Pediatric COVID-19 patients with multisystem inflammatory syndrome treated by extracorporeal membrane oxygenation: A systematic review

To the editor,

Multisystem inflammatory syndrome in children (MIS-C) is a critical scenario for pediatric patients with corona virus disease 2019 (COVID-19) infection. We performed a systematic review and 28 articles were retrieved from the database (MEDLINE, PUBMED, EMBASE). There were 1 review article and 8 articles which were overlapped or included in other studies, thus 19 articles were left for analysis. Among the 19 articles, there were 5383 MIS-C patients and extra-corporeal membrane oxygenation (ECMO) was used for 110 patients (2.0%). The mortality rates of the MIS-C patients with ECMO support were only reported by 17 studies and the pooled mortality rate was 20% (8/40). Among the 40 patients, the initial symptoms were detailed described for 15 MIS-C patients only (mean age 15.7 ± 5.6 years old, age range 2–19 years old) needing veno-arterial ECMO support, including fever (100%), abdominal pain (53.3%), vomiting (33.3%), hypotension (26.7%), diarrhea (20%), chest pain (6.7%), cough (6.7%) and so on. There was no significant increase of white blood cell (WBC) count (mean 11475/μL, range 6130–20000/μL), lymphocyte percentage (mean 6.5%, range 1%–15%) and platelet count (mean 144000/μL, range 89000–252000/μL) initially after symptom onset. However, there was significant increase of C-reactive protein (mean 13.8 mg/dL, range 1.81–45 mg/dL), D-dimer (mean 7597 ng/mL, range 168–18300 ng/mL), B-type natriuretic peptide (BNP) (mean 32888 pg/mL, range 2095–67725 pg/mL), and NT-pro BNP (mean 19329 pg/mL, range 3658–35000 pg/mL). The supporting duration of veno-arterial ECMO was 5.2 days (range 3–7 days). Right cerebral infarction was the main cause of death and was the sequela of dissection of right carotid artery for one of the survivors. The references for the systematic review were listed in a supplement file.

According to the systematic review, ECMO was only necessary for a small proportion of the MIS-C patients (2.0%). Regarding the initial presentations, there were significantly fewer patients who suffered from vomiting and diarrhea for the study group than for the nationwide data from USA¹ (Table 1 ). Moreover, there was a trend of fewer patients who suffered from hypotension initially for the study group, which indicated that hypotension was not always one of the initial presentations for the MIS-C patients who needed ECMO support.

Table 1.

Initial clinical presentation.

	Study group (n = 15)	Control group (n = 4470)	P value
Fever	100%	100%	1.000
Abdominal pain	53.3%	68.5%	0.264
Vomiting	33.3%	66.6%	0.011
Diarrhea	20.0%	53.8%	0.008
Chest pain	6.7%	14.1%	0.710
Cough	6.7%	29.4%	0.083
Hypotension	26.7%	51.7%	0.069

There was no significant increase of the initial WBC count, and even lymphocyte percentage did not show significant increase, which was not the typical pattern of viral infection. However, BNP or NT-pro BNP level was significantly elevated at the time of initial presentation, which should not be neglected and should be carefully monitored. The non-survivors mainly suffered from cerebral infarction in which right cerebrum was most frequently affected. The cannulation of right carotid artery for ECMO setup could be one of the most probable causes for the vulnerability of right cerebrum which could be further adversely affected by highly elevated D-dimer level which was one of the featured abnormalities for the MIS-C patients.

Study group: MIS-C patients for whom ECMO was used during hospitalization.

Control group: nationwide data for MIS-C patients in USA (reference 1).

ECMO: extra-corporeal membrane oxygenation.

Declaration of competing interest

No financial and non-financial conflicts of interest.

Appendix A. Supplementary data

The following is the supplementary data to this article: