Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study

Abstract

Background: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households.

Methods: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires.

Findings: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]).

Interpretation: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful.

Funding: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

Keywords: Adolescents; COVID-19; Children and young people; Families; Long COVID; Paediatric; Post-COVID syndrome; SARS-CoV-2.

Figure 1

Flowchart of participant enrollment in study of long COVID symptoms in households with children. T1, timepoint 1; T2, timepoint 2; RT-PCR, reverse transcription PCR; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Figure 2

Percentage of adults, adolescents (14-18 years) and children (<14 years) in each response category for the RAND-36 health change score, comparing current health to health before the earliest infection in their household. *** The Mann-Whitney U-test indicated that the distribution of responses for infected vs exposed adults was significantly different, p<.001. The distributions of responses for infected vs. exposed groups were not significantly different for adolescents (p=.820) or children (p=.336).

Figure 3

Moderate and severe persistent symptoms in adults, adolescents and children <14 years. Left panel: Percentage of participants in each age group who reported that each moderate or severe symptom was still present at T2, 11-12 months after the earliest household infection. Right panel: Percentage of participants in each group who reported one or more moderate and severe symptoms still present at T2. Overall participant numbers for each group were as follows: adults: 113 exposed females, 255 infected females, 116 exposed males, 236 infected males; adolescents 14-18 years: 45 exposed females, 28 infected females, 36 exposed males, 31 infected males; children <14 years: 128 exposed females, 70 infected females, 125 exposed males, 81 infected males. Numbers of participants for individual symptoms varied slightly due to missing data; precise values are given in the Supplementary Materials.

Figure 4

Associations between the total number of moderate and severe persistent symptoms at T2 reported by other household members and the number of moderate and severe symptoms reported by an individual, based on uni-variable Poisson regression model with the centre included as random intercepts, in exposed (dotted line) and infected (solid line) groups across all age and gender subgroups. The grey area shows 95% confidence intervals.