key: cord-1015910-t2qzwsbm
authors: Smit, Liezl; Redfern, Andrew; Murray, Sadia; Lishman, Juanita; van der Zalm, Marieke M.; van Zyl, Gert; Verhagen, Lilly M.; de Vos, Corné; Rabie, Helena; Dyk, Annemarie; Claassen, Mathilda; Taljaard, Jantjie; Aucamp, Marina; Dramowski, Angela
title: SARS-CoV-2 IN CHILDREN AND THEIR ACCOMPANYING CAREGIVERS: IMPLICATIONS FOR TESTING STRATEGIES IN RESOURCE LIMITED HOSPITALS
date: 2022-04-25
journal: Afr J Emerg Med
DOI: 10.1016/j.afjem.2022.04.007
sha: 79669e172f4e2074fa36132f2359648cdd40baef
doc_id: 1015910
cord_uid: t2qzwsbm

BACKGROUND: : Identification of SARS-CoV-2 infected individuals is imperative to prevent hospital transmission, but symptom-based screening may fail to identify asymptomatic/mildly symptomatic infectious children and their caregivers. METHODS: : A COVID-19 period prevalence study was conducted between 13-26 August 2020 at Tygerberg Hospital, testing all children and their accompanying asymptomatic caregivers after initial symptom screening. One nasopharyngeal swab was submitted for SARS-CoV-2 using real-time reverse-transcription polymerase chain reaction (rRT-PCR). An additional Respiratory Viral 16-multiplex rRT-PCR test was simultaneously done in children presenting with symptoms compatible with possible SARS-CoV-2 infection. RESULTS: : SARS-Co-V 2 RT-PCR tests from 196 children and 116 caregivers were included in the analysis. The SARS-CoV-2 period prevalence in children was 5.6% (11/196) versus 15.5% (18/116) in asymptomatic caregivers (p<0.01). Presenting symptoms did not correlate with SARS-CoV-2 test positivity; children without typical symptoms of SARS-CoV-2 were more likely to be positive than those with typical symptoms (10.2% [10/99] vs 1% [1/97]; p<0.01). Children with typical symptoms (97/196; 49.5%) mainly presented with acute respiratory (68/97; 70.1%), fever (17/97; 17.5%), or gastro-intestinal complaints (12/97; 12.4%); Human Rhinovirus (23/81; 28.4%) and Respiratory Syncytial Virus (18/81; 22.2%) were frequently identified in this group. Children-caregiver pairs’ SARS-CoV-2 tests were discordant in 83.3%; 15/18 infected caregivers’ children tested negative. Symptom-based COVID-19 screening alone would have missed 90% of the positive children and 100% of asymptomatic but positive caregivers. CONCLUSION: : Given the poor correlation between SARS-CoV-2 symptoms and RT-PCR test positivity, universal testing of children and their accompanying caregivers should be considered for emergency and inpatient paediatric admissions during high COVID-19 community transmission periods. Universal PPE and optimising ventilation is likely the most effective way to control transmission of respiratory viral infections, including SARS-CoV-2, where universal testing is not feasible. In these settings, repeated point prevalence studies may be useful to inform local testing and cohorting strategies.

. Many low resource settings also have over-crowded emergency centres and scarce critical care and even basic care resources, including heathcare workers [4] , making cost-effective and appropriate use of SARS-CoV-2 testing a critical part of the medical and infection, prevention and control preparedness of these healthcare facilities [5] .

Symptom screening has been adopted to identify individuals with possible SARS-CoV-2 infection for targeted laboratory testing in South African workplaces as part of the Coronavirus-19 (COVID-19) disease pandemic response [6, 7] . Asymptomatic / early infection phase transmission however plays an important role in the spread of SARS-CoV-2, complicating infection control strategies in congregate settings like emergency centres or open wards [8] [9] [10] . Children with SARS-CoV-2 may further present with a number of nonspecific symptoms rather than the more "typical" symptoms such as cough, fever, sore throat, myalgia, and diarrhoea [11, 12] . These symptoms overlap considerably with non-SARS-CoV-7 departments" paediatric admissions [13] . The recent surge in non-SARS-CoV-2 respiratory infections seen in many countries makes it even more important to have appropriate logistics in place to discriminate between SARS-CoV-2 and non-SARS-CoV-2 related illnesses. [14, 15] . This lack of specificity of signs or symptoms, and the substantial proportion of asymptomatic or mild infections in children, hampers the reliability of symptom-based screening for identification of SARS-CoV-2 in children attending hospital.

