https://orcid.org/0000-0001-9671-8161
Correction
9 Nov 2022: The PLOS Medicine Staff (2022) Correction: Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study. PLOS Medicine 19(11): e1004126. https://doi.org/10.1371/journal.pmed.1004126 View correction
Figures
Abstract
Background
During the initial phase of the Coronavirus Disease 2019 (COVID-19) pandemic, reduced numbers of acutely ill or injured children presented to emergency departments (EDs). Concerns were raised about the potential for delayed and more severe presentations and an increase in diagnoses such as diabetic ketoacidosis and mental health issues. This multinational observational study aimed to study the number of children presenting to EDs across Europe during the early COVID-19 pandemic and factors influencing this and to investigate changes in severity of illness and diagnoses.
Methods and findings
Routine health data were extracted retrospectively from electronic patient records of children aged 18 years and under, presenting to 38 EDs in 16 European countries for the period January 2018 to May 2020, using predefined and standardized data domains. Observed and predicted numbers of ED attendances were calculated for the period February 2020 to May 2020. Poisson models and incidence rate ratios (IRRs), using predicted counts for each site as offset to adjust for case-mix differences, were used to compare age groups, diagnoses, and outcomes.
Reductions in pediatric ED attendances, hospital admissions, and high triage urgencies were seen in all participating sites. ED attendances were relatively higher in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, p < 0.001) and in children aged <12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, p < 0.001). The lowering of pediatric intensive care admissions was not as great as that of general admissions (IRR 1.30, 95% CI 1.16 to 1.45, p < 0.001). Lower triage urgencies were reduced more than higher triage urgencies (urgent triage IRR 1.10, 95% CI 1.08 to 1.12; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57; versus nonurgent triage category, p < 0.001). Reductions were highest and sustained throughout the study period for children with communicable infectious diseases. The main limitation was the retrospective nature of the study, using routine clinical data from a wide range of European hospitals and health systems.
Author summary
Why was this study done?
- Reduced numbers of children visiting urgent and emergency care services were reported following the introduction of infection prevention measures during the first phase of the Coronavirus Disease 2019 (COVID-19) pandemic.
- Concerns were raised about potential delays in, and higher acuity of, emergency department (ED) presentations.
What did the researchers do and find?
- This study compared routine clinical data from children aged 18 years and under presenting to EDs of 38 study sites in 16 European countries between January 2018 until May 2020.
- Reductions in ED attendances were seen for all age groups, with smaller reductions for younger children in some sites.
- More severely ill children continued to attend hospital more frequently compared to those with minor injuries and illnesses, although absolute numbers fell.
What do these findings mean?
- The findings suggest that the introduction of infection prevention measures can decrease the burden of acute childhood illnesses and injuries.
- There was no clear association of infection prevention measures with an increase in more severe, possibly delayed, presentations.
- For this first phase of the COVID-19 pandemic, the relative increase in cases of diabetic ketoacidosis or mental health issues might have contributed to a biased perception about increased occurrence.
Citation: Nijman RG, Honeyford K, Farrugia R, Rose K, Bognar Z, Buonsenso D, et al. (2022) Presentations of children to emergency departments across Europe and the COVID-19 pandemic: A multinational observational study. PLoS Med 19(8): e1003974. https://doi.org/10.1371/journal.pmed.1003974
Academic Editor: Zulfiqar A. Bhutta, The Hospital for Sick Children, CANADA
Received: March 18, 2022; Accepted: July 28, 2022; Published: August 26, 2022
Copyright: © 2022 Nijman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All study data are available from via https://doi.org/10.14469/hpc/10685.
Funding: RGN was supported by National Institute of Health Research, award number ACL-2018-021-007. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: CI, confidence interval; COVID-19, Coronavirus Disease 2019; ECDC, European Centre for Disease Prevention and Control; ED, emergency department; EPISODES, Epidemiology, severity and outcomes of children presenting to emergency departments across Europe during the SARS-CoV-2 pandemic; IRR, incidence rate ratio; LRTI, lower respiratory tract infection; MIS-C, Multi Inflammatory Syndrome in Children; PERUKI, Pediatric Emergency Research in the United Kingdom and Ireland; PICU, pediatric intensive care unit; REPEM, Research in European Pediatric Medicine; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2
Introduction
Healthcare systems across Europe continue to be greatly affected by the Coronavirus Disease 2019 (COVID-19) pandemic. Early in the COVID-19 pandemic, urgent and emergency facilities prepared for a potential influx of acutely unwell children and young people [1]. However, evidence emerged that children were less likely to develop symptoms of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, when compared with adults [2–6]. Moreover, reduced numbers of unwell or injured children visiting urgent and emergency care services were reported, and these seemed to be greatest for children with infectious communicable diseases [7–11]. Typically, these studies did not compare patterns between countries or in relation to different public health strategies.
At the same time, concerns were raised about potential delays in, and higher acuity of, presentations to appropriate healthcare services, as a result of difficulties accessing these services, changes in healthcare provision preferencing virtual consultations, fear of exposure to SARS-CoV-2 in healthcare facilities, and blanket “Stay at Home” statements [12–14]. In the United Kingdom, this resulted in a statement from the Royal Society of Pediatrics and Child Health to reassure parents and caregivers, urging them to seek appropriate urgent and emergency medical attention when worried about the acute illness or injury of their child [15]. Additionally, mostly anecdotal evidence reported increased numbers of specific childhood diagnoses, such as diabetic ketoacidosis [16] and intussusception [17]. These hypothesized a possible link with acute or prior SARS-CoV-2 infection, yet evidence from large-scale cohorts is lacking. Concerns were also raised for the mental health of children resulting from school closures and stay at home orders [18,19].
In this study, we aimed to compare the number of children presenting to emergency departments (EDs) across Europe during the first phase of the COVID-19 pandemic with the 2 previous years; investigating any change in severity of illness and describing the associations with specific diagnoses potentially related to SARS-CoV-2.
Methods
Study design, setting, and participants
This retrospective, observational study included 38 sites from 16 European countries as part of the “Epidemiology, severity and outcomes of children presenting to emergency departments across Europe during the SARS-CoV-2 pandemic” (EPISODES) study (trial registration number: ISRCTN91495258) (S1 and S2 Files). Sites were selected from the Research in European Pediatric Medicine (REPEM) and the Pediatric Emergency Research in the United Kingdom and Ireland (PERUKI) networks following the earlier work of Bressan and colleagues [1]. Routine clinical data from all children presenting to the ED were extracted from electronic health records for the period January 1, 2018 to May 17, 2020. The upper age limit varied between sites at between 16 and 18 years old. This study is reported as per the REporting of studies Conducted using Observational Routinely collected health Data (RECORD) statement (S1 Checklist) and the study protocol is available in the Supporting information (S1 File).
Aggregated, standardized data were uploaded using the REDCap online platform. For the period January 1, 2018 and February 1, 2020, data were collected on a monthly basis. For the period February 2, 2020 to May 17, 2020, on a weekly basis. This amounted to a total of 40 time windows (S1 Table). The clinical report form included 10 different data domains: (1) moment of presentation; (2) patient characteristics; (3) mode of arrival and referral pathway; (4) triage urgency; (5) type of presenting problem and vital signs; (6) diagnostics performed in the ED; (7) treatment in the ED; (8) diagnosis; (9) hospital admission; and (10) duration of ED and hospital stay (S3 File); data availability varied between sites (S1 Fig).
