Diagnostic accuracy of rapid point-of-care tests for diagnosis of current SARS-CoV-2 infections in children: a systematic review and meta-analysis

Abstract

To systematically assess the diagnostic accuracy of rapid point-of-care tests for diagnosis of current SARS-CoV-2 infections in children under real-life conditions.

Design

Systematic review and meta-analysis.

Data sources

MEDLINE, Embase, Cochrane Database for Systematic Reviews, INAHTA HTA database, preprint servers (via Europe PMC), ClinicalTrials.gov, WHO ICTRP from 1 January 2020 to 7 May 2021; NICE Evidence Search, NICE Guidance, FIND Website from 1 January 2020 to 24 May 2021.

Review methods

Diagnostic cross-sectional or cohort studies were eligible for inclusion if they had paediatric study participants and compared rapid point-of care tests for diagnosing current SARS-CoV-2 infections with reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was used to assess the risk of bias and the applicability of the included studies. Bivariate meta-analyses with random effects were performed. Variability was assessed by subgroup analyses.

Results

17 studies with a total of 6355 paediatric study participants were included. All studies compared antigen tests against RT-PCR. Overall, studies evaluated eight antigen tests from six different brands. Only one study was at low risk of bias. The pooled overall diagnostic sensitivity and specificity in paediatric populations was 64.2% (95% CI 57.4% to 70.5%) and 99.1% (95% CI 98.2% to 99.5%), respectively. In symptomatic children, the pooled diagnostic sensitivity was 71.8% (95% CI 63.6% to 78.8%) and the pooled diagnostic specificity was 98.7% (95% CI 96.6% to 99.5%). The pooled diagnostic sensitivity in asymptomatic children was 56.2% (95% CI 47.6% to 64.4%) and the pooled diagnostic specificity was 98.6% (95% CI 97.3% to 99.3%).

Conclusions

The performance of current antigen tests in paediatric populations under real-life conditions varies broadly. Relevant data were only identified for very few antigen tests on the market, and the risk of bias was mostly unclear due to poor reporting. Additionally, the most common uses of these tests in children (eg, self-testing in schools or parents testing their toddlers before kindergarten) have not been addressed in clinical performance studies yet. The observed low diagnostic sensitivity may impact the planned purpose of the broad implementation of testing programmes.

PROSPERO registration number

CRD42021236313.

SciScore for 10.1101/2021.08.11.21261830: (What is this?)

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

Table 1: Rigor

NIH rigor criteria are not applicable to paper type.

Table 2: Resources

Software and Algorithms
Sentences	Resources
Besides journal articles, reports (including clinical study reports) that adhered to reporting standards such as STARD [18] or recommendations given by government agencies [10, 19] were considered eligible for inclusion.	STARD suggested: None
Information Sources: We performed a comprehensive search for primary studies and secondary publications (systematic reviews and Health Technology Assessment (HTA) reports) in the following electronic bibliographic databases: MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), and preprint servers (Europe PMC) including medRxiv and bioRxiv …

SciScore for 10.1101/2021.08.11.21261830: (What is this?)

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

Table 1: Rigor

NIH rigor criteria are not applicable to paper type.

Table 2: Resources

Software and Algorithms
Sentences	Resources
Besides journal articles, reports (including clinical study reports) that adhered to reporting standards such as STARD [18] or recommendations given by government agencies [10, 19] were considered eligible for inclusion.	STARD suggested: None
Information Sources: We performed a comprehensive search for primary studies and secondary publications (systematic reviews and Health Technology Assessment (HTA) reports) in the following electronic bibliographic databases: MEDLINE (Ovid), Embase (Ovid), the Cochrane Library (Wiley), and preprint servers (Europe PMC) including medRxiv and bioRxiv (see [20] for full list of included preprint servers).	Cochrane Library suggested: (Cochrane Library, RRID:SCR_013000) bioRxiv suggested: (bioRxiv, RRID:SCR_003933)
Search Strategy: In accordance with the Cochrane Handbook for DTA Reviews [21], the search strategy included concepts addressing the index test and the target condition.	Cochrane Handbook suggested: None
Furthermore, brand names of tests included in the Cochrane Review were added to increase sensitivity.	Cochrane Review suggested: None
Since Embase and MEDLINE provided comprehensive search filters for SARS-CoV-2 related literature via Ovid, our concept addressing the target condition was not used in these two searches.	MEDLINE suggested: (MEDLINE, RRID:SCR_002185)
After exporting all identified references from Ovid, duplicates were identified in R by comparing DOIs of references from MEDLINE and Embase, and the Embase records of duplicates were removed.	Embase suggested: (EMBASE, RRID:SCR_001650)
Remaining duplicates were manually removed in EndNote X9.3 and by using Endnote’s “find duplicates” function.	EndNote suggested: (EndNote, RRID:SCR_014001) Endnote’s suggested: None
At first, a standardized Excel spreadsheet was developed for data extraction.	Excel suggested: None

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:

Limitations: The results presented in this review should be considered in light of the following limitations: 1) As visualized in the QUADAS-2 summary graph, the majority of studies were at unclear risk of bias in at least three of the four domains of the QUADAS-2 tool because of poor reporting by authors. Therefore, the results reported in this review should be interpreted with caution. The issue of insufficient reporting has been addressed previously and led to the publication of comprehensive guidance to authors evaluating the clinical performance of tests for SARS-CoV-2 [87]. 2) We acknowledge that infectiousness as target condition is of higher practical relevance than current SARS-CoV-2 infection, which was chosen as the target condition of this review. While RT-PCR as the corresponding reference standard is a highly sensitive method that is used to detect the presence of viral ribonucleic acid (RNA) in a specimen, this does not necessarily indicate that infectious virus is present. Therefore, the actual transmission risk from individuals who tested RT-PCR positive remains unknown. Testing for infectiousness would allow to identify (and isolate) exclusively individuals who could pass the virus to others. However, while there have been attempts to use viral load (estimated from Ct values) or virus viability in cell culture as a proxy to determine infectious individuals, up to now, there is no adequate reference standard for infectiousness [82]. 3) Screening testing progr...

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.

Read the original source