Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies

S. A. Behnood; R. Shafran; S. D. Bennett; A. X.D. Zhang; L. L. O'Mahoney; T. J. Stephenson; S. N. Ladhani; B. L. De Stavola; R. M. Viner; O. V. Swann

doi:10.1016/j.jinf.2021.11.011

Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies

S. A. Behnood, R. Shafran, S. D. Bennett, A. X.D. Zhang, L. L. O'Mahoney, T. J. Stephenson, S. N. Ladhani, B. L. De Stavola, R. M. Viner, O. V. Swann^*

^*Corresponding author for this work

Immunisation Hepatitis and Blood Safety

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

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Abstract

Background: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration.

Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153.

Findings: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99–231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms.

Interpretation: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.

Original language	English
Pages (from-to)	158-170
Number of pages	13
Journal	Journal of Infection
Volume	84
Issue number	2
Early online date	20 Nov 2021
DOIs	https://doi.org/10.1016/j.jinf.2021.11.011
Publication status	Published - Feb 2022

Bibliographical note

Funding Information: AB, RS, SDB, AXDZ, LLO, SNL, BLDS, RMV and OVS have no conflicts of interest. TJS is the Chair of the Health Research Authority for England who reimburse his university for his time. He is not paid personally. He has recused himself from research studies in which he is personally involved and which require ethical approval from the HRA.

Open Access: . This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/)

Publisher Copyright: © 2021 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association.

Citation: Behnood, Sanaz A., et al. "Persistent symptoms following SARS-CoV-2 infection among children and young people: a meta-analysis of controlled and uncontrolled studies." Journal of Infection (2021).

DOI: https://doi.org/10.1016/j.jinf.2021.11.011

Keywords

COVID-19
Children and young people
Long COVID
Paediatric
Post-COVID syndrome
SARS-CoV-2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Behnood2022PersistentSymptomsFollowingSARS-CoV-2InfectionAmongstChildrenJInfectFinal published version, 2.02 MBLicence: CC BY-NC-ND

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Behnood, S. A., Shafran, R., Bennett, S. D., Zhang, A. X. D., O'Mahoney, L. L., Stephenson, T. J., Ladhani, S. N., De Stavola, B. L., Viner, R. M., & Swann, O. V. (2022). Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies. Journal of Infection, 84(2), 158-170. https://doi.org/10.1016/j.jinf.2021.11.011

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title = "Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies",

abstract = "Background: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration. Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. Findings: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99–231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms. Interpretation: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.",

keywords = "COVID-19, Children and young people, Long COVID, Paediatric, Post-COVID syndrome, SARS-CoV-2",

author = "Behnood, {S. A.} and R. Shafran and Bennett, {S. D.} and Zhang, {A. X.D.} and O'Mahoney, {L. L.} and Stephenson, {T. J.} and Ladhani, {S. N.} and {De Stavola}, {B. L.} and Viner, {R. M.} and Swann, {O. V.}",

note = "Funding Information: AB, RS, SDB, AXDZ, LLO, SNL, BLDS, RMV and OVS have no conflicts of interest. TJS is the Chair of the Health Research Authority for England who reimburse his university for his time. He is not paid personally. He has recused himself from research studies in which he is personally involved and which require ethical approval from the HRA. Open Access: . This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Publisher Copyright: {\textcopyright} 2021 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. Citation: Behnood, Sanaz A., et al. {"}Persistent symptoms following SARS-CoV-2 infection among children and young people: a meta-analysis of controlled and uncontrolled studies.{"} Journal of Infection (2021). DOI: https://doi.org/10.1016/j.jinf.2021.11.011",

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Behnood, SA, Shafran, R, Bennett, SD, Zhang, AXD, O'Mahoney, LL, Stephenson, TJ, Ladhani, SN, De Stavola, BL, Viner, RM & Swann, OV 2022, 'Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies', Journal of Infection, vol. 84, no. 2, pp. 158-170. https://doi.org/10.1016/j.jinf.2021.11.011

TY - JOUR

T1 - Persistent symptoms following SARS-CoV-2 infection amongst children and young people

T2 - A meta-analysis of controlled and uncontrolled studies

AU - Behnood, S. A.

AU - Shafran, R.

AU - Bennett, S. D.

AU - Zhang, A. X.D.

AU - O'Mahoney, L. L.

AU - Stephenson, T. J.

AU - Ladhani, S. N.

AU - De Stavola, B. L.

AU - Viner, R. M.

AU - Swann, O. V.

N1 - Funding Information: AB, RS, SDB, AXDZ, LLO, SNL, BLDS, RMV and OVS have no conflicts of interest. TJS is the Chair of the Health Research Authority for England who reimburse his university for his time. He is not paid personally. He has recused himself from research studies in which he is personally involved and which require ethical approval from the HRA. Open Access: . This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Publisher Copyright: © 2021 The Authors. Published by Elsevier Ltd on behalf of The British Infection Association. Citation: Behnood, Sanaz A., et al. "Persistent symptoms following SARS-CoV-2 infection among children and young people: a meta-analysis of controlled and uncontrolled studies." Journal of Infection (2021). DOI: https://doi.org/10.1016/j.jinf.2021.11.011

PY - 2022/2

Y1 - 2022/2

N2 - Background: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration. Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. Findings: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99–231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms. Interpretation: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.

AB - Background: Data on the long-term impact of SARS-CoV-2 infection in children and young people (CYP) are conflicting. We assessed evidence on long-term post-COVID symptoms in CYP examining prevalence, risk factors, type and duration. Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021. Eligible studies reported CYP ≤19 years with confirmed or probable SARS-CoV-2 with any symptoms persisting beyond acute illness. Random effects meta-analyses estimated pooled risk difference in symptom prevalence (controlled studies only) and pooled prevalence (uncontrolled studies also included). Meta-regression examined study characteristics hypothesised to be associated with symptom prevalence. Prospectively registered: CRD42021233153. Findings: Twenty two of 3357 unique studies were eligible, including 23,141 CYP. Median duration of follow-up was 125 days (IQR 99–231). Pooled risk difference in post-COVID cases compared to controls (5 studies) were significantly higher for cognitive difficulties (3% (95% CI 1, 4)), headache (5% (1, 8)), loss of smell (8%, (2, 15)), sore throat (2% (1, 2)) and sore eyes (2% (1, 3)) but not abdominal pain, cough, fatigue, myalgia, insomnia, diarrhoea, fever, dizziness or dyspnoea. Pooled prevalence of symptoms in post-COVID participants in 17 studies ranged from 15% (diarrhoea) to 47% (fatigue). Age was associated with higher prevalence of all symptoms except cough. Higher study quality was associated with lower prevalence of all symptoms, except loss of smell and cognitive symptoms. Interpretation: The frequency of the majority of reported persistent symptoms was similar in SARS-CoV-2 positive cases and controls. This systematic review and meta-analysis highlights the critical importance of a control group in studies on CYP post SARS-CoV-2 infection.

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KW - Children and young people

KW - Long COVID

KW - Paediatric

KW - Post-COVID syndrome

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DO - 10.1016/j.jinf.2021.11.011

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AN - SCOPUS:85122193645

SN - 0163-4453

VL - 84

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JF - Journal of Infection

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ER -

Persistent symptoms following SARS-CoV-2 infection amongst children and young people: A meta-analysis of controlled and uncontrolled studies

Abstract

Bibliographical note

Keywords

UN SDGs

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