In April 2020, amid the coronavirus disease 2019 (COVID-19) pandemic, providers in the United Kingdom described a group of pediatric hospital admissions secondary to fever and multisystem inflammation which has subsequently been described in several countries, including the United States. ^{Reference Feldstein, Rose and Horwitz1–Reference Godfred-Cato, Bryant and Leung4} Since then, several countries have described an epidemiologic association of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) and this clinical presentation, ^{Reference Simpson and Newburger5} with the development of cases noted a few weeks following peaks in community COVID-19 activity. ^{Reference Feldstein, Rose and Horwitz1} The condition has been named Multisystem Inflammatory Syndrome in Children (MIS-C) in the United States and Paediatric Inflammatory Multisystem Syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in Europe. ^{Reference Simpson and Newburger5}

Patients present variably along a spectrum, including fever, conjunctival injection, rash, abdominal pain, and vomiting. ^{Reference Feldstein, Rose and Horwitz1,Reference Whittaker, Bamford and Kenny2,Reference Godfred-Cato, Bryant and Leung4} Laboratory evidence of inflammation is routinely present. ^{Reference Feldstein, Rose and Horwitz1,Reference Godfred-Cato, Bryant and Leung4} The clinical presentation in patients has been similar to other pediatric inflammatory conditions, to include Kawasaki disease, toxic shock syndrome, bacterial sepsis, and macrophage activation syndrome. ^{Reference Feldstein, Rose and Horwitz1,Reference Ramcharan, Nolan and Lai3,Reference Godfred-Cato, Bryant and Leung4,Reference Ng, Kothari and Bandi6–Reference Chiotos, Bassiri and Behrens9} Although MIS-C has been compared to Kawasaki disease, several symptoms are more notable in MIS-C disease: presentation in older aged children, a predominance of abdominal symptoms, frequent lymphopenia, increased incidence of left ventricular systolic dysfunction, and acute heart failure. ^{Reference Ramcharan, Nolan and Lai3,Reference Godfred-Cato, Bryant and Leung4,Reference Pouletty, Borocco and Ouldali10,Reference Ebina-Shibuya, Namkoong, Shibuya and Horita11} MIS-C is likely a rare complication of SARS-CoV-2 infection, ^{Reference Feldstein, Rose and Horwitz1,Reference Godfred-Cato, Bryant and Leung4,Reference Panupattanapong and Brooks12} with a reported incidence of ˜2 in 100,000 persons <21 years of age. ^{Reference Chiotos, Hayes and Kimberlin19} Reported mortality is ˜1%–2%. ^{Reference Shields, Atlas, Strohm Farber and Lebet23–Reference Kwak, Lee and Choi25}

The pathogenesis of this syndrome is not completely delineated. ^{Reference Chiotos, Hayes and Kimberlin19–Reference Jiang, Tang and Levin22} However, it is thought to be a post–SARS-CoV-2 infection inflammatory syndrome based on the following (1) MIS-C incidence generally reaches its peak ˜1 month after a region’s peak in acute COVID-19 cases; (2) preceding symptoms consistent with acute COVID-19 are noted in certain children; and (3) many of the affected children demonstrate the presence of SARS-CoV-2 antibody in the setting of negative RT-PCR testing. ^{Reference Chiotos, Hayes and Kimberlin19,Reference Jiang, Tang and Levin22}

Role of SARS-CoV-2 testing in MIS-C for personal protective equipment (PPE) considerations

Several case reports and case series describing pediatric patients with MIS-C have been published, and some of these include information about the SARS-CoV-2 infection status. ^{Reference Feldstein, Rose and Horwitz1–Reference Godfred-Cato, Bryant and Leung4,Reference Ng, Kothari and Bandi6,Reference Chiotos, Bassiri and Behrens9,Reference Cheung, Zachariah and Gorelik13} In these studies, SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) positivity ranged from 13% to 70% of patients, and evidence of serologic conversion was noted in 73%–100%. ^{Reference Feldstein, Rose and Horwitz1–Reference Godfred-Cato, Bryant and Leung4,Reference Ng, Kothari and Bandi6,Reference Chiotos, Bassiri and Behrens9,Reference Cheung, Zachariah and Gorelik13} The presence of IgG in many of the patients with MIS-C suggests a postinfectious syndrome occurring outside the primary infection. ^{Reference Galeotti and Bayry8} However, the demonstration of SARS-CoV-2 virus RT-PCR positivity in these patients potentially suggests that the syndrome may occur in a later stage of primary infection. ^{Reference Galeotti and Bayry8}

Testing strategy and validity play important roles in PPE determination. Several factors influence the outcome of viral detection with RT-PCR, including intermittent viral shedding, ^{Reference Beeching, Fletcher and Beadsworth14} low viral levels in the upper respiratory tract, ^{Reference Fang, Naccache and Greninger15} and sampling error. ^{Reference Fang, Naccache and Greninger15} However, Greninger et al ^{Reference Greninger, Gombar and Hogan16} reported only 3.5% of a cohort of patients who initially tested negative for SARS-CoV-2 RT-PCR developed a positive test within 7 days, while most of those necessitating additional testing for any reason within the 7-day period remained negative for any additional testing.

Much remains unknown regarding the infectivity of patients with MIS-C who demonstrate SARS-CoV-2 RT-PCR positivity upon hospital admission. In light of current evidence, this article provides guidance on potential strategies for managing PPE in pediatric patients diagnosed with MIS-C.

Table 1. Admission and De-escalation Recommendations for SARS-CoV-2 Isolation Precautions in Children with Suspected MIS-C

Note. MIS-C, multisystem inflammatory syndrome in children; RT-PCR, reverse-transcriptase polymerase chain reaction.

^a Some institutions may require ≥2 consecutively negative SARS-CoV-2 RT-PCR testing.

^b Some institutions may require repeat SARS-CoV-2 RT PCR testing if admission presentation concerning for active COVID-19 infection.