Disentangling post-vaccination symptoms from early COVID-19

Liane S Canas; Marc F Österdahl; Jie Deng; Christina Hu; Somesh Selvachandran; Lorenzo Polidori; Anna May; Erika Molteni; Benjamin Murray; Liyuan Chen; Eric Kerfoot; Kerstin Klaser; Michela Antonelli; Alexander Hammers; Tim Spector; Sebastien Ourselin; Claire Steves; Carole H Sudre; Marc Modat; Emma L Duncan

doi:10.1016/j.eclinm.2021.101212

Disentangling post-vaccination symptoms from early COVID-19

Liane S Canas, Marc F Österdahl, Jie Deng, Christina Hu, Somesh Selvachandran, Lorenzo Polidori, Anna May, Erika Molteni, Benjamin Murray, Liyuan Chen, Eric Kerfoot, Kerstin Klaser, Michela Antonelli, Alexander Hammers, Tim Spector, Sebastien Ourselin, Claire Steves, Carole H Sudre, Marc Modat, Emma L Duncan

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Abstract

Background: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. DesignMethods: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation: Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. Acknowledgements: ZOE Limited provided in-kind support for all aspects of building, running and supporting the app and service to all users worldwide. This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z) and the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. Investigators also received support from Medical Research Council (MRC), British Heart Foundation (BHF), Alzheimer’s Society, European Union, NIHR, COVID-19 Driver Relief Fund (CDRF) and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre (BRC) based at GSTT NHS Foundation Trust in partnership with KCL. SO was supported by the French government, through the 3IA Côte d’Azur Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-19-P3IA-0002. This research was funded in part by the Wellcome Trust [215010/Z/18/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission.

Original language	English
Article number	101212
Journal	EClinicalMedicine
Volume	42
Early online date	1 Dec 2021
DOIs	https://doi.org/10.1016/j.eclinm.2021.101212
Publication status	Published - Dec 2021

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10.1016/j.eclinm.2021.101212

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Canas, L. S., Österdahl, M. F., Deng, J., Hu, C., Selvachandran, S., Polidori, L., May, A., Molteni, E., Murray, B., Chen, L., Kerfoot, E., Klaser, K., Antonelli, M., Hammers, A., Spector, T., Ourselin, S., Steves, C., Sudre, C. H., Modat, M., & Duncan, E. L. (2021). Disentangling post-vaccination symptoms from early COVID-19. EClinicalMedicine, 42, Article 101212. https://doi.org/10.1016/j.eclinm.2021.101212

@article{2b67412490e945059780c0bbf5293c08,

title = "Disentangling post-vaccination symptoms from early COVID-19",

abstract = "Background: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. DesignMethods: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation: Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. Acknowledgements: ZOE Limited provided in-kind support for all aspects of building, running and supporting the app and service to all users worldwide. This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King{\textquoteright}s College London (WT 203148/Z/16/Z) and the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy{\textquoteright}s & St Thomas{\textquoteright} NHS Foundation Trust in partnership with King{\textquoteright}s College London and King{\textquoteright}s College Hospital NHS Foundation Trust. Investigators also received support from Medical Research Council (MRC), British Heart Foundation (BHF), Alzheimer{\textquoteright}s Society, European Union, NIHR, COVID-19 Driver Relief Fund (CDRF) and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre (BRC) based at GSTT NHS Foundation Trust in partnership with KCL. SO was supported by the French government, through the 3IA C{\^o}te d{\textquoteright}Azur Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-19-P3IA-0002. This research was funded in part by the Wellcome Trust [215010/Z/18/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission. ",

author = "Canas, {Liane S} and {\"O}sterdahl, {Marc F} and Jie Deng and Christina Hu and Somesh Selvachandran and Lorenzo Polidori and Anna May and Erika Molteni and Benjamin Murray and Liyuan Chen and Eric Kerfoot and Kerstin Klaser and Michela Antonelli and Alexander Hammers and Tim Spector and Sebastien Ourselin and Claire Steves and Sudre, {Carole H} and Marc Modat and Duncan, {Emma L}",

note = "{\textcopyright} 2021 The Authors.",

year = "2021",

month = dec,

doi = "10.1016/j.eclinm.2021.101212",

language = "English",

volume = "42",

journal = "EClinicalMedicine",

issn = "2589-5370",

publisher = "Lancet Publishing Group",

}

Canas, LS , Österdahl, MF, Deng, J, Hu, C, Selvachandran, S, Polidori, L, May, A, Molteni, E , Murray, B, Chen, L, Kerfoot, E , Klaser, K , Antonelli, M , Hammers, A , Spector, T , Ourselin, S , Steves, C , Sudre, CH , Modat, M & Duncan, EL 2021, 'Disentangling post-vaccination symptoms from early COVID-19', EClinicalMedicine, vol. 42, 101212. https://doi.org/10.1016/j.eclinm.2021.101212

