Balkan Journal of Medical Genetics

THE IMPACT OF THE COVID-19 PANDEMIC ON INDIVIDUALS WITH DOWN SYNDROME: A CROATIAN SURVEY
Barišić A, Ergović Ravančić M, Majstorović D, Vraneković J
*Corresponding Author: Assoc. Prof. Jadranka Vraneković, Faculty of Medicine, University of Rijeka, Department of Medical Biology and Genetics, B. Branchetta 20, 51000 Rijeka, Croatia; tel: +385 (0)51 651 131, fax: +385 (0)51 678 896. Email: jadranka.vranekovic@medri.uniri.hr
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DISCUSSION

It is known that individuals with DS have specific co- morbidities and immune response dysfunctions that lead to a significantly higher risk of developing severe symptoms of infectious disease, in this specific case, COVID-19 [4]. While the difference in severity of COVID-19 between individuals with and without DS is well established, the question is whether we can apply the conclusions from the international T21RS online survey to different cultural and demographic groups [7,18]. To investigate this, we con- ducted an online survey in Croatia to collect COVID-19 information on the clinical presentation of COVID-19 and disease progression in individuals with DS and the chal- lenges for their parents during the COVID-19 pandemic. Our group of DS individuals were children with a mean age of 8.7± 8.1 years. This is important to note be- cause previous studies suggest that children do not have the same risk of COVID-19 related mortality as older adults [19]. However, compared with children without intellec- tual and developmental disabilities, the mortality rate from COVID-19 was reported as increased in individuals with DS [20]. Our results showed a statistically significant posi- tive association between age and the number of symptoms. This may serve as one of the markers for the severity of COVID-19. Interestingly, post-hoc analysis showed that the least affected age group was that of 5-12-year-olds. The reasons for the differences in clinical manifestations between children and adults are likely age-related comor- bidities, along with age-related factors that may modulate the antiviral immune response: a more vigorous innate response that promotes more efficient viral clearance, a stronger local innate IFN response in the airways medi- ated by cells producing IL-17A and IFN-γ, higher baseline innate activity in nasal mucosae, and increased frequency of naïve T cells, depletion of natural killer (NK) cells, and lower frequency of cytotoxic T cells in peripheral blood immune cells [21,22]. Moreover, our analysis showed a significant and posi- tive correlation between BMI and clinical presentation of COVID-19. Obesity is the other known risk factor for more severe cases of COVID-19, and obesity is common in individuals with DS [23]. The proposed mechanism that leads to COVID-19 is immune system dysregulation leading to chronic meta-inflammation that can blunt the host antiviral response [24]. In addition, obesity is as- sociated with upper airway obstruction, obstructive sleep apnoea, lower lung capacity and reserve, which can make ventilation more difficult, especially with DS, where this is exacerbated by specific anatomical differences. The T21RS survey highlights obesity as a significant risk factor for hospitalisation in paediatric COVID-19 patients with DS [7]. Another statistically significant pattern found in our study is the increase in BMI with age, which is consistent with data from the literature [24, 25]. The unusual distri- bution is seen in the different types of trisomy 21. Indeed, the full/standard type is represented by only 74.7%, while the other types (mosaic; translocated) have the expected distribution (4.1%; 6.3%). This can be explained by the high percentage of parents (14.9%) who do not know the type of T21, which is probably regular and therefore, con- sistent with the expected numbers and the reports from HICs. Similar pattern can be observed in the levels of intellectual disabilities [7]. As expected, the most common comorbidity in our group was CHD. Structural heart defects were reported in approximately 40% of DS individuals, with AVSDs, being the most common, which is consistent with the literature [26,27]. In DS individuals, the interplay of complicated cardiovascular and respiratory anatomy and pathophysi- ology may lead to increased severity and mortality of re- spiratory infections [28]. Nevertheless, we did not find any statistically significant correlation between CHDs and symptom severity in our group. Dietary supplementation as the main reason of im- proved immunity has continued to increase, especially during COVID-19 pandemics [29]. In addition, there is considerable clinical interest in whether children with DS benefit from therapeutic supplementation to improve their development, cognitive decline, and overall health [30]. Accordingly, we analysed this field and found that the most commonly used supplements were probiotics, multivitamins and vitamin D. However, there was no significant association with the milder COVID-19 disease symptoms. As with the general population, fever, cough and shortness of breath were the most common signs and symp- toms associated with COVID-19 in individuals with DS [31]. Interestingly, less than 10% of DS individuals were hospitalized and developed complications due to infection with COVID-19 in our study, while T21RS reported 38.8% hospitalised DS patients [7]. Accordingly, the medications used for treatment were predominantly paracetamol, azithromycin, and natu- ral remedies. Possible explanations for this phenomenon include non-participation of older adults with DS, the most vulnerable group, or underrepresentation of patients from the lowest socioeconomic groups who may have been at increased risk for poor outcomes. It would also be interesting to consider whether intellectual disability and young age are also associated with underdiagnoses of symptoms. The final part of the survey addressed parents’ (care- givers’) experiences with health services and support dur- ing the pandemic. Overall, the largest proportion of parents reported being moderately satisfied with the medical sup- port they received. This is consistent with the European survey of parents’ experiences with health services related to COVID -19 and children with congenital anomalies. Reports for Croatia were in a similar range [32]. In addi- tion, many participants reported disruptions in their child’s routine care that appeared to affect the physical health and emotional well-being of some children. Most of the disruptions were related to discontinued therapies, lack of social activities, and psychological problems, similar to the European survey reports [32]. Our study has some limitations. Since we included only DS patients, we could not consider some specific differences compared to DS the rest of the population infected with COVID-19. In addition, our sample was limited to Croatian individuals and was therefore smaller compared to data from some other T21RS countries. Most of the respondents were parents of children with DS, so we lacked data from the DS adult group. This is a possible reason for the small sample of hospitalized patients, which prevented us from inferring any severe complications of COVID-19.

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