Overall Impact of Coronavirus Disease 2019 Outbreak in Children With Functional Abdominal Pain Disorders: Results From the First Pandemic Phase

Abstract

Objective: 

We aimed to assess how the first phase of coronavirus disease 2019 (COVID-19) pandemic influenced symptoms in children with functional abdominal pain disorders (FAPDs) and to characterize their quality of life (QoL), anxiety and global health.

Methods: 

This was a multicenter, observational, international study conducted between April and July 2020 at six different referral centers. Children diagnosed with FAPDs between October 2019 and February 2020 were enrolled and prospectively interviewed at 4 months of follow-up during the first pandemic phase (Quarantine group). Patients were asked to complete PedsQL 4.0 Generic Core Scale and PROMIS Anxiety and Global Health questionnaires. A cohort of children diagnosed with FAPDs between October 2018 and February 2019 was used as a Control group.

Results: 

Three-hundred-fifty-six children were enrolled of whom 180 (mean age at diagnosis: 14 ± 2.8 years) in the Quarantine group and 176 (mean age at diagnosis: 13 ± 2.8 years) in the Control group. At 4 months of follow-up, we observed a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline, in both groups (Quarantine group: 63.9% vs 42.2%, P < 0.001; Control group: 83.5% vs 50%, P < 0.001). The Quarantine group had median QoL values of 84.8 with 16.6% of children showing high anxiety values and 55% having decreased global health score.

Conclusions: 

We demonstrated symptoms’ improvement at 4 months of follow-up in both cohorts. During the first months of the COVID-19 quarantine children with FAPDs showed satisfactory QoL and anxiety scores, suggesting positive effects of school closure and increased parental attention.

What Is Known

• Coronavirus disease 2019 (COVID-19) pandemic and the related life changes may have serious repercussions on patients with chronic disorders.
• There is still no clear evidence on how the quarantine may affect the symptoms and the quality of life (QoL) of children with functional gastrointestinal disorders (FGIDs).

What Is New

• Our study shows overall symptom improvement at 4 months of follow-up in two different cohorts of children diagnosed with FAPDs 1 year before and immediately before the COVID-19 pandemic.
• Prospective evaluation of QoL and anxiety during the first months of the COVID-19 quarantine showed satisfactory scores, suggesting possible positive effects of school closure and increased parental attention.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and since December 2019 progressively spread worldwide with over 110 million cases to date ⁽¹⁾. This unprecedented public health crisis led to the implementation of strict quarantine measures around the world with profound consequences on daily living. Data from public opinion polls show that COVID-19 has had a significant psychological impact, termed as coronaphobia ⁽²⁾. There is still no clear evidence on how the quarantine may have affected the quality of life (QoL) of patients with functional gastrointestinal disorders (FGIDs), especially in children ⁽³⁾. Nevertheless, the disruption of daily routines combined with both child and parental anxiety about COVID-19 may have serious repercussions on children. This is particularly true for those who are affected by FGIDs, such as functional abdominal pain disorders (FAPDs). Functional abdominal pain affects 8–25% of school-age children and accounts for 2–4% of pediatric clinic visits ^(4–6). Although the burden of FAPDs is increasing over time, their pathogenesis remains unclear ⁽⁷⁾. Comorbid anxiety and depressive disorders are highly prevalent in patients with FAPDs, suggesting a primary brain–gut dysfunction as a plausible mechanism ⁽⁸⁾. The COVID-19 pandemic offers an opportunity to clarify some aspects of FAPDs pathogenesis with coronaphobia possibly exerting negative effects on patients’ symptoms, while decreased school stress and increased parental attention may constitute mitigating factors. The primary aim of the present study was to assess how societal changes imposed by COVID-19 and the related quarantine influenced symptoms in patients receiving a diagnosis of FAPDs at the beginning of the pandemic and to compare with a group of children diagnosed with FAPDs 1 year before; the secondary aims were to prospectively characterize anxiety, quality of life and the global health of children affected by FAPDs during the first COVID-19 quarantine.

