Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts

Hamish Houston; Seran Hakki; Timesh D Pillay; Kieran Madon; Nieves Derqui-Fernandez; Aleksandra Koycheva; Anika Singanayagam; Joe Fenn; Rhia Kundu; Emily Conibear; Robert Varro; Jessica Cutajar; Valerie Quinn; Lulu Wang; Janakan S Narean; Mica R Tolosa-Wright; Jack Barnett; Onn Min Kon; Richard Tedder; Graham Taylor; Maria Zambon; Neil Ferguson; Jake Dunning; Jonathan J Deeks; Ajit Lalvani

doi:10.1183/13993003.02308-2021

Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts

Hamish Houston, Seran Hakki, Timesh D Pillay, Kieran Madon, Nieves Derqui-Fernandez, Aleksandra Koycheva, Anika Singanayagam, Joe Fenn, Rhia Kundu, Emily Conibear, Robert Varro, Jessica Cutajar, Valerie Quinn, Lulu Wang, Janakan S Narean, Mica R Tolosa-Wright, Jack Barnett, Onn Min Kon, Richard Tedder, Graham TaylorMaria Zambon, Neil Ferguson, Jake Dunning, Jonathan J Deeks, Ajit Lalvani

Centre for Stem Cells & Regenerative Medicine

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

6 Citations (Scopus)

Abstract

INTRODUCTION: The success of case isolation and contact tracing for the control of SARS-CoV-2 transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS) - fever; cough; loss or change in smell or taste - could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.

METHODS: Two prospective longitudinal London-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and AUC-ROC. Improvements in sensitivity and time-to-detection were compared to penalties in terms of specificity and number-needed-to-test.

RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%).

CONCLUSIONS: Broadening symptom criteria to include individuals with at least 2 of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time-to-detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

Original language	English
Journal	European Respiratory Journal
DOIs	https://doi.org/10.1183/13993003.02308-2021
Publication status	E-pub ahead of print - 25 Nov 2021

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Houston, H., Hakki, S., Pillay, T. D., Madon, K., Derqui-Fernandez, N., Koycheva, A., Singanayagam, A., Fenn, J., Kundu, R., Conibear, E., Varro, R., Cutajar, J., Quinn, V., Wang, L., Narean, J. S., Tolosa-Wright, M. R., Barnett, J., Kon, O. M., Tedder, R., ... Lalvani, A. (2021). Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts. European Respiratory Journal. Advance online publication. https://doi.org/10.1183/13993003.02308-2021

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title = "Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts",

abstract = "INTRODUCTION: The success of case isolation and contact tracing for the control of SARS-CoV-2 transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS) - fever; cough; loss or change in smell or taste - could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.METHODS: Two prospective longitudinal London-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and AUC-ROC. Improvements in sensitivity and time-to-detection were compared to penalties in terms of specificity and number-needed-to-test.RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion {"}≥1 of the CS, or ≥2 of the EP{"} identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than {"}≥1 of the CS{"}, with only modest reduction in specificity (5.7%).CONCLUSIONS: Broadening symptom criteria to include individuals with at least 2 of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time-to-detection, providing greater opportunities to prevent SARS-CoV-2 transmission.",

author = "Hamish Houston and Seran Hakki and Pillay, {Timesh D} and Kieran Madon and Nieves Derqui-Fernandez and Aleksandra Koycheva and Anika Singanayagam and Joe Fenn and Rhia Kundu and Emily Conibear and Robert Varro and Jessica Cutajar and Valerie Quinn and Lulu Wang and Narean, {Janakan S} and Tolosa-Wright, {Mica R} and Jack Barnett and Kon, {Onn Min} and Richard Tedder and Graham Taylor and Maria Zambon and Neil Ferguson and Jake Dunning and Deeks, {Jonathan J} and Ajit Lalvani",

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year = "2021",

month = nov,

day = "25",

doi = "10.1183/13993003.02308-2021",

language = "English",

journal = "European Respiratory Journal",

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Houston, H, Hakki, S, Pillay, TD, Madon, K, Derqui-Fernandez, N, Koycheva, A, Singanayagam, A, Fenn, J, Kundu, R, Conibear, E, Varro, R, Cutajar, J, Quinn, V, Wang, L, Narean, JS, Tolosa-Wright, MR, Barnett, J, Kon, OM, Tedder, R, Taylor, G, Zambon, M, Ferguson, N, Dunning, J, Deeks, JJ & Lalvani, A 2021, 'Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts', European Respiratory Journal. https://doi.org/10.1183/13993003.02308-2021

TY - JOUR

T1 - Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts

AU - Houston, Hamish

AU - Hakki, Seran

AU - Pillay, Timesh D

AU - Madon, Kieran

AU - Derqui-Fernandez, Nieves

AU - Koycheva, Aleksandra

AU - Singanayagam, Anika

AU - Fenn, Joe

AU - Kundu, Rhia

AU - Conibear, Emily

AU - Varro, Robert

AU - Cutajar, Jessica

AU - Quinn, Valerie

AU - Wang, Lulu

AU - Narean, Janakan S

AU - Tolosa-Wright, Mica R

AU - Barnett, Jack

AU - Kon, Onn Min

AU - Tedder, Richard

AU - Taylor, Graham

AU - Zambon, Maria

AU - Ferguson, Neil

AU - Dunning, Jake

AU - Deeks, Jonathan J

AU - Lalvani, Ajit

PY - 2021/11/25

Y1 - 2021/11/25

N2 - INTRODUCTION: The success of case isolation and contact tracing for the control of SARS-CoV-2 transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS) - fever; cough; loss or change in smell or taste - could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.METHODS: Two prospective longitudinal London-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and AUC-ROC. Improvements in sensitivity and time-to-detection were compared to penalties in terms of specificity and number-needed-to-test.RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%).CONCLUSIONS: Broadening symptom criteria to include individuals with at least 2 of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time-to-detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

AB - INTRODUCTION: The success of case isolation and contact tracing for the control of SARS-CoV-2 transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS) - fever; cough; loss or change in smell or taste - could improve case definitions and accelerate case identification in SARS-CoV-2 contacts.METHODS: Two prospective longitudinal London-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and AUC-ROC. Improvements in sensitivity and time-to-detection were compared to penalties in terms of specificity and number-needed-to-test.RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%).CONCLUSIONS: Broadening symptom criteria to include individuals with at least 2 of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time-to-detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

U2 - 10.1183/13993003.02308-2021

DO - 10.1183/13993003.02308-2021

M3 - Article

C2 - 34824057

SN - 0903-1936

JO - European Respiratory Journal

JF - European Respiratory Journal

ER -

Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts

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