Extended hospital stay for a pediatric patient with multisystem inflammatory syndrome (MIS-C) and human enteric rhinovirus infection: a case report.

Pediatric multisystem inflammatory syndrome (MIS-C) is a serious consequence of severe SARS infection. It is unclear whether the co-occurrence of other viral respiratory diseases, such as human rhinovirus 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 child with MIS-C and HRV/ENT infection, who tested positive for HRV/ENT a few days before re-introduction of six days of fever, one day of vomiting, bilateral conjunctivitis and dyspnea, All are MIS-C compliant. Due to worsening hypotension, he was admitted to the pediatric intensive care unit (ICU) in a third center, where he received vasoactive support, intravenous immunoglobulin, and high doses of intravenous steroids. Due to his deteriorating respiratory condition, he was also started on anakinra with gradual improvement. He was hospitalized for 15 days. Co-occurrence of other viral infections may prolong hospitalization for patients with MIS-C.

an introduction

Pediatric multisystem inflammatory syndrome (MIS-C) is a post-infection inflammatory syndrome with a range of symptoms, including fever, mucocutaneous, gastrointestinal, cardiac, respiratory, and/or neurological symptoms. [1]. MIS-C usually occurs two to four weeks after an acute infection with SARS CoV 2. As of May 2022, more than 4,000 cases of MIS-C have been reported in the United States [1]. Several studies looking at clinical outcomes for pediatric patients with MIS-C in the United States indicate that the mean or median duration of hospitalization for MIS-C is seven days. [2-4]. Our patient, who developed severe multisystem disease including neurological involvement, was admitted for 15 days. It is possible that the hospital course and refractory respiratory features were exacerbated by HRV/ENT infection. Furthermore, the effect of co-viral infection on the MIS-C clinical phenotype has not yet been fully elucidated.

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We report the case of a three-year-old man who presented to an external emergency room (ER) with six days of fever and one day of bilateral conjunctivitis, vomiting and dyspnea. He was initially evaluated in the same emergency room for fever three days earlier. At that time, he tested positive for rhinovirus enterovirus (HRV/ENT), but negative for severe acute respiratory syndrome coronavirus-2 (SARS‐CoV‐2) by nasopharyngeal polymerase chain reaction. On re-presentation to the emergency room, he had a fever to 39°C and respiration to 60 breaths/min. Its oxygen saturation was 98% over room air. He had a bilateral conjunctival injection. His laboratory data showed hyponatremia with 126 mmol/L (range 135-148). C-reactive protein was elevated at >190 mg/L (range 0.00–3.00). The SARS‐CoV‐2 polymerase reaction was positive. His chest radiograph showed blurry densities around the auricle and peribronchial constriction (Fig. 1). 1). He had a brief, self-resolving episode with unilateral ocular deviation and treatment-resistant hypotension which prompted his transfer to the Pediatric Intensive Care Unit (ICU).

In the pediatric intensive care unit, he was started with 2 liters of oxygen via a nasal cannula, intravenous fluids, an anti-vascular, and experimental antibiotics. Additional study of anemia with thrombocytopenia, hyponatraemia revealed slight improvement since admission, elevation of ferritin, triglycerides, troponin, de-dimer, and urine protein to creatinine ratio (Table) 1). The SARS‐CoV‐2 antibodies were A and G positive. Chest radiograph showed diffuse pulmonary opacity with bilateral pleural effusion tracking (Fig 2). His ECHO showed normal functional coronary arteries and ventricles. He received intravenous immunoglobulin (IVIG) at 2 g/kg on admission, and was given high-dose intravenous (IV) methylprednisolone, aspirin, and enoxaparin. He discontinued his potency after an IVIG infusion with some improvement in inflammatory markers and was weaned off vascular handles and supplemental oxygen by day 4 of hospitalization. However, he soon after developed increased work of breathing, tachypnea, and desaturation that required restarting of supplemental oxygen. A chest X-ray showed right-sided deterioration of the pleural effusion, and his ECHO showed a small but normal pericardial effusion and coronary arteries. He was started on anakinra on the fifth day of hospitalization and completed a six-day course. Signs of inflammation continued to improve, and he was weaned to room air on day 10. He was discharged from the hospital on the fifteenth day of treatment with aspirin and oral prednisolone. It is followed longitudinally by heart disease and rheumatic diseases in children.

lab test Laboratory values ​​in the intensive care unit reference group
sodium 130 135-148 mmol/L
hemoglobin 9.4 11.6-13.6 g/dL
blood platelet 139 150-350 K/mm3
albumin 2.9 3.5-5.3 g/dL
ferritin 591 30-400 ng/ml
Triglyceride 305 0-150 mg/dL
Pro-BNP 1766 0-125 pg/ml
troponin 0.09 <0.04 ng/ml
d-dimer 1.16 0-0.49 mg/L
Urine protein to creatinine ratio 2.55 0.00-0.19 mg/mg

Discuss

Our patient presented with severe MIS-C, evidenced by its clinical features and laboratory findings. He also had a concurrent infection in the HRV/ENT. The reported rate of other respiratory viral infections in pediatric patients with SARS-CoV 2 varied from 3-12%. [5]. While bacterial co-infection is generally accepted to lead to a worse prognosis in severe SARS-CoV 2 infection, the impact of co-infection in MIS-C remains incomplete. [5]. A recent study showed that respiratory viral co-infection may contribute to increased oxygen requirements in MIS-C . [6]. However, respiratory syncytial virus (RSV) infection was more common in that population [6]. Before the SARS-CoV 2 pandemic, rhino/enterovirus was responsible for half to two-thirds of cold cases. HRV/ENT has also been associated with a more severe course of hospitalization than RSV and influenza A/B infection. [7]. While there are studies looking at the epidemiology of respiratory viral infections in children, case reports of co-infection with COVID-19 and mycoplasma or 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 inpatients with MIS-C often includes 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 biological therapy, and reduced length of stay. [9]. Anakinra (an IL-1 receptor antagonist), has been used for the off-label treatment of severe MIS-C based on clinical experience. Currently, there are limited pediatric studies on the effect of subcutaneous or intravenous anakinra on duration of hospitalization in MIS-C. Our case demonstrates that concurrent respiratory HRV/ENT may lead to more severe clinical outcomes, requiring combined therapy such as IVIG, steroids and/or anakinra, thus prolonging hospitalization.

Conclusions

MIS-C is an inflammatory complication of acute SARS-CoV-2 infection, often associated with serious involvement of peripheral organs, warranting intensive care level care. While MIS-C is a post-viral outcome, co-existence with respiratory HRV/ENT may prolong hospital stay, as demonstrated by our patient who required 15 days of hospitalization, which is more than double the seven-day average. reported by previous observational 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.