In order to identify those with SARS-CoV-2 infection, universal laboratory testing of all children and their accompanying caregivers may be required, but this strategy could overload healthcare resources, particularly in LMICs such as South Africa. Given the concerns regarding the use of symptom-based SARS-CoV-2 testing strategies in children and their caregivers, we conducted a 2-week period prevalence study in all children and their asymptomatic caregivers presenting to the paediatric department of a large teaching hospital in Cape Town, South Africa, to inform testing and patient cohort strategies towards the end of a COVID-19 epidemiological wave. [16, 17] for symptom(s) typically reported of SARS-CoV-2 infection (fever, acute onset cough, runny nose or sore throat, loss of smell or taste, flu-like symptoms, gastro-intestinal symptoms e.g. diarrhoea and vomiting or abdominal pain) at presentation and daily during admission on symptom screening forms.

Symptomatic caregivers of children requiring admission were asked to isolate at home. All asymptomatic caregivers were offered a voluntary test for SARS-CoV-2 at the time of admission of their child. They were not refused entry to the wards if they declined to be tested. Caregivers were initially tested with their child on admission, but due to the high testburden caregivers were referred to the COVID-19 testing site on the hospital premises in week two of the study. This lead to some caregivers declining the test. Children and caregivers already admitted prior to the surveillance period or neonates and their caregivers admitted to the neonatal wards were excluded.

South Africa was placed under national level 5 lockdown on 23 March 2020. A gradual and phased easing of the lockdown restrictions began in May 2020, with an amended alert level 2 in place during this study [18] . During this period 149 paediatric cases per week were recorded in the Western Cape Province from a high of 505 in July 2020 [19] . Statistical analysis: Children were categorised into two groups: those presenting with symptoms of SARS-CoV-2 infection typically reported in the literature [16, 17] and those without. Children presenting with typical symptoms were sub-categorised according to their main presenting symptoms; "acute respiratory", "fever", or "gastro-intestinal". These summary categories are in alignment with presenting symptoms in children with possible SARS-Cov-2 infection and were chosen for analysis rather than the listing of individual complaints.

Children without typical symptoms were sub-categorised as "surveillance" or "pre-procedure"

if admitted for elective surgery/interventions. Child and caregiver pairs were grouped together to compare their SARS-CoV-2 results. Data was processed and analysed utilising descriptive statistics, calculating the frequency distribution of variables and measuring central tendency and spread. Differences between groups were calculated using t-tests and chi-square tests as appropriate. Statistical significance was set at a p-value of <0.05. Stata version 15 (Stata corp version 27., College Station, Texas, USA) was used for data analysis.

In total three hundred and twenty four SARS-CoV-2 tests were performed during the twoweek period prevalence study with an average of 23 tests per day. Three child-caregiver pairs and six tests in children were excluded from the analysis due to testing being performed outside of the study period, or an inability to verify laboratory results. the study period reflected the overall decline in COVID-19 incidence in the Western Cape

Province following the pandemic peak in June/July 2020, which was substantially lower than that documented in earlier months of the pandemic or during subsequent waves [19] .

Despite symptom screening being recommended, distinguishing between truly asymptomatic or pre-symptomatic patients remains challenging [22] [23] [24] . Similar to our report, a Republic of Korean study [22] reported that symptom screening failed to identify most of their paediatric SARS-CoV-2 cases, with 22% of children being asymptomatic at presentation and remaining asymptomatic after COVID-19 diagnosis. These children were tested when in close contact with confirmed cases, epidemiologically linked to COVID-19 outbreaks, arrived from abroad, or had symptoms suspicious of COVID-19 as judged by doctors. In a Canadian cohort of 2 463 children [23] tested because of high risk exposure or epidemiologically linked to COVID-19 outbreaks, a 35.9% SARS-CoV-2 positivity rate was reported in asymptomatic children. In the Republic of Korea"s cohort of 91 patients, with a median age of 10 years, respiratory (60%), followed by gastro-intestinal symptoms (18%) were the most common presenting complaints [22] , in keeping with our findings. Loss of smell and taste were further common (16%) in this cohort, whereas these symptoms were not reported in our study population, likely owing to the younger age of our cohort in whom these symptoms may go unrecognized. Respiratory symptoms were similarly the most commonly reported symptoms in the Canadian cohort [23], which was not found to be predictive of positive SARS-CoV-2 results.

Asymptomatic elective admissions had the highest SARS-CoV-2 positivity rate in our study.

This is in contrast with point prevalence studies from Japan [24] , Canada [25] and Italy [26] that reported low positivity rates varying from 0.03% to 0.4% in asymptomatic individuals admitted for elective procedures or presenting to emergency departments. These results most likely reflected the low level of community transmission in the settings during these studies.

The cost-effectiveness and labour intensity of universal PCR testing could thus be questioned during periods of low community transmission.

