The Coronavirus Disease 2019 (COVID-19) worldwide pandemic presented a serious challenge with regard to health systems around the globe. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the natural course of the disease were initially unknown. Institutions and governments hastily adopted groundbreaking policies to prevent the spread of the virus such as sealing country borders and enforcing lockdowns (or “stay-at-home” policies) [1]. These altered many facets of daily life including medicine. The fear and uncertainty of the public, along with a multitude of other factors, contributed to the postponement of regular medical examinations or procedures. Such delays and difficulties in access also applied to emergency department (ED) visits, with a sharp decline in emergency non-COVID-19 cases noted during the lockdown period ^[2][3][4][2,3,4]. The burden on healthcare systems attributed to COVID-19, especially in densely populated areas, highlighted the need for significant changes in the management of emergency non-infectious surgical diseases. The aforementioned changes varied across countries, cities and institutions. The reluctance shown by both patients and their families to visit EDs, as well as the hurried clinical evaluations by medical staff, led to the delayed diagnosis and treatment of other common diseases, which resulted in severe manifestations that could otherwise have been avoided ^[5][6][7][8][5,6,7,8].

Pediatric appendicitis is one of the most common pediatric surgical emergencies. In general, appendicitis as a disease, in both adults and children, has been well documented [9]. Emphasis has always been placed on prompt diagnosis so that optimal outcomes with lower rates of complication can be achieved. However, the accurate diagnosis of appendicitis can be difficult and remains a challenge in pediatrics, especially in cases involving younger patients. Delays in time from the presentation of symptoms to surgery have linear associations with complications including perforation, peritonitis, sepsis and overall increased morbidity ^[9][10][9,10]. Younger patient age also correlates with perforation risk [10]. There is consensus among authors on the natural history of appendicitis although some authors have hinted at appendicitis not necessarily being a progressive disease ^[9][11][9,11].

2. Reasons for Delayed Diagnosis

2.1. Public Health and Social Measures (PHSMs)

After the initial outbreak in December 2019 and the spread of the SARS-CoV-2 virus from China to the rest of the world, efforts were made to limit the spread of COVID-19 ^[12][52]. Governments responded by implementing a series of lockdowns or stay-at-home orders and enforced travel restrictions between areas, cities, regions and countries. The stringency of social distancing or isolation varied across nations as referenced by numerous studies ^[13][14][15][20,27,53]. Stricter policies could, however, amplify fear and uncertainty, thus delaying presentation to the hospital as was potentially the case for New Zealand vs. Australia ^[13][20]. The World Health Organization has completed a database project to collect and archive PHSMs as implemented by individuals, institutions, communities, local and national governments and international bodies to limit the spread of COVID-19 [1]. These policies focused on several aspects to slow the spread of COVID-19 ^[16][54] but contributed to perceived significant delays in the diagnosis of common emergency conditions like appendicitis. Healthcare resource limitations were deemed necessary in order to allocate as many beds, staff, etc. as possible to the treatment of COVID-19 patients. Many surgical and medical departments were converted to COVID-19 wards and even operating rooms (ORs) were transformed into makeshift I.C.Us. ^[17][55]. Elective surgeries were postponed. This also meant physicians and nurses could be assigned from surgical to infectious departments during peak periods. These strategies were devised and executed to conserve health system resources and prevent hospitals from being overwhelmed by the surge in COVID-19 cases, which could lead to unacceptably high mortality [3]. The peak of the first wave of COVID-19 during March 2020 was arguably the most overwhelming for health systems in several countries ^[18][56]. The shift to the NOM of appendicitis as a strategy to spare hospital resources in cities stricken by the pandemic must also be mentioned. Travel restrictions between cities, provinces and regions and the assignment of pediatric hospitals or wards to adult COVID-19 care could have delayed pediatric appendicitis diagnosis by lengthening the times to examination by a surgeon and admission to a hospital ^[14][27]. Studies focusing on rural area populations have illustrated such delays during pre-pandemic periods ^[19][57]. Curfews and fines for their violation also constitute reasons for delays. Pediatric appendicitis outcomes can also be affected by lower socio-economic status as a consequence of hindered access to healthcare. This was studied before the pandemic ^{[19][20][21][22][23]}[28,57,58,59,60]. The associations between pediatric appendicitis outcomes and lower socio-economic status groups and poor nations that were highly affected by the pandemic warrant further study as there is no relevant evidence to date. The restriction of healthcare access may have had the opposite intended effect regarding resource deployment given that increases in complicated case numbers, length of stay (LOSs), operation durations and numbers of admissions and readmissions were recorded ^{[3][24][25][26][27]}[3,13,33,37,39]. Higher ratios of complicated pediatric appendicitis were demonstrated in countries that were hit harder by the pandemic including the USA, Germany and other countries where uncomplicated appendicitis case volume dropped ^{[7][8][28][29][30][31]}[7,8,38,61,62,63], but this was not always the case ^[32][24]. This effect was mostly associated with the first peak period of COVID-19 and was later reversed ^[31][63]. The importance of this secondary effect of the pandemic, namely the hampered access to specialized pediatric care that could delay diagnosis, must not be underestimated. Taking into consideration the data from most of the included studies, rwesearchers s strongly recommend that all children with symptoms suggestive of surgical emergencies must be examined and accurately diagnosed if optimal outcomes with minimal complications are to be achieved ^[13][14][20,27]. The provision of healthcare pathways for medical examination is vital, even during a pandemic ^[33][64]. While predictions of potential health crises in the future cannot be made, there is a wide consensus that preparing strategies for policy making and staff and resource allocation with current knowledge is imperative ^[25][34][33,65].

