Potential KD resistant targeted genes predicted by bioinformatics analysis included LY6E, HERC5 and IDO1. In December 2019, a new infectious disease named Coronavirus disease 2019 (COVID-19) pneumonia infected by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared and spread rapidly worldwide. was called multisystem inflammatory syndrome. Simultaneously, the incidence rate of KD-like diseases are increased after the outbreak of COVID-19, suggesting the virus may be associated with KD. New intervention is important to overcome the problem of IVIG treatment resistance. This review Saridegib aims to introduce the current pharmacological intervention and possible resistance genes for the discovery of new drug for IVIG resistant KD. Current Opinion in Pharmacology 2020, 54:72C81 This review comes from a themed issue on Drug resistance Edited by Vincent Kam Wai Wong For a complete overview see the Issue and the Editorial Available online 18th September 2020 https://doi.org/10.1016/j.coph.2020.08.008 1471-4892/? 2020 Elsevier Ltd. All rights reserved. Introduction Kawasaki Disease (KD) was first described as the mucocutaneous lymph node syndrome in 1967 [1]. It is an acute systemic vasculitis and a multi-system disease that can lead to severe complications such as stenosis, thrombosis or coronary artery aneurysms (CAA) which can lead to sudden death [2]. According to the American Heart KLHL22 antibody Association (AHA) guideline, typical diagnostic symptoms and signs for children are fever, bulbar conjunctival injection, chapped lips, strawberry tongue, desquamation and skin peeling, rash, and cervical lymphadenitis [3,4]. Single Intravenous immunoglobulin (IVIG) therapy can reduce the risk of bulging of the artery wall and CAA which can lead to a heart attack [5?]. Up to now, Saridegib combined use of high dose of IVIG and aspirin remains the standard treatment for KD. In fact, about 10C20% of patients did not respond to standard primary treatment and developed resistance to IVIG. Unresponsiveness such as persistent fever after the standard IVIG treatment was considered as resistant KD [6] with increased risk of life-threatening complications such as the Kawasaki Disease Shock Syndrome (KDSS) or KD-MAS (KD-Macrophage activation syndrome) (Figure 1 ). Open in a separate window Figure 1 Symptoms, complications, possible treatments, and potential resistant target genes of IVIG resistant KD patient. KD patients commonly shared symptoms including fever, bulbar conjunctival injection, chapped lips, strawberry tongue, desquamation and skin peeling, rash and cervical lymphadenitis (in blue dotted circles). List of major complications for example, the coronary artery lesions (in red dotted rectangle) were presented. Other complications included coronary thrombosis, KDSS and MAC. Possible treatments for IVIG resistant KD patients including methylprednisolone, prednisone, infliximab, anakinra, canakinumab, cyclosporine, methotrexate, and plasmapheresis are listed. Potential KD resistant targeted genes predicted by bioinformatics analysis included LY6E, HERC5 and IDO1. In December 2019, a new infectious disease named Coronavirus disease 2019 (COVID-19) pneumonia infected by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) appeared and spread rapidly worldwide. On January 30th 2020, the World Health Organization (WHO) has announced SARS-CoV-2 as a health emergency of international concern. By March 11th 2020, the WHO recognized COVID19 as a pandemic. As of June 2020, the number of confirmed cases in the world has exceeded 10?000?000. Recently, many literatures reported the number of SARS-CoV-2 infected children with KD multisystem inflammatory syndrome (MIS-C) has increased sharply. While KD and MIS-C shared some common symptoms such as lymphadenopathy, skin rash, prolonged fever, diarrhea and upregulation of inflammation related protein markers [7,8], recent statistics have shown that the incidence rate of KD-like diseases increased by 30 times after the popularity of COVID-19 [9??]. Although without known pathophysiology, the recent increased cases of KD symptoms occurrence in COVID-19 patients have drawn researchers attention to the identification of alternate therapeutic drugs and molecular gene targets for both typical or resistant KD Saridegib [10]. Standard treatment of classical and refractory Kawasaki disease Intravenous immunoglobulin treatment and resistance in Kawasaki disease IVIG Saridegib treatment generally provide its anti-inflammatory effects via neutralization of the infectious antigens or pathogenic autoantibodies, inhibition of tumor necrosis factors (TNF)- and the release of inflammatory cytokines, and regulation on the function of both B and T cells [11, 12, 13]. According to AHA guidelines, patients with persistent fever lasting for 36?hours to a maximum of 7 days after first IVIG infusion is defined as IVIG resistant [4]. Although optimal therapeutic response can be observed when IVIG therapy is administered within 10 days since the symptom existed, or when a high dose of 2?g/kg was administered within 12?hours of symptom onset [4], around 5% of patients who received an appropriate IVIG treatment at an early stage still developed CAA [14]. Aspirin treatment and resistance in Kawasaki disease Single Acetylsalicylic acid (ASA) treatment shows significant anti-inflammatory activity (at a high dose of 30?100?mg/kg/day), anti-platelet activity (at a low dose of 3?5?mg/kg day), and may reduce the risk of vascular thrombosis. ASA combined with IVIG.