key: cord-0291384-3kjnnzyi
authors: Webster, R. J.; Reddy, D.; Harrison, M.-A.; Farion, K. J.; Willmore, J.; Foote, M.; Thampi, N.
title: Predicting SARS-CoV-2 infections for children and youth with single symptom screening
date: 2021-08-23
journal: nan
DOI: 10.1101/2021.08.19.21262310
sha: f91a2a2fe93196c8371575fbab7ed28d89898288
doc_id: 291384
cord_uid: 3kjnnzyi

Symptom-based SARS-CoV-2 screening and testing decisions in children have important implications on daycare and school exclusion policies. Single symptoms account for a substantial volume of testing and disruption to in-person learning and childcare, yet their predictive value is unclear, given the clinical overlap with other circulating respiratory viruses and non-infectious etiologies. We aimed to determine the relative frequency and predictive value of single symptoms for paediatric SARS-CoV-2 infections from an Ottawa COVID-19 assessment centre from October 2020 through April 2021. Overall, 46.3% (n=10,688) of pediatric encounters were for single symptoms, and 2.7% of these tested positive. The most common presenting single symptoms were rhinorrhea (31.8%), cough (17.4%) and fever (14.0%). Among children with high-risk exposures children in each age group, the following single symptoms had a higher proportion of positive SARS-CoV-2 cases compared to no symptoms; fever and fatigue (0-4 years); fever, cough, headache, and rhinorrhea (5-12 years); fever, loss of taste or smell, headache, rhinorrhea, sore throat, and cough (13-17 years). There was no evidence that the single symptom of either rhinorrhea or cough predicted SARS-CoV-2 infections among 0-4 year olds, despite accounting for a large volume (61.1%) of single symptom presentations in the absence of high-risk exposures. Symptom-based screening needs to be responsive to changes in evidence and local factors, including the expected resurgence of other respiratory viruses following relaxation of social distancing/masking, to reduce infection-related risks in schools and daycare settings.

Introduction: 31 Enhanced health and safety measures have helped to reduce the spread of severe acute 32 respiratory syndrome coronavirus 2 (SARS-CoV-2) among students, parents and staff in 33 schools. [1] [2] [3] [4] [5] [6] [7] [8] A key strategy has been symptom-based screening, exclusion from school, and 34 testing for SARS-CoV-2. 6, 9 However, more than one-third of children who test positive for of keeping children out of schools, including learning disruption and caregiver productivity 45 losses. 12, 13 As circulating non-SARS-CoV-2 respiratory pathogens increase, symptom-based 46 testing for SARS-CoV-2 will determine which students can return when symptoms improve, 47 and which students must continue to isolate due to a positive or unknown COVID-19 status. 14 

Given that children under 12 years of age remain vulnerable to infection as a vaccine-49 ineligible population, and that they may present initially with single symptoms, knowing 50 which symptoms are more likely to be associated with SARS-CoV-2 infection may help to 51 direct screening, exclusion and testing strategies among school-aged children and youth. 52 Research into pediatric evidence-based symptom screening is important. 15, 16 Currently there 53 is an evidence gap for symptom-based screening, with no studies evaluating the predictive 54 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08. 19.21262310 doi: medRxiv preprint Symptoms: 78 In this study, single symptoms were classified according to the Ontario Ministry of Health's 79 list of symptoms to be screened. 18 Only symptoms with more than five encounters were 80 included in this study for privacy reasons. Each record represents a separate screening test 81 encounter, with multiple records per child possible. Symptoms were self-or proxy-reported.

While our study selection criteria were consistent, the Ontario provincial criteria for testing 83 changed during the course of the study. Until February 21, 2021, children with a single mild 84 symptom (e.g., rhinorrhea/congestion, sore throat) were advised to present for testing only if 85 symptoms persisted >24 hours and/or new symptoms emerged. 19 

PPV was reported with 95% CI (derived using the Wilson's score method). 20 In the HRE 98 group, to test for differences between the PPV of single and no symptoms, a two proportion 99 Z-test with Holm's false-discovery correction was used. Likelihood ratios were bootstrapped 100 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) were asymptomatic (Fig 1) . Almost all patients in the study period had a nasopharyngeal Table 1 ).

The relative frequency of single symptoms varied across age groups; in the daycare group, 120 rhinorrhea was the most common single-symptom presentation, followed by fever and cough 121 (43.2%, 23.2%, 17.9%, respectively; Fig 3) . Among the primary school age group, rhinorrhea 122 was again the most common presentation, followed by sore throat and cough (24.3%, 19.5%, 123 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint 17.3%, respectively), whereas the most frequent single symptom in the secondary school age 124 group was sore throat, followed by cough and headache (29.8%, 16.0%, 14.3%).

Positive predictive value (PPV) 126 Among the 10,688 encounters with single symptoms, test positivity was 17.3% (197/1140) 127 and 1.0% (92/9548) among those with HRE compared to non-HRE, respectively. The PPV 128 for single symptoms was highly variable across age groups ( shows PPV by relative frequency for each single symptom, stratified by age groups.