2.2. Fear of Exposure by Parents/Caregivers and/or Patients

The number of ED visits decreased worldwide as parents were consumed with the fear of exposing children to SARS-CoV-2 ^[2][3][4][2,3,4]. A multitude of studies in Italy, Spain, the U.S.A., the U.K., Canada and France have stated that parents delayed hospital visits out of fear. The same studies demonstrated worse outcomes, higher complication rates and LOSs, in particular for pediatric patients treated during the first wave of COVID-19 ^{[2][3][14][24][26][35][36][37]}[2,3,13,15,19,27,37,46]. Parental fear could have been exacerbated by being in countries with higher COVID-19 alert levels. In other studies, parents did not hesitate to bring their children to EDs, although these studies reported an increase in the percentage of patients presenting at EDs at least 48 h following symptom onset ^[38][31]. The lack of clear public health guidance on presenting to EDs for severe symptoms could confuse parents and delay the assessment of their children ^[13][20]. Parental anxiety and the psychosocial impact of COVID-19 on society as a whole, termed Coronaphobia, have been analyzed further by Dubey et al. ^[39][66]. Level of family education level did not correlate with delayed visits to hospitals ^[20][39][28,66]. The fear experienced by children, secondary to parents’ anxiety regarding the ongoing pandemic, could explain their hesitation to mention their initial symptoms. The recognition of symptoms by parents could also be hampered by their subjective nature when parents actively tried to avoid healthcare or ED visits [4]. Van Amstel et al. remark on the gradual removal of lockdown measures after the first months of the pandemic, which led to less fear and a lower threshold for seeking medical care even for milder symptoms ^[31][63]. Öztaş et al. mention that their results showed no difference in the overall frequency of appendicitis during the first year of the pandemic ^[40][47]. They attributed this finding to the fact that the included parents thought that children were not as likely to be infected by COVID-19 in general and that pediatric emergency departments were viewed as safer in that regard. Hence, there was no decrease in hospital visits ^[40][47].

