Validity of reported post-acute health outcomes in children with SARS-CoV-2 infection: a systematic review

Abstract

Importance: There is concern that post-acute SARS-CoV-2 infection health outcomes ("post-COVID syndrome") in children could be a serious problem but at the same time there is concern about the validity of reported associations between infection and long-term outcomes. Objective: To systematically assess the validity of reported post-acute SARS-CoV-2 infection health outcomes in children. Evidence Review: A search on PubMed and Web of Science was conducted to identify studies published up to January 22, 2022, that reported on post-acute SARS-CoV-2 infection health outcomes in children (<18 years) with a minimum follow-up of 2 months since detection of infection or 1 month since recovery from acute illness. We assessed the consideration of confounding bias and causality, and the risk of bias. Findings: 21 studies including 81,896 children reported up to 97 symptoms with follow-up periods of 2-11.5 months. Fifteen studies had no control group. The reported proportion of children with post-COVID syndrome was between 0% and 66.5% in children with SARS-CoV-2 infection (n=16,986) and 2% to 53.3% in children without SARS-CoV-2 infection (n=64,910). Only 2 studies made a clear causal interpretation of an association of SARS-CoV-2 infection and the main outcome of "post-COVID syndrome" and provided recommendations regarding prevention measures. Two studies mentioned potential limitations in the conclusion of the main text but none of the 21 studies mentioned any limitations in the abstract nor made a clear statement for cautious interpretation. The validity of all 21 studies was seriously limited due to an overall critical risk of bias (critical risk for confounding bias [n=21]; serious or critical risk for selection bias [n=19]; serious risk for misclassification bias [n=3], for bias due to missing data [n=14] and for outcome measurement [n=12]; and critical risk for selective reporting bias [n=16]). Conclusions and Relevance: The validity of reported post-acute SARS-CoV-2 infection health outcomes in children is critically limited. None of the studies provided evidence with reasonable certainty on whether SARS-CoV-2 infection has an impact on post-acute health outcomes, let alone to what extent. Children and their families urgently need much more reliable and methodologically robust evidence to address their concerns and improve care.

Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1 284 437 patients

“…Second, the risk profile in different age strata, especially in children, has not been well characterised. 8 Neurological manifestations of COVID-19 in paediatric populations (aged <18 years) have been reported, 9 but only one controlled study has investigated the risk of neurological and psychiatric outcomes after SARS-CoV-2 infection. 10 This study was limited to a 3-month follow-up period and measured neurological and psychiatric outcomes as two broad categories, without reporting the risk of individual diagnoses.…”

Robustness of reported postacute health outcomes in children with SARS-CoV-2 infection: a systematic review

“…We used a similar search strategy and study selection as a previous related analysis 10. Our study protocol is published10 and no major deviations occurred.…”

“…Two researchers (two of JH, PJ, SS, TVP or VG) independently extracted study characteristics, assessed the consideration of confounding bias and causality, and the risk of bias 8 9 18 19. Details on extracted items and algorithms for assessments were prespecified 10. Disagreements were resolved by discussion or third-party arbitration (LGH).…”

“…We recorded the proportions of children presenting the main outcome. The main outcome was defined as stated by the authors or, if not available, the most inclusive one (eg, any symptoms) 10. We also assessed if the main outcome was analysed in relation to specific participant characteristics (eg, comorbidities) or infection-related factors (eg, severity acute disease).…”

“…We assessed the risk of bias for an estimated effect of SARS-CoV-2 infection on the main postacute symptom outcome using “Risk Of Bias In Non-randomised Studies of Interventions” (ROBINS-I),19 23 replacing the notion of ‘intervention’ by ‘infection’ (see protocol for full details) 10. The ROBINS-I categories are ‘low’, ‘moderate’, ‘serious’ and ‘critical’ risk of bias 10…”