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Meta-Analysis
. 2022 Feb;84(2):158-170.
doi: 10.1016/j.jinf.2021.11.011. Epub 2021 Nov 20.

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

S A Behnood  1 , R Shafran  2 , S D Bennett  2 , A X D Zhang  2 , L L O'Mahoney  3 , T J Stephenson  2 , S N Ladhani  4 , B L De Stavola  2 , R M Viner  2 , O V Swann  5
Affiliations
Meta-Analysis

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

S A Behnood et al. J Infect. 2022 Feb.

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Methods: Systematic search of published and unpublished literature using 13 online databases between 01/12/2019 and 31/07/2021.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.

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Conflict of interest statement

Declaration of Competing Interest SAB, 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.

Figures

Fig 1
Fig. 1
PRISMA 2020 flow diagram for included studies.
Fig 2
Fig. 2
Meta-analyses of risk difference in symptom prevalence between cases and control participants in controlled studies: analyses including symptoms reported in 4 or more studies.
Fig 3
Fig. 3
Meta-analyses of risk difference in symptom prevalence between cases and control participants in controlled studies: analyses including symptoms reported in 3 or more studies.
See this image and copyright information in PMC

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