Short follow-up of multisystem inflammatory syndrome after covid19 infection in children: case report


 Background: covid19 infection, in children compared to adults, often occurs in a pauci and/or asymptomatic manner, but in some cases, a multisystem inflammatory syndrome (MIS) may occur in the 4-6 weeks following the infection. There are few data on the features of MIS after the clinical recovery phase, therefore we have described three cases of children with post-covid19 infection syndrome. Case presentation: out of the three cases described, in two children the onset clinical symptoms were similar to Kawasaki syndrome, while in the other neurological impairment was prevalent. In none of the three there were gastrointestinal symptoms, while the signs of interstitial disease were constant on lung ultrasound. In all of them, there was an increase in the inflammatory markers, high levels of ferritin, lymphocytopenia and thrombocytopenia only in one case. The lipid profile at onset was characterized by an increase in triglyceride levels. In all cases the course was benign with resolution of the symptoms upon admission within 4-5 days. After 1 month from the clinical recovery phase, the patients showed normalization of cytokines, inflammatory markers and triglyceride levels, while the total cholesterol value increased. Covid19 infection leads to an acute phase response with increase of the triglyceride in addition to inflammatory markers and the signs of interstitial disease on lung ultrasound. Conclusions: the inflammatory markers and lung involvement normalize over 30 days, while an initial increase of the triglyceride - and later in total cholesterol - suggest a direct relationship between triglyceride and inflammatory markers at the beginning, and between total cholesterol and host immune response during the follow-up.


BACKGROUND
The covid19 infection, in children compared to adults, often occurs in a pauci and/or asymptomatic manner and gets better easily but, in some cases, a multisystem inflammatory syndrome (MIS) may occur in the 4-6 weeks following the infection [1,2]. This syndrome, described in both the USA and Europe, can have different clinical features [3]; it is triggered by the release of cytokines and is due to an abnormal immune response to Covid19 infection [4]. Recent studies [5,6] have shown the clinical features and treatment of MIS following Covid19 infection, but there are few data on the characteristics of MIS after clinical recovery phase. We report three cases in children with MIS after covid19 infection to describe the onset symptoms, the course and the relative follow-up.

Patients
Case 1: 14-month-old child without previous illnesses and with normal growth. He had been hospitalized for 5 days for hyperpyrexia without reporting other associated symptoms. Upon admission, the child showed skin pallor, pharyngeal hyperemia with fibrin deposition on the right tonsil, asthenia and difficult feeding. In the hours immediately after admission, the little one experienced extreme drowsiness associated with a slight neck rigidity and photophobia for which, in the suspicion of encephalitis, a computerized axial tomography of the brain and brainstem and a fundus oculi were performed and both of them were negative. No lumbar puncture for CSF examination was performed as the symptoms of meningism disappeared the next day and general health conditions improved. Case 2: 3 years and 11 months old child who came to our observation for hyperpyrexia for 4 days, treated at home with macrolides and antipyretics, with negative history for previous illnesses and normal growth. Upon admission, a state of general neglect was noticed with the appearance of maculo-papular rash in the supraorbital region and cheeks, back, palm and soles of the feet and 4 hands and pretibial region, laterocervical and retronucal lymphadenopathy, conjunctival hyperemia and cheilitis with pharyngeal hyperemia.
Case 3: 18-month-old child with hyperpyrexia for 5 days associated with cough. The growth was normal and no previous illnesses were reported. Upon admission, maculo-papular rash appeared on the trunk and soles of the feet, conjunctival hyperemia, cheilitis and sour breath diffused when listening to the chest.

Outcome and follow-up
In case 2 and 3 the onset clinical symptoms (Table1) were similar to Kawasaki syndrome while in the first case neurological impairment was prevalent and in none of them gastrointestinal symptoms were found. In all of them, there was an increase in inflammation markers including interleukin 6 (IL-6), high levels of ferritin, lymphocytopenia and thrombocytopenia only in one case (Table2). The lipid profile showed a significant increase in triglyceride levels (Table2) but with normal total, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol values. In all cases, the molecular nasopharyngeal swab was negative for covid19 infection but both IGM and IGG antibodies to covid19 (with higher IGG than IGM) were present in all children. None of them reported pulmonary lesions on chest X-ray, changes in cardiac conduction, morphology and/or dynamics or coronary lesions (negative electro and echocardiogram). On chest ultrasound signs of interstitial disease were found: in case 1 and 2 in the left parasternal site, in case 3 bilaterally. In all patients, we started intravenous therapy with ceftriaxone (100 mg/kg/day) and methylprednisolone and a third group similar, in all, to Kawasaki syndrome according to the AHA criteria [9]. Our cases, from a clinical point of view, are similar to those described by Taffarel et Al. [10] in which the children did not present any hepatic and cardiac impairment so as to require the aid of subintensive therapies, and the alterations highlighted by us on ultrasound thoracic symptoms were not related to lung disease and/or severe respiratory symptoms. In childhood, Lee and Al. [11] describe the clinical and laboratory features of MIS post-covid19 in which, in addition to the complete and/or incomplete clinical manifestations of Kawasaki syndrome, cytokine production patterns and simultaneous detection of cytopenia occur. In our three cases, a lymphocytopenia was always present and only in case 2 a thrombocytopenia was also highlighted, however it was short-lived. Covid infection induces an acute phase response which also leads to alterations in lipid metabolism [12]. The increase in triglycerides is caused by an increase in the secretion of VLDL as a result of lipolysis, by an increase in hepatic synthesis of free fatty acids and by the suppression of oxidation of fatty acids. The increase in total cholesterol found about 30 days after clinical recovery phase is less clear, because even if in adults with covid19 infection blood cholesterol 6 levels are reduced and continue to decrease during hospitalization [13,14], its increase could be attributed to the host immune response [15].

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