Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children

Abstract

To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection.

Design

Multicentre retrospective cohort study.

Setting

18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021.

Patients

Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C).

Main outcome measure

Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses.

Results

We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53–10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45–9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease.

Conclusion

We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

SciScore for 10.1101/2021.10.28.21265616: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: Ethics approval was obtained from each participating institution’s ethics research board, with waiver for informed consent for health records research (Supplementary methods). Consent: Ethics approval was obtained from each participating institution’s ethics research board, with waiver for informed consent for health records research (Supplementary methods).
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

Software and Algorithms
Sentences	Resources
19 Data Collection: Data on primary indication for admission, demographics, comorbidities, clinical presentation and course, coinfections, treatments, and …

SciScore for 10.1101/2021.10.28.21265616: (What is this?)

Please note, not all rigor criteria are appropriate for all manuscripts.

Table 1: Rigor

Ethics	IRB: Ethics approval was obtained from each participating institution’s ethics research board, with waiver for informed consent for health records research (Supplementary methods). Consent: Ethics approval was obtained from each participating institution’s ethics research board, with waiver for informed consent for health records research (Supplementary methods).
Sex as a biological variable	not detected.
Randomization	not detected.
Blinding	not detected.
Power Analysis	not detected.

Table 2: Resources

Software and Algorithms
Sentences	Resources
19 Data Collection: Data on primary indication for admission, demographics, comorbidities, clinical presentation and course, coinfections, treatments, and complications were abstracted by the investigators from the patient’s medical charts and managed using REDCap electronic data capture tools.	REDCap suggested: (REDCap, RRID:SCR_003445)

Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

Our study has limitations. First, reporting may not have been uniform across centers despite the use of a study protocol and a standardized data capture tool. This includes but is not limited to the interpretation of chest radiographs, definition of obesity, and the severity of comorbidities. Also, the respective comorbidities can represent a heterogeneous group of diseases with different etiologies. Second, despite being one of the largest pediatric cohort studies with more than 100 severe cases, the numbers of some individual comorbidities are small. This might overestimate or underestimate the impact of infrequent comorbidities such as anemia and/or hemoglobinopathy, chromosomal, or cardiac disorders. Third, laboratory investigations were not systematically performed. Complete blood counts, CRP, and albumin values were missing in 4.2%, 15%, and 67%, respectively. We therefore could not assess the latter in multivariable models. Moreover, laboratory investigations were done at the clinicians’ discretion, not at set time points during the illness. Other parameters previously described as risk factors could not be evaluated. This includes ethnicity4,7,9,12 which was not readily accessible from hospital records. In addition, viral sequencing data was not available, accordingly we cannot evaluate the impact of different SARS-CoV-2 variants. Fourth, indications for testing for SARS-CoV-2 likely varied by center and over time, which might have affected the clinical spectrum of in...

Results from TrialIdentifier: No clinical trial numbers were referenced.

Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

Results from JetFighter: We did not find any issues relating to colormaps.

Results from rtransparent:

Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
No protocol registration statement was detected.

Results from scite Reference Check: We found no unreliable references.

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