METHODS

This multicenter, observational study was conducted between April and July 2020 at six different European, Israel and North American referral centers for Pediatric Gastroenterology (Table 1, Supplemental Digital Content, https://links.lww.com/MPG/C491). The study design consisted of a prospective and a retrospective phase. In the prospective phase, data from children diagnosed with a FAPD between October 2019 and February 2020 (Quarantine group) were collected. The inclusion criteria for the Quarantine group were: age from 8 to 18 years; diagnosis of a FAPD according to Rome IV criteria ⁽⁹⁾; and living in an area that underwent COVID-19 quarantine. In the Quarantine group, the patients were interviewed during the early phases of the COVID-19 quarantine, between April and July 2020. All the centers participating in the study were located in areas that at the time of the study were under similar COVID-19 related quarantine measures, which at least included: school closures, limited access to the hospital services, limitations of all the non-necessary public activities and implementation of smart working for all the non-essential workers. The interview was conducted by phone by the physician. The patients with the help of parents were asked to complete Rome IV questionnaire ⁽⁹⁾, Pediatric Quality of Life Inventory 4.0 (PedsQL 4.0) Generic Core Scale ⁽¹⁰⁾, Patient-Reported Outcomes Measurement Information System (PROMIS) anxiety ⁽¹¹⁾ and global health questionnaires ⁽¹²⁾. In the retrospective phase, we enrolled a Control group of children diagnosed with a FAPD between October 2018 and February 2019. The inclusion criteria were: age from 8 to 18 years and diagnosis of a FAPD according to Rome IV criteria ⁽⁹⁾. Data regarding symptoms’ evolution during the follow-up period between February 2019 and May 2019 were retrospectively collected. In both groups, the exclusion criteria included: patients with systemic or gastrointestinal infections and patients with other known chronic pathologies. Figure 1, Supplemental Digital Content, https://links.lww.com/MPG/C489 shows the structure of the study.

Pediatric Quality of Life Inventory 4.0 Generic Core Scales

The PedsQL 4.0 Generic Core Scales is a 23-item measure, which assesses four core domains of health-related QoL: physical, emotional, social and school functioning ⁽¹⁰⁾. Responses are based on a Likert-type scale and assess the level of impairment in each domain over the previous month. Items are reverse-scored and linearly transformed to a scale of 0–100, with higher scores indicating better QoL ⁽¹⁰⁾. Total score is calculated by summing all 4 domains of functioning, and the measure provides two summary scores: the Physical Health Summary Score (based on the physical functioning subscale) and the Psychosocial Health Summary Score (calculated using the Emotional, Social, and School Functioning Subscales) ⁽¹⁰⁾.

Patient-Reported Outcomes Measurement Information System Measures

The PROMIS Pediatric Bank v 2.0 Anxiety is a 15-item measure assessing anxiety, fears, hyperarousal and somatic symptoms related to arousal ⁽¹¹⁾. The PROMIS Pediatric Global Health 7 is a 7-item measure evaluating child's overall physical, mental and social health ⁽¹²⁾. Both instruments use a 5-point Likert scale from never to almost always to recall functioning over the previous 7 days. Scores are converted on the PROMIS T-score scale, which standardizes the instrument to a norm-referenced population with a mean of 50 and a standard deviation (SD) of 10. Higher anxiety scores are associated with increased symptoms’ burden ⁽¹¹⁾, whereas for Global health higher scores are associated with better function ⁽¹²⁾.

Outcomes Definitions

In order to assess symptom progression over time, the primary outcome of the study was the number of children reporting 5 or more days of abdominal pain per month based on the Rome IV questionnaire. Additionally, as secondary outcome, we asked patients in the Quarantine group at follow-up whether they experienced worsening, improvement or no change in symptoms with respect to their baseline.

Statistical Analysis

Variables were screened for their distribution, and appropriate parametric or non-parametric tests were used. The Mann-Whitney test for continuous variables and the χ² and Fisher exact tests for categorical variables were used. Correlations between PedsQL 4.0 Generic Core Scale, PROMIS anxiety and global health questionnaires were evaluated through the Spearman coefficient. Statistical significance was predetermined as P < 0.05. Percentages were rounded to the nearest whole numbers. SPSS version 20 and R version 3.6.0 were used for all statistical analyses.

Sample Size

To provide statistical power of at least 80% with a significance level α = 0.05, we calculated a minimum sample size of 66 patients per center with 33 patients in each group. Considering that the percentage of children with FAPDs who have multiple abdominal pain episodes a month has been reported at 43% ⁽¹³⁾, we estimated that the effect of the COVID-19 pandemic may reduce the percentage to 20% in the Quarantine group, whereas for the Control group the reduction would be only to 35%.

