Covid19 pandemic and pediatric endocrinology and metabolism—Are we through with it?

The coronavirus disease 2019 (Covid19) pandemic has caused a tremendous amount of grief, societal unrest, societal changes and economic consequences globally. Millions of lives have been lost, many people have suffered, families have lost their loved ones and the consequences on daily life have been enormous. On the one hand side, it is essential that these facts are remembered and documented. On the other hand, life goes on, and the full extent of changes caused by the pandemic will only be observed over the coming years. Malfunctioning of health systems and governance strategies has been revealed pointedly by the pandemic and its consequences as has been the case over many centuries in the aftermath of numerous previous epidemics [1].

Covid19 infections have been less severe and less frequent in the pediatric population. However, Covid19 incidences in children have followed the incidence rates in the adult population, at least in areas with low Covid19 incidence [2]. Overweight and obesity rates, however, have increased in children and adolescents during the pandemic crisis and the associated closure of schools and preschools [3]. In addition, pediatric services, in particular well baby clinics, have been used less frequently in some societies [4]. Last but not least, leisure activities of children have changed during periods of lockdown and school closures [5]. Also, severe and very stressful psychological sequelae of school closures are being reported [6].

It has been reported that during the pandemic crisis, care for children with endocrine and metabolic diseases may have deteriorated. The severity of, for example diabetes manifestations, may have increased during lockdown periods and or for fear of becoming infected may have hindered families from seeking medical help. In our Journal of Pediatric Endocrinology and Metabolism, a number of such reports have been collected and are being published:

Erat et al. reported a previously healthy 16-month-old female patient who developed a secondary transient benign hyperphosphatasemia (THI) associated with Covid19. THI is a benign condition associated with marked elevation of alkaline phosphatase (ALP) without any other kidney, bone, and liver pathologies. This patient’s whole family tested positive for SARS-CoV-2. Since THI is a diagnosis of exclusion, other reasons that may cause ALP elevation had to be ruled out. ALP activity decreased and turned to normal ranges within the following month in this particular patient. THI is associated with a number of different conditions. Importantly, its relationship with many virus infections has been reported previously. It is suggested that if ALP elevation is detected in patients with Covid19, THI should be considered if there is no other accompanying pathology [7].

During the period of March 21st to May 6th 2020, the region of Madrid, epicenter of Spain’s Covid19, was under home confinement and health care resources were redistributed. Although children appear to be less frequently and severely affected by Covid19 than adults, they can develop other intercurrent illnesses and accompanying diseases such as type 1 diabetes (T1DM) which might be aggravated and become severe. Of note, during the Covid19 pandemic period, the age at presentation of T1DM debut was younger than in the previous years in Madrid [8].

In India, lockdown was imposed in March 2020 and extended till 31st May to combat the spread of Coronavirus. Implementation of lockdown and limited outdoor activities resulted in changes in routines of children with diabetes. In this one observational study, 77 children and youth (5–20 years) with T1DM having disease duration of ≥6 months were investigated. Demographic data and investigations were recorded pre lockdown from medical records and post lockdown when the children came for follow up visits. Glycemic control actually improved (pre lockdown HbA1c 79.4 ± 19.2 vs. post lockdown HbA1c 74.5 ± 16.9 mmol/mol, p<0.05) and there was weight gain post lockdown (pre lockdown weight z-score −0.4 ± 0.8 vs. post lockdown weight z-score −0.2 ± 0.8, p<0.05) without any significant change in BMI and insulin requirements. Improved glycemic control was seen in the lower social economic (SE) group post lockdown (p<0.05), whereas in higher SE group, it remained unchanged. Children whose parents were at home during lockdown showed an improved glycemic control (p<0.05) as compared to children whose parents continued to work during lockdown. In conclusion, during pandemic lockdown, glycemic control was adequately maintained in children with T1DM. This may highlight the importance of strong family support and a more steady daily routine in the lockdown period facilitating good metabolic control [9].

