Prolonged Hospitalization in a Pediatric Patient With Multisystem Inflammatory Syndrome (MIS-C) and Human Rhino-Enterovirus Infection: A Case Report -…

Multisystem inflammatory syndrome in children (MIS-C) is a serious sequelaof acute SARS-CoV-2 infection. It is unclear whether the co-occurrence of other viral respiratory illnesses, such as the human rhino-enterovirus (HRV/ENT), prolongs hospitalization or affects the clinical phenotype of patients with MIS-C. We report the hospital course of a three-year-old with MIS-C and HRV/ENT infection, who tested positive for HRV/ENT infection a few days prior to re-presenting for six days of fever, one day of emesis, bilateral conjunctivitis, and shortness of breath, all consistent with MIS-C. Due to worsening hypotension, he was admitted to a pediatric intensive care unit (ICU) at a tertiary center, where he received vasoactive support, intravenous immunoglobulin, and high-dose intravenous steroids. Because of his worsening respiratory status, he was also started on anakinra with resultant gradual improvement. He was hospitalized for a total of 15 days. Concurrence of other viral infections may prolong hospitalization for patients with MIS-C.

Multisystem inflammatory syndrome in children (MIS-C) is a post-infectious inflammatory syndrome with a spectrum of presentations, including fever, mucocutaneous, gastrointestinal, cardiorespiratory, and/or neurological symptoms [1]. MIS-Ctypically occurstwo to four weeksfollowing an acute SARSCoV2 infection.As ofMay 2022, over 4,000cases ofMIS-Chadbeen reported in the United States [1]. Several studies investigating the clinical outcomes of pediatric patients with MIS-C in the United States suggest that the mean or median duration of hospitalization for MIS-C is seven days [2-4]. Our patient, who presented with severe multisystem disease including neurologic involvement, was admitted for a total of 15 days. It is possible that his hospital course and refractory respiratory features were compounded by his HRV/ENT infection. Furthermore, the impact of viral co-infection on MIS-C clinical phenotype is yet to be fully elucidated.

We report the case of athree-year-oldmale who presented to an outside emergency room (ER) with six days of fever and one day of bilateral conjunctivitis, emesis, and shortness of breath.He was initially evaluated in the same ER for fever three days prior. At that time, he had tested positive forrhino-enterovirus (HRV/ENT), but negative for severe acute respiratory syndrome coronavirus-2 (SARSCoV2) by nasopharyngeal PCR. Upon re-presenting to the ER, he was febrile to 39Cand tachypneic to 60 breaths/min. His oxygen saturation was 98% on room air. He had bilateral conjunctival injection. His laboratorydatashowed hyponatremia with sodium of 126 mmol/L (range 135-148). C-reactive protein was elevated at greater than 190 mg/L (range 0.00-3.00). His SARSCoV2 nasopharyngeal PCR was positive.His chest radiograph showed hazy peri-hilar densities andperi-bronchialcuffing (Figure 1).He had a brief, self-resolved seizure with unilateral eyedeviation and refractory hypotension prompting transfer to a tertiary pediatric intensivecare unit (ICU).

In thepediatric ICU, he was startedon 2 liters ofoxygen via nasal cannula, intravenous fluids, vasopressors, and empiric antibiotics. Additional workup revealedanemia with thrombocytopenia, slightly improved hyponatremia since admission, elevated ferritin, triglyceride, troponin, d-dimer, and urine protein to creatinine ratio (Table 1). His SARSCoV2 immunoglobulin A and G antibodies were positive.His chest radiograph showed diffuse pulmonary opacities with trace bilateral pleural effusions (Figure 2). His ECHO showed normal biventricular functional and coronary arteries.He received intravenous immunoglobulin (IVIG) at 2 g/kg on admission, and was placed on high-dose intravenous (IV) methylprednisolone, aspirin, andenoxaparin.He defervesced after IVIG infusion with some improvement of his inflammatory markers and wasweaned off vasopressors and supplemental oxygen by day 4 of hospitalization. However, he shortly developed increased work of breathing, tachypnea, and desaturations requiring re-initiation of supplemental oxygen.His chest X-ray showed worsening right-sided pleural effusion, and his ECHO showed a small pericardial effusion but normal function and coronaries. He was started on anakinra on day 5 of hospitalization and completed a six-day course.His inflammatory markers continued to improve, and he was weaned to room air on day 10. He was discharged on day 15 ofhospitalization on aspirin and an oral prednisolonetaper. He is followed longitudinally by pediatriccardiology and rheumatology.

Our patient presented with severe MIS-C, evidenced by his clinical features and laboratory findings. He also had a concurrent HRV/ENT infection. Thereportedrate of other respiratory viral coinfectioninpediatric patientswith SARSCoV2 hasvaried from 3-12% [5]. While bacterial co-infection is generally accepted to lead to a worse prognosis in acute SARSCoV2 infection, the impact of viral coinfections in MIS-C remains understudied [5]. A recent study showed that respiratory viral coinfections may contribute to the increased oxygen requirement in MIS-C [6]. However, respiratory syncytial virus infection (RSV) was most common in that population [6]. Prior to the SARSCoV2 pandemic, rhino/enterovirus was responsible for one-half to two-thirds of common colds. HRV/ENT has also been associated with a more severe hospitalization course than RSV and influenza A/B infections [7]. While there are studies looking at the epidemiology of respiratory viral coinfections in children, and case reports of co-infection with COVID-19 and mycoplasma or human metapneumoviruses in children [8], there is limited data on whether HRV/ENT in MIS-C specifically leads to adverse outcomes, including prolonged hospitalization.

Treatment of hospitalized patients with MIS-C often involves IVIG and steroids. There is some evidence that initiation of combination therapy with IVIG and steroids, compared to IVIG alone, is associated with a lower rate of treatment failure, escalation to biologic therapy, and decreased length of stay [9]. Anakinra (an IL-1 receptor antagonist), has been used for off-label treatment of severe MIS-C based on clinical expertise.Currently, there are limited pediatric studies on the impact of subcutaneous or intravenous anakinra on the duration of hospitalization in MIS-C. Our case highlights that concurrent HRV/ENT respiratory virus may lead to a more severe clinical outcome, requiring combination therapy such as IVIG, steroids, and/or anakinra, thereby prolonging the length of hospitalization.

MIS-C is an inflammatory complication of acute SARS-CoV-2 infection, and is often associated with serious end-organ involvement, warranting ICU-level of care. While MIS-C is a post-viral sequela, its co-occurrence with HRV/ENT respiratory virus may prolong hospital stay, as evidenced by our patient who required 15 days of hospitalization, which is more than twice the average of seven days reported by previous surveillance studies. Our case demonstrates the need for additional studies to better understand outcomes for patients with MIS-C and concurrent HRV/ENT infection, as well as to establish optimal treatment protocols.

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Prolonged Hospitalization in a Pediatric Patient With Multisystem Inflammatory Syndrome (MIS-C) and Human Rhino-Enterovirus Infection: A Case Report -...