Ethical Considerations

The study was approved by the Institutional Review Board (IRB) of the University of Campania “Luigi Vanvitelli” on April 14, 2020, with the protocol registration number 7910/2020. Subsequently, all the remaining enrolling centers obtained approval by their respective local IRBs. Informed consent was obtained from all parents and from children, where appropriate.

RESULTS

Baseline Characteristics

Three hundred fifty-six children with a diagnosis of FAPD were enrolled. Of these, 180 children were diagnosed between October 2019 and February 2020 (Quarantine group) (mean age at diagnosis: 14 ± 2.8 years; male/female: 58/120) and 176 children were diagnosed between October 2018 and February 2019 (Control group) (mean age at diagnosis: 13 ± 2.8 years; male/female: 59/117). Relative numbers of recruited children by the different enrolling centers are showed in Table 1, Supplemental Digital Content, https://links.lww.com/MPG/C491, whereas baseline characteristics of Quarantine group and Control group are presented in Table 1. In the Quarantine group, 76 of 180 (42.2%) children fulfilled the criteria for irritable bowel syndrome (IBS), 58 of 180 (32.2%) functional abdominal pain non-otherwise specified (FAP-NOS), 41 of 180 (22.8%) functional dyspepsia (FD) and 5 of 180 (2.8%) abdominal migraine (AM). In the Control group, 70 of 176 (39.8%) children fulfilled the criteria for FAP-NOS, 54 of 176 (30.7%) IBS, 47/176 (26.7%) FD and 5 of 176 (2.8%) AM. When comparing the Quarantine group versus the Control group for FAPDs distribution, we only identified a statistically significant higher frequency of IBS in the Quarantine group (42.2% vs 30.7%, P = 0.03) (Table 1). When considering all FAPDs, 147 out of 176 (Control group, 83.5%) children reported to have a >5 of episodes of abdominal pain per month versus 115 of 180 (63.9%) in the Quarantine group (P = 0.001) (Fig. 1). Regarding the different treatments used to control symptoms, a higher frequency of paracetamol/NSAIDs use was observed in Control group compared to Quarantine group (25% vs 15.1%, P = 0.02) (Table 1).

TABLE 1 - Baseline characteristics of children diagnosed with FAPDs between October 2019 and February 2020 (Quarantine group) and between October 2018 and February 2019 (Control group)

Characteristics (N, %)	Quarantine group (N = 180)	Control group (N = 176)	P
Age at diagnosis (mean±SD, y)	14 ± 2.8	13 ± 2.8	0.07
Male sex	58 (32.2)	59 (33.5)	0.8
Ethnicity
Western European	89 (49.4)	63 (35.7)	0.01
Other Caucasian	46 (25.5)	62 (35.2)	0.05
Non-Ashkenazi Jewish	23 (12.8)	17 (9.6)	0.4
Ashkenazi Jewish	9 (5)	14 (7.9)	0.2
Black/African/African American	2 (1.2)	5 (2.8)	0.2
Other	11 (6.1)	15 (8.5)	0.4
Community type			0.9
Rural	42 (23.3)	40 (22.7)
Urban	138 (76.7)	136 (77.3)
School absenteeism∗	73 (41)	57 (32.3)	0.1
FAPDs type
Abdominal migraine	5 (2.8)	5 (2.8)	1
FAP-NOS	58 (32.2)	70 (39.8)	0.1
Functional dyspepsia	41 (22.8)	47 (26.7)	0.4
Irritable bowel syndrome	76 (42.2)	54 (30.7)	0.03
Therapeutic strategies
Behavioral treatment	74 (41.5)	67 (38)	0.5
Antispasmodics	36 (20.2)	40 (22.7)	0.6
Rifaximin	3 (1.6)	2 (1.3)	1
Dietary elimination	45 (25.2)	56 (31.8)	0.1
Neuromodulators	4 (2.2)	7 (4)	0.3
Paracetamol/NSAIDs	27 (15.1)	44 (25)	0.02
PPI	30 (16.8)	19 (10.8)	0.1
Probiotics	14 (7.8)	5 (2.8)	0.06

^∗In the Quarantine group, the question was referred to the period preceding the COVID-19 pandemic.FAPDs = functional abdominal pain related disorders; FAP-NOS = functional abdominal pain non-otherwise specified; NSAIDs = non-steroidal inflammatory drugs; PPI = proton pump inhibitors; SD = standard deviation.