TY - JOUR

T1 - Disentangling post-vaccination symptoms from early COVID-19

AU - Canas, Liane S

AU - Österdahl, Marc F

AU - Deng, Jie

AU - Hu, Christina

AU - Selvachandran, Somesh

AU - Polidori, Lorenzo

AU - May, Anna

AU - Molteni, Erika

AU - Murray, Benjamin

AU - Chen, Liyuan

AU - Kerfoot, Eric

AU - Klaser, Kerstin

AU - Antonelli, Michela

AU - Hammers, Alexander

AU - Spector, Tim

AU - Ourselin, Sebastien

AU - Steves, Claire

AU - Sudre, Carole H

AU - Modat, Marc

AU - Duncan, Emma L

PY - 2021/12

Y1 - 2021/12

N2 - Background: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. DesignMethods: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation: Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. Acknowledgements: ZOE Limited provided in-kind support for all aspects of building, running and supporting the app and service to all users worldwide. This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z) and the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. Investigators also received support from Medical Research Council (MRC), British Heart Foundation (BHF), Alzheimer’s Society, European Union, NIHR, COVID-19 Driver Relief Fund (CDRF) and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre (BRC) based at GSTT NHS Foundation Trust in partnership with KCL. SO was supported by the French government, through the 3IA Côte d’Azur Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-19-P3IA-0002. This research was funded in part by the Wellcome Trust [215010/Z/18/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission.

AB - Background: Identifying and testing individuals likely to have SARS-CoV-2 is critical for infection control, including post-vaccination. Vaccination is a major public health strategy to reduce SARS-CoV-2 infection globally. Some individuals experience systemic symptoms post-vaccination, which overlap with COVID-19 symptoms. This study compared early post-vaccination symptoms in individuals who subsequently tested positive or negative for SARS-CoV-2, using data from the COVID Symptom Study (CSS) app. DesignMethods: We conducted a prospective observational study in 1,072,313 UK CSS participants who were asymptomatic when vaccinated with Pfizer-BioNTech mRNA vaccine (BNT162b2) or Oxford-AstraZeneca adenovirus-vectored vaccine (ChAdOx1 nCoV-19) between 8 December 2020 and 17 May 2021, who subsequently reported symptoms within seven days (N=362,770) (other than local symptoms at injection site) and were tested for SARS-CoV-2 (N=14,842), aiming to differentiate vaccination side-effects per se from superimposed SARS-CoV-2 infection. The post-vaccination symptoms and SARS-CoV-2 test results were contemporaneously logged by participants. Demographic and clinical information (including comorbidities) were also recorded. Symptom profiles in individuals testing positive were compared with a 1:1 matched population testing negative, including using machine learning and multiple models including UK testing criteria. Findings: Differentiating post-vaccination side-effects alone from early COVID-19 was challenging, with a sensitivity in identification of individuals testing positive of 0.6 at best. Most of these individuals did not have fever, persistent cough, or anosmia/dysosmia, requisite symptoms for accessing UK testing; and many only had systemic symptoms commonly seen post-vaccination in individuals negative for SARS-CoV-2 (headache, myalgia, and fatigue). Interpretation: Post-vaccination side-effects per se cannot be differentiated from COVID-19 with clinical robustness, either using symptom profiles or machine-derived models. Individuals presenting with systemic symptoms post-vaccination should be tested for SARS-CoV-2 or quarantining, to prevent community spread. Acknowledgements: ZOE Limited provided in-kind support for all aspects of building, running and supporting the app and service to all users worldwide. This work is supported by the Wellcome EPSRC Centre for Medical Engineering at King’s College London (WT 203148/Z/16/Z) and the UK Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. Investigators also received support from Medical Research Council (MRC), British Heart Foundation (BHF), Alzheimer’s Society, European Union, NIHR, COVID-19 Driver Relief Fund (CDRF) and the NIHR-funded BioResource, Clinical Research Facility and Biomedical Research Centre (BRC) based at GSTT NHS Foundation Trust in partnership with KCL. SO was supported by the French government, through the 3IA Côte d’Azur Investments in the Future project managed by the National Research Agency (ANR) with the reference number ANR-19-P3IA-0002. This research was funded in part by the Wellcome Trust [215010/Z/18/Z]. For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript (AAM) version arising from this submission.

U2 - 10.1016/j.eclinm.2021.101212

DO - 10.1016/j.eclinm.2021.101212

M3 - Article

C2 - 34873584

SN - 2589-5370

VL - 42

JO - EClinicalMedicine

JF - EClinicalMedicine

M1 - 101212

ER -

Disentangling post-vaccination symptoms from early COVID-19

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