Triage urgency levels, used to determine the urgency of care in the ED, were categorized in 3 predefined categories, defined as emergent-very urgent (or RED-ORANGE, or level 1 to 2), urgent (or YELLOW, or level 3), and standard-nonurgent (or GREEN-BLUE, or level 4 to 5) to allow uniform coding between sites. For diagnosis coding, ICD-10 codes were issued for guidance (S2 Table), but an internally and temporally consistent coding approach was encouraged for each of the individual sites, acknowledging different coding systems and strategies in the ED. This was checked by plotting the diagnoses coding in time as percentage of total number of attendances for each site. To achieve reliable and accurate transformation of local (non-ICD-10) coding systems into the predefined diagnosis categories, training sessions were held and support offered to study sites by the lead investigators. Diagnoses were selected to reflect the broad spectrum of presenting problems to EDs, and their perceived change in incidences during the initial phase of the COVID-19 pandemic, following a consensus methodology among the study steering group. Final selection of diagnoses for analyses, after completion of data quality control process, included (1) common communicable diseases (e.g., tonsillitis, otitis media, lower respiratory tract infection (LRTI), gastrointestinal infection); (2) common minor injuries (e.g., minor head injury, radius fracture); (3) mental health issue; (4) diabetic ketoacidosis; and (5) surgical presentations (e.g., appendicitis, volvulus-intussusception-malrotation, testicular torsion). Severity was defined based on level 1 to 2 urgency classification at triage, any hospital admissions, pediatric intensive care unit (PICU) admission, or death in ED.
Data analyses
The completeness, quality, and internal consistency of data were checked by plotting the absolute numbers, as well as percentage of total attendances, for each variable of interest in time for the whole study period 2018 to 2020. In order to quantify changes in attendances, we compared observed attendances with predicted numbers of attendances. Predicted numbers of attendances were estimated using monthly data for the 25 months prior to February 3, 2020. As the data had both a trend and seasonal component, we used Holt–Winters exponential smoothing to make short-term monthly forecasts for February, March, April, and May 2020. We adjusted these to weekly estimates of predicted numbers. We plotted predicted ED attendances against the introduction of national infection prevention measures [20]. We also calculated 28-day mean numbers for selected diagnoses, PICU and hospital admission, and death in ED for each month from January through April for the years 2018 to 2020.
We used a Poisson model, adjusted for time since February 3, 2020, to determine if there were differences between age groups, diagnoses, and disposition for patients. For each model, the outcome was the count of attendances per week from the week beginning February 3, 2020 to the week beginning May 4, 2020, with an offset of the predicted number of attendances in each week. An incidence rate ratio (IRR) >1 indicates higher numbers compared with the reference group, whereas an IRR <1 reflects a higher reduction in numbers. For age groups, the analysis was adjusted for site; for diagnoses and disposition, numbers were too small to make forecasts at site level and we therefore aggregated these across the whole sample. For diagnoses, we completed 2 models, one with 8 separate diagnoses and one where these were divided into 3 groups: surgical presentation (i.e., appendicitis), communicable diseases (i.e., tonsillitis, otitis media, LRTI, and gastroenteritis) and “other” (i.e., mental health issue, radius fracture, and minor head trauma). For 3 diagnosis groups, the number of attendances was too low to make sensible forecasts, namely diabetic ketoacidosis, testicular torsion, and the combined group of intussusception, volvulus, and malrotation. In addition, we determined if there were associations between the change in hospital attendances and the prevalence of SARS-CoV-2 in the country, as per the European Centre for Disease Prevention and Control (ECDC), and the number of COVID-19 measures that were introduced in each hospital in response to the pandemic as previously detailed by Rose and colleagues [21]. Rose and colleagues performed a survey study describing changes in local and regional healthcare pathways, including the diverting of patient groups to or away from the ED, and service provision. The survey covered a total of 37 possible points of change in provision of care for sites without a short stay unit (20 pertaining to service provision and 17 to patient pathways) and 38 possible points of change for those that did (21 service provision and 17 patient pathways).
High-prevalence countries were defined as a cumulative 14-day rate of >80 new cases per 100,000 of the population. For countries with multiple sites, we used an ANOVA to determine if there was evidence that within country differences were greater than between country differences, for total attendances in March and April, adjusted for predicted numbers to account for differences in site sizes. One site (MAL001) was unable to provide information on diagnosis so it was excluded from this section of analysis; 3 sites (SLO001, POR005, and TUR001) did not provide triage data. Two sites were excluded (NL002 and HUN002) from the forecasting analyses and Poisson models as they had missing data in the period before the pandemic (2018). One site (IRE003) was excluded from the Poisson models because it closed to pediatric attendances in response to the pandemic. One site (TUR003) accounted for 18% of all attendances, and we carried out sensitivity analysis to confirm the changes to our findings when including this site. Analyses were performed using R v4.0.0.
Ethics
Following initial approval by the UK Health Research Authority, all participating sites obtained approval from their national/local institutional review boards (S3 Table). The need for individual patient informed consent was waived. Data sharing agreements were in place.
Results
Description of sites, infection prevention measures, and SARS-CoV-2 prevalence
Sites included in the study varied in terms of size and service provision (S4 Table and S2 Fig). The annual number of ED attendances ranged from 4,961 (NL001, 2019) to 295,787 (TUR003, 2019) (S3 Fig). All but 3 sites were tertiary academic hospitals with specialized pediatric EDs; the remaining 3 sites were general teaching hospitals, two of which had dedicated pediatric sections and staff, and one of which had a mixed ED. Sites in Austria, Slovenia, and the Netherlands mainly saw medical presentations, whereas the other sites saw both medical and surgical/trauma presentations. Timing and degree of infection prevention measures were similar across European countries (Fig 1 and S5 Table). Notably, Iceland and Sweden did not close day care, nurseries, or primary education; Germany and the UK kept higher education open; Sweden did not close any public spaces; Hungary and Sweden did not advocate use of face masks; Malta, Iceland, and Sweden did not introduce stay-at-home recommendations; and Germany, Hungary, and Iceland did not formally close workspaces. Highest national prevalence of SARS-CoV-2 varied between countries (Fig 1 and S6 Table).
Timelines of the introduction of national infection prevention measures (“Response measures”), as well as dates for the first and first 100 cases of SARS-CoV-2 for each of the countries participating in the EPISODES study. The black circle depicts the date of the highest 14-day cumulative rate of new SARS-CoV-2 cases per 100,000, with the size reflecting the actual case rate. COVID-19, Coronavirus Disease 2019; EPISODES, Epidemiology, severity and outcomes of children presenting to emergency departments across Europe during the SARS-CoV-2 pandemic; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.
