Atypical Hemolytic Uremic Syndrome in a Post-COVID-19 Child: Its Differential Diagnosis with COVID-19, Multisystemic Inflammatory Syndrome and Outcome

Pediatric Multisystemic Inflammatory Syndrome (MIS-C) is one of the most severe manifestations of SARS-CoV-2 in pediatrics [1]. This is a report of MIS-C with clinical presentation in infants with atypical Hemolytic Uremic Syndrome (aHUS).


Introduction
COVID-19, a disease caused by a new coronavirus called SARS-CoV-2, was initially related to involvement only of the respiratory tract, affecting mainly adults.
Subsequently, as the pandemic progressed, clinical manifestations were observed in children, predominantly mildly. In April 2020, the Royal College of Paediatrics and Child Health in the United Kingdom issued an alert reporting a new clinical presentation in children and adolescents associated with COVID-19 [1].

Case Report
We report a case of a 2-year-old female infant with a severe and atypical clinical evolution of SARS-CoV-2. The patient had presented abdominal pain and fever. Two days later, she developed diarrhea, prostration, drowsiness, dyspnea, and oliguria. On presentation she was pale, hypotensive, appearing with dyspnea, anasarca, hepatosplenomegaly, stomatitis with bleeding lesions, seizures, and coma (Glasgow Scale 6). Orotracheal intubation was performed, continuous adrenaline infusion was titrated, and ceftriaxone was administered. The child has a previous diagnosis of COVID-19, confirmed by real-time polymerase chain reaction (RT-PCR), ten days before starting the first symptoms. The admission and evaluation laboratory tests are shown in Table 1. The exams were visualized: normal echocardiogram computed tomography of the chest with consolidative opacities with air bronchograms, and predominantly peripheral "frosted glass" opacities. Initial differential diagnoses included (MIS-C), atypical Hemolytic Uremic Syndrome (aHUS), COVID-19 complicated with sepsis, septic shock, and Disseminated Intravascular Coagulation (DIC). In the initial evolution, the patient presented renal failure and arterial hypertension and, later, evolved with hypotension and anuria, when the association of dobutamine with norepinephrine was installed and hemodialysis was initiated. The main diagnostic hypothesis was raised as aHUS, however, the differential diagnosis with MIS-C was proposed, even though the time interval between the current disease and the diagnosis of COVID-19 was only 10 days. In addition, the presence of schistocytes in peripheral blood was visualized ( Figure   1 & Figure 2), in addition to haptoglobin < 6 mg/dl and normal C3 and C4 complement. Due to the absence of clinical response to the aHUS and previous exposure to SARS-CoV-2, the diagnosis of MIS-C was reconsidered, and immunoglobulin (IVIG) 2g/kg associated with methylprednisolone (30 mg/kg) was performed on the 5th day of hospitalization. Eculizumab was not initiated due to the unavailability of the medication in Brazil. The child evolved with refractory septic shock, disseminated intravascular coagulation and multiple organ dysfunction, evolving with death on the fifteenth day of hospitalization.
Other conditions, usually triggered by viruses, such as diabetes, have already been described as related to SARS-CoV-2 and, possibly, other conditions may be related, requiring greater attention from pediatricians in the face of these conditions usually related to the virus as a trigger, as already described for H1N1 influenza [13].
The diagnostic hypothesis of MIS-C was also less robust, because it is a condition that compromises fewer infants, being more commonly diagnosed in older age groups, especially schoolchildren and adolescents. The hypothesis of aHUS was the most evidence, being, at the first moment, related to the infection predicted by SARS-CoV-2. Unfortunately, due to the severity of the child's evolution, it was not possible to perform the pulmonary biopsy, and the postmortem examination was not authorized by the family.

Conclusions
This report demonstrates the importance of the differential diagnosis of systemic inflammatory conditions caused by SARS-CoV-2, as well as their severity, which leads to the need for ICU admission and early intervention due to the chances of death.
With the report of the current case, the authors emphasize that patients with COVID-19 are at potential risk of developing virus-induced diseases, especially those with uncontrolled complement activation, such as MIS-C and aHUS. Early diagnosis and treatment can reduce morbidity and mortality.