Paediatric appendicitis: international study of management in the COVID-19 pandemic

impact of the COVID-19 pandemic on paediatric appendicitis, speci ﬁ cally the proportion of children with complex appendicitis, alterations in the diagnostic work-up and treatment strategies, and its outcomes.


Introduction
The COVID-19 pandemic had a huge impact on healthcare systems worldwide, forcing policymakers to reorganize hospital resources to prioritize COVID care. Recommendations were made by surgical societies to postpone elective surgery and apply non-operative alternatives if available for surgical diseases [1][2][3] . The aim of this multicentre international study was to investigate the impact of the COVID-19 pandemic on paediatric appendicitis, specifically the proportion of children with complex appendicitis, alterations in the diagnostic work-up and treatment strategies, and its outcomes.

Methods
An international retrospective study was conducted at 40 hospitals from 23 countries (Appendix S1). The study was overseen by an international study steering group (RG/AZ/AP/ NH/TW/FM/AG/PA) that developed the study protocol. This study was endorsed by the European Paediatric Surgeons' Association (EUPSA), which assisted in the recruitment of participating hospitals through the EUPSA Network Office. Principal investigators of participating sites obtained local ethical approval in accordance with local requirements. The study was reported according to the STROBE guidelines 4 .
Patients (aged less than 18 years) treated for acute appendicitis between January 2019 and December 2020 were screened for eligibility. Those who had non-operative treatment without an imaging-confirmed diagnosis of acute appendicitis were excluded. Diagnosis of acute appendicitis was defined by intraoperative and histopathological confirmation of appendicitis, and, in the event of non-operative treatment (Appendix S2), based on clinical, biochemical, and radiological criteria. Local investigators were asked to define the start of the COVID-19 pandemic at their institution based on the start of the interval during which regular healthcare was affected by the pandemic. The COVID group included patients treated between the start of the COVID period and 31 December 2020. The control group consisted of patients treated during the corresponding interval in 2019. To understand healthcare protocols and management strategies for acute appendicitis before and during the pandemic at each centre, all participating sites were asked to complete a survey that was sent on 23 March 2021 (Appendix S3).
Variables of interest and their definitions were agreed by the study steering group based on the globally supported core outcome set for studies reporting the treatment of acute simple appendicitis in children [5][6][7][8] . Primary outcomes were the proportions of children treated for complex appendicitis, children who underwent imaging procedures for confirmation of appendicitis, children treated using non-surgical treatment strategies, and complications directly related to treatment. Secondary outcomes and definitions are shown in Appendix S2.
Comparative analyses were undertaken by calculating differences in proportions and 95 per cent confidence intervals. Subgroup analyses based on time interval of presentation, age, and region were performed for appendicitis severity and complications. For all subgroup analyses, Bonferroni correction was applied to adjust for multiple testing. Statistical analyses were carried out using SPSS ® version 26 (IBM, Armonk, NY, USA).

Results
Between January 2019 and December 2020, some 10 655 children were treated for acute appendicitis, of whom 2062 were excluded for the reasons outlined in Appendix S4. Therefore, 8593 patients were included, 4113 in the COVID group and 4480 in the control group. Baseline characteristics were similar in the two groups (Appendix S5).
The survey showed that, in the majority of participating centres, non-operative treatment and same-day discharge were not standard care during the pandemic, and that there was no change in referral pathways or shift of patients with complex disease to the participating centres (Appendix S1).

Appendicitis severity
In the COVID group, 47.7 per cent of patients were treated for complex appendicitis versus 45.0 per cent in the control group (difference 2.7 (95 per cent c.i. 0.6 to 4.8) per cent; P = 0.014) ( Table 1). This increased proportion of complex appendicitis was apparent only during the first 3 months of the pandemic (difference 5.6 (1.8 to 9.3) per cent; P = 0.003, adjusted P = 0.007) and was predominantly caused by an absolute decrease in patients with simple appendicitis. The subgroup analysis based on region showed that the proportion of patients treated for complex appendicitis increased by 3.5 (1.2 to 5.8) per cent in Europe (P = 0.004, adjusted P = 0.020). No differences were found for other continents ( Table 2).

Diagnostic work-up and initial treatment
In  Table 1).

Complications
Both the primary and subgroup analyses showed no differences in the number of patients experiencing any complication between the COVID and control groups, nor in the severity of complications. In both groups, intra-abdominal abscess was the most frequent postoperative complication (Tables 1 and 2).

Discussion
This large international study found that the number of patients presenting with simple appendicitis decreased during the first months of the pandemic, resulting in a higher proportion of complex appendicitis than in the control interval. The proportion of patients who had non-operative treatment and the proportion of complications were comparable to those in the control period. These data suggest that the management and outcomes of children with acute appendicitis were relatively unaffected by the pandemic, reflecting the resilience of the participating centres. Several small single-centre studies 9-14 have reported contradictory results on the influence of the pandemic on the proportion of patients treated for complex appendicitis; some reported increased proportions of complex appendicitis (7-18 per cent), whereas others could not detect any difference. In the present study, the increased proportion of complex appendicitis seems to be the result of an absolute decrease in patients with simple appendicitis. A possible explanation could be the resolution of mild cases of simple appendicitis in patients who did not seek medical care and recovered spontaneously or were treated with antibiotics by general practitioners 15,16 . After the first months of the pandemic, proportions of simple and complex appendicitis were comparable to those in the control group, which was predominantly the result of an absolute increase in patients with simple appendicitis. This could be explained by the fact that the threshold for seeking medical care for mild appendicitis possibly decreased after the first few months of the pandemic, as lockdown measures were slowly lifted and COVID-19-related fear declined. These findings are in line with those of other population-based studies [17][18][19] that noted an absolute decrease in both adult and paediatric patients presenting with simple appendicitis early in the pandemic. This international multicentre study is limited by possible information and selection bias, which is inherent to retrospective selection of patients and data collection. Furthermore, the regional subgroup analysis was limited by a skewed distribution, as the majority of patients were included in Europe. Finally, the survey found no shift of patients with complex disease to participating centres, but this might still have occurred. The major strength of this study is the international collaboration and subsequent large sample size of more than 8500 patients.