Changes in total attendances
All 38 sites had significant reductions in attendances in spring 2020 (Table 1 and Figs 2 and S4). The largest reduction was seen in AUS001 with observed numbers at 5% (95% CI 5% to 6%) of predicted in the week starting March 30, 2020; the smallest peak reduction in ED attendances was at 56% (95% CI 52% to 60%) of predicted in SWE001 during the same week. IRE003 closed for pediatric visits from March 30, 2020 onwards, with most patients diverted to IRE001. Poisson models, adjusted for time since intervention and predicted numbers of attendances, showed that there were significant differences between sites. Observed attendances, with respect to predicted, were relatively higher in sites in France, Sweden, Ireland, Iceland, Latvia, and the Netherlands, where observed attendance rates were greater than 50% of predicted. However, there was considerable overlap between all sites when 95% confidence intervals were considered. Results of the Poisson models suggest that attendances in Spring 2020 were higher in EDs in countries with lower SARS-CoV-2 prevalence (IRR 2.26, 95% CI 1.90 to 2.70, P < 0.001) (Table 2). We found a relationship between the number of introduced organizational COVID-19 measures and ED attendances and more organizational COVID-19 measures were associated with lower numbers of ED attendances when adjusted for predicted ED attendances (IRR 0.13, 95% CI 0.11 to 0.16, when sites with 4 or more measures were compared to sites with no measures, P < 0.001). Similarly, larger reductions in ED attendances were seen in mixed adult and pediatric academic hospitals (versus standalone children’s hospital, IRR 3.49, 95% CI 2.89 to 4.24, P < 0.001; general nonuniversity hospital, IRR 2.73, 95% CI 2.28 to 3.30, P < 0.001) and urban hospitals (versus mixed urban and rural hospitals, IRR 5.33, 95% CI 4.44 to 6.46, P < 0.001). ED attendances across all age groups significantly reduced (S5 and S6 Figs). Attendances in children aged above 12 months were reduced more than children below 12 months (12 to <24 months IRR 0.86, 95% CI 0.84 to 0.89; 2 to <5 years IRR 0.80, 95% CI 0.78 to 0.82; 5 to <12 years IRR 0.68, 95% CI 0.67 to 0.70; 12 to 18 years IRR 0.72, 95% CI 0.70 to 0.74; versus age <12 months as reference group, all P < 0.001) (Table 2). There was insufficient evidence to conclude that this pattern continued with increasing age for children aged 12 months and older. Patterns between sites within the same country appeared similar (S7 Fig) with strong evidence that between country differences were greater than within country differences (F value: 6.453; p: 0.002).
The observed versus predicted number of children presenting to EDs in countries across Europe in the weeks following February 2, 2020 until May 11, 2020, for all sites combined. The color and the size of the dots reflect the actual number of ED attendances for each site and for each time window. The line connects the mean of the observed vs. predicted point estimates for each of the individual sites for each time window.
Triage urgency
Overall, there was a higher reduction (observed compared to predicted) in children with lower triage urgency when compared to children with higher triage classification (urgent triage, IRR 1.10, 95% CI 1.08 to 1.12, P < 0.001; emergent and very urgent triage IRR 1.53, 95% CI 1.49 to 1.57, P < 0.001; versus nonurgent triage category), even though clear reductions were seen for all triage categories (S8 Fig).
Hospital and PICU admissions
Hospital and PICU admissions were fewer than predicted (Figs 3, 4 and S9). We did not observe an increase in the number of deaths in ED (IRR 1.75, 95% CI 0.88 to 3.07, p = 0.08). The change in PICU admissions (IRR 1.30, 95% CI 1.16 to 1.45, versus general admissions) was not as great as the change in general admissions.
The observed versus predicted number of children admitted to hospital from the ED in countries across Europe in the weeks following February 2, 2020 until May 11, 2020, for all sites combined. The color and the size of the dots reflect the actual number of ED attendances for each site and for each time window. The line connects the mean of the observed vs. predicted point estimates for each of the individual sites for each time window.
Percentages of total ED attendances (left) and absolute numbers (right) of children admitted to hospital (top), PICUs (middle), or died in the ED (bottom); comparing the 28-day mean numbers for the months of January–April for 2018 vs. 2019 vs. 2020. ED, emergency department; PICU, pediatric intensive care unit.
Diagnoses
The 28-day mean numbers for common communicable diseases decreased in absolute and relative frequencies (Table 3 and Fig 5A), in particular for tonsillitis, otitis media, gastrointestinal infections, and LRTIs. Decreases were also seen in common childhood injuries such as minor head injuries and radius fractures (Fig 5B). No increase in absolute numbers were seen for several uncommon diagnoses suggested to be linked with SARS-CoV-2 infection, such as diabetic ketoacidosis (Fig 5C), intussusception, and testicular torsion (Fig 5B), even when stratified for high-SARS-CoV-2 prevalence countries (S10 Fig). Mental health attendances declined during the first phase of the COVID-19 pandemic in absolute terms, but this corresponded with an increase in relative frequency (Fig 5C). Fig 6, reflecting the observed versus predicted numbers for the 8 selected diagnoses, shows that the change of children and young people with appendicitis was less than for the other diagnoses groups. Mental health issues, radius fractures, and minor head injuries were all affected, but there was evidence that attendances increased from the end of March. In contrast, attendances for LRTI, otitis media, gastrointestinal infections, and tonsillitis remained low. Poisson models showed no significant difference between mental health, minor head trauma, and radius fracture. There was evidence of significant difference between infections and trauma and mental health, with bigger reductions in infections. When communicable diseases were combined, there was a clear difference between surgical presentation (appendicitis), communicable diseases, and “other” (mental health, radius fracture, and head trauma) (Table 2).
Percentages of total ED attendances (left) and absolute numbers (right) of children with diagnosis of (A) common communicable diseases (tonsillitis, otitis media, LRTI, GI infections), (B) minor injuries and surgical presentations (radius fracture, minor head injury, appendicitis, intussusception, volvulus and malrotation (combined group), testicular torsion,), and (C) mental health issues and diabetic ketoacidosis; comparing the 28-day mean numbers for the months of January–April for 2018 vs. 2019 vs. 2020. ED, emergency department; GI, gastrointestinal; LRTI, lower respiratory tract infection.
The observed versus predicted numbers of 8 selected diagnoses for all sites combined, for the period following February 2, 2020 until May 4, 2020. The error bars indicate the 80% prediction intervals.
Sensitivity analyses
The sensitivity analyses for the Poisson modelling without TUR003 resulted in IRRs slightly nearer to one, meaning all associations were slightly weaker (S7 Table). The change of the coefficient for tonsillitis was notable, increasing the IRR from 0.19 (95% CI 0.17 to 0.21) to 0.37 (95% CI 0.34 to 0.41). There was also a change between PICU admissions (IRR 1.13, 95% CI 1.00 to 1.28, p = 0.045) and admissions in general. Though the comparison remained statistically significant, the association was weaker.
Discussion
Reductions in the numbers of children attending EDs were consistently seen across Europe during the first phase of the COVID-19 pandemic. There was variation between countries, but within countries patterns were similar. The levels to which ED attendances decreased appeared to be related to the introduction and extend of infection prevention measures, changes made to local health systems, type of hospital, and national SARS-CoV-2 prevalence. Attendances were relatively higher in some sites with fewer or less strict national infection prevention measures (e.g., Sweden, Iceland), but this was not true for others (e.g., France). ED attendances were seen for all age groups, with smaller reductions in children aged below 1 year. The reduction in numbers was largest and sustained for communicable diseases, whereas other groups of diagnoses trended towards normal levels of ED attendances by the end of the study period after initial reduced ED attendance rates.