2.3. Fear of Exposure by Medical Staff

The diagnosis of pediatric appendicitis can be delayed by numerous factors including, but not limited to, inconsistency in clinical presentation, varying gravity of symptoms, and difficulty in communication and the clinical examination of children, especially younger children ^[41][42][67,68]. Many authors have identified the deleterious effect that fear of exposure by medical professionals had in multiplying these already established difficulties. It has been mentioned that an emergency doctor’s fear of contact with patients can lead to haste in the examination of a patient, the cornerstone of diagnosis; this has been commented on by some authors ^[24][40][13,47]. Snapiri et al. allude to potential misdiagnoses caused by rushed examination, telemedicine use and reluctance to instruct patients to visit EDs. These factors led to serious clinical deterioration and complications for their reported cases ^[24][13]. The skyrocketing demand for and ineffective distribution of Personal Protective Equipment while the first wave peaked contributed to fear of contamination by staff and delays for many components of effective healthcare. Meanwhile, concern for staff protection from exposure to SARS-CoV-2 indicated that avoiding or delaying surgery could protect surgery personnel by limiting their exposure to possibly contaminated body fluids or generated aerosols from patient tissues ^[43][44][45][32,69,70]. A reduction in the volumes of diagnostic imaging modalities such as ultrasound or computed tomography scans in general during the first months of the pandemic has been clearly demonstrated ^[46][47][48][29,71,72]. However, rwesearchers can assume that delays in imaging could have led to the delayed diagnosis of pediatric appendicitis given the increase in diagnostic imaging use for suspected appendicitis during the pandemic as reported by some authors ^[49][43]. As Kim et al. point out, the positive imaging pediatric appendicitis case numbers were similar to those of previous years, and Horst et al. noted that the numbers of patients treated surgically were also similar ^[46][47][29,71]. These findings could be attributed either to pediatric patients presenting in a timely fashion to EDs as before or to having pediatric cases routed to dedicated pediatric hospitals and thus inflating these numbers ^[46][47][29,71].

2.4. Telemedicine Use

Telemedicine use became more widespread during the pandemic, mostly via phone or video calls ^[50][73]. Telemedicine is at the intersection where the previous three reasons meet. Fear of infection by healthcare professionals, fear experienced by parents and public health policy all promoted its use. Telemedicine evaluation is inherently incomplete because examination is unfeasible, and so, management could be varied. Where the main aim of a consultation is to promote home care, e.g., with antibiotics, delays in the diagnosis of appendicitis could occur ^[51][74]. Video use could possibly help in recognizing critically ill children ^[24][13]. An interesting side effect of greater telemedicine use could be the resolution of some cases of simple appendicitis, either spontaneously or with oral antibiotic therapy, due to its being essentially non-operatively managed at home with a presumed diagnosis. This has been suggested by Tankel et al. ^[52][75].

2.5. COVID-19-Positive Pediatric Patients with Suspected Appendicitis

SARS-CoV-2 infection has not been commonly associated with causing pediatric appendicitis ^[53][76] although such a connection was initially hypothesized ^[54][77]. It is necessary to point out that while research had to validate this causative relationship, the management of patients was ongoing. Potential perioperative morbidity in COVID-19-positive children with suspicion of appendicitis was an initial concern, and so, surgery was delayed to prevent perioperative pulmonary complications. This line of thinking was supported by adult-population experience as originally reported by the Lancet’s “COVIDSurg” Collaborative ^[43][55][32,78]. This was not later confirmed by the same author for the pediatric population during the pandemic ^[56][79]. Similar perioperative safety for infected children wasdemonstrated by other authors, making these delays for surgery inappropriate ^{[43][56][57][58][59]}[32,79,80,81,82]. Multisystem inflammatory syndrome in children (MIS-C) comprises a dangerous clinical entity with multiple-system involvement and possible multiorgan damage or failure ^[60][83]. It can manifest with a multitude of symptoms including but not limited to a rash, fever, abdominal pain, diarrhea, vomiting, conjunctivitis and shock. Differential diagnosis from Kawasaki disease and toxic shock syndrome can be challenging ^[61][84]. Prior infection or contact with a positive SARS-CoV-2 case and lack of an alternative diagnosis are among the criteria for establishing a diagnosis of MIS-C ^[62][85]. MIS-C abdominal pain can be severe and can mimic appendicitis ^[61][63][64][84,86,87]. MIS-C can also manifest with severe gastrointestinal diagnoses including appendicitis ^[65][88]. Increased clinical suspicion of MIS-C could have delayed diagnosis of appendicitis and vice versa ^[66][67][68][34,89,90]. Avoiding surgery for MIS-C and administering corticosteroid therapy while expediting surgery for complicated appendicitis is rational, given their respective complications ^[66][69][70][34,91,92].

