key: cord-1039480-pvwbxvna
authors: Hoehl, Sebastian; Schneider, Felix; Eckrich, Martin; Gründler, Tim Ole; Jerkic, Pera Silvija; Lichtenstein, Geri; Melcher, Birgit; Melcher, Hansjörg; Moebus, Ralf; Mühlfeld, Barbara; Rieger, Ilonka; Seger‐Fritz, Beate; Sgoll, Stefan; Walter, Christian; Werner, Sebastian; Herrmann, Eva; Berger, Annemarie; Ciesek, Sandra
title: COVID‐19 among children seeking primary paediatric care with signs of an acute infection
date: 2021-09-20
journal: Acta Paediatr
DOI: 10.1111/apa.16101
sha: 4b36e542112f9aec7dff2034f3096b9e1c0df2f4
doc_id: 1039480
cord_uid: pvwbxvna

AIM: It can be challenging to distinguish COVID‐19 in children from other common infections. We set out to determine the rate at which children consulting a primary care paediatrician with an acute infection are infected with SARS‐CoV‐2 and to compare distinct findings. METHOD: In seven out‐patient clinics, children aged 0–13 years with any new respiratory or gastrointestinal symptoms and presumed infection were invited to be tested for SARS‐CoV‐2. Factors that were correlated with testing positive were determined. Samples were collected from 25 January 2021 to 01 April 2021. RESULTS: Seven hundred and eighty‐three children participated in the study (median age 3 years and 0 months, range 1 month to 12 years and 11 months). Three hundred and fifty‐eight were female (45.7%). SARS‐CoV‐2 RNA was detected in 19 (2.4%). The most common symptoms in children with as well as without detectable SARS‐CoV‐2 RNA were rhinitis, fever and cough. Known recent exposure to a case of COVID‐19 was significantly correlated with testing positive, but symptoms or clinical findings were not. CONCLUSION: COVID‐19 among the children with symptoms of an acute infection was uncommon, and the clinical presentation did not differ significantly between children with and without evidence of an infection with SARS‐CoV‐2.

This study was conducted in seven specialised primary care paediatric practices with a total of 13 practicing specialists in paediatrics from the larger Rhein-Main metropolitan region, Hesse, Germany.

Parents and their children, up to and including the age of 12 years, who presented to these clinics for consultation with symptoms of an acute infection, were invited to participate in the study. The presence of fever was not mandatory, and symptoms could include those of an airway infection, such as cough or rhinitis, or gastrointestinal symptoms, such as a stomach ache or diarrhoea. Testing for SARS-CoV-2 ribonucleic acid (RNA) was conducted independently of the local testing strategy and symptom severity. Only one test per episode of an illness was analysed. The caregivers were asked to fill in a questionnaire (Table S1 ) with questions about exposure history and symptoms. The paediatrician recorded the clinical findings in a standardised form (Table S2 ). The study duration was 25 January 2021 to 01 April 2021.

Mid-turbinate nasal swabs were collected during the consultation of the study participants. Swabs were tested with the SARS-CoV-2

and Influenza A/B assay on the Cobas 6800 instrument (Roche diagnostics) according to manufacturer's instructions. This is a reverse transcription polymerase chain reaction (RT-PCR) assay using primers targeted at the E-gene and the open reading frame (ORF) 1 a/b non-structural region of SARS-CoV-2, respectively, and one target for the influenza A and influenza B virus, respectively. The number of cycles performed is 40.

were rhinitis, fever and cough. Known recent exposure to a case of COVID-19 was significantly correlated with testing positive, but symptoms or clinical findings were not.

Conclusion: COVID-19 among the children with symptoms of an acute infection was uncommon, and the clinical presentation did not differ significantly between children with and without evidence of an infection with SARS-CoV-2.

COVID-19, influenza, out-patient paediatrics, respiratory tract infection, SARS-CoV-2

• There are limited data to help clinicians discern the presentation of COVID-19 in children from other common causes of infection.

• At out-patient paediatric clinics, 783 children with symptoms of an acute infection were tested for SARS-CoV-2. Nineteen were positive (2.4%).

• Testing positive was significantly correlated with recent exposure to a known case of COVID-19; there were no significant differences in age distribution, symptoms or clinical findings.

In positive samples, key mutations of the SARS-CoV-2 variant of concern Alpha (B.1.1.7), N501Y, del69/70 and E484K were examined by melt curve analysis (VirSNiP SARS-CoV-2 Spike N501Y, del69/70 and E484K assays; TIB Molbiol).

Individual symptoms and medical history items were correlated with the positive detection of SARS-CoV-2 RNA in the nasal swab using a logistical regression model. Odds ratios (ORs), 95% confidence intervals (95% CI) and p values were calculated using Prism 9 (GraphPad Software Inc.).

Written consent was obtained from the parents for all study participants. The study protocol has been approved by the ethics committee of the University Hospital Frankfurt, Goethe University Frankfurt, Germany.

A total of 783 children were enrolled in the study ( Table 1 ). The median age was 3 years and 0 months (range 0 years and 1 month to 12 years and 11 months). Of these children, 358 were female (45.7%) and 425 were male. The most frequent symptoms reported by the caregivers were rhinitis (69.5%), cough (59.0%) and fever (31.8%). Gastrointestinal symptoms were less common, with 13.6% reporting stomach ache and 7.4% reporting diarrhoea (Table 2 ).

Reverse transcription polymerase chain reaction testing was valid in all 783 samples, as the internal control was correctly detected.

Neither influenza A nor influenza B was detected in any of the swabs.

Both RT-PCR targets of SARS-CoV-2 were detected in 18 samples (Table 1) All newborns were tested negative for SARS-CoV-2 RNA. The positivity rate was low in all other age groups and ranged between 1.3% in children aged 3-6 years and 3.9% in children aged 6-12 years (Table 1 ).

The median age of children with a positive detection of SARS-CoV-2 RNA was 3 years and 0 months (range 4 months to 11 years and 1 month) ( Table 1 ).

Symptoms that were most frequently reported by the caregiver for the 19 cases of COVID-19 were rhinitis (57.9%), fever (47.4%) and cough (42.1%). The most common findings on clinical examination were obstructed nasal breathing (63.2%), rhinorrhoea (52.6%), pharyngitis (33.3%) and fever (31.6%) ( Table 2 ).

There was no statistically significant correlation of any symptom or clinical finding with testing positive ( Figure 1B ,C). No child with COVID-19 had dyspnoea, tonsillitis (Table 3) 

The exposure history showed a significant correlation between recent exposure to a case of COVID-19 (Odds ratio 25.9, 95% CI:

9.78-70.00, p < 0.0001) and a negative and significant correlation with an attendance of day care or school (p = 0.01; Table 3 ; Figure 1A ). Parental suspicion that the child may be infected with SARS-CoV-2 was correlated with testing positive for SARS-CoV-2 (pvalue < 0.0001; Figure 1A ). However, no child in which the parents suspected an infection with SARS-CoV-2 was infected with the virus when there had not been a known recent exposure.

The analysis for key mutations of the SARS-CoV-2 variant of concern Alpha was successful in 13 of the 19 positive samples. case of COVID-19 in day care or school was not significantly correlated with testing positive for SARS-CoV-2.

We do not believe that the case numbers in our study were large enough to establish that attending day care or school were a factor that made testing positive for SARS-CoV-2 less likely. Importantly, the median age (3 years, 0 months) was too low to allow conclusions on the risk of attending school. However, we could also not identify (Table 4) .

During the study period, the variant of concern Alpha, also known as B. 

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