Our findings of reduced pediatric ED attendances are consistent with other studies from around the world [7–11,22–24]. The observed reduction in ED attendances will likely be multifactorial, including changed parental health-seeking behavior, modified and newly introduced healthcare pathways, and fewer circulating and reduced transmission of infectious pathogens. For example, children with asthma often frequent EDs, but they had fewer exacerbations needing ED visits during the first phase of the COVID-19 pandemic. Proposed reasons include reduced air pollution, reduced social mixing with exposures to viral trigger, and improved compliance with medication at home [25,26]. All this appeared to have affected presentations of children and young people with a low triage urgency and with minor injuries and illnesses most.
Earlier studies suggested that infection prevention measures may have resulted in delayed presentations to hospitals [12,13,27–29]. In our study, children with more severe conditions, as measured by triage urgency, need for hospital admission, and PICU and death, continued to attend hospital more frequently compared to those with minor injuries and illnesses, although overall absolute numbers fell. This was in line with other studies reporting similar reductions in children with high triage urgency or need for hospital admission [7,30–38].
Defining the harm of delayed presentations, as well as establishing what contributed to a possible delay, can be difficult [39]. In an attempt to distinguish the delay in seeking care from harm sustained, Roland and colleagues concluded that only a minority (6 out of 51 (11.8%)) of children with a potential delay in presentation were admitted to 1 of 7 hospitals [40]. Contradictory conclusions have been reported for the delay in presentations and for potential harm sustained for diagnoses of appendicitis [41,42] and testicular torsion [43–46], portraying a picture that organizing regional healthcare delivery is important to ensure continued access to pediatric urgent and emergency care during a pandemic. In addition, our data showed that, despite overall falling ED attendances, presentations requiring surgical interventions remained stable, reiterating that access to surgical teams and the ability to perform emergent surgical procedures are crucial.
Evidence is mounting that SARS-CoV-2 is directly involved in the pathogenesis of new onset diabetes [47,48]. Unsworth and colleagues first reported an increase of new onset type 1 diabetes in children and a possible link with SARS-CoV-2 in the UK [16]. Additional cohort studies found divergent associations between SARS-CoV-2, new onset diabetes, and decompensation of preexisting diabetes [49–52]. Our data did not identify increased incidence of diabetic ketoacidosis during the first phase of the COVID-19 pandemic. It might well be that clusters of new onset diabetes can be found in high-prevalence areas and that we failed to capture this in our study. Likewise, if SARS-CoV-2 acts as a precipitator, there might be a delay in the manifestation of new onset diabetes, and with reduced prevalence of typical viral triggers, this increase might only become apparent later in the pandemic [53]. We were not able to differentiate between new onset diabetes and decompensation of preexisting diabetes.
We found a reduction of children with mental health conditions presenting to the EDs during the first phase of the COVID-19 pandemic in Europe, similar to findings from studies elsewhere [9,54–57]. This is unlikely to reflect the considerable mental health issues encountered in the wider pediatric and adolescent populations [58] and of the experiences later in the pandemic, with, among others, reported increases in eating disorders in children and young people [59]. Joyce and colleagues observed an overall decrease in mental health issues in ED, albeit an increase in self-harm and deliberate ingestions [60]. Despite the reduction in absolute numbers, there was an increase in the proportion of attendances attributable to mental health potentially contributing to the heightened awareness for mental health issues in the first COVID-19 wave.
Prior to the current COVID-19 pandemic, limited data were available describing the association of infection prevention measures on urgent and emergency pediatric care in high-income countries. One study found a decrease in respiratory infections of 42% and decreased ED attendances of 28% following school closures for an influenza outbreak in Israel [61]. Similar patterns were seen during the SARS outbreak in 2003 [62–64] and the MERS outbreak in 2015 [65]. These studies also reported a larger reduction in ED utilization for children than for adults. In contrast, the 2009 H1N1 influenza pandemic generally led to increased ED utilization, with higher levels of acuity [66–68]. One previous study had reported reduced pediatric ED attendance rates for flu-like illness and respiratory tract infections following school closures [69]. Another study reported increased pediatric ED attendance numbers following media reports on health threats of the H1N1 virus [70]. Altogether, previous evidence of infectious disease outbreaks suggests a similar impact on pediatric urgent and emergency care following the introduction of public health and infection prevention measures. However, this is to a lesser extent than what was observed with the COVID-19 pandemic and one that is dependent on childhood susceptibility for the infectious pathogen.
Strengths and limitations
Our study presents multinational data enabling the comparison between infection prevention measures, national SARS-CoV-2 prevalence, and the association with acute illness and injuries in children between European countries. Most participating sites were tertiary institutions, with dedicated pediatric emergency medicine teams, with potential implications for the generalizability of our findings. At present, no standardized data extraction system for pediatric urgent and emergency care exists between European countries; and the EPISODES study is, to our knowledge, the first to navigate the difficulties of dealing with different data systems, data availability, and varying coding practices. Hence, also limited by the time restrictions caused by the COVID-19 pandemic, some sites were not able to provide data for all domains, and 2 sites (NL002 and HUN002) were only able to provide data for part of the study duration.
Limitations of electronic health records to describe patients’ diagnoses are well known [71]. Some of the participating study sites had unique non-ICD-10-based coding systems, and we urged all study teams to be consistent in transforming local data to fit the study clinical report form and we implemented a rigorous data quality process to ensure validity of coding in time. Although most diagnoses linked to SARS-CoV-2 in children were included in the predefined clinical report form, other diagnoses might be of interest in future studies. Of note, coding for children with Multi Inflammatory Syndrome in Children (MIS-C) proved unreliable, with no unique diagnostic codes available for this new disease in automated coding systems.
As the data were collected in aggregated form, thereby negating some of the difficulties with data protection regulations, we were not able to stratify for severity of specific diagnosis or age groups. This also introduced risks of overstratification during analyses. We observed large differences between sites for the number of annual ED attendances and the number of patients with high triage urgency and hospital admissions, reflecting both case-mix and diversity of patient management. We analyzed data mostly on a site-by-site basis, by using predicted versus observed ratios, and thus dealing with heterogeneity between sites. In addition, although very few study sites restructured local healthcare pathways diverting urgent and emergency care to alternative healthcare facilities, this does not fully rule out changes to access to healthcare or parental health-seeking behavior. Mongru and colleagues showed that, for one of the sites included in this study, the distribution of patients across primary and secondary care was similar before and during the first year of the COVID-19 pandemic, suggesting the observed reductions in patient numbers, especially for those with minor injuries and illnesses, were a true reflection of fewer children in the community in need of urgent and emergency care [72].
We used the cumulative 14-day rate of new cases per 100,000 of the population to identify high-prevalence countries, but indications for SARS-CoV-2 testing and reporting mechanisms differed between countries, and this could have led to under- or overestimation of national prevalence rates. Moreover, national prevalence numbers might wrongly reflect any regional variation, but, for example, in the UK, identical patterns in ED attendances were seen across the 5 sites, despite large variations in SARS-CoV-2 prevalence during the first phase of the COVID-19 pandemic [73]. Due to the rapid escalation and near-universal introduction of infection prevention measures in European countries during the study period, we were not able determine the role of each of the individual measures on reducing ED attendances.