Respiratory viruses other than SARS-CoV-2 were detected more frequently in children with symptoms typical of SARS-CoV-2 infection in our study, with HRV and RSV being the most prevalent viruses. Among SARS-CoV-2 infected children, co-infection with other viruses was detected in more than half, comparable to findings from China where 19/34 (51.4%) patients showed co-infection with pathogens other than SARS-CoV-2 [27] . The high rate of RSV detection coincided with the surge in RSV infections identified in South Africa after the COVID-19 pandemic peak when lockdown measures were lifted [28] . This is in keeping with studies reporting a reduction of non-SARS-CoV-2 seasonal illnesses during periods of strict social restrictions as part of non-pharmaceutical interventions against COVID-19 [29, 30] followed by an increased prevalence once social restrictions are eased [31] [32] [33] [34] [35] . The importance of adult caregivers as possible transmitters of SARS-CoV-2 within paediatric services has been highlighted before [36] . There is a paucity of published reports of caregiver SARS-CoV-2 surveillance testing in paediatric units in Africa, but up to 80% of adults with SARS-CoV-2 are reportedly asymptomatic [37] which might be higher than in children [3, 38] . Our findings support this, as the SARS-CoV-2 positivity rate was higher in asymptomatic adult caregivers than their children. Similarly Hassoun and colleagues [3] reported a higher positivity rate in asymptomatic caregivers (7.5%) compared to asymptomatic children (2.5%) during a point prevalence study at a pediatric emergency department in New York. Their reported caregiver-child SARS-CoV-2 RT PCR test concordance of 95% was however much higher than our study findings. Although children less than 10 years of age may be less likely to cause nosocomial infection spread [1, 39] , risk of transmission remains of concern in LMICs where overcrowded emergency centres, the lack of isolation rooms and use of large cohort rooms for admission of multiple childcaregiver pairs may contribute to healthcare-associated COVID-19 transmission [40, 41] .

Caregiver transmission risk needs specific attention when designing paediatric COVID-19

testing strategies and infection control measures in hospitals.

A lack of both human and laboratory resources in LMICs may limit the implementation of universal SARS-CoV-2 testing of hospitalised children and their caregivers. The risk of false negative PCR tests during the virus incubation period makes a pre-admission testing strategy alone not sufficient to prevent nosocomial transmission infection, with guidelines recommending re-screening of admitted patients after 5-7 days [42, 43] . Low cost, point of care antigen tests have potential advantages, especially in emergency settings, and should be considered. [25, 44] . However, antigen testing may be able to distinguish children with a high viral load who may be infectious, but are overall less sensitive in children compared to adults, making a negative test potentially unreliable [45] . Appropriate social distancing, hand hygiene, environment surface cleaning, isolation of infected people and universal facemasking remain the best strategies to avoid spread of infection [46] , as patient cohorting according to symptoms seems unreliable. Health systems in LMICs are under-resourced and in many settings may be unable to effectively implement these public health measures [47] .

Repeated local period prevalence surveys could be used to inform local testing strategies and assist with the implementation of effective IPC activities and appropriate resource allocation [48] .

Universal PCR testing of both children and caregivers presenting to the emergency unit were not feasible at Tygerberg Hospital, with only children requiring admission to wards tested for SARS-CoV-2 irrespective of presenting symptoms or complaints. Universal IPC precautions were rather implemented, with only SARS-CoV-2 positive children cohorted in a dedicated ward. Local prevalence data will continue to inform future testing and cohort strategies.

Limitations of this study are the single centre, small sample size and timing of the surveillance period at the "tail end" of a pandemic wave. Another limitation may be the possibility of false negative test results. Several factors may contribute to a lack of RT-PCRtesting sensitivity including the amount of material sampled and the assay sensitivity [49] .

As some data were collected retrospectively, variables may be missing or not documented.

Strengths of this study are the inclusion of testing for other respiratory viruses in symptomatic children and the inclusion of testing results for asymptomatic caregivers. 

Results from this point prevalence study was shared with the Department of Paediatrics and Child Health staff during a COVID-19 academic session. The results were also shared with the Tygerberg Hospital management team, and specifically the COVID-19 hospital response team.

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All authors approved the version to be published and agreed to be accountable for all aspects of the work.

The authors declared no conflict of interest. 

We thank Drs. Josiaas Coetsee, Megan Govender, Courtney Elliot-Wilson, Josh Clacher, and other interns who performed the patient and caregiver SARS-CoV-2 testing during the study period. Bianca Hamman"s assistance in the laboratory was invaluable and our nursing and administrative colleagues" support during the survey is similarly appreciated.

Authors contributed as follows to the conception of the work; the acquisition, analysis, or interpretation of data for the work; and drafting the work or revisiting it critically for important intellectual content: LS contributed 15%; SM, AR, LMV, JL, HR, MvdZ and AD 10%, CdV 5% and GvZ, MC, JT, AD and MA 2% each.