Multisystem inflammatory syndrome in children (MIS-C) is a unique clinical complication of SARS-CoV-2 infection observed in pediatric patients. Covid19 is emerging as a potential trigger for the development of diabetes in children. Naguib et al. reported a patient presenting with MIS-C and new onset diabetes: An eight-year-old female presented with hyperglycemia, ketosis and metabolic acidosis consistent with diabetic ketoacidosis (DKA) in the setting of fever, rash, respiratory distress, hemodynamic instability, reduced systolic function with dilation of the left anterior descending artery, and positive SARS-CoV-2 antibodies suggestive of MIS-C [10].

Patients with diabetes may be at increased risk of developing Covid19 infections, as well as exhibiting an increased risk of morbidity and mortality. Despite the fact that current data have shown that the coronavirus infection generally has a milder course in children Rabizadeh et al. presented a teenage patient with severe diabetic ketoacidosis (DKA) as the first manifestation of his diabetes during a Covid19 infection. He was treated for DKA and Covid19 and fortunately recovered [11].

It has become obvious that most of the health system capacities in many countries have been directed to Covid19 patients, and routine outpatient clinics especially for children have been suspended. Chronic disease patients, such as patients with inherited metabolic disorders (IMD), increasingly have had trouble accessing healthcare services. Therefore Enver et al. conducted an online cross-sectional survey among patients with IMDs who presented for a follow-up at a specialized clinic to address their problems during the pandemic period. In addition, the clinic’s Instagram and Facebook accounts were used to invite patients to participate. A total of 213 patients completed the survey, and from these 175 questionnaires were evaluated. Most of patients had a special diet, and 51% of them had difficulties with their diet during the lockdown period. The reported rate of using a special treatment was 38%, and most of these patients (91%) had no problem receiving these special therapies during the time of the study. Parents who were wearing masks while caring for their child were very few (17%), but a vast majority of parents (73.7%) reported high handwashing rates. None of the patients had a SARS-CoV-2 infection during the study period. Problems faced by patients with IMD during the Covid19 period might be underestimated. Since the pandemic will not immediately pass, recognizing the problems faced by patients with chronic diseases and developing solutions for these would help to avoid long-term damage [12].

Telemedicine has been shown to improve rural diabetic patient outcomes in a number of studies conducted before the Covid19 pandemic. Potential gains from telemedicine are especially important to examine for patients with diabetes, who appear to be at an increased risk for adverse outcomes of Covid19, compared to patients without. Building on the importance of telemedicine in the new Covid19 environment, further studies should incorporate telehealth encounters into measures of adherence to a pediatric diabetes management plan. In a study from LePage et al. the impact of geographic distance from the clinic on adherence to recommended clinic visits and diabetes control among patients with T1DM seen in a pediatric endocrinology clinic serving a rural region in eastern North Carolina was analyzed. The analysis included 368 patients, of whom 218 (59%) completed at least one visit every three months. The median HbA1c was 9.1 at the initial visit, and 9.3 at the final visit. Patients living further away from the clinic were less likely to adhere to the recommended visit schedule, but neither distance to the clinic nor clinic visit adherences were associated with HbA1c levels. It is unclear whether such observation would have been different during Covid19 lockdown periods [13].

In summary, pandemics change societies and society [1]. Health care systems show that indeed their organizations are vulnerable. As long as hospitals are thought to be cash providers and for profit institutions, they may be ill-prepared to meet sudden high demands during crisis and pandemics. Hospitals are understaffed in many countries during normal periods, and this might be aggravated during a pandemic. Lastly, resources in the health care systems are reallocated and redistributed during a pandemic and very often being removed from the weakest, that is from children and the elderly. Importantly, people with chronic afflictions might suffer most and might lack specialized care and even fail to obtain their medicines and obligatory medicinal support. We need to rethink our ethics and beliefs and reset priorities in our societies to support the weak and help the children.