Conclusions
Reductions in overall ED attendances were seen across our study sites during the first phase of the COVID-19 pandemic, with health systems across Europe affected similarly. In most sites, there was no suggestion of disproportionate numbers of more severely unwell children. In the first phase of the COVID-19 pandemic, the relative increase in cases of diabetic ketoacidosis or mental health issues might have contributed to a biased perception about increased occurrence, yet this is not supported by an increase in absolute numbers of cases in our data. Our study informs how pediatric emergency medicine can prepare for future pandemics, taking into account that different infectious diseases outbreaks can affect children differently, and illustrates the potential of electronic health records to monitor trends in urgent and emergency care for children.
Supporting information
S1 Appendix. Membership of the EPISODES study group.
https://doi.org/10.1371/journal.pmed.1003974.s001
(PDF)
S1 Checklist. RECORD checklist.
The RECORD statement—checklist of items, extended from the STROBE statement, which should be reported in observational studies using routinely collected health data.
https://doi.org/10.1371/journal.pmed.1003974.s005
(PDF)
S1 Table. List of time windows for data entry.
https://doi.org/10.1371/journal.pmed.1003974.s006
(PDF)
S2 Table. ICD-10 guidance for coding of diagnosis.
https://doi.org/10.1371/journal.pmed.1003974.s007
(PDF)
S4 Table. Overview of participating study sites.
https://doi.org/10.1371/journal.pmed.1003974.s009
(PDF)
S5 Table. List of national social distancing measures.
https://doi.org/10.1371/journal.pmed.1003974.s010
(PDF)
S6 Table. List of national SARS-CoV-2 rates.
The dates and numbers of SARS-CoV02 infections in each of the study sites’ countries participating in the EPISODES study.
https://doi.org/10.1371/journal.pmed.1003974.s011
(PDF)
S7 Table. Sensitivity analyses: Poisson regression models for ED attendances without TUR003.
https://doi.org/10.1371/journal.pmed.1003974.s012
(PDF)
S2 Fig. Map of European with all participating study sites.
All participating study sites are highlighted with their study site ID; represented countries in red.
https://doi.org/10.1371/journal.pmed.1003974.s014
(PDF)
S3 Fig. Annual ED attendance numbers in 2018 and 2019.
The total number of pediatric ED attendances for each of the study sites for 2018 and 2019 (pre-COVID-19). Overall, the numbers of ED attendances in 2018 and 2019 were similar for each of the study sites, with considerable diversity between the study sites and TUR003 seeing more children in their ED than the other study sites.
https://doi.org/10.1371/journal.pmed.1003974.s015
(PDF)
S4 Fig. Annual ED attendance numbers 2018 to 2020 for all sites separately.
The total number of pediatric ED attendances for each of the study sites for the entire study duration (January 2018–May 2020). The y-axis is depicted in log scale.
https://doi.org/10.1371/journal.pmed.1003974.s016
(PDF)
S5 Fig. Observed versus predicted ED attendances (%) for different age categories.
The observed versus predicted number of children presenting to EDs in countries across Europe in the weeks following February 2, 2020 until May 11, 2020, for all sites combined, for children (a) aged 0–1 years; (b) 1–2 years; (c) 2–5 years; (d) 5–12 years; and (e) 12–18 years. The color and the size of the dots reflect the actual number of ED attendances for each site and for each time window. The line connects the mean of the observed vs. predicted point estimates for each of the individual sites for each time window.
https://doi.org/10.1371/journal.pmed.1003974.s017
(PDF)
S6 Fig. Observed versus predicted ED attendances (%) for different age categories, for individual sites.
https://doi.org/10.1371/journal.pmed.1003974.s018
(PDF)
S7 Fig. Observed versus predicted ED attendances (%) for each country.
The observed versus predicted number of children presenting to EDs in countries across Europe for which data from only 1 study site were available in the weeks following February 2, 2020 until May 11, 2020. A timeline is plotted (dashed line) to show the dates of the introduction of national social distancing measures.[20] One site from the Netherlands and 1 site from Hungary were excluded from these analyses as these sites could not provide data for the entire study duration.
https://doi.org/10.1371/journal.pmed.1003974.s019
(PDF)
S8 Fig. Observed versus predicted triage categories (%).
The observed versus predicted number of children presenting to EDs in countries across Europe in the weeks following February 2, 2020 until May 11, 2020, for all sites combined, for children (a) nonurgent and standard triage classification; (b) urgent triage classification; (c) emergency and very urgent triage classification. The color and the size of the dots reflect the actual number of ED attendances for each site and for each time window. The line connects the mean of the observed vs. predicted point estimates for each of the individual sites for each time window. UK001 did not use a triage system with the emergency and very urgent triage category.
https://doi.org/10.1371/journal.pmed.1003974.s020
(PDF)
S9 Fig. Percentage of children admitted to hospital for individual sites.
Percentages of total ED attendances (left) and absolute numbers (right) of children admitted to hospital (top) and PICUs (bottom); comparing the 28-day standardized numbers for the months of January–April for 2018 vs. 2019 vs. 2020. ED, emergency department; PICU, pediatric intensive care unit.
https://doi.org/10.1371/journal.pmed.1003974.s021
(PDF)
S10 Fig. Selected clinical diagnoses in the ED for the period January–April over a 3-year period, for high-prevalence countries.
Percentages of total ED attendances (left) and absolute numbers (right) of children with diagnosis of (a) tonsillitis; (b) otitis media; (c) LRTIs; (d) GI infections; (e) appendicitis; (f) testicular torsion; (g) intussusception; (h) mental health issues; (i) diabetic ketoacidosis; (j) radius fracture; and (k) minor head injury; comparing the 28-day standardized numbers for the months of January–April for 2018 vs. 2019 vs. 2020, shown for countries with of a cumulative 14-day rate of new SARS-CoV-2 cases per 100,000 of 80 or more. ED, emergency department; GI, gastrointestinal; LRTI, lower respiratory tract infection; SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2.
