A second case of multisystem inflammatory syndrome associated with SARS-CoV-2 in a liver-transplanted child.

Alanine transaminase

Aspartate aminotransferase

C‐reactive protein

Erythrocyte sedimentation rate

Multisystem inflammatory syndrome in children

To the editor,

We read Petters et al.’s case report of a 3‐year‐old liver transplant recipient with multisystem inflammatory syndrome in children (MIS‐C) with great interest. Since MIS‐C is a very rare complication of COVID‐19, the probability of a child with liver transplant developing MIS‐C should be extremely low. We present another case of MIS‐C in a liver transplant recipient, that of a 5‐year‐old boy of Comorian origin, with NBAS deficiency who received a reduced deceased donor transplant at the age of 2 years (previously reported in Chavany et al. ). He developed hepatic artery thrombosis postoperatively and EBV‐related lymphoproliferative disease, which resolved after immunosuppression was decreased. He was on tacrolimus monotherapy at presentation and was admitted to the emergency department for fever (39°C) with abdominal pain and non‐bloody diarrhea. Initial laboratory tests showed inflammatory syndrome (C reactive protein (CRP), 58 mg/L; fibrinogen, 5.64 g/L; white blood cells, 6.8 G/L; neutrophils, 4.5 G/L; lymphocytes, 1.4 G/L) and normal hepatic function and enzymes. Fever persisted for 6 days with headaches, asthenia, anorexia, abdominal pain, vomiting, and diarrhea. Ultrasound imaging on hospital days 1 and 5 showed a thickening of the terminal ileum with multiple mesenteric nodes. On day 3, CRP levels had increased up to 247 mg/L, ferritin was at 500 µg/L, triglyceride levels were normal (1.4 mmol/L). He had transient lymphopenia (0.7 G/L). He developed renal failure, with a nadir creatinine level on day 4 of 47 µmol/L (Schwartz creatinine clearance, 63 mL/min) and urea at 10.4 mmol/L with a normal therapeutic tacrolimus level. He also had mildly increased liver enzymes on day 5 which normalized spontaneously. He was treated empirically by triple antibiotic therapy: ceftriaxone for 7 days, metronidazole for 5 days, and amikacin for 2 days. His status improved on day 6 with resumption of feeding and gastrointestinal function. Chest X‐ray, electrocardiogram and cardiac ultrasonography results were all normal. Etiological investigations were negative. Specific anti SARS‐CoV‐2 IgG antibodies were detected. He had been in contact six weeks earlier with a person who had COVID‐19 and had rhinitis for 48 h the following week. Our patient, therefore, met the CDC case definition for MIS‐C: 5 years of age, fever, elevated inflammatory markers, clinically severe illness requiring hospitalization with organ involvement (renal and gastrointestinal), no plausible alternative diagnoses, COVID‐19 exposure, and SARS‐CoV‐2 positive serology (82 AU, N<1). The diagnosis was made on day 6, when the patient's condition had improved, therefore, he received no immunoglobulin or steroid treatment, and there was no cardiac involvement. At 2 weeks’ follow‐up, clinical examination and laboratory findings were normal (normal liver enzyme levels, CRP at 8 mg/L). We thought that NBAS deficiency may have been a risk factor, but the case reported by Petters et al. suggests that MIS‐C can occur in patients with other liver conditions. The similarities between the two cases are the patients’ non‐European ancestry (African‐American and Comorian), which has been linked to an increased risk of MIS‐C, their gastrointestinal symptoms and mild COVID‐19 course, which may have been a consequence of immunosuppressive therapy. Given that there are about 1200 liver‐transplanted children in France (https://rams.agence‐biomedecine.fr/greffe‐hepatique‐pediatrique‐0), and that the current seroprevalence of SARS‐CoV‐2 antibodies in France is about 20%, even one case would represent an approximately 20‐fold higher risk than expected (about 1/250 versus 1/5000). We cannot rule out that our case and Petters et al.’s are simply random occurrences but pediatric hepatologists should be aware of a possibly increased risk of MIS‐C in liver‐transplanted children. An international investigation should be conducted to assess this risk. Figure 1.

FIGURE 1

Timeline of key clinical events with associated laboratory evidence of inflammation during the patient's hospital stay Timeline. (A): Timeline of key clinical events, (B) laboratory evidence of inflammation during the patient's hospital stay

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare.

AUTHOR CONTRIBUTIONS

Duvant Pauline: Case design and writing. Roquelaure Bertrand: Case design. Morand Aurélie, Bosdure Emmanuelle, Garaix Florentine, and Zandotti Christine: Article review. Fabre Alexandre: Case design and supervision.