COVID-19, and 770 (14%) as Uncertain. Compared to relying solely on PCR/RAT results, integrating serology in the algorithm reduced the proportion of Uncertain classifications by more than half. Among the COVID-19 episodes, 89% were identified by positive PCR/RAT results, and the remaining 11% (with missing or negative PCR/RAT tests) were identified by serology. Discordance between PCR/RAT and serology occurred in 9% of episodes.CONCLUSIONS: An algorithm integrating PCR/RAT and serology results in the context of test timing and vaccine status enabled the accurate identification of COVID-19 episodes and minimised the number of episodes that would otherwise have been classified as Uncertain.TRIAL REGISTRATION: The BRACE trial: BCG vaccination to reduce the impact of COVID-19 in healthcare workers.CLINICALTRIALS: gov NCT04327206, Registration date:27 March 2020.

AB - BACKGROUND: Accurately identifying COVID-19 episodes was crucial during the pandemic for evaluating interventions. Results from diagnostic tools like PCR, rapid antigen test (RAT) and serology are affected by factors such as timing of tests and vaccination status. The BRACE trial developed an algorithm integrating these diagnostic tools for illness episode classification.METHODS: In the BRACE trial, 3988 participants reported 5512 febrile/respiratory illness episodes and provided longitudinal blood samples over one year. SARS-CoV-2 diagnosis relied on a three-component algorithm: (1) a serology algorithm assessing anti-SARS-CoV-2 nucleocapsid antibody seroconversion, (2) a PCR/RAT algorithm, and (3) an episode interpretation algorithm combining serology and PCR/RAT results to categorise episodes as COVID-19, Not COVID-19 or Uncertain. The algorithms accounted for vaccination status and timing of testing relative to symptom onset to refine episode classifications.RESULTS: Of 5512 illness episodes, 890 (16%) were classified as COVID-19, 3852 (70%) as Not COVID-19, and 770 (14%) as Uncertain. Compared to relying solely on PCR/RAT results, integrating serology in the algorithm reduced the proportion of Uncertain classifications by more than half. Among the COVID-19 episodes, 89% were identified by positive PCR/RAT results, and the remaining 11% (with missing or negative PCR/RAT tests) were identified by serology. Discordance between PCR/RAT and serology occurred in 9% of episodes.CONCLUSIONS: An algorithm integrating PCR/RAT and serology results in the context of test timing and vaccine status enabled the accurate identification of COVID-19 episodes and minimised the number of episodes that would otherwise have been classified as Uncertain.TRIAL REGISTRATION: The BRACE trial: BCG vaccination to reduce the impact of COVID-19 in healthcare workers.CLINICALTRIALS: gov NCT04327206, Registration date:27 March 2020.

KW - Humans

KW - COVID-19/diagnosis

KW - SARS-CoV-2/immunology

KW - Algorithms

KW - COVID-19 Serological Testing/methods

KW - Male

KW - Middle Aged

KW - Female

KW - Adult

KW - Antibodies, Viral/blood

KW - Polymerase Chain Reaction/methods

U2 - 10.1186/s12879-026-13128-6

DO - 10.1186/s12879-026-13128-6

M3 - Article

C2 - 41947067

SN - 1471-2334

VL - 26

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

IS - 1

ER -

Optimising COVID-19 episode identification using serology and PCR/rapid antigen testing: insights from the BRACE trial

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