https://doi.org/10.1371/journal.pmed.1003974.s022
(PDF)
Acknowledgments
We would like to thank and acknowledge the support and their contributions to the EPISODES study of the following persons: Celia Nekrouf (Pediatric Emergency Department, Hopital Universitaire Robert-Debre, Paris, France); Marcello Covino (Emergency Department, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy); Benita Lund (Medical Secretary; Pediatric emergency department, Sachs’ Children and Youth Hospital, Stockholm, Sweden); Izabella Lottiger (Pediatric Emergency department, Astrid Lindgren Children Hospital, Stockholm, Sweden); Sharna Crosdale (Contracts office; Imperial College London, UK); Sarah Sheedy (Research nurse; Emergency Department, Bristol Royal Hospital for Children, Bristol, UK); James Allbones (Information & Performance Analyst; Birmingham Women’s and Children’s NHS Foundation Trust, UK), William Jones (University Hospitals of Leicester NHS Trust, UK); Frazer Snowdon and Matthew Ryan (Pediatric emergency department, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK), Carlos Saiz-Hernando (IT analyst; Department of Medical Documentation, Cruces University Hospital, Bilbao, Spain); Ellen Barry (research nurse; National Children’s Research Centre, Dublin, Ireland) and Fiona Leonard (data analyst, Children’s Health Ireland, Ireland); Ernst Eigenbauer (data analyst) and Katharina Lieb (medical student; Department of Pediatrics and Adolescent Medicine, Vienna, Austria); Sanne Vrijland (medical student; Erasmus MC–Sophia Children’s hospital, Rotterdam, The Netherlands); Catarina Cordeiro (Pediatric Emergency Service, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Portugal); Mark Camenzuli (Senior systems administrator; Mater Dei Hospital, Malta); Sandra Distefano (Clinical Performance Unit, Mater Dei Hospital, Malta); Karin Kittl-Mitteregger (HIS Management and Clinical Processes, Paracelsus Medical University, Salzburg, Austria); Marta Arpone (Research Assistant, University of Padova, Italy)
References
- 1. Bressan S, Buonsenso D, Farrugia R, Parri N, Oostenbrink R, Titomanlio L, et al. Preparedness and Response to Pediatric COVID-19 in European Emergency Departments: A Survey of the REPEM and PERUKI Networks. Ann Emerg Med. 2020 Jun 21;76(6):788–800. Available from: pmid:32419713
- 2. Götzinger F, Santiago-García B, Noguera-Julián A, Lanaspa M, Lancella L, Calò Carducci FI, et al. COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study. Lancet Child Adolesc Heal. 2020 Jun 29;4(9):653–61. Available from: pmid:32593339
- 3. Swann O V., Holden KA, Turtle L, Pollock L, Fairfield CJ, Drake TM, et al. Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: Prospective multicentre observational cohort study. Baillie JK, Semple MG, Openshaw PJM, Alex B, Bach B, Barclay WS, et al., editors. BMJ. 2020;370. Available from: https://www.bmj.com/content/370/bmj.m3249 pmid:32960186
- 4. Lu X, Zhang L, Du H, Zhang J, Li YY, Qu J, et al. SARS-CoV-2 Infection in Children N Engl J Med. 2020 Mar 18;382(17):1663–5. Available from:
- 5. Parri N, Lenge M, Buonsenso D. Children with Covid-19 in Pediatric Emergency Departments in Italy. N Engl J Med. 2020 May 1;383(2):187–90. Available from: pmid:32356945
- 6. DeBiasi RL, Song X, Delaney M, Bell M, Smith K, Pershad J, et al. Severe Coronavirus Disease-2019 in Children and Young Adults in the Washington, DC, Metropolitan Region. J Pediatr. 2020 Aug 1;223:199–203.e1. Available from: pmid:32405091
- 7. Isba R, Edge R, Jenner R, Broughton E, Francis N, Butler J. Where have all the children gone? Decreases in paediatric emergency department attendances at the start of the COVID-19 pandemic of 2020. Arch Dis Child. 2020 May 5;105(7):704. Available from: http://adc.bmj.com/content/early/2020/05/05/archdischild-2020-319385.abstract pmid:32376695
- 8. Angoulvant F, Ouldali N, Yang DD, Filser M, Gajdos V, Rybak A, et al. Coronavirus Disease 2019 Pandemic: Impact Caused by School Closure and National Lockdown on Pediatric Visits and Admissions for Viral and Nonviral Infections—A Time Series Analysis. Clin Infect Dis. 2021;72(2):319–22. Available from: pmid:33501967
- 9. Finkelstein Y, Maguire B, Zemek R, Osmanlliu E, Kam AJ, Dixon A, et al. Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments: A Nationwide Study. Pediatr Emerg Care. 2021 Jun;37(8):427–34. pmid:34074990
- 10. Kruizinga MD, Peeters D, van Veen M, van Houten M, Wieringa J, Noordzij JG, et al. The impact of lockdown on pediatric ED visits and hospital admissions during the COVID19 pandemic: a multicenter analysis and review of the literature. Eur J Pediatr. 2021 Jul;180 (7):2271–2279. pmid:33723971
- 11. DeLaroche AM, Rodean J, Aronson PL, Fleegler EW, Florin TA, Goyal M, et al. Pediatric emergency department visits at US children’s hospitals during the COVID-19 pandemic. Pediatrics. 2021;147(4). Available from: https://pediatrics.aappublications.org/content/147/4/e2020039628 pmid:33361360
- 12. Lynn RM, Avis JL, Lenton S, Amin-Chowdhury Z, Ladhani SN. Delayed access to care and late presentations in children during the COVID-19 pandemic: A snapshot survey of 4075 paediatricians in the UK and Ireland. Arch Dis Child. 2021;106(2):archdischild-2020-319848. Available from: https://adc.bmj.com/content/early/2020/06/24/archdischild-2020-319848 pmid:32586927
- 13. Lazzerini M, Barbi E, Apicella A, Marchetti F, Cardinale F, Trobia G. Delayed access or provision of care in Italy resulting from fear of COVID-19. Lancet Child Adolesc Heal. 2020 May 1;4(5):e10–1. Available from: pmid:32278365
- 14. Honeyford K, Coughlan C, Nijman RG, Expert P, Burcea G, Maconochie I, et al. Changes in emergency department activity and the first covid-19 lockdown: A cross-sectional study. West J Emerg Med. 2021 May;22(3):603–7. pmid:34125034
- 15. Royal College for Paediatrics and Child Health. Advice for parents and young people during coronavirus—posters [Internet]. 2020. [cited 2022 Jun 10]. Available from: https://www.rcpch.ac.uk/resources/advice-parents-young-people-during-coronavirus-posters
- 16. Unsworth R, Wallace S, Oliver NS, Yeung S, Kshirsagar A, Naidu H, et al. New-onset type 1 diabetes in children during COVID-19: Multicenter regional findings in the U.K. Diabetes Care. 2020 Nov;43(11):e170–1. pmid:32816997
- 17. Giovanni JE, Hrapcak S, Melgar M, Godfred-Cato S. Global Reports of Intussusception in Infants with SARS-CoV-2 Infection. Pediatr Infect Dis J. 2020 Jan;40(1):35–6.
