**1. Introduction**

The infection caused by the new coronavirus SARS-CoV-2 spread rapidly in the world. At the beginning of 2020, the year in which the disease was declared a pandemic by the World Health Organization (WHO) there was no certainty of its behavior in the adult population, even less how it would affect the children [1]. Time showed that COVID-19 mainly affects adults with fast-spreading lung disease, high rates of hospitalization by respiratory failure secondary to severe pneumonia, and with significant morbidity and mortality [2]. The massive need for medical care caused emergency rooms and hospitalizations around the world to collapse, yet the reality of childhood population at that time was very different. In children, COVID-19 presented as a mild and rare disease, often asymptomatic, with low need for hospitalization and low mortality [3]. Due to this opposite behavior between children and

adults and the collapse of health systems around the world, many pediatric services and pediatric intensive care units had to change their care and transform into adult units. These seriously ill adults were treated by staff usually dedicated to child care [4]. Many hypotheses tried to explain this phenomenon in which children were less susceptible to getting sick. No theory seemed to explain by itself the disease opposite behavior between children and adults, but the only clear thing is that infants seemed to cope very well with COVID-19. This is until April 2020, when a series of reports from the United Kingdom and Italy reported the presence of a childhood disease with a clinical presentation similar to Kawasaki Disease or Toxic Shock Syndrome, but temporarily associated with an infection by SARS-CoV-2 [5, 6]. It was a syndrome of generalized inflammation with skin and mucous membrane involvement, which could potentially seriously compromise children. The disease was soon described in the rest of Europe, America, and then around the world. It was called Multisystem Inflammatory Syndrome in children associated with COVID-19 (MIS-C) or Pediatric Inflammatory Multisystem Syndrome (PIMS). Clinical and laboratory criteria were developed to have suspicion and early diagnosis. These recommendations were initially published by WHO and the Centers of Disease Control and Prevention (CDC) and then massified by countless guidelines of pediatric scientific societies and health services throughout the world [7, 8]. The syndrome occurred with severity in a small group of children, even requiring critical care support and connection to mechanical ventilation. It was a diagnostic and therapeutic challenge for pediatric critical care teams, since the severity of these patients was determined by a multisystem compromise of uncertain behavior and not by severe pneumonia as had been seen so far in adults infected with SARS-C0V-2. We know now that MIS-C is rare and has low mortality. Although critical care is required in a small group of pediatric patients, the evolution is favorable if the diagnosis and immunomodulatory treatment is instituted in time, with complete recovery of organ involvement in most affected children [9]. The fall in the incidence of COVID-19, as well as the lower severity and decrease in mortality, was the consequence of the massive vaccination in both adults and children. This allowed the viral circulation to decrease, resulting in less SARS-CoV-2 infection in children and therefore a lower incidence of MIS-C [10]. MIS-C is rare; however, it is a differential diagnosis that should be taken into account in pediatric patients, while there is circulation of SARS-CoV-2 in the world. This diagnostic suspicion should be greater in any country with temporary peaks of infection and mainly in countries with low vaccination rates where high viral circulation can cause an increase in the presence of new variants. The SARS-CoV-2 virus is here to stay and consequently, the multisystemic inflammatory response of children to this infection is a real possibility as long as there is viral circulation.