2.6. Recurrent Appendicitis after Non-Operative Management

Delayed diagnosis might occur as recurrent appendicitis could be underappreciated by physicians not familiar with NOM and its complication rates, namely high failure or early recurrence and late recurrence after NOM ^[71][93]. NOM was sparingly employed for pediatric appendicitis cases before the pandemic. The novel application of NOM during the initial pandemic assault has shown that NOM can be an effective management strategy ^[11][72][73][11,94,95]. When proper standards and strict patient selection criteria for applying NOM are set, informed decision making by parents can be made with acceptable cost effectiveness ^[9][74][75][9,35,42].

2.7. Delays in Primary Operative Management or Increased Time to Operating Room

Given that appendicitis poses a diagnostic challenge, consideration must be given to aspects of delays in primary operative management during the pandemic since the diagnosis of appendicitis is ultimately verified intraoperatively, predominantly for equivocal cases [9]. It is possible that during the pandemic, more effort was made to establish a correct diagnosis preoperatively. This could have been due to greater imaging use, more direct senior consultant involvement and a higher threshold for surgical exploration ^[49][76][43,45]. Cases that were diagnostically uncertain were more likely to be managed non-operatively during the pandemic, as recommended by guidelines ^[77][78][96,97]. This led to two outcomes: higher numbers of false-positive appendicitis cases treated by NOM and lower negative appendicectomy rates ^[49][43]. Conversely, lower negative appendicectomy rates can be associated with either treating patients more easily with NOM or better diagnostic accuracy. However, improving diagnostic accuracy includes serial imaging, laboratory results and clinical examinations after an observation period; hence, inherent delays in this process can be assumed ^[9][70][79][9,49,92]. On a side note, achieving lower negative appendicectomy rates is interesting because it conserves resources and protects children from risks inherent to surgery ^[49][80][43,98]. Surgery was delayed during the first wave of COVID-19 due to knowledge gaps regarding the course of the disease. Aerosol generation by diathermy/electrosurgery and laparoscopy had to be eliminated as possible vectors of viral transmission so as to safeguard surgery staff safety ^[81][40]. This was suggested by the Royal College of Surgeons of England ^[78][97] but not by the Royal Australasian College of Surgeons ^[82][99] or the American College of Surgeons ^[71][93]. As stated earlier, there was uncertainty regarding whether operating on COVID-19-positive children with suspected appendicitis could increase perioperative pulmonary and immune-system morbidity. This may have contributed to delays in surgery and thus diagnosis. Reference must be made to SARS-CoV-2 PCR testing or rapid antigen tests. At the outset of the pandemic, these tests were either unavailable, costly or had long waiting times for result retrieval. There is evidence that SARS-CoV-2 testing delayed appendicectomies during the pandemic ^[83][51]. As the pandemic continued, all these factors improved; however, wide testing meant that most surgeons waited for SARS-CoV-2 PCR patient results before operating. The study by Ergün et al. established with statistical significance that time from hospital admission to surgery or NOM was indeed greater during the pandemic but did not lead to increased perforation rates for children ^[84][41]. This has been the case for adults ^[9][70][9,92]. Consequently, waiting for PCR results is cost-effective and safe in general. RWesearches can therefore surmise that some—mainly equivocal—cases, treated and diagnosed by primary surgical management, could have faced delays caused by hospital logistics and appendicitis management changes.