Table 3.

Stepwise pathway to diagnosis.

	(A)	(B)	(C)	(D)
	IDENTIFICATION OF CARDINAL SYMPTOMS AND SIGNS	CONSIDERATION OF LIKELY DIAGNOSIS	SELECTION OF APPROPRIATE WORK-UP	INITIATION OF TREATMENT
1	Increased fever and inflammatory markers (CRP, ESR, WBC)	Bacterial infection	Search for source of infection (e.g., urinalysis, chest X-ray, microbiology); SARS-CoV-2 PCR	Antibiotics
NO IMPROVEMENT WITH ANTIBIOTIC TREATMENT
2	Persistent fever Abdominal pain Vomiting Rash Conjunctivitis Pleural effusion Arrhythmia Hematuria Proteinuria (dipstick test)	Resistant bacterial infection (e.g., intra-abdominal infection, pyelonephritis) Immune-mediated diseases (e.g., sJIA, MAS, Kawasaki disease, MIS-C) Glomerulonephritis (primary and secondary)	Electrolytes and acid-base status Liver function tests Lipid blood test Ferritin Coagulation Troponin I and proBNP Urea, creatinine, cystatin C 24-h urine protein test SARS-CoV-2 serology ECG Echocardiography Kidney ultrasound	None
MIS-C DIAGNOSIS ESTABLISHED
3	SARS-CoV-2 IgG	Vasculitis	Complement	IVIG
	Elevated d-dimers, fibrinogen and proBNB	SLE PIGN
	Persistent hematuria
	Persistent proteinuria (24-h urine test)
	Left diastolic dysfunction
COMPLETE RESOLUTION OF SYMPTOMS AND SIGNS
4	No relevant symptoms or signs	None	Follow up urine analysis, CBC, CRP, ESR, urea, and creatinine;	None
			ANA, ANCA, kidney biopsy (in case of hematuria and/or proteinuria relapse)
NO RELAPS OF SYMPTOMS AND SIGNS