Recently the relationship between SARS-CoV-2 exposition and the incidence or evolution of clinical autoimmune diabetes has attracted the attention of diabetologists based on the hypothesis that diabetes may occur as an acute complication following SARS-CoV-2 infection at least in predisposed subjects. Recent investigations suggest that the occurrence of infection in pediatric patients affected by autoimmune diseases does not seem to affect the severity and evolution of the clinical manifestations or the management of the autoimmune disease [8].
The medical history of the patient presented here confirms the recent clinical experiences of pediatric diabetologists, in which SARS-CoV-2 infection does not appear to cause persistent glycemic decompensation in children and adolescents with T1D [8]. Moreover, young patients with disease onset most often have asymptomatic or paucisymptomatic SARS- CoV-2 infection. On a general ground, people with diabetes do not exhibit increased susceptibility to SARS-CoV-2 infection [8].
It is, however, of interest to remark that in the clinical history of the patient reported here the autoimmune process preceded the clinical manifestations of T1D with the symptom of polydipsia, occurring a few months before COVID-19 infection, which was paucisymptomatic. This was also observed in another 8 year old male referred to our Hospital with T1D onset manifested with polyuria and polydipsia in the absence of ketoacidosis associated to celiac disease (Table 1). We confirm that the management of the disease in the patient so far was not significantly affected, being that presently his glycemic status is controlled by the established insulin administration regiment.
Based on previous epidemiological observations, a few months generally lapse between a triggering unknown event, including stress, infectious agents or hormonal perturbations, and the onset of an autoimmune clinical disease [5]. T1D is consequently caused by primary mediators, i.e. activated autoreactive T cells, that invade the pancreatic islets leading to insulitis. During the long-preclinical period that precedes the disease onset and often lasts for years [9], the insulitis would remain innocuous until incited to destruction by any possible secondary event, i.e. the systemic or local reactivity to a viral superantigen [10]. Activated T cells at this stage expand and destroy insulin-producing beta cells as they react to pancreatic antigens. As a general effect, infectious agents may enhance self-antigen presentation, lead to the involvement of different autoantigens or of different epitopes of the same protein [10].
In light of the foregoing, we advance the hypothesis that the SARS-CoV-2 infection, even if paucisymptomatic could have acted in the present case report as a downstream precipitating factor; whilst the inciting autoimmune triggering event leading to insulitis, as confirmed by the presence of circulating autoantibodies, could have occurred even before, as generally assumed for this category of disorders [5]. SARS-CoV-2 infection could have precipitated the clinical disease onset through the acute interaction between the virus and the ACE receptor on the beta cells leading to massive destruction of their reservoir already compromised by the insulitis previously evoked by the triggering agent. Whilst the putative contribution of the virus on the activation of infiltrating T cells remains to be demonstrated.
Indeed SARS-CoV-2 infection occurred in our patient at the time that hyperglycemia and glycosuria were ascertained, and HbA1c levels confirmed a metabolic dysregulation over the previous 3 months in absence of ketoacidosis.
