Corrigendum: MIS-C Treatment: Is IVIG Always Necessary?

[This corrects the article DOI: 10.3389/fped.2021.753123.].

Detection of faecal SARS-CoV-2 RNA in a prospective cohort of children with multisystem inflammatory syndrome (MIS-C).

BACKGROUND: Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare but severe illness associated with SARS-CoV-2 infection. A dysregulated immune response is recognized as the main pathogenic mechanism. Previous studies demonstrated the presence of SARS-CoV-2 RNA in faeces of almost one-third of patients with COVID-19, while data are currently missing about MIS-C. OBJECTIVES: to evaluate faecal sample positivity to SARS-CoV-2 in MIS-C and to compare the positivity rate between MIS-C and COVID-19 hospitalised children.  DESIGN: observational descriptive study with prospective patient enrollment. SETTING AND PARTICIPANTS: the SARS-CoV-2 positivity was evaluated in stool samples obtained in a prospective series of 63 paediatric patients admitted to Regina Margherita Children's Hospital (Azienda Ospedaliero Universitaria - Città della Salute e della Scienza, Turin, Northern Italy) with diagnosis of MIS-C (N. 31) or COVID-19 (N. 32), during the first year of pandemic emergency. The real-time reverse transcription polymerase chain reaction (real-time RT-PCR), was performed using a validated kit measuring 3 target SARS-CoV-2 genes: E gene, N gene, and ORF1ab gene MAIN OUTCOME MEASURES: SARS-CoV-2 stool positivity and concomitant gastrointestinal symptoms. RESULTS: overall, 16/63 (25%) stool samples revealed the presence of SARS-CoV-2 mRNA. In patients with COVID-19, faecal samples were collected 8 days as median (IQR 7) after the presumed viral exposure and were positive in 12/31 (39%; 95%CI 23.2-56.2); among children with MIS-C, stools were collected 27.5 days as median (IQR 26.25) after presumed contact and the positivity rate was 12.5% (95%CI 4.4-27.0) (4/32). More than 80% of the children with MIS-C presented gastrointestinal symptoms, but the frequency of gastrointestinal symptoms in patients with positive stools for SARS-CoV-2 RNA is not higher than patients tested negative (p=0.092). CONCLUSIONS: MIS-C patients frequently experienced gastrointestinal symptoms, confirming the intestinal involvement in MIS-C already described in the literature. The presence of SARS-CoV-2 mRNA in faecal samples is confirmed in more than 10% of MIS-C patients and stool positivity was also detected many days after presumed first contact with the virus. This data suggests the possibility of tracing SARS-COV-2 also in faeces for a better description of its circulation and spread in the environment.

MIS-C Treatment: Is IVIG Always Necessary?

Background: MIS-C is a potentially severe inflammatory syndrome associated with SARS-CoV-2 exposure. Intravenous immunoglobulin (IVIG) is considered the first-tier therapy, but it implies infusion of large fluid volumes that may worsen cardiac function. Patients and Methods: Since April 2020, we have developed a treatment protocol that avoids the infusion of IVIG as first-line therapy in the early phase of MIS-C. In this study, we retrospectively analyzed a cohort of consecutive patients treated according to this protocol between 01/04/2020 and 01/04/2021. Results: In the last year, 31 patients have been treated according to the protocol: 25 with high-dose pulse MP (10 mg/kg) and 6 with 2 mg/kg. 67.7% of the patients responded to the initial treatment, while the others needed a step-up, either with Anakinra (25.8%) or with MP dose increase (6.5%). IVIG was administered in four patients. Overall, only one patient (3.2%) needed ICU admission and inotropic support; one patient developed a small coronary artery aneurysm. Conclusions: Timely start of MP therapy and careful fluid management might improve the outcomes of MIS-C patients.

First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED.

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration.

SARS-CoV-2-Induced Kawasaki-Like Hyperinflammatory Syndrome: A Novel COVID Phenotype in Children.

We describe 2 children with persistent fever and profuse diarrhea who developed signs of mucocutaneous involvement (conjunctivitis, fissured lips, skin rash, erythema, and edema of the hands and feet). Blood tests revealed elevated markers of inflammation, lymphopenia, thrombocytopenia, and complement consumption. Afterward, diffuse edema with hypoalbuminemia appeared in the context of a capillary leak syndrome. In both patients, repeated nasal swabs were negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but each patient had high titers of immunoglobulin G and immunoglobulin M against the SARS-CoV-2 virus. The negative PCR results in the presence of immunoglobulin M and immunoglobulin G suggested that the inflammatory response developed in the late phase of viral infection, when SARS-CoV-2 was not detectable in the upper airway. In this report, we describe patients with what we propose to name as SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome. SARS-CoV-2-induced Kawasaki-like hyperinflammatory syndrome seems to be caused by a delayed response to SARS-CoV-2. It resembles Kawasaki disease complicated by macrophage activation syndrome, although it has peculiar features, such as prodromal diarrhea, capillary leak syndrome, and myocardial dysfunction. Intravenous corticosteroid treatment appears to be helpful.