Likelihood ratio 144 These LRs represent how much more likely is a child with a HRE to receive a SARS-CoV-2 145 positive test with one specific symptom compared to an exposed child without symptoms 146 ( Table 2 ; Fig 5) . Across all age groups, fever as a single presenting symptom was found to 147 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint increase the probability of SARS-CoV-2 detection. In children aged 0-4 years, the presence 148 of rhinorrhea/congestion or cough had a low LR of 0.9 (95% CI: 0.5-1.5) and 1.2 (95% CI: 149 0.5, 2.4) respectively. In primary and secondary school-aged children, the presence of 150 rhinorrhea/congestion, cough, sore throat, or headache were each found to increase the 151 probability of SARS-CoV-2 detection, whereas fatigue and nausea/vomiting were more likely 152 to be associated with a positive test in daycare age groups. Consistent between PPV and LR 153 is that loss of taste or smell in secondary school aged children has the highest LR estimate Number needed to test 157 We sought to determine the number needed to test (NNT) to find one additional SARS-CoV-158 2-positive case among individuals with HRE presenting with single symptoms, stratified by 159 age groups (Table 2) . Among students presenting with isolated fever, 4 daycare-aged (95% 160 CI: 2, 8) and 3 primary school-aged children (95% CI: 2, 5) would need to be tested in order 161 to find one positive case. Among secondary school-aged HRE children with isolated fever, 162 NNT 95% CI had negative estimates, indicating uncertainty about its predictive effect (Table   163 2).

For isolated cough, the NNT to find one additional positive case among HREs in primary and 165 secondary school-aged groups was 5 (95% CI: 4, 9) and 7 (95% CI: 4, 47), respectively.

Rhinorrhea/congestion single symptom screening required 15 primary school-aged (95% CI: 167 9, 48) and 6 secondary school-aged children (95% CI: 3, 15) to be tested in order to find one 168 positive case; among daycare-aged HRE children with either of these single symptoms, NNT 169 95% CI had negative estimates, indicating uncertainty about its predictive effect. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint Discussion: 172 In this study at a large urban pediatric COVID-19 assessment centre, 32% of children and 173 youth presented with a single symptom, most commonly rhinorrhea/congestion, followed by 174 cough or fever, and least commonly shortness of breath, muscle/body ache and loss of taste In the daycare age group, combined, rhinorrhea/congestion or cough as a single symptom 180 accounted for 61% of all single-symptom presentations, consistent with provincial patterns. 16 

While rhinorrhea/congestion was not predictive of testing positive for SARS-CoV-2 in the 182 daycare group, the likelihood of a positive test in older ages was elevated.

Our data are consistent with the pediatric literature and regional patterns of multi-symptom 184 presentations. 15, 16 A particular strength of the study was the stratification by childcare and 185 school age groups, as the predictive values were found to vary accordingly, and can be used Critically, no research study can determine a threshold appropriate for all jurisdictions, as this 219 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint will be influenced by local transmission, vaccination rates, and screening program goals and 220 constraints.

This study has several notable limitations. It was undertaken during a period of reduced co-222 circulation of respiratory viruses due to masking, distancing and stay-at-home orders. As the is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021.

Our two-cohort approach aims to minimize risk of selection bias such as Berkson's paradox. 244 Our concern was that those children and youth arriving at testing centres were different from 245 the general population (e.g., presenting with more severe symptoms, risk sensitivities, more 246 health literate, socio-economic makeup). This bias is called Berkson's paradox, and has been 247 a noted limitation for studies in which data collection is focused on assessment centres 27, 28 . 248 We assume that the symptomatic children in the HRE cohort made the decision to get tested 249 primarily due to an exposure (rather than symptom severity), while single-symptom cohort provided epidemiological and statistical comments. We would also like to thank all the 284 frontline assessment centre workers who collected these data.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint breath, and headache were removed from the analysis due to n ≤ 5. In the primary schoolaged HRE cohort, muscle/body ache, loss of taste or smell, and shortness of breath were removed. In the secondary school-aged HRE cohort, diarrhea, muscle/body ache, shortness of breath, and sneezing were removed.

. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 23, 2021. Sneezing 13-17 yrs n < 6 n < 6 n < 6 n < 6

Muscle/body ache 0-4 yrs n < 6 n < 6 n < 6 n < 6

Muscle/body ache 5-12 yrs 0.0 (0.0, 16.8) n < 6 n < 6 n < 6

Muscle/body ache 13-17 yrs 0.0 (0.0, 39.0) n < 6 n < 6 n < 6

Shortness of breath 0-4 yrs n < 6 n < 6 n < 6 n < 6

Shortness of breath 5-12 yrs 5.6 (1.0, 25.8) n < 6 n < 6 n < 6

Shortness of breath 13-17 yrs 16.7 (4.7, 44.8) n < 6 n < 6 n < 6

Olfactory/taste 0-4 yrs n < 6 n < 6 n < 6 n < 6

Olfactory/taste 5-12 yrs n < 6 n < 6 n < 6 n < 6 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint

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The copyright holder for this preprint this version posted August 23, 2021. ; https://doi.org/10.1101/2021.08.19.21262310 doi: medRxiv preprint