- 18. Orben A, Tomova L, Blakemore SJ. The effects of social deprivation on adolescent development and mental health. Lancet Child Adolesc Heal. 2020 Aug;4(8):634–40. pmid:32540024
- 19. Newlove-Delgado T, McManus S, Sadler K, Thandi S, Vizard T, Cartwright C, et al. Child mental health in England before and during the COVID-19 lockdown. Lancet Psychiatry. 2021 May 1;8(5):353–4. Available from: pmid:33444548
- 20. European Centre for Disease Prevention and Control. COVID-19 [Internet] 2020. [cited 2022 Jun 10] Available from: https://www.ecdc.europa.eu/en/covid-19
- 21. Rose K, Bressan S, Honeyford K, Bognar Z, Buonsenso D, Da Dalt L, et al. Responses of paediatric emergency departments to the first wave of the COVID-19 pandemic in Europe: a cross-sectional survey study. Rybak A, Simões AS, Chiaretti A, Haraldsson A, Gomez B, Aupiais C, et al., editors. BMJ Paediatr Open. 2021;5(1). Available from: https://bmjpaedsopen.bmj.com/content/5/1/e001269
- 22. Keyes D, Hardin B, Sweeney B, Shedden K. Change in urban and non-urban pattern of ED use during the COVID-19 pandemic in 28 Michigan hospitals: An observational study. BMJ Open. 2021;11(2). Available from: https://bmjopen.bmj.com/content/11/2/e043024 pmid:33550257
- 23. Pines JM, Zocchi MS, Black BS, Carlson JN, Celedon P, Moghtaderi A, et al. Characterizing pediatric emergency department visits during the COVID-19 pandemic. Am J Emerg Med. 2021;41:201–4. Available from: https://www.sciencedirect.com/science/article/pii/S0735675720310615 pmid:33257144
- 24. Westgard BC, Morgan MW, Vazquez-Benitez G, Erickson LO, Zwank MD. An Analysis of Changes in Emergency Department Visits After a State Declaration During the Time of COVID-19. Ann Emerg Med. 2020;76 (5):595–601. pmid:33008651
- 25. Gupta A, Bush A, Nagakumar P. Asthma in children during the COVID-19 pandemic: lessons from lockdown and future directions for management. Lancet Respir Med. 2020 Jun;8(11):1070–1. pmid:32593314
- 26. Taquechel K, Diwadkar AR, Sayed S, Dudley JW, Grundmeier RW, Kenyon CC, et al. Pediatric Asthma Health Care Utilization, Viral Testing, and Air Pollution Changes During the COVID-19 Pandemic. J Allergy Clin Immunol Pract. 2020;8(10):3378–3387.e11. pmid:32827728
- 27. Valitutti F, Zenzeri L, Mauro A, Pacifico R, Borrelli M, Muzzica S, et al. Effect of Population Lockdown on Pediatric Emergency Room Demands in the Era of COVID-19. Front Pediatr. 2020;8:521. pmid:33072657
- 28. Raucci U, Musolino AM, Di Lallo D, Piga S, Barbieri MA, Pisani M, et al. Impact of the COVID-19 pandemic on the Emergency Department of a tertiary children’s hospital. Ital J Pediatr. 2021 Jan;47(1):21. pmid:33514391
- 29. Isba R, Edge R, Auerbach M, Cicero MX, Jenner R, Setzer E, et al. COVID-19: Transatlantic declines in pediatric emergency admissions. Pediatr Emerg Care. 2020 Nov;36(11):551–3. pmid:32925702
- 30. Vierucci F, Bacci C, Mucaria C, Dini F, Federico G, Maielli M, et al. How COVID-19 Pandemic Changed Children and Adolescents Use of the Emergency Department: the Experience of a Secondary Care Pediatric Unit in Central Italy. SN Compr Clin Med. 2020 Sep;2(11):1959–69. pmid:32984767
- 31. Morello F, Bima P, Ferreri E, Chiarlo M, Balzaretti P, Tirabassi G, et al. After the first wave and beyond lockdown: long-lasting changes in emergency department visit number, characteristics, diagnoses, and hospital admissions. Intern Emerg Med. 2021 Mar;16(6):1683–90. pmid:33683538
- 32. Shanmugavadivel D, Liu JF, Gilhooley C, Elsaadany L, Wood D. Changing patterns of emergency paediatric presentations during the first wave of COVID-19: Learning for the second wave from a UK tertiary emergency department. BMJ Paediatr Open. 2021;5(1):e000967. pmid:34192192
- 33. Sano K, Nakamura M, Ninomiya H, Kobayashi Y, Miyawaki A. Large decrease in paediatric hospitalisations during the COVID-19 outbreak in Japan. BMJ Paediatr Open. 2021;5(1):e001013. pmid:34192195
- 34. Raman R, Madhusudan M. Impact of the COVID-19 Pandemic on Admissions to the Pediatric Emergency Department in a Tertiary Care Hospital. Indian J Pediatr. 2021 Apr;88(4):392. pmid:33146879
- 35. McIntosh A, Bachmann M, Siedner MJ, Gareta D, Seeley J, Herbst K. Effect of COVID-19 lockdown on hospital admissions and mortality in rural KwaZulu-Natal, South Africa: Interrupted time series analysis. BMJ Open. 2021 Mar;11(3):e047961. pmid:33737445
- 36. McDonnell T, Nicholson E, Conlon C, Barrett M, Cummins F, Hensey C, et al. Assessing the impact of COVID-19 public health stages on paediatric emergency attendance. Int J Environ Res Public Health. 2020 Sep;17(18):1–25. pmid:32942698
- 37. Dann L, Fitzsimons J, Gorman KM, Hourihane J, Okafor I. Disappearing act: COVID-19 and paediatric emergency department attendances. Arch Dis Child. 2020;105(8):810–1. Available from: https://adc.bmj.com/content/105/8/810 pmid:32518141
- 38. Chong SL, Soo JSL, Allen JC, Ganapathy S, Lee KP, Tyebally A, et al. Impact of COVID-19 on pediatric emergencies and hospitalizations in Singapore. BMC Pediatr. 2020 Dec;20(1):562. pmid:33353540
- 39. Roland D, Nijman RG, Ponmani C, Munro APS. Arriving late, delayed, or not at all—presentations to paediatric emergency departments during covid-19 pandemic [Internet]. [cited 2022 Jun 10]. BMJ. 2020. Available from: https://blogs.bmj.com/bmj/2020/08/15/arriving-late-delayed-or-not-at-all-presentations-to-paediatric-emergency-departments-during-covid-19-pandemic/
- 40. Roland D, Harwood R, Bishop N, Hargreaves D, Patel S, Sinha I. Children’s emergency presentations during the COVID-19 pandemic. J Clean Prod. 2020 Jun 30; Available from: pmid:32598871
- 41. Delgado-Miguel C, Munõz-Serrano AJ, Miguel-Ferrero M, De Ceano-Vivas M, Calvo C, Martínez L. Complicated Acute Appendicitis during COVID-19 Pandemic: The Hidden Epidemic in Children. Eur J Pediatr Surg. 2022 Jun 22;32(03):268–73. Available from: http://www.thieme-connect.de/DOI/DOI?10.1055/s-0041-1723992 pmid:33618382
- 42. Gaitero Tristán J, Souto Romero H, Escalada Pellitero S, Espiñera CR, Andina Martín D, Espinosa Góngora R, et al. Acute Appendicitis in Children During the COVID-19 Pandemic: Neither Delayed Diagnosis Nor Worse Outcomes. Pediatr Emerg Care. 2021 Mar;37(3):185–90. pmid:33651763
- 43. Nelson CP, Kurtz MP, Logvinenko T, Venna A, McNamara ER. Timing and outcomes of testicular torsion during the COVID-19 crisis. J Pediatr Urol. 2020 Dec;16(6):841.e1-841.e5. pmid:33223456
- 44. Littman AR, Janssen KM, Tong L, Wu H, Wang MD, Blum E, et al. Did COVID-19 Affect Time to Presentation in the Setting of Pediatric Testicular Torsion? Pediatr Emerg Care. 2021 Feb;37(2):123–5. pmid:33512891
