Association of SARS-CoV-2 Seropositivity With ME and/or CFS Among Children and Adolescents in Germany 2022 Sorg et al

Key Points

Question Is SARS-CoV-2 seropositivity associated with symptoms of myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) in children and adolescents?

Findings This cross-sectional study of hospital-based SARS-CoV-2 seroprevalence surveys in Germany compared seropositive and seronegative children and adolescents and identified an excess of possible ME/CFS symptoms with serological evidence of preceding SARS-CoV-2 infection. This association almost disappeared with adjustment for confounders and restriction to children and adolescents unaware of preceding infection.

Meaning These findings suggest that the risk of ME/CFS after SARS-CoV-2 infection in children and adolescents may be small and that recall bias may contribute to risk estimates.


Abstract

Importance During the COVID-19 pandemic, a reduction in quality of life and physical and mental health among children and adolescents has been reported that may be associated with SARS-CoV-2 infection and/or containment measures.

Objective To assess the association of SARS-CoV-2 seropositivity with symptoms that may be related to myalgic encephalomyelitis and/or chronic fatigue syndrome (ME/CFS) among children and adolescents.

Design, Setting, and Participants This substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) was performed in 9 pediatric hospitals from May 1 to October 31, 2021. Pediatric patients were recruited during an inpatient or outpatient visit regardless of the purpose of the visit. Parental questionnaires and serum samples were collected during clinically indicated blood draws. The parental questionnaire on demographic and clinical information was extended by items according to the DePaul Symptom Questionnaire, a pediatric screening tool for ME/CFS in epidemiological studies in patients aged 5 to 17 years.

Exposures Seropositivity was determined by SARS-CoV-2 IgG antibodies in serum samples using enzyme-linked immunosorbent assays.

Main Outcomes and Measures Key symptoms of ME/CFS were evaluated separately or as clustered ME/CFS symptoms according to the DePaul Symptom Questionnaire, including fatigue.

Results Among 634 participants (294 male [46.4%] and 340 female [53.6%]; median age, 11.5 [IQR, 8-14] years), 198 (31.2%) reported clustered ME/CFS symptoms, including 40 of 100 SARS-CoV-2–seropositive (40.0%) and 158 of 534 SARS-CoV-2–seronegative (29.6%) children and adolescents. After adjustment for sex, age group, and preexisting disease, the risk ratio for reporting clustered ME/CFS symptoms decreased from 1.35 (95% CI, 1.03-1.78) to 1.18 (95% CI, 0.90-1.53) and for substantial fatigue from 2.45 (95% CI, 1.24-4.84) to 2.08 (95% CI, 1.05-4.13). Confinement to children and adolescents with unknown previous SARS-CoV-2 infection status (n = 610) yielded lower adjusted risks for all symptoms except joint pain ME/CFS–related symptoms. The adjusted risk ratio was 1.08 (95% CI, 0.80-1.46) for reporting clustered ME/CFS symptoms and 1.43 (95% CI, 0.63-3.23) for fatigue.

Conclusions and Relevance These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small. Recall bias may contribute to risk estimates of long COVID-19 symptoms in children. Extensive lockdowns must be considered as an alternative explanation for complex unspecific symptoms during the COVID-19 pandemic.

Open access, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2796733

 

This paper is weak. The population studied is children who visited a hospital (either outpatient or inpatient). They claim around 30-40% of them have "Clustered ME/CFS symptoms." We know that ME/CFS has a prevalance of, at most, about 1%, and is less in children, meaning their classification has incredibly poor specificity. (In layman's terms, "poor specificity" means a ton of children without ME will be lumped in here.) I don't have the cognitive ability to drill down into this paper, but it looks like the only thing they found is that parents who know their kids got Covid are more likely to report the kids had symptoms of any severity. This is not incredibly surprising. It's totally different from whether people are more likely to get a serious disease. So by no means does this paper show that children who get Covid are no more likely to get ME.

If you truly wanted to determine whether Covid caused ME in children, you'd need to be much more rigorous. You'd probably need thousands (?) of participants because pediatric ME is uncommon. You'd also need doctors who understand ME to thoroughly diagnose kids using one of the modern criteria that require PEM.

 

The paper speaks of ME/CFS but it did not assess ME/CFS. It said it uses the paediatric DePaul Symptom Questionnaire but they ignored how it should be scored and instead made up their own rules. The result is that 30% of their control group where cases, "reporting clustered ME/CFS symptoms".

They then couldn't find large differences with the adolescents who had sars-cov-2, so they argue that symptoms might be the result of extensive lockdowns. I very much get the impression that this is the conclusion the authors were aiming for.

Why did they make up their own definition of "clustered ME/CFS symptoms"? If they had simply used the normal DePaul algorithm for ME/CFS the number of cases would have been much lower. Only 4.5% met the criteria of substantial fatigue for example, which is already 6 times lower than the definition the authors invented and used in their study.

EDIT: it looked like they used the DSQ-PSQ (PEDIATRIC SCREENER), not the pediatric version of the DePaul Symptom Questionnaire as explained here: https://www.frontiersin.org/articles/10.3389/fped.2018.00330/full#h6

 

@ME/CFS Skeptic What you're saying is basically what I was trying to say, but more coherent.

 

This paper has received media coverage:
Does COVID Infection Carry a Small Risk of Chronic Fatigue Syndrome?

 

Thanks for posting.

It includes a brief commentary by Leonard Jason:

"This is a study of a small number of fatigued kids," said Leonard Jason, PhD, creator of the DSQ and the director of the Center for Community Research at DePaul University in Chicago, who cautioned that the German researchers "may have overreached" in their conclusion.

"There's a large difference between youth who are feeling unwell, feeling fatigue, and having something more severe called ME/CFS," Jason told MedPage Today. "Those distinctions are critical to understanding ME/CFS."

Jason noted that the researchers never asked parents, "'Has your kid ever been diagnosed with CFS?' -- This is the basic question to ask."​

 

When they looked at substantial fatigue, which does require a minimum level of severity, there was a clear difference: 11% in the sars-cov-2 group and 4.5% in the control group.

The authors highlight, however, that the effect sizes for all outcomes were "reduced markedly" when they only examined patients who were unaware of their SARS-CoV-2 status. At this point there were only 7 patients who had substantial fatigue and a positive SARS-CoV-2 status without knowing about it. The percentage was still twice as high but, because of the very small sample size, the difference was not statistically significant.

I suspect it may be that those patients who did not know about their SARS-CoV-2 status, were less severely ill and thus less likely to develop long-lasting symptoms afterwards.

 

@ME/CFS Skeptic @RedFox Could you send a reply to the paper with your observations?

 

Gosh...I'm not a scientist or anything. And I've never done that before.

 

If you were interested in trying and had the energy, I am sure people here would be happy to discuss a draft before you sent it off, if that would make you feel more confident.