Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: 2022, Haddad et al

[Sly Saint]

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

Summary
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.

https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(22)00427-3/fulltext

 

[Hutan]

There's the usual problem of defining who exactly had Covid-19, and who did not. Given all the participants had household exposure, the potential for an incorrect assignment to the Covid-negative group is considerable. It was possible for people to test positive on one serological assay and still be classed as Covid-negative.

The following serological assays were used at both time points: (1) EuroImmun-Anti-SARS-CoV-2 ELISA IgG (S1), (2) Siemens Healthineers SARS-CoV-2 IgG (RBD) and (3) Roche Elecsys Ig (N). Participants were defined as seropositive if at least two of these three assays were positive and as seronegative if at least two out of three were negative. ...

Participants were defined as “infected” if they either (1) reported having had a positive RT-PCR test for SARS-CoV-2 prior to T1 or (2) were seropositive at T1 in at least two out of three commercial antibody tests, as defined above. Participants were defined as “exposed” controls if they both (1) did not report having had a positive SARS-CoV-2 RT-PCR test prior to T1 and (2) were seronegative at T1 as defined above.

 

[Hutan]

Further on that:

Amongst adults, 124 infected cases were identified by serology only (at least 2 of 3 antibody tests seropositive); 44 infected cases were identified by self-reported RT-PCR only; and 317 infected cases identified via both methods. Amongst adolescents, 35 infected cases were identified by serology only; no infected cases were identified by self-reported PCR only; and 24 infected cases identified by both methods. Amongst children, 114 infected cases were identified by serology only; 6 infected cases were identified by self-reported PCR only; and 30 infected cases identified by both methods. Thus in total 50 participants (6 children, 44 adults) reported having had a positive RT-PCR test for SARS-CoV-2 prior to T1 but were seronegative at T1 (“non-seroconverters”); these individuals were defined as infected, since they met the first criterion for the “infected” definition.

There were significant numbers of people only identified by the serology (ie at least 2 out of the 3 antibody tests positive). And yet, 50 participants reported having a positive PCR test earlier in their illness, but were seronegative at the study baseline test. These 'non-seroconverters' were defined as infected.

So, it's possible that the Covid positive group contained people who were in fact Covid negative.
It's also possible that the Covid negative group contained people who had had Covid, but were non-seroconverters.

There were also complications around people becoming infected after the baseline and before followup.

 

[Hutan]

Freiberg, Germany study, by the way.

125 (17·6%) participants had experienced ongoing reductions in physical functioning at T2 on the RAND-36 physical functioning scale, whereas the remaining 585 (82·4%) reported no or only temporarily reduced physical functioning. However, infected adults were statistically significantly more likely (21·6%) to have reduced physical function that persisted until T2 than exposed adults (8·9%, RR=2.44, 95% CI [1.55–3.83], p<·001). The difference was apparent in both men and women (Supplementary Figure S3).

Based on dichotomized Fatigue Assessment Scale scores, 132 adults, 20 adolescents and 10 children continued to have fatigue or severe fatigue at T2. All remaining participants were considered non-fatigued at T2 on this measure (578 adults, 119 adolescents, 388 children). 20·6% of infected adults were fatigued/severely fatigued at T2, compared to 14·3% of exposed adults (RR=1.44, 95% CI [1.00–2.08], p=·049). This association was present amongst men (RR=2.05, 95% CI[1.03-4.0], p=·044) but not women. For adolescents and children, there were no statistically significant differences between infected and exposed groups, including when split by gender (Supplementary Figure S4).

Our data suggest that acute diarrhoea and dysgeusia may be particularly associated with higher likelihood of persistent symptoms, which could help to identify individuals at risk of long COVID.

That was interesting. Dysgeusia at baseline might be associated with dysgeusia at followup, but the presence of that symptom doesn't necessarily mean that the symptoms required for a post-Covid ME/CFS diagnosis were present. ie it depends how you define Long Covid.

Another key finding of this study is that the number of moderate or severe persistent symptoms in both exposed and infected individuals was associated with the number of moderate or severe persistent symptoms in other household members.This finding was reinforced by the association between parents’ health status at T1 and reported symptoms in their children at T2.

The authors note that there are various possible explanations for the household association including:
1. a genetic tendency


2.

Parents’ perceptions of their own symptoms may have influenced their perception or reporting of their children's symptoms.

They quote the French study that found that self-reported Covid infection was more likely to be associated with persistent physical symptoms than confirmed Covid infection. The inference is that parents who perceive that they have symptoms are making the reporting their children's symptoms less accurate. However, it's possible that experiencing ongoing symptoms might make parents better at identifying similar symptoms in their children, actually making them more accurate reporters of their children's symptoms when they filled out the questionnaires for them.


3.

Another possible explanation is that family members’ symptoms or behaviour affected symptomatology in children. This would be consistent with previous studies showing that parents’ symptoms and behaviour can be associated with children's symptoms in a range of pediatric health conditions.
It would also fit with evidence that negative mental health outcomes of lockdown in children may be mediated by parents’ stress and overreactivity.
These findings have important implications, since support for parents or family-level therapeutic interventions could prove useful in preventing or treating long COVID in this age group.

And that last paragraph is the point of the whole study - the identification of dysfunctional overly reactive families that are the cause of Long Covid. Whole families are therefore fodder for psychotherapy interventions. If a family reports that their child has Long Covid, then all the members of the family become liable to having their behaviour and perceptions 'fixed'.

It's possible that stressed parents are producing stressed children in a stressful time. I don't think a study that identifies individual symptoms is going to properly separate these out from people with the constellation of symptoms that is post-Covid ME/CFS.