FIGURE 1: Number of children affected by functional abdominal pain disorders reporting >5 episodes of abdominal pain per month in the Quarantine group and the Control group at baseline and after 4 months of follow-up; ^∗∗∗ P < 0.001, Fisher exact test.

Data at 4-Month Follow up

In the Quarantine group at 4 months of follow-up, during the early phases of the COVID-19 pandemic, 76 of 180 (42.2%) patients reported >5 episodes of abdominal pain per month with a significant decrease compared to baseline (115/180 [63.9%]; P < 0.001). Likewise, in the Control group we also observed a significant reduction of children reporting >5 episodes of abdominal pain per month when compared to baseline (88/176 [50%] vs 147/176 [83.5%]; P < 0.001) (Fig. 1). At follow-up, no significant differences were observed between the Quarantine group and the Control group when comparing the number of children reporting >5 episodes of abdominal pain (P = 0.1). The same trend was observed for all type of FPADs in both groups (Table 2, Supplemental Digital Content, https://links.lww.com/MPG/C492). Overall, in the Quarantine group, 102 of 180 (57%) patients showed a significant improvement of all symptoms, 57 of 180 (31.5%) reported no changes and 21 of 180 (11.5%) experienced a worsening. In the Control group, 112 of 176 (63.5%) patients improved all symptoms, whereas 49 of 176 (28%) reported no changes and 15 of 176 (8.5%) a significant worsening. When comparing the two groups, these findings did not statistically differ (P = 0.6, P = 0.3, respectively) (Table 3, Supplemental Digital Content, https://links.lww.com/MPG/C493). This result applied to all different types of FAPDs (Table 3, Supplemental Digital Content, https://links.lww.com/MPG/C493).

Quality of Life, Anxiety and Global Health Questionnaires During the Coronavirus Disease 2019 Related Quarantine

When considering all FAPDs the QoL showed a median value of 84.8 with a range from 35.87 to 100. No significant differences were observed when comparing QoL among FAPDs (Table 2). When analyzing the specific domains of the scale, we identified a significantly different distribution within the emotional functioning domain, with children affected by FD showing the lowest median value (67.5, P = 0.03) (Table 2). A large variability was observed among the different enrolling centers with the North American centers showing the lowest QoL values (Fig. 2). PROMIS anxiety median score was 44.9 with a range of 38–73 when considering all FAPDs. Thirty of 180 (16.6%) children showed anxiety values outside the reference range of 50. Similar values were observed when considering each individual FAPD and each center had no significant differences among values. PROMIS global health median score was 38.8 with a range of 26.1–51.1. Ninety-nine of 180 (55%) children showed values lower than the mean reference standard. When analyzing FAPD subtypes we found a statistically significant difference with FD showing the lowest median value of global health (35.6, range 26.1–51.1, P < 0.001) (Table 2). No significant differences were observed among the enrolling centers. PedsQL 4.0 total score was inversely correlated with PROMIS anxiety score (r = –0.27, P < 0.001) and directly correlated with PROMIS global health score (r = 0.52, P < 0.001) (Figure 2, Supplemental Digital Content, https://links.lww.com/MPG/C490).

TABLE 2 - Parents-reported PedsQL 4.0 General Well-Being Scale, PROMIS Anxiety and PROMIS Global Health questionnaires during the COVID-19 related quarantine in 180 children diagnosed with functional abdominal pain disorders between October 2019 and February 2020

Scores median (range)	Irritable bowel syndrome (n = 76)	Functional dyspepsia (n = 41)	Abdominal migraine (n = 5)	Functional abdominal pain NOS (n = 58)	P ∗
PedsQL 4.0 overall score	83.7 (36–100)	83.7 (45–100)	78.2 (59–95)	86.9 (52–100)	0.2
PedsQL 4.0 domains
Physical health	85.9 (25–100)	87.5 (50–100)	75 (56–100)	92.1 (50–100)	0.3
Psychosocial health	83.3 (36–100)	82.5 (43–100)	85 (61–93)	85.9 (48–100)	0.3
Emotional functioning	75 (30–100)	67.5 (0–100)	80 (55–95)	82.5 (25–100)	0.03
Social functioning	100 (0–100)	91.6 (8.3–100)	100 (66–100)	91.6 (16–100)	0.8
School functioning	80 (20–100)	87.5 (20–100)	65 (45–100)	85 (30–100)	0.5
PROMIS Anxiety overall score	44.9 (38–62.4)	45.8 (38–71.8)	44.9 (43–48.3)	44.9 (38–71.8)	0.7
PROMIS Global Health overall score	38.8 (27.6–49.2)	35.6 (26.1–51.1)	40.4 (37.2–49.2)	41.2 (29.2–51.1)	<0.001

