A temporality relationship between SIM-P and SARS-CoV-2 infection has been described with the advance of the pandemic. A full understanding of the pathological mechanisms that this virus uses to develop SIM-P is needed. The formation of autoantibodys by cell and humoral recognition of autoantigens, celland humoral recognition of viralantigens expressed in infected cells, formation of immune complexes that activate inflammation, and sequences of viral superantigens that activate immune cells (2) have been described. In addition, inhibition of interferon typeI and type III responses hasbeen reported, causing longer and more severe disease. There are also the presence of autoantiantibodys involved in the activation of lymphocytes, and in intracellular signaling pathways. Finally, increased IL-18 and IL-6 con increased chemotaxis and lymphocytic/myeloid activation, and immunological deregulation of mucous membranes have been reported. Thus, hyperinflation differs from acute COVID-19 and EK, and the cytokine storm in SIM-P is different from that observed in adults with COVID-19 (7).
All systematic reviews (8, 9, 10, 11) found and most large sample case series (12, 13, 14, 15, 16, 17) were conducted in Europe, the United States, and some Asian countries. There are few reports from Latin America (4, 18, 19, 20, 21). Most systematic reviews describe predominance in school and men’s age (above 50%), most ofthem sanos, of Hispanic and black origin. Fever, gastrointestinal and cardiovascular symptoms are the most frequently reported. With noticeably altered inflammatory, coagulation and cardiac markers (8, 9, 10, 11). In Latin America,he has published a multinational study reporting 95 cases, with similar characteristics (most schoolchildren, men, healthy, predominating gastrointestinal symptoms). In addition, it preliminaryly determined that the diagnosis of SIM-P was associated with older tener, gastrointestinal symptoms, low socioeconomic status, and with increased use of inotropics, IVIG and corticosteroids (4). Similar characteristics are described in Chile (18) and Brazil (19, 20, 21), similar characteristics are described at the Latin American and global levels. A caringbra study (19) suggests that the onset of SIM-P could be associated with gastrointestinal manifestations and hypoxemia. In this study the most common filing age was in schoolchildren, with men predominating in all three phenotypes, most of them exceptin the shocksubgroup. Most had proof negative molecular and positive IgG, only 6.9% (3/43) presented positive molecular test but 30% (3/10) were positive in the shock subgroup. Other studies have reported positivemolecular prueb in one third of cases (2). In addition, the positive O group, intradomyciliary contact (up to half of cases in the shock subgroup), gastrointestinal and mucocutaneus manifestations, has predominated. The median time ofillness and days with fever was four and three days, respectively. There was also a greater increase in inflammatory markers (lymphopenia, C-reactive protein, ferritin, D-dimer, hypoalbuminemia), and increased commitment of markers of myocardial injury (Troponin C, CPK-MB, NT-proBNP) in subgroup shock.
Therapeutic recommendations are aimed at intervening early, providing respiratory, hemodynamic support, and treatment of the underlying inflammatory process (22.23). In ourstudy, IVIG (97.7%), AAS (86.1%) corticosteroids (62.8%) in most patients. More than a quarter required a second dose of IVIG, and more than three-quarters in the subgroup with EK. No second-line immunomodulators were used. More thanthree-quarters received antibiotic coverage at first for possibility of bacterial infection explaining the clinical picture or overinfection. A lower percentage received anticoagulation. Other studies also used IVIG, corticosteroids, AAS,antibiotics, anticoagulation and second-line immunomodulators; with a variable frequency of use (8, 9, 10, 11). A systematic review describes that 76.4% used IVIG, 52.3% corticosteroids, and 16.8% AAS, requiring second-line immunomodulators such as anakinra and infliximab in a lower percentage, 8.5% and 6%, respectively. In addition, antibiotics were administered less frequently than this study (16.3%) (8). Other studies report 6.2% of patients who required second doses of IGIV (10). Other systematic reviewsreport IVIG use of 63–78.1%, corticosteroids from 44–57.6%, and AAS use by 46.2% (9.11). With use of infliximab (6%), anakinra (12%), and tocilizumab (6.3%) (11). A Latin American multicenter study reporteduse of IVI G by40%, corticosteroids by 28.4%, and tocilizumab by 2.1% (4). In Brazil, the use of IVIG was reported at 89%, and corticosteroids, antibiotics and enoxaparin by about 50%. In addition, AAS by 45% (20). In Chile, 89% used antibiotics, 63% AAS, orn 70% IGIV, and 63% corticosteroids (18). In Lima, out of a series of eight cases, it was reported that they all received IGIV, corticosteroids and ASS, and two patients required a second dose of IGIV. This is because most (87.5%) belonged to the EK sub-group (5). In this study 51.2% had criteria for EK, but it was mostly used IVIG, corticosteroids and AAS.