- 45. Holzman SA, Ahn JJ, Baker Z, Chuang KW, Copp HL, Davidson J, et al. A multicenter study of acute testicular torsion in the time of COVID-19. J Pediatr Urol. 2021 Aug;17(4):478.e1-478.e6. pmid:33832873
- 46. Pogorelić Z, Milanović K, Veršić AB, Pasini M, Divković D, Pavlović O, et al. Is there an increased incidence of orchiectomy in pediatric patients with acute testicular torsion during COVID-19 pandemic?–A retrospective multicenter study. J Pediatr Urol. 2021 Aug;17(4):479.e1–479.e6. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1477513121002254 pmid:33994321
- 47. Müller JA, Groß R, Conzelmann C, Krüger J, Merle U, Steinhart J, et al. SARS-CoV-2 infects and replicates in cells of the human endocrine and exocrine pancreas. Nat Metab. 2021 Feb;3(2):149–65. pmid:33536639
- 48. Fignani D, Licata G, Brusco N, Nigi L, Grieco GE, Marselli L, et al. SARS-CoV-2 Receptor Angiotensin I-Converting Enzyme Type 2 (ACE2) Is Expressed in Human Pancreatic β-Cells and in the Human Pancreas Microvasculature. Front Endocrinol (Lausanne). 2020;11:596898. pmid:33281748
- 49. Salmi H, Heinonen S, Hästbacka J, Lääperi M, Rautiainen P, Miettinen PJ, et al. New-onset type 1 diabetes in Finnish children during the COVID-19 pandemic. Arch Dis Child. 2022 Feb;107(2):180–5. Available from: pmid:34045208
- 50. Tittel SR, Rosenbauer J, Kamrath C, Ziegler J, Reschke F, Hammersen J, et al. Did the COVID-19 lockdown affect the incidence of pediatric type 1 diabetes in Germany? Diabetes Care. 2020 Nov;43(11):e172–3. pmid:32826282
- 51. Rabbone I, Schiaffini R, Cherubini V, Maffeis C, Scaramuzza A. Has covid-19 delayed the diagnosis and worsened the presentation of type 1 diabetes in children? Diabetes Care. 2020 Nov;43(11):2870–2. pmid:32778554
- 52. Jacob R, Weiser G, Krupik D, Takagi D, Peled S, Pines N, et al. Diabetic Ketoacidosis at Emergency Department Presentation During the First Months of the SARS-CoV-2 Pandemic in Israel: A Multicenter Cross-Sectional Study. Diabetes Ther. 2021 May;12(5):1569–74. pmid:33730335
- 53. Gottesman BL, Yu J, Tanaka C, Longhurst CA, Kim JJ. Incidence of New-Onset Type 1 Diabetes Among US Children During the COVID-19 Global Pandemic. JAMA Pediatr. 2022. Available from: pmid:35072727
- 54. Leeb RT, Bitsko RH, Radhakrishnan L, Martinez P, Njai R, Holland KM. Mental Health–Related Emergency Department Visits Among Children Aged <18 Years During the COVID-19 Pandemic—United States, January 1–October 17, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(45):1675–1680. pmid:33180751
- 55. Ougrin D, Wong BH, Vaezinejad M, Plener PL, Mehdi T, Romaniuk L, et al. Pandemic-related emergency psychiatric presentations for self-harm of children and adolescents in 10 countries (PREP-kids): a retrospective international cohort study. Eur Child Adolesc Psychiatry. 2021 Mar:1–13. pmid:33677628
- 56. Carr MJ, Steeg S, Webb RT, Kapur N, Chew-Graham CA, Abel KM, et al. Effects of the COVID-19 pandemic on primary care-recorded mental illness and self-harm episodes in the UK: a population-based cohort study. Lancet Public Health. 2021 Feb;6(2):e124–35. pmid:33444560
- 57. Leff RA, Setzer E, Cicero MX, Auerbach M. Changes in pediatric emergency department visits for mental health during the COVID-19 pandemic: A cross-sectional study. Clin Child Psychol Psychiatry. 2021 Jan;26(1):33–8. pmid:33183097
- 58. Ford T, John A, Gunnell D. Mental health of children and young people during pandemic. BMJ. 2021 Mar 10;372:n614. Available from: https://www.bmj.com/content/372/bmj.n614 pmid:33692087
- 59. Lin JA, Hartman-Munick SM, Kells MR, Milliren CE, Slater WA, Woods ER, et al. The Impact of the COVID-19 Pandemic on the Number of Adolescents/Young Adults Seeking Eating Disorder-Related Care. J Adolesc Health. 2021 Jul;69(4):660–3. pmid:34266715
- 60. Joyce LR, Richardson SK, McCombie A, Hamilton GJ, Ardagh MW. Mental health presentations to Christchurch Hospital Emergency Department during COVID-19 lockdown. Emerg Med Australas. 2021 Apr;33(2):324–30. pmid:33078509
- 61. Heymann A, Chodick G, Reichman B, Kokia E, Laufer J. Influence of school closure on the incidence of viral respiratory diseases among children and on health care utilization. Pediatr Infect Dis J. 2004 Jul;23(7):675–7. pmid:15247610
- 62. Boutis K, Stephens D, Lam K, Ungar WJ, Schuh S. The impact of SARS on a tertiary care pediatric emergency department. CMAJ. 2004 Nov;171(11):1353–8. pmid:15557588
- 63. Heiber M, Lou WYW. Effect of the SARS outbreak on visits to a community hospital emergency department. Can J Emerg Med. 2006 Sep;8(5):323–8. pmid:17338843
- 64. Huang HH, Yen DHT, Kao WF, Wang LM, Huang CI, Lee CH. Declining emergency department visits and costs during the severe acute respiratory syndrome (SARS) outbreak. J Formos Med Assoc. 2006 Jan;105(1):31–7. pmid:16440068
- 65. Paek SH, Kim DK, Lee JH, Kwak YH. The impact of middle east respiratory syndrome outbreak on trends in emergency department utilization patterns. J Korean Med Sci. 2017 Oct;32(10):1576–80. pmid:28875599
- 66. Progression and impact of the first winter wave of the 2009 pandemic H1N1 influenza in New South Wales, Australia. Euro Surveill. 2009 Oct;14(42). pmid:19883546
- 67. Graham J, Shirm S, Storm E, Lyle K, Linam WM, Romero J. Challenges and solutions: pandemic 2009 H1N1 influenza A in a pediatric emergency department. Am J Disaster Med. 2011;6(4):211–218. pmid:22010598
- 68. Blumental S, Huisman E, Cornet MC, Ferreiro C, De Schutter I, Reynders M, et al. Pandemic A/H1N1v influenza 2009 in hospitalized children: A multicenter Belgian survey. BMC Infect Dis. 2011 Nov;11:313. pmid:22060843
- 69. Copeland DL, Basurto-Davila R, Chung W, Kurian A, Fishbein DB, Szymanowski P, et al. Effectiveness of a school district closure for pandemic influenza A (H1N1) on acute respiratory illnesses in the community: A natural experiment. Clin Infect Dis. 2013 Feb;56(4):509–16. pmid:23087391
- 70. McDonnell WM, Nelson DS, Schunk JE. Should we fear “flu fear” itself? Effects of H1N1 influenza fear on ED use. Am J Emerg Med. 2012 Feb;30(2):275–282. pmid:21208765
- 71. Armstrong BG. Effect of influenza vaccination on excess deaths occurring during periods of high circulation of influenza: Cohort study in elderly people. BMJ. 2004;329(7467)):660. Available from: https://www.bmj.com/content/341/bmj.c4226 pmid:15313884
- 72. Mongru R, Rose DF, Costelloe C, Cunnington A, Nijman RG. Retrospective analysis of North West London healthcare utilisation by children during the COVID-19 pandemic. BMJ Paediatr Open. 2022 Jan 13;6(1):e001363. Available from: https://bmjpaedsopen.bmj.com/content/6/1/e001363
- 73.
GOV.UK Coronavirus (COVID-19) in the UK [Internet]. [cited 2022 Jun 10]. Available from: https://coronavirus.data.gov.uk/details/download