^∗Mann-Whitney test.GH = global health; HRQL = health related quality of life; NOS = non-otherwise specified; PedsQL 4.0 = Pediatric Quality of Life Inventory 4.0; PROMIS = Patient-Reported Outcomes Measurement Information System.

FIGURE 2: Median and range of the PedsQL 4.0 total score in the Quarantine group at 4 months of follow-up during the COVID-19 pandemic among different enrolling centers; ^∗∗∗ P < 0.001, ^∗∗ P < 0.01, ^∗ P < 0.05; Mann-Whitney U-test. COVID-19 = coronavirus disease 2019; PedsQL 4.0 = Pediatric Quality of Life Inventory 4.0.

DISCUSSION

To the best of our knowledge this is the first multicenter study investigating the evolution of FAPDs symptoms and assessing the quality of life and anxiety in a cohort of children during the first COVID-19 pandemic phase. Taking into account the highly heterogeneous clinical course of FAPDs, we used a control group consisting of a cohort of patients diagnosed a year before the pandemic at the same centers and within the same time period with a similar follow up interval. We demonstrated in both groups a significant decrease in the number of children reporting >5 abdominal pain episodes per month and an overall improvement of symptoms over time in approximately 60% of the enrolled subjects, highlighting that a considerable proportion of children diagnosed with FAPDs tends to experience symptoms’ improvement by 4 months of follow-up. The quality of life and the level of anxiety during the COVID-19 related quarantine were generally satisfactory when compared to the previous literature. This finding although strongly limited by the absence of a control group may potentially suggest that during the first phase of the pandemic the reassuring effects of decreased school-related stress and the increased parental attention counteracted the negative effects of the decreased socialization and general fears related to the global pandemic.

FAPDs are some of the most frequent gastrointestinal disorders in childhood with a high burden on national healthcare systems ^(14,15). In 2015, Hoekman et al ⁽¹⁶⁾ recruited 258 children with FAPDs in a multicenter, randomized, controlled trial and quantified a total annual cost of 2512.31 euros per patient. Despite their high prevalence, the natural history of FAPDs remains poorly characterized in children. In 2008, a systematic review of 18 pediatric studies demonstrated that in 29.1% of children with chronic abdominal pain, symptoms persisted after a median follow-up of 5 years ⁽¹⁷⁾. In line with the chronic nature of these disorders, longitudinal studies have highlighted that IBS symptoms starting in childhood and adolescence will persist into adulthood in roughly one-third to one-half of affected patients ^(18,19). In contrast to these findings, a prospective, observational study that included 83 children diagnosed with IBS by Rome III criteria who were followed for 24 months demonstrated that only 42.2% of the initial cohort fulfilled diagnostic criteria for IBS at follow-up, and 57.8% of the children had symptoms’ resolution with no influence of sex, age or IBS subtype ⁽²⁰⁾. In the present study, we decided to compare the symptoms’ evolution of a retrospective FAPD cohort with a more recent cohort of children, hypothesizing a different outcome in the newly diagnosed group due to potentially stressful societal changes related to the concomitant COVID-19 pandemic. We were surprised not to identify significant differences between the two groups and to observe an overall improvement for both primary and secondary outcomes with an almost identical trend for different types of FAPDs in all centers. In line with the earlier data ⁽²⁰⁾, our study shows that a sizable percentage of children diagnosed with FAPDs tend to experience symptoms’ improvement by 4 months of follow-up. This finding strengthens the concept that adequate information and reassurance can by itself be therapeutic in at least a subset of patients. This is especially relevant when considering the huge economic burden associated with healthcare resource utilization by pediatric patients with abdominal pain. In this setting, improving patients’ awareness of the benign course of FAP symptoms could hopefully result in a costs’ reduction for management of the condition.

Multiple studies have demonstrated lower QoL in children with FGIDs when compared with healthy controls and even with patients with organic diseases ^(15,21–23). Analysis of QoL in 689 families of children affected by FGIDs using PedsQL 4.0 Generic Core Scale demonstrated an overall mean QoL of 70, which was significantly lower compared to healthy controls but also in comparison to children with inflammatory bowel disease and gastroesophageal reflux disease ⁽²³⁾. In order to fully characterize the effect of the COVID-19 pandemic on children with a diagnosis of FADPs, we prospectively evaluated the Quarantine group with QoL, anxiety and global health questionnaires. At 4 months of follow-up, in the midst of the COVID-19 pandemic, children from the Quarantine group showed a satisfactory overall QoL median score of 84.8. Likewise, the PROMIS anxiety median score was 44.9, with only 16.6% children showing levels of anxiety outside the normal range. Even though we do not have a baseline comparison, these data may provide some insights on the prevailing psychological factors in this subset of patients during the complex initial phase of the COVID-19 quarantine. We hypothesize that increased parental attention as well as decreased stress due to school closures and limited extracurricular activities may have initially helped reassure our patients and decrease their level of anxiety. The variation of QoL among countries, and in particular the lower values from the North American centers, may be related to specific local factors, but we could also speculate that the difference was secondary to a dissimilar impact of the COVID-19 pandemic and quarantine. The pandemic affected Europe and Israel first before reaching the USA, where at the time of data collection the quarantine had just recently started. Also, in view of the different medical systems in different countries, it is possible that patients seen in referral centers in USA have more chronic or severe forms of FAPDs.

Despite the data on QoL, global health as measured through the PROMIS questionnaire was still below mean reference values in >50% of the children. The PROMIS global health represents a complete assessment of general health and includes multiple items on physical, psychological, social and general health ⁽¹²⁾. The impairment of global health based on the PROMIS score in a high percentage of children should signal that the symptom improvement we observed may only tell part of the story and demonstrates the importance of a global approach to treatment for children affected by FAPDs. Despite the efficacy of many psychological interventions such as cognitive behavioral therapy or hypnotherapy ^(24–26), the current management of FAPDs is still mostly based on addressing GI symptoms, as further demonstrated by the therapeutic strategies used in our cohorts. Targeting GI symptoms without characterizing the full extent of the disorder and possible psychosocial modifiers may therefore contribute to treatment failure concerning global health over time. As stated in the Rome IV criteria with the inclusion of the multidimensional clinical profile ⁽²⁷⁾, clinicians need to identify if and which psychological factors contribute to the disease burden in the individual patient and consider psychological treatments.

Interestingly, within our cohort patients with FD showed the lowest global health scores and demonstrated a significant impairment in emotional functioning based on the PedsQL 4.0 score. This finding is an agreement with an elegant study demonstrating that children with dyspeptic symptoms, both with and without abnormal esophageal histology, had greater functional disability and increased risk of poorer QoL compared to controls in adolescence and young adulthood ⁽²⁸⁾.

Our study has both strengths and limitations. The major strengths consist in the prospective observation carried out during the COVID-19 pandemic and the inclusion of multiple referral centers from different countries. This allowed us to have a more precise picture of the evolution of FAPDs during the initial phases of the pandemic. On the other hand, we acknowledge that the relatively short period of evaluation may have led to the misinterpretation of temporary improvement as definitive resolution of symptoms. Indeed, the chronic/recurrent nature of FAPD symptoms entails the possibility of a cyclical evolution. Additionally, we are aware that the lack of a control group for the QoL, anxiety and global health assessments represents a weakness of the study. Finally, we recognize that not all the centers reached the estimated sample size due to recruitment difficulties.

CONCLUSIONS

Our study shows overall symptom improvement at 4 months of follow-up in two different cohorts of children diagnosed with FAPDs one year before and immediately before the COVID-19 pandemic. These findings underline that a considerable proportion of children with FAPDs may show a spontaneous resolution of the symptoms during the follow-up and once more reinforce the view that a conservative approach, including adequate education and careful reassurance, can be successful in the majority of these patients. The evaluation of QoL and anxiety during the first months of the COVID-19 quarantine showed satisfactory scores when compared to the previous literature, suggesting possible positive effects of school closure and increased parental attention. However, due to the absence of a control group and long term follow-up, our data need to be confirmed with a prospective evaluation of the cohort within the successive phases of the ongoing pandemic.