In relation to unfavorable outcomes, in this study 39.5% required ICU, and 32.7% VMI. Organic dysfunction developed by 48.8%. Another study in Peru reported SAM in 50% of cases, and only one patient had cardiomyocarditis, shockandrequisitioned admission to ICU (5). In other studies, immediate unfavorable events were variable. Systematic reviews report ICU needs 68.2 to 70%, and VMI from 12.6 to 26.1% (8.10.11). In Latin America, there is a lower income to ICU (12.5%-21%) (4.5) and a variable VMI requirement (11–44.4%) (18.20),probably due to the reduced availability of ICU beds and specialized medical personnel. On the other hand, in this study the majority (51.2%) they had criteria for EK, 23.3% shock, and 25.6% fever with altered inflammatory markers (but no shock or EK). SatO2 ≤ 92 in emergency, organ dysfunction, ICU and VMI admission were more common in the shock subgroup. However, the other subgroups alsorequisitioned VMI and had white organ damage but in less proportion, with a stay in ICU and similar VMI time in all subgroups. In a systematic review, 28% (186/655) had hypotension, 36%(235/655) classic or atypical EK, and the rest (36%, 234/655) belonged to the subgroup with fever and inflammatory markers (10). Unfortunately, it does not describe clinical characteristics or unfavorable outcomes by subgroups. It is necessary to be vigilant in all clinical forms of SIM-P, the shock subgroup is the one with thegreatest short-term involvement, but also the other subgroups required ICU with the use of VMI and vasoactive drugs. On the other hand, there is no medium- and long-term evidence of SIM-P complications. In this way, the pediatrician plays a transcendental role for an accurate diagnosis of the entire SIM-P spectrum.
Also worrying is the lethality found (4.6%), increased to 20% in the shock subgroup. Systematic reviews and larger sample series describe a lethality of 1.4 to 2.1% (8.9,10,11,12,13), describing in some cases comorbidity, malnutrition, shock, and shorter time between exposure to the virus and clinical manifestations (21). On the other hand, coronary aneurysm was evident in 5 patients (14.7%). A systematic review describes abnormalities in echocardiography by up to 54% (8), including in a 11.5–61% in Latin America (4.20). Coronary aneurysm is also described at 5.4-8% in anumber of systematic reviews (8.11). In addition, they describe other alterations such as decreased left ventricle ejection fraction, myocarditis, pericardial effusion, mainly (8, 10, 11, 13, 18). In Peru, none of the eight reported casesdeveloped coronary aneurysm. Only one had myocarditis, and shock (5). SIM-P also has a negative impact on health, it is necessary to report that SARS-CoV-2 infection in the paediatric population canalso have a sfavorable evolution and cause complications. There is a significant percentage of SIM-P with severe involvement, even causing death. On the other hand, when performing the multivariate analysis, it was shown that patients with some comobility, protein C reactive ≥ 10 mg/dL, and SatO2 ≤ 92 in emergency were more likely to be transferred to ICU. In addition, those with some comorbidity, with lymphopenia < 500cel/mL, and with D ≥ 3 mg/L were more likely to require VMI. We have not founde studios on factors associated with unfavorable outcomes in the SIM-P. Therefore, in the paediatric population it is also necessary to constantly monitor SatO2, inflammatory markers and recognition of comorities in order to improve their morbidity.
The strengths of the study are that the included cohort represents the largest number of patients with SIM-P reported in Peru so far. In addition, a thorough review of the data was carried out, using the electronicmedical history and corroborating with physics, being reviewed and corrected when finding inconsistent values. Likewise, the selection of the cohort was based on international criteria (2) and a consensus among the authors of the study (pediatricians, pediatric infectologist and intensivist pediatricians). On the other hand, this study has limitations related to the origin of secondary source data (medical records) and collection retrospectively, with the possibility of greater selection bias, informationand confusion. Finally, a multivariate analysis was performed in order to adjust confusing ones, but because the SIM-P is a new and rare entity a small sample was obtained obtaining a low statistical power. Therefore, theconclusions are preliminary, especially those related to the study of factors associated with adverse outcomes. Multicenter studies are needed in order to increase the number of cases and have more accurate and straight conclusions.
In conclusion, in this study SIM-P predominated in male and healthy school children, presenting gastrointestinal and mucocutaneous symptoms. More than half presented criteria for EK, with negative molecular testing and positive IgG. With aumento of inflammatory markers and increased commitment of markers of myocardial injury, especially in the shock subgroup. More than a third required ICU, VMI and developed organic dysfunction, with a lethality of 4.6%. Likewise, the coronaries aneurysm was presented at 14.7%. In the shock subgroup, lethality increased to 20% and unfavorable outcomes dominated. Monitoring of SatO2, inflammatory markers and recognition of comobility is important. Therefore, active monitoringfor early diagnosis and management is necessary to improve the prognosis.