key: cord-0838208-4lpr3kn5
authors: Vaos, George; Zavras, Nikolaos
title: Severe acute respiratory syndrome coronavirus 2 pandemic related morbidity and mortality in patients with pediatric surgical diseases: A concerning challenge
date: 2022-01-20
journal: World J Methodol
DOI: 10.5662/wjm.v12.i1.20
sha: f67b9da751106fd1e3f20c044ebcb198be182b69
doc_id: 838208
cord_uid: 4lpr3kn5

The global spread of the novel severe acute respiratory syndrome coronavirus 2 has had serious consequences in terms of patient morbidity and mortality and overburdened health care systems as well as the socioeconomic implications. In the absence of effective therapies and vaccinations during the viral outbreak, the major and most concise means to control viral spread is spread prevention. Although information concerning the impact of severe acute respiratory syndrome coronavirus 2 on pediatric surgical patients has greatly expanded, relevant comprehensive studies are scarce. However, pandemic related morbidity has increased, while under normal circumstances mortality could have been minimized.

It has been approximately 1 year since the outbreak of novel pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in the city of Wuhan in China. The disease was subsequently named coronavirus disease 2019 (COVID-19) [1] . The global spread of this new virus forced the World Health Organization to declare it a pandemic on March 11, 2020 [2] . It is estimated that up to June 23, 2021, about 180079074 people worldwide have already been infected, and the number of confirmed deaths had reached 3900967 [3] .

In an attempt to restrict the accelerated transmission of the disease, governments and health organizations across the world adopted various measures [4] . The pediatric surgical community responded accordingly, both globally and locally. The American College of Surgeons and the American Pediatric Surgical Association proposed certain criteria for the management and prioritization of pediatric surgical procedures, taking into account elective procedures that could be postponed and balancing the risk between disease progression and viral vulnerability [5, 6] . Similarly, the European Association of Urology issued a statement of recommendations for pediatric urological cases during the SARS-CoV-2 era [7] . In the same spirit, the Spanish Association of Pediatric Surgery published and announced elective surgery restrictions, with the exception of emergencies and oncological cases [8] . Several organizations in the United Kingdom also provided evidence-based guidelines for elective pediatric surgical services [9] . In addition to these measures, many hospitals at the local level established extensive protocols for the security, protection, and proper management of sick children and their parents [10] .

Apart from the resultant drop in elective surgeries amid SARS-CoV-2 cases[11,12], many pediatric surgical centers also noted a decline in emergency cases [11] . Moreover, the pandemic has seen the emergence of a new clinical entity, defined as multisystem inflammatory syndrome in children (MIS-C), which is considered by many to be a complication of SARS-CoV-2[13].

This study aims to identify the influence of the SARS-CoV-2 pandemic on morbidity and mortality among children with surgical diseases.

A data-based search retrieved 939 articles from the period January 1, 2020 to June 23, 2021. After subtracting duplicates, out of the 809 articles that emerged, we assessed 118 manuscripts in full text and finally reviewed 46 studies (Figure 1 ). The details of these studies are described below and summarized in Table 1 . Two children aged 7 wk and 6 years respectively, both positive for SARS-CoV-2 infection, presented with clinical signs of acute abdomen. The clinical and diagnostic investigation showed necrotizing enterocolitis (NEC), which was successfully treated with antibiotics. The authors considered infection to be responsible for this emergency clinical manifestation [36, 37] .

Seven articles [38] [39] [40] [41] [42] [43] [44] referred to cases of ileocolic intussusception. Eight infants, aged 4-10 mo, presented with clinical symptoms related to intussusception (abdominal cramps, bilious vomiting, currant jelly stools) and were confirmed by ultrasound. On admission, seven infants were found to be positive for SARS-CoV-2, and one was found to be positive on the third postoperative day; four[38,40-42] had relatives with suspected or confirmed SARS-CoV-2 infection. Reduction (pneumatic or hydrostatic) was attempted in seven patients, six of whom had a successful outcome. Only two cases were treated surgically. Notably, in one case, at laparotomy, malrotation was found in addition to intussusception, and a Ladd's procedure was performed [41] . In the other case, intestinal resection with consequent ileostomy and mucous fistula was performed due to intestinal ischemia and peritonitis [44] . Moreover, following successful pneumatic reduction of intussusception, one female infant with documented SARS-CoV-2 infection went on to develop acute respiratory infection and multiorgan complications during hospitalization, including abdominal ascites and intestinal failure, which subsequently led to her death [41] .

A total of four articles was extracted for SARS-CoV-2 in children with burns [45] [46] [47] [48] . All of them disclosed useful information. Specifically, they recorded an increase in admissions of children with moderate and severe fire-related burns in comparison to earlier years, while the greater difference in burned total body surface area was statistically significant [46] [47] [48] .

One article from Spain was included [49] that reported clinical and surgical data, complications, and readmissions of all children who underwent procedures for various urological conditions. The authors developed an escalation program based on the different phases of the pandemic and the European Association of Urology recommendations. They concluded that this strategy allowed them to manage successfully urological diseases.

Three studies[50-52] that screened pediatric oncology/hematology patients for SARS-CoV-2 infection were evaluated. In the first study, 334 nasopharyngeal swabs were taken from 247 patients, only 10 (4%) of whom tested positive for SARS-CoV-2 infection (eight patients were asymptomatic and two had a mild fever). In nine patients, chemotherapy was postponed until they had tested negative (time period ranges from 12-26 d), while only one patient on chemotherapy and radiation was positive after 30 d [50] . In a multicenter survey performed in 25 countries involving 200 suspected patients, only nine tested positive for SARS-CoV-2 infection [51] . Notably, none required admission to pediatric intensive care or mechanical ventilation. Finally, a retrospective, multicenter study among 13 institutions including 578 patients examined test-positive SARS-CoV-2 patients aged ≤ 21 years receiving active anticancer treatment [52] . Among those 578 patients, 98 (16.95%) were positive, 78 (79.6%) of whom were symptomatic, and four died (4%). Delay of anticancer therapy occurred in 67% of these patients. Overall, these studies raised the question concerning the benefits of discontinuing or delaying chemotherapy in mild or asymptomatic SARS-CoV-2 positive patients.

This study provides descriptive data on pediatric surgical patients infected with the novel coronavirus SARS-CoV-2. The data show that the impact of SARS-CoV-2 seems to be multifactorial as it interferes directly with human health due to the vulnerability of the virus and indirectly with the resources to access care, thereby increasing morbidity and mortality [12] .

SARS-CoV-2 infection can affect all ages of children with median age of infection of 6.7 years (1 d to 15 years) [53] , with no gender predominance [54] . The angiotensinconverting enzyme 2 is the main host receptor of SARS-CoV-2 and is frequently expressed in ciliated epithelial cells in human lungs. The second most common site of angiotensin-converting enzyme 2 receptors is the gastrointestinal cells [53] . Notwithstanding, gastrointestinal symptoms attributed to SARS-CoV-2 infection are more prevalent in children, while respiratory involvement is more common in adults [55, 56] . The predominant association of gastrointestinal infection and SARS-CoV-2 might also explain the cases of intussusception [38] [39] [40] [41] [42] [43] [44] and the two cases of NEC [36, 37] . Intussusception is the most common cause of intestinal obstruction in infancy [57] . Although in most cases it is thought to be idiopathic, a preceding viral infection due to adenovirus and rotavirus has been reported in approximately 30% of cases [58] . Notably, all cases described here were positive for SARS-CoV-2 infection, while a previous history of upper respiratory tract infection was diagnosed in three cases [38] [39] [40] . In the two cases of NEC, the association of SARS-CoV-2 test positivity with coexistence of pneumatosis intestinalis and bloody stools suggests ischemic necrosis in both cases and hence NEC [36, 37] .

The increase in the number of children presenting with burns during the outbreak could be ascribed to the fact that the lockdown obliged children to stay home where they may have had less surveillance, since parents were constrained to work from home and were thus unable to keep a close watch on children. Educational programs are needed to increase parents' knowledge concerning safety behaviors during a prolonged stay at home [45] [46] [47] [48] .

The impact of SARS-CoV-2 outbreak on children with urological problems is not known. An escalation program based on different phases of the pandemic has been proposed by Merino-Mateo et al [49] for the management of urological problems. However, the lengthy postponement of certain crucial surgical procedures, such as cryptorchidism, or obstructive uropathies including ureteropelvic junction obstruction, ureterovesical junction obstruction, or neurogenic bladder may lead to loss of a testicle function or loss of renal function. Three articles referred to testicular torsion [59] [60] [61] . The conclusions were contradictory, as increased rate of orchidectomies was noticed in the two articles due to delayed presentation [59, 60] , while in the remaining one article the authors found early presentation in testicular torsion and no differences in rates of orchidectomies between SARS-CoV-2 period and preceding era [61] .

Children with cancer face significant health problems in view of the rapid changes in the health system and restrictions in accessing medical support. Compromised immunity due to malignancy and the unknown behavior of SARS-CoV-2 lead to further insecurity. Although the studies mentioned above[54-56] did not show significant consequences from the virus itself, it was clear that postponement of therapies owing to the heavily burdened health system could result in insufficient medical support.

In May 2020, the Centers for Disease Control in the United States expressed concern for a new entity termed MIS-C associated with SARS-CoV-2[34,62]. MIS-C is defined by clinically severe illness requiring hospitalization that presents with fever, elevated inflammatory markers, and multisystem organ dysfunction in the setting of recent proven or probable SARS-CoV-2 infection and the absence of a plausible alternative explanation [34] . However, there are no data available as to whether the mechanism that can lead to severe respiratory failure resembles that of MIS-C. Current data raise the suspicion for a distinct entity related to severe SARS-CoV-2 infection [62] . MIS-Crelated AA was suspected in three studies [25, 33, 34] in which the coexistence of CAA and positive was tested.

This study is not without its limitations inasmuch as it is based on all types of articles, most of which included retrospective studies, letters to the Editor, case reports, and case series, all of which were written during the pandemic within a short period of time in an effort to share experiences and divulge information that could help the scientific community. Furthermore, in order to achieve a better understanding, a substantial number of studies compared their results with those to pre-SARS-CoV-2 era, which can lead to a significant bias. Another limitation is that most data were collected within 204 mo. Consequently, there is a lack of acceptable follow-up that would have helped us gain precise knowledge as concerns postoperative outcomes and readmissions of patients treated during the pandemic.

Pediatric surgical practice during the SARS-CoV-2 pandemic is challenging. Summarizing the information and results of studies, we conclude that SARS-CoV-2 infection could have a negative influence on virtually the entire pediatric surgical spectrum. Morbidity has increased for various reasons in children with burns, urological problems, and cancer including fear of contracting the virus in health centers, lockdown, telemedicine, postponement of medical consultation and elective surgeries, or unknown manifestations of SARS-CoV